Search "razergold.cfm?freicontent= site:".de"" - Uptodate Free (2024)

Patients undergoing chemotherapy for cancer using molecularly targeted agents, which take advantage of molecular abnormalities that drive cancer progression, require careful assessment of liver function both prior to and during therapy. Potential interactions between the liver and chemotherapy fall

Metastases to bone are a common site of cancer tumor burden for many types of solid tumors. Bone metastases cause substantial morbidity, including the need for radiation and/or surgery to bone, pathologic fractures, hypercalcemia of malignancy, and spinal cord compression [1,2]. (See"Epidemiology, c

A variety of kidney diseases and electrolyte disorders can result from the drugs that are used to treat malignant disease, including conventional cytotoxic agents; molecularly targeted agents, which take advantage of molecular abnormalities that drive cancer progression; and immunotherapeutic agents

Tendons are tough bands of tissue that connect muscles to bones. There are several types of tendon problems (called tendinopathies):●Repetitive activities and sudden trauma can injure tendons and lead to inflammation, pain, and difficulty using the joint. This is called tendinitis or tenosynovitis a

Intimate partner violence (IPV) is a serious, preventable public health problem affecting more than 32 million Americans [1]. In countries around the world, 10 to 69 percent of females report physical assault by an intimate partner at some time in their life [2].The term "intimate partner violence"

CloseSociety guideline links: Cystic fibrosisSociety guideline links: Cystic fibrosis Introduction — This topic includes links to society and government-sponsored guidelines from selected countries and regions around the world. We will update these links periodically; newer versions of some guidelines may be available on each society's website. Some societies may require users to log in to access their guidelines.The recommendations in the following guidelines may vary from those that appear in UpToDate topic reviews. Readers who are looking for UpToDate topic reviews should use the UpToDate search box to find the relevant content.Links to related guidelines are provided separately.●(See"Society guideline links: Hemoptysis".)●(See"Society guideline links: Nontuberculous mycobacteria".)●(See"Society guideline links: Pediatric liver disease".)●(See"Society guideline links: Chronic pancreatitis and pancreatic exocrine insufficiency".)●(See"Society guideline links: Lung transplantation".)●(See"Society guideline links: Bronchiectasis".)International●International Society for Pediatric and Adolescent Diabetes (ISPAD): Clinical practice consensus guidelines for the management of cystic fibrosis-related diabetes in children and adolescents (2018)●European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN): Nutritional considerations in pediatric pancreatitis (2018)●International Committee on Mental Health in Cystic Fibrosis (ICMH-CF): Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus statements for screening and treating depression and anxiety (2016)●ESPGHAN and NASPGHAN: Clinical report on the assessment of exocrine pancreatic function and pancreatitis in children (2015)United States●Cystic Fibrosis Foundation (CFF): Clinical care guidelines•Age-specific care guidelines•CFTR modulator therapy care guidelines•Diagnosis clinical care guidelines•Infection prevention and control care guidelines•Nutrition and GI care guidelines•Other CF-related conditions care guidelines•Respiratory care guidelines•Screening and treating depression and anxiety guidelines●Academy of Nutrition and Dietetics (AND): Cystic fibrosis (CF) guideline (2020)●AND: CF – Guideline recommendations and supporting evidence (2020)●CFF: Consensus guidelines for the care of individuals with advanced cystic fibrosis lung disease (2020)●Cystic Fibrosis Colorectal Cancer Screening Task Force: Cystic fibrosis colorectal cancer screening consensus recommendations (2017)●CFF and European Cystic Fibrosis Society (ECFS): Consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis (2015)●American Thoracic Society (ATS): An official workshop report on optimal lung function tests for monitoring cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheezing in children less than 6 years of age (2013)●American Diabetes Association (ADA) and CFF: Clinical care guidelines for cystic fibrosis-related diabetes (2010)Europe●European Respiratory Society (ERS)/Thoracic Society of Australia and New Zealand (TSANZ): Statement on the management of reproduction and pregnancy in women with airways diseases (2020)●European Cystic Fibrosis Society (ECFS): Best practice guidelines (2018)●European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN): Nutritional considerations in pediatric pancreatitis (2018)●Cystic Fibrosis Foundation (CFF) and ECFS: Consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis (2016)●ERS/ECFS: Report on the care of adults with cystic fibrosis (2016)●European Society for Clinical Nutrition and Metabolism (ESPEN)-ESPGHAN-ECFS: Guidelines on nutrition care for infants, children, and adults with cystic fibrosis (2016) ●ESPGHAN and NASPGHAN: Clinical report on the assessment of exocrine pancreatic function and pancreatitis in children (2015)●ECFS: Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease (2011)●ECFS: End of life care for patients with cystic fibrosis (2011)●ECFS: European cystic fibrosis bone mineralisation guidelines (2011)●ECFS: Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients (2011)●ECFS: Guiding principles on how to manage relevant psychological aspects within a CF team – Interdisciplinary approaches (2011)●ESPGHAN: Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS (2010)●ECFS: European best practice guidelines for cystic fibrosis neonatal screening●ECFS: Guidelines for the management of pregnancy in women with cystic fibrosis (2008)United Kingdom●Cystic Fibrosis Trust: Consensus documents●National Institute for Health and Care Excellence (NICE): Quality standard on cystic fibrosis (2018)●NICE: Guideline on cystic fibrosis – Diagnosis and management (2017)●Royal College of Paediatrics and Child Health (RCPCH): Guidelines for the performance of the sweat test for the investigation of cystic fibrosis in the UK, 2nd version (2014)Australia-New Zealand●European Respiratory Society (ERS)/Thoracic Society of Australia and New Zealand (TSANZ): Statement on the management of reproduction and pregnancy in women with airways diseases (2020)●TSANZ: Position paper on work environment risks for health care workers with cystic fibrosis (2018)●TSANZ: Nutrition guidelines for cystic fibrosis in Australia and New Zealand (2017)●TSANZ: Clinical practice guideline for physiotherapy for cystic fibrosis in Australia and New Zealand (2016)●Asian Pacific Society of Respirology (APSR): Clinical practice guideline on Australian standards of care for cystic fibrosis-related diabetes (2013)●Cystic Fibrosis Australia: Cystic fibrosis standards of care, Australia (2008)Topic 109226 Version 25.0

ClosePharmaco*kinetic properties of proton pump inhibitors in adultsPharmaco*kinetic properties of proton pump inhibitors in adults Agent Regimen tested Oral bioavailability Time to peak (hours) Cmax (micrograms/mL) AUC0-24 (mg•h/L) Metabolism and clearance Half-life (hours)* pKa¶ Dexlansoprazole 30 mg once daily Absorbed to a similar extent under fasting and fed conditions1-2 (peak 1) 4-5 (peak 2) 0.7 3.3 Hepatically by CYP2C19Δ and 3A4; inactive metabolites are excreted in urine and feces 1-2 Not available Esomeprazole 20 mg once daily64% (single dose); 90% (after multiple doses if taken on an empty stomach; bioavailability is reduced by ~50% if taken with food) 1-1.6 2.1 (micromol/L) 4.2 (micromol•h/L) Hepatically by CYP2C19Δ and 3A4; inactive metabolites are excreted in urine and feces 1.2-2.5 4.0 Lansoprazole 30 mg once daily 85% (taken on an empty stomach; absorption is reduced by ~50% if taken with food) 1.5-3 0.5-1.0 3.2 Hepatically by CYP2C19Δ and 3A4; inactive metabolites are excreted in feces via bile and in urine 0.9-1.5 4.0 Omeprazole 20 mg once daily (delayed release capsule)45% (single dose) Varies by formulation; absorption is significantly increased after multiple doses 0.5-3.5 0.7 3.3 Hepatically by CYP2C19Δ and 3A4; inactive metabolites are excreted in urine and bile 0.5-3 4.0 Pantoprazole 40 mg once daily 77% 2-2.5 2.5 5.0 Hepatically by CYP2C19Δ and 3A4; inactive metabolites are excreted in urine and feces via bile 1 (increased to 3.5-10 hours in CYP2C19 poor-metabolizers) 3.9 Rabeprazole 20 mg once daily 52% 2-5 0.4-0.48 0.9 Hepatically by CYP2C19Δ and 3A4; inactive metabolites are excreted in urine and feces via bile 1-2 5.0AUC0-24: cumulative systemic drug exposure as measured by the area under the plasma concentration versus time curve over 24 hours; Cmax: maximum plasma concentration; pKa: acid dissociation constant transformed by negative log; PPI: proton pump inhibitor.* Duration of antisecretory effect of PPIs exceeds that predicted by drug half-life due to irreversible binding at site of action (ie, parietal proton pumps).¶ PPIs are converted to their active form (ie, protonated) when pH of parietal cell is lower than pKa of the individual PPI (ie, in presence of gastric acidity). For detail, refer to accompanying text.Δ Drug metabolism via hepatic CYP2C19 enzymes is polymorphic; thus, PPI systemic exposure (AUC0-24) can be increased several (ie, 2 to 12) times in patients who are intermediate or poor-metabolizers compared with those who are extensive-metabolizers (ie, most patients). 15-20% of persons of Asian descent are CYP2C19 poor-metabolizer phenotypes.Prepared with data from: United States prescribing information available at US National Library of Medicine DailyMed website (https://dailymed.nlm.nih.gov/dailymed/index.cfm).Graphic 72598 Version 6.0

The development of novel anticancer therapies over the past two decades has improved patient survival rates compared with conventional chemotherapy. Several of these agents take advantage of molecular abnormalities that have been detected in certain types of cancer and are collectively referred to a

ClosePatient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (Beyond the Basics)Author:Daniel H Solomon, MD, MPH Section Editor:Daniel E Furst, MD Deputy Editor:Philip Seo, MD, MHSLiterature review current through: Nov 2022. | This topic last updated: Mar 08, 2022.Please read the Disclaimer at the end of this page.NONSTEROIDAL ANTIINFLAMMATORY DRUG OVERVIEW — Nonsteroidal antiinflammatory drugs (NSAIDs) are medications used to relieve pain and to reduce inflammation. They are some of the most commonly used medications in adults. A variety of NSAIDs are available, including at least 20 in the United States and more elsewhere. Many are available as pills that can be purchased without a prescription ("over-the-counter"), and some are available as topical creams or gels.Because of the wide availability and frequency of use of NSAIDs, it is important to be aware of their proper use, dose, and potential side effects.CHOOSING A NONSTEROIDAL ANTIINFLAMMATORY DRUG — It can be difficult to know which NSAID is best for a given individual. In addition, a person's response to a particular NSAID is hard to predict. If two people take identical drugs and doses, their individual responses may be considerably different. It is sometimes necessary to try one drug for a few weeks and then try a different one to find the optimal NSAID.A health care provider is the most qualified person to help choose an NSAID, although you can assist in the decision-making process.TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUGS — Several NSAIDs are available as creams and gels for topical use (to be applied directly to the skin). These agents have been shown to have similar benefits to taking NSAIDs in pill form in osteoarthritis and low back pain. Topical use may be safer than the pill form.HOW NONSTEROIDAL ANTIINFLAMMATORY DRUGS WORK — NSAIDs work to reduce pain and inflammation by inhibiting enzymes, called cyclooxygenases (COX). By inhibiting COX, NSAIDs help to prevent and/or reduce pain and inflammation. COX enzyme inhibition is also responsible for many of the side effects of NSAIDs.TYPES OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS — There are two main types of NSAIDs, nonselective and selective. The terms nonselective and selective refer to different NSAIDs' ability to inhibit specific types of COX enzymes; the primary types are COX-1 and COX-2.●Nonselective NSAIDs – Nonselective NSAIDs inhibit both COX-1 and COX-2 enzymes to a significant degree.●Selective NSAIDs – Selective NSAIDs inhibit COX-2, an enzyme found at sites of inflammation, more than COX-1, the type that is normally found in the stomach, blood platelets, and blood vessels.Nonselective NSAIDs — Nonselective NSAIDs include drugs commonly available without prescription, such as aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve), as well as many prescription-strength NSAIDs.People with known coronary artery disease (eg, past history of heart attack, angina [chest pain due to narrowed heart arteries], history of a stroke, or narrowed arteries to the brain) and people who are at a higher than average risk for these conditions should avoid using nonselective NSAIDs.Selective NSAIDs — Selective NSAIDs (also called COX-2 inhibitors) are as effective in relieving pain and inflammation as nonselective NSAIDs and are less likely to cause gastrointestinal injury. Celecoxib (Celebrex) is a selective NSAID that is available in the United States. Other selective NSAIDs that can be found elsewhere in the world include etoricoxib (Arcoxia) and lumiracoxib (Prexige).Selective NSAIDs are sometimes recommended for people who have had a peptic ulcer, gastrointestinal bleeding, or gastrointestinal upset when taking nonselective NSAIDs. Selective NSAIDs have less potential to cause ulcers or gastrointestinal bleeding.Precautions with selective NSAIDs — Two selective NSAIDs, rofecoxib (brand name: Vioxx) and valdecoxib (brand name: Bextra), were taken off the market in 2004 when it was discovered that people who took these medications had a slightly increased risk of heart attack and stroke.People with known coronary artery disease (eg, past history of heart attack, angina [chest pain due to narrowed heart arteries], history of a stroke, or narrowed arteries to the brain) and people who are at a higher than average risk for these conditions should avoid using COX-2 inhibitors.NSAIDs are generally not recommended for people with kidney disease, heart failure, or cirrhosis, or for people who take diuretics. Some patients who are allergic to aspirin may be able to take selective NSAIDs safely, although this should be discussed in advance with a health care provider.Dose of NSAIDs — Lower doses of NSAIDs, as recommended for use with nonprescription NSAIDs, are adequate to relieve pain in most people.If the initial dose of NSAIDs does not improve symptoms, a clinician may recommend increasing the dose gradually or switching to another NSAID. People taking one NSAID should not take a second NSAID at the same time. If low doses of NSAIDs are not fully effective, clinicians may recommend using a higher dose of the NSAID on a regular basis for several weeks to improve the antiinflammatory benefits of these drugs.NONSTEROIDAL ANTIINFLAMMATORY DRUG SIDE EFFECTS — Most people tolerate NSAIDs without any difficulty. However, side effects can occur. The most notable side effects include the following:●Cardiovascular system – Blood pressure may rise with use of NSAIDs. Control of treated hypertension may be adversely affected by the addition of either selective or nonselective NSAIDs.●Gastrointestinal system – Short-term use of NSAIDs can cause stomach upset (dyspepsia). Long-term use of NSAIDs, especially at high doses, can lead to peptic ulcer disease and bleeding from the stomach. (See 'Ulcer disease' below.)●Liver toxicity – Long-term use of NSAIDs, especially at high doses, can rarely harm the liver. Monitoring the liver function with blood tests may be recommended in some cases.●Kidney toxicity – Use of NSAIDs, even for a short period of time, can harm the kidneys. This is especially true in people with underlying kidney disease. The blood pressure and kidney function should be monitored at least once per year but may need to be checked more often, depending on a person's medical conditions. (See 'Kidney disease' below.)●Ringing in the ears – Ringing in the ears (tinnitus) is common in people who take high doses of aspirin, although it is very uncommon for this to occur in people who take other NSAIDs. The ringing usually resolves when the dose is decreased.MEDICAL CONDITIONS AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS — People with some medical problems and those taking various medications are at increased risk of complications related to NSAIDs. Potential complications of NSAIDs include the following:Hypertension — As noted above, the addition of either a selective or a nonselective NSAID to the medications taken by someone with hypertension can result in a loss of blood pressure control. If NSAIDs are required, they should be used at the lowest effective dose and for the shortest duration necessary for the given indication. If chronic use of NSAIDs is anticipated, changes in blood pressure medications may be required.Cardiovascular disease — Anyone who is at risk for or who has cardiovascular disease (coronary artery disease) may have a further increase in risk of heart attacks when taking an NSAID. This includes people who have experienced a heart attack, angina (chest pain due to narrowed arteries in the heart), procedures to widen clogged arteries, a stroke, or narrowed arteries to the brain. As a result, people who have or who are at high risk for coronary artery disease are generally advised to avoid NSAIDs or, if that is not possible, to take the lowest possible dose of NSAID for the shortest possible time.Although aspirin is an NSAID, the recommendation to avoid or limit the use of NSAIDs does NOT apply to people who have been advised to take low-dose aspirin to treat or prevent heart attacks or strokes. However, the use of any dose of aspirin plus an NSAID is associated with an increased risk of bleeding. There is also an increased risk of bleeding when NSAIDs are used in patients taking other drugs that reduce clotting, such as anticoagulants (eg, warfarin) or antiplatelet agents (eg, clopidogrel). There is also some concern that nonselective NSAIDs may reduce the cardiovascular benefits of low-dose aspirin. (See 'Interaction with other medications' below.)Ulcer disease — Those who have had a stomach or intestinal ulcer are at an increased risk of another ulcer while taking an NSAID. People being treated for ulcers should consult their health care provider about the safety of taking NSAIDs or drugs containing aspirin. People over 65 years of age have an increased risk of developing ulcers when taking NSAIDs. (See"Patient education: Peptic ulcer disease (Beyond the Basics)".)Reducing ulcer risk — The risk of developing ulcers can be reduced by taking an anti-ulcer medication in addition to an NSAID. Anti-ulcer agents that reduce gastrointestinal damage from NSAIDs include:●Inhibitor of stomach acid production – High doses of antacid histamine blockers, such as famotidine (Pepcid), and ordinary doses of the acid production inhibitors, such as omeprazole (Prilosec) or lansoprazole (Prevacid), can reduce the risk of developing an ulcer (related to use of an NSAID).Bleeding — People who have had bleeding from the stomach, upper intestine, or esophagus have an increased risk of recurrent bleeding when taking NSAIDs.People with platelet disorders such as von Willebrand disease, abnormal platelet function from uremia, and a low platelet count (thrombocytopenia) are advised to avoid NSAIDs.Before surgery — Most clinicians recommend stopping all NSAIDs approximately one week before elective surgery to decrease the risk of excessive bleeding. This usually includes aspirin, ibuprofen, naproxen, and most prescription NSAIDs. Specific instructions regarding NSAIDs and surgery should be discussed with the surgeon and with the clinician who prescribed the NSAID.Interaction with other medications●Warfarin and heparin – People using anticoagulant medications such as warfarin (brand name: Jantoven) and heparin; a newer anticoagulant such as dabigatran (brand name: Pradaxa), rivaroxaban (brand name: Xarelto), apixaban (brand name: Eliquis) or edoxaban (brand name: Savaysa); or an anti-platelet drug such as clopidogrel (brand name: Plavix), should generally not take NSAIDs or aspirin because of an increased risk of bleeding when both classes of drugs are used. (See"Patient education: Warfarin (Beyond the Basics)".)Celecoxib may be safe in such instances but should be used with caution and under the guidance of a clinician.●Aspirin – As noted above, the combination of low-dose aspirin and an NSAID may increase the risk of bleeding. To preserve the benefit of low-dose aspirin for the heart, aspirin should be taken at least two hours before the NSAID.●Phenytoin – Taking an NSAID and phenytoin (Dilantin, Phenytek) can increase the phenytoin level. As a result, people who take phenytoin should have a blood test to monitor the phenytoin level when starting or increasing the dose of an NSAID.●Cyclosporine – People who take cyclosporine (eg, to prevent rejection after an organ transplant or for a rheumatic disease, such as rheumatoid arthritis) should take particular care when taking an NSAID. There is a theoretical risk of kidney damage when cyclosporine and NSAIDs are taken together. To monitor for this complication, blood testing may be recommended.●People taking one NSAID should not take a second NSAID at the same time because of the increased risk of side effects.Fluid retention — People with medical conditions that require diuretics, including heart failure, liver disease, and kidney damage, are at increased risk of developing kidney damage while taking nonselective NSAIDs (eg, ibuprofen) as well as selective NSAIDs (eg, celecoxib [Celebrex]).Kidney disease — NSAIDs can worsen kidney function in people whose kidneys are not functioning normally. Most people with chronic kidney disease are advised to avoid all types of NSAIDs. (See"Patient education: Chronic kidney disease (Beyond the Basics)".)Aspirin allergy — People who have had hives (urticaria) or other symptoms of an allergy to aspirin should generally avoid NSAIDs, unless they have specifically discussed their reaction with a health care provider. People with certain types of reactions to one NSAID may be able to take another type safely. It may be necessary to consult with an allergy specialist who has experience with allergic reactions to NSAIDS. (See"Patient education: Hives (urticaria) (Beyond the Basics)".)Aspirin and other NSAIDs may also cause worsening of asthma and related symptoms in some people with these conditions. This is not a true allergy but can be a significant problem for some people, who may need to avoid these medications if this occurs.Celecoxib may be a safe alternative to aspirin in such people, but should be used with caution under the supervision of a clinician.Pregnancy and breastfeeding — NSAIDS are not generally recommended for pregnant women during the third trimester due to an increased risk of complications in the newborn. NSAIDs are safe for use during breastfeeding. (See"Patient education: Health and nutrition during breastfeeding (Beyond the Basics)".)NONSTEROIDAL ANTIINFLAMMATORY DRUG OVERDOSE — Accidentally or intentionally taking a larger than recommended dose of an NSAID does not usually cause serious complications. However, taking large doses of other pain medications may have more serious consequences. For example, overdose with salicylates (eg, aspirin) or acetaminophen (eg, Tylenol) can be harmful or even fatal.People who accidentally or intentionally take an overdose of any medication should contact their health care provider or the Poison Control Hotline (in the United States, 1-800-222-1222). If the person is not breathing or is not conscious, emergency medical attention is needed; this is available in most areas of the United States by calling 911.WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.Patient level information — UpToDate offers two types of patient education materials.The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Patient education: Nonsteroidal antiinflammatory drugs (NSAIDs) (The Basics) Patient education: Osteoarthritis (The Basics) Patient education: Bursitis (The Basics) Patient education: von Willebrand disease (The Basics) Patient education: Ankylosing spondylitis (The Basics) Patient education: Calcium pyrophosphate deposition disease (The Basics) Patient education: Biceps tendinopathy (The Basics) Patient education: Elbow tendinopathy (tennis and golf elbow) (The Basics) Patient education: Separated shoulder (The Basics) Patient education: Giving your child over-the-counter medicines (The Basics) Patient education: Hand pain (The Basics) Patient education: Achilles tendon injury (The Basics) Patient education: Reactive arthritis (The Basics) Patient education: Toxic hepatitis (The Basics) Patient education: Clavicle fracture (The Basics) Patient education: de Quervain tendinopathy (The Basics) Patient education: Tenosynovitis (The Basics) Patient education: Rib fractures in adults (The Basics) Patient education: Shinbone fracture (The Basics) Patient education: Vertebral compression fracture (The Basics) Patient education: Nose fracture (The Basics) Patient education: Juvenile idiopathic arthritis (The Basics) Patient education: Boxer's fracture (The Basics) Patient education: Meniscal tear (The Basics) Patient education: Muscle strain (The Basics) Patient education: Patellofemoral pain (The Basics) Patient education: Metatarsalgia (The Basics) Patient education: Toe fracture (The Basics) Patient education: Pelvic fracture (The Basics) Patient education: Neck fracture (The Basics) Patient education: Hemophilia (The Basics) Patient education: Groin strain (The Basics) Patient education: Chondromalacia patella (The Basics) Patient education: Erythema nodosum (The Basics) Patient education: Opioid medicines for short-term treatment of pain (The Basics) Patient education: Chronic hives (The Basics) Patient education: Iliotibial band syndrome (The Basics) Patient education: Psoriatic arthritis in adults (The Basics) Patient education: Psoriatic arthritis in children (The Basics) Patient education: Diffuse idiopathic skeletal hyperostosis (The Basics) Patient education: Ehlers-Danlos syndrome (The Basics) Patient education: Microscopic colitis (The Basics) Patient education: Choosing a medicine for blood clots (The Basics) Patient education: Taking medicines for blood clots (The Basics)Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon. Patient education: Peptic ulcer disease (Beyond the Basics) Patient education: Warfarin (Beyond the Basics) Patient education: Chronic kidney disease (Beyond the Basics) Patient education: Hives (urticaria) (Beyond the Basics) Patient education: Health and nutrition during breastfeeding (Beyond the Basics)Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading. COX-2 inhibitors and gastroduodenal toxicity: Major clinical trials NSAIDs: Adverse cardiovascular effects Nonselective NSAIDs: Overview of adverse effects NSAIDs (including aspirin): Pathogenesis and risk factors for gastroduodenal toxicity NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity NSAIDs (including aspirin): Role in prevention of colorectal cancer NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity NSAIDs (including aspirin): Treatment of gastroduodenal toxicity NSAIDs and acetaminophen: Effects on blood pressure and hypertension NSAIDs: Acute kidney injury NSAIDs: Adverse effects on the distal small bowel and colon NSAIDs: Electrolyte complications NSAIDs: Pharmacology and mechanism of action NSAIDs: Therapeutic use and variability of response in adults Overview of COX-2 selective NSAIDsThe following organizations also provide reliable health information.●National Library of Medicine(www.nlm.nih.gov/medlineplus/healthtopics.html)●American Academy of Orthopaedic Surgeons(http://orthoinfo.aaos.org/topic.cfm?topic=A00284)●United States Food and Drug Administration(www.fda.gov)[1-6]Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. BMJ 2004; 329:324.Simon LS, Grierson LM, Naseer Z, et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009; 143:238.Brooks PM, Day RO. Nonsteroidal antiinflammatory drugs--differences and similarities. N Engl J Med 1991; 324:1716.Walker JS, Sheather-Reid RB, Carmody JJ, et al. Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis: support for the concept of "responders" and "nonresponders". Arthritis Rheum 1997; 40:1944.Ray WA, Stein CM, Daugherty JR, et al. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002; 360:1071.Solomon DH, Schneeweiss S, Glynn RJ, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004; 109:2068.This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circ*mstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof.The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms ©2023 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.Topic 519 Version 35.0References1 : Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials.2 : Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis.3 : Nonsteroidal antiinflammatory drugs--differences and similarities.4 : Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis: support for the concept of "responders" and "nonresponders".5 : COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease.6 : Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults.

ClosePatient education: Anterior cruciate ligament injury (Beyond the Basics)Patient education: Anterior cruciate ligament injury (Beyond the Basics)Author:Ryan P Friedberg, MD Section Editor:Karl B Fields, MD Deputy Editor:Jonathan Grayzel, MD, FAAEMLiterature review current through: Nov 2022. | This topic last updated: Oct 04, 2022.Please read the Disclaimer at the end of this page.ANTERIOR CRUCIATE LIGAMENT INJURY OVERVIEW — The anterior cruciate ligament (ACL) is an important stabilizing ligament in the knee. It is frequently injured by athletes and trauma victims; in the United States alone, there are between 100,000 and 200,000 ACL tears per year.This topic review will discuss the causes, signs and symptoms, diagnostic tests, and treatment options (including surgery) for ACL injuries.WHAT IS THE ANTERIOR CRUCIATE LIGAMENT? — The knee joint is held tightly together by four ligaments: the inner and outer fan-shaped hinge ligaments (medial and lateral collateral ligaments) and the crossing (cruciate) ligaments, which sit in the middle of the joint (the anterior and posterior cruciate ligaments) (figure 1).The collateral ligaments are firmly attached to the far end of the femur (thigh bone) and the near end of the tibia and fibula (lower leg bones). The ligaments hold the two bones together and prevent side to side motion. The anterior cruciate ligament (ACL) prevents forward and backward motion. You can partially or completely tear the ligament(s).Other structures can be damaged during an acute ACL injury, including:●The meniscus●The joint capsule (the tissue that surrounds the joint)●Articular cartilage (cartilage that covers the ends of bones where they meet in a joint)●The ends of the femur or tibia●Other ligaments (medial collateral ligament [MCL], lateral collateral ligament [LCL], posterior cruciate ligament [PCL]) (figure 2)One common injury is called the "athlete's triad," in which the ACL, MCL, and medial meniscus are all torn.CAUSES OF ANTERIOR CRUCIATE LIGAMENT INJURY — Non-contact anterior cruciate ligament (ACL) injuries typically occur when a person is running or jumping and then suddenly slows and changes direction (eg, cutting) or pivots in a way that involves rotating or bending the knee sideways. Women appear to be at a higher risk of non-contact ACL injuries than men, although the exact reason for this is not clear.Contact-related ACL injuries usually occur from a direct blow causing hyperextension or when the knee is forced inwards towards the other leg. This is often seen in American football when a player's foot is planted and an opponent strikes him on the outside or front of that thigh.ACL injuries most commonly occur during the following activities:●Noncontact sports, such as downhill skiing, gymnastics, and tennis●Certain contact sports, including rugby, American football, soccer, and basketball●Motor vehicle collisionsANTERIOR CRUCIATE LIGAMENT INJURY SYMPTOMS — People who have an anterior cruciate ligament (ACL) injury often complain of feeling a "pop" in their knee at the time of injury and have a feeling the knee is unstable or "giving out." Within a few hours of the ACL injury, nearly everyone develops swelling in the knee, caused by bleeding from injured blood vessels; this is called an effusion.After the initial swelling has improved, most people are able to bear weight but feel unsteady on the affected knee. Movements such as squatting, pivoting, and stepping sideways, and activities such as walking down stairs, in which the entire body weight is placed on the affected leg, can cause the feeling of unsteadiness.ANTERIOR CRUCIATE LIGAMENT INJURY TESTS — If you have a knee injury followed by pain, swelling, and/or an unsteady feeling while standing, see a healthcare provider for evaluation. He or she will do a physical examination and may recommend imaging tests to look at your bones and ligaments.ANTERIOR CRUCIATE LIGAMENT INJURY TREATMENT — Anterior cruciate ligament (ACL) injuries are treated with surgery and post-surgical rehabilitation or a non-surgical rehabilitation program. The decision to have surgery is based upon several factors, including your age, how active you are, and whether you have other knee injuries. When deciding whether to have surgery, it's also important to think about how the recovery process will impact your life. (See 'What to expect after surgery' below.)You may choose to have surgery if you:●Participate in high-level sports or have a job that requires a strong and stable knee (eg, requires twisting and pivoting)●Are unsteady when standing on the injured knee●Have multiple injuries (eg, meniscal tear and ACL tear)●Have completed rehabilitation and still have instability in the knee●Are willing to complete the rigorous post-surgical rehabilitation program. Most programs require daily strengthening and stretching exercises and one or more weekly visits with a physical therapist for the first three to six months after surgery (see 'Post-surgical rehabilitation' below). Failure to follow this program could increase the risk of re-injury, allow scar tissue to develop, and lead to limited movement of the knee.You may decide not to have surgery if you:●Have a small partial tear in the ACL that may heal with rest and rehabilitation●Do not participate in sports that require pivoting or stopping quickly, especially if you are older than 55 years●Are willing to complete a non-surgical rehabilitation program to strengthen and stabilize the knee (see 'Non-surgical rehabilitation' below)If you do not have surgery to reconstruct your ACL, you may be at an increased risk of future knee problems, including chronic pain, a decreased level of activity, and injury to other parts of the knee (the meniscus). However, surgery is also not a "quick fix," as it involves a challenging recovery period and requires committing to a rigorous rehabilitation program.Presurgical rehabilitation — Surgery is not usually performed immediately after an ACL injury because this could cause excessive scar tissue (arthrofibrosis) to develop, which would limit knee motion. In most cases, surgery is delayed until the swelling has resolved and the person is able to bend and straighten the knee without difficulty. Using ice packs and elevating the knee above the chest can help to reduce swelling. The time between an ACL injury and surgical reconstruction depends upon how quickly the person recovers, but it is often at least two to four weeks from the date of injury. In some cases, patients are uncertain about surgery or do not want surgical repair initially but subsequently change their mind, causing the procedure to be delayed for weeks or months. Provided no further injury occurs, such delays do not appear to alter the effectiveness of surgical repair. During the time between the injury and the surgery, many surgeons recommend a "pre-habilitation" exercise program to help reduce pain and swelling, improve range of motion (the ability to flex and extend the knee), and increase strength in the muscles of the thigh, knee, and hip. Walking, bike riding, and swimming (with light kicks and no breast stroke) can be continued, although other sports should be avoided.An example of a presurgical rehabilitation exercise program is detailed below. (See 'Non-surgical rehabilitation' below.)Surgery — After the ACL is torn, it is not possible to repair the ligament. This is due to several factors, including a damaged blood supply to the ligament (blood vessels damaged during injury) and cells inside the synovial fluid (normal fluid in the knee), that prevent healing. Research is underway to determine how to repair the native tendon, but the only way to repair the ACL currently is to reconstruct it.Surgical reconstruction of the ACL is usually done in a hospital or surgical center. Most people are given general anesthesia to induce sleep and prevent pain. The surgery itself usually takes less than two hours.To reconstruct the torn ligament, a piece of healthy tendon, called an autograft, is removed or "harvested" from another area in the leg. There are several common autograft sites, including the patellar tendon, hamstring tendon, or rarely the quadriceps tendon (figure 3). Another option is to use a tendon from a deceased donor, called an allograft. No one type of graft has been proven to be better than another. Thus, the type of graft that is used depends upon the surgeon's preference and experience.●Patellar autograft – When harvesting a patellar autograft, an extra incision is made in the skin to remove a strip of tendon with a piece of bone at each end. The graft site usually heals quickly and regains normal strength. Some people have soreness in this area for several months after surgery, especially if pressure is applied to the area (eg, while kneeling).●Hamstring autograft – If using a hamstring autograft, there are no extra incisions needed and the pain at the harvest site is usually less than that seen with a patellar autograft. Hamstring strength usually returns to normal within three to six months.●Allograft – Allografts do not require any extra incisions, and there is no risk of pain or weakness at the site of graft harvest.The torn ACL is removed and replaced with the graft using a narrow telescope-like device, called an arthroscope. The scope contains a camera and light source, and can be inserted into the knee joint through a small skin incision. Instruments are inserted into other small incisions, allowing the physician to place the graft with precision. After the graft is secured, the knee is wrapped with sterile dressings and an immobilizer is placed around the knee to allow the person to walk more easily with crutches.Most people are able to go home after spending several hours in the recovery room; it is not usually necessary to spend the night in the hospital. Many surgeons recommend using a machine that moves the knee through a range of motion, called a continuous passive motion (CPM) machine. CPM can help prevent the formation of scar tissue. If your surgeon recommends this machine, you will get specific instructions about how often to use it at home. You will also get a prescription for pain medications and a cooling device to help decrease inflammation and pain after surgery. The device is a wrap that goes around your knee and connects to a cooler filled with ice water. Another option that may be available is a machine that compresses the knee in addition to cooling (see 'What to expect after surgery' below). Most people visit their surgeon for follow-up one to two weeks after surgery.The recovery period can be difficult, but it can help to know what to expect. There may be things you can do ahead of time to help make things a bit easier for yourself. (See 'What to expect after surgery' below.)Potential complications — Most people do well after ACL reconstruction and have no major complications. However, complications occasionally occur during surgery or during the rehabilitation period. The most common complications include:●Bleeding into the joint (effusion)●Joint infection●Blood clot in the deep veins of the leg (deep vein thrombosis)●Arthrofibrosis (scar tissue)●Loosening of the graftWhat to expect after surgery — ACL reconstruction is major surgery and recovery can be very challenging, both physically and emotionally. Having realistic expectations can be helpful in both making the decision to have surgery and preparing for the recovery period.During the first few days, the goal is to control swelling and pain. Elevating your knee above your chest and applying ice are the best ways to do this (see 'First phase' below). Most people use crutches to assist with walking for the first week or so after surgery, although you will likely be encouraged to begin bearing weight on the affected leg as soon as possible. (If your surgery was more extensive, your surgeon may recommend delaying weight bearing for a longer period.) You will probably need to wear a brace that keeps your leg straight for at least two weeks after surgery. This brace protects your knee, but many surgeons recommend removing it to do gentle range-of-motion exercises (with a CPM machine) beginning about three to five days after surgery. Stretching and strengthening exercises can usually begin within the first few days after surgery. (See 'Post-surgical rehabilitation' below.)Some other issues to think about and plan for include:●Getting around your house – It might help to practice using crutches before your surgery. Ask your surgeon how long you will need to use them. You may also need to rearrange your living space; for example, if your bedroom is on the second floor, you may have to set up a sleeping area on the main level. Take note of where your home has steps, which will be challenging especially while you are in the brace, or other obstacles that may make it more difficult to get around.●Sleeping – It can be hard to find a comfortable position for sleeping, especially during the first phase of recovery when you can't bend your leg. It might help to get extra pillows for support and comfort.●Entertainment – Since you will have to spend a lot of time resting during the first few weeks, it might help to have something relaxing you enjoy doing.●Driving - While you are in the knee brace, you will not be able to drive; it may be even longer if the surgery was on your right knee. It's a good idea to plan ahead for help getting to your doctor's appointments as well as for other transportation help (eg, driving your children to school or activities).●Showering – Showering is also difficult while you are wearing the brace and unable to bend your leg. A shower chair can be helpful; you may also need someone to help you get into and out of the shower. Some doctors recommend buying a shower chair prior to your surgery.●Cold compression machine – Your doctor might recommend a cold compression device to help with pain relief. This is a machine that you plug in and connect to a plastic sleeve that goes on your knee; the machine inflates the sleeve to provide compression and circulates cold water to the area. The combination of cold and compression can help to reduce swelling and pain, often more than ice alone. In the United States, the cost of these machines may not be covered by insurance, so it is helpful to talk with your surgeon ahead of time about whether this is an option for you. If your surgeon recommends it, his or her office may be able to coordinate getting the machine to you before your surgery, so you can start using it right away when you get home. Some doctors feel that cold compression devices are helpful for relieving pain and decreasing the need for strong pain medication. However, they are cumbersome to move around and can also be cost prohibitive. If you do not have one of these machines, it can still help to use the cooling wrap given to you after surgery.●Support at home – Particularly during the first several weeks after surgery, regular daily activities (such as cooking, cleaning, and caring for children and pets) can be difficult. It can be very helpful to organize assistance in these areas ahead of time.●Work – Discuss with your surgeon how much time off from work you will need for recovery. The time will vary depending on the physical demands of your job. If your job allows for any flexibility or the ability to work from home, you may want to discuss this ahead of time so you have options for when you are ready to return to work.●Post-operative depression – In addition to the physical challenges around recovery, it can be very hard to feel immobile and dependent on other people, especially if you are a very independent and active person. In some cases, this can lead to post-operative depression. This usually gets better within a few weeks as you become more active, start physical therapy, and have fewer restrictions. However, if you are feeling sad or down, talk to your doctor about it. It may be helpful to talk to a counselor or other mental health professional.It's important to keep in mind that everyone heals differently. While your surgeon can give you a general idea of how long your recovery will take and how you will feel at each stage, this can vary. It can be frustrating to have to rebuild your strength and range of motion. It may help to keep in mind that even though the recovery can be very challenging, especially in the early weeks, you will likely be back to most of your normal activities after about six months. Depending on your sport(s), it may take a bit longer to return to full participation. (See 'Return to sports' below.)ANTERIOR CRUCIATE LIGAMENT INJURY REHABILITATION — Rehabilitation is a several month long program that is designed to stretch and strengthen the knee after anterior cruciate ligament (ACL) injury or reconstruction. No one program is best for everyone, although the following exercises are one example of a program that may be recommended.Non-surgical rehabilitation — If you do not plan to have surgery, rehabilitation can help to reduce your risk of further injury. Rehabilitation should begin as soon as swelling and pain begin to improve. Use the stretching and strengthening exercises listed below at least once per day for four to six weeks. These exercises are also recommended as a pre-surgical rehabilitation program. (See 'Presurgical rehabilitation' above.)These exercises may cause some discomfort but should not cause significant pain, especially after the exercise session is over. If your pain is severe or continues after resting and icing the knee, talk to your health care provider.●Assisted knee flexion – Sit on the floor with your legs extended in front of your body. Place your hands behind the thigh of your injured leg, bend your knee and pull it towards your chest, keeping your back straight (picture 1). Hold for five seconds then straighten leg. Repeat 10 to 15 times (one set). Perform a total of three sets.●Quad sets – Sit on the floor with your legs extended in front of your body. Place the hands behind your injured knee. Keep your leg straight and contract your quadriceps muscle (just above the knee), which should cause your knee cap to move towards the body (picture 2). Hold for a count of 10 seconds. Release and rest as needed. Repeat 10 to 15 times (one set). Perform a total of three sets.●Straight leg raises – Lie on a bed or the floor. Bend your non-injured knee and keep your foot on the floor. Keep your injured leg straight. On the injured side, tighten your quadriceps (as above), keep the leg straight, and lift your leg about 18 inches off the floor (picture 3). Slowly lower the leg back to the bed or floor. Rest as needed. Repeat 10 to 15 times (one set). Perform a total of three sets.●Calf raises – Stand behind a chair, holding onto the chair. Slowly rise up and stand on the balls of your feet and toes (picture 4). Hold for five seconds then slowly roll down onto your entire foot. Rest as needed. Repeat 10 to 15 times (one set). Increase the difficulty of this exercise by rising higher, holding longer, or moving up and down more quickly. Perform a total of three sets.●Hip extension – You will need 18 to 24 inches of rubber tubing or an elastic band (eg, Theraband) for these exercises. Secure the tubing around the leg of a heavy piece of furniture or close it in a door. Stand facing the furniture/door and place your injured leg in the loop of the tubing. You should not have any slack in the tubing. Hold the door/furniture and extend your injured leg backwards, stretching the tubing as far as possible (picture 5). Hold for five seconds. Slowly return your leg to the floor. Rest as needed. Repeat 10 to 15 times (one set). Perform a total of three sets.●Hip abduction – As above, you will need a piece of rubber tubing or elastic band. Stand with the legs shoulder width apart, with your non-injured leg closest to the furniture or door. The tubing should loop around the outside of your injured leg. Lift the injured leg to the side, 18 to 24 inches away from your body, stretching the tubing (picture 6). Hold for five seconds, then slowly release. Rest as needed. Repeat 10 to 15 times (one set). Perform a total of three sets.Stretching and strengthening should then continue as discussed below. (See 'Second phase' below.)Post-surgical rehabilitation — Most people who have ACL reconstruction will be under the care of a surgeon and physical therapist who will work together to design a rehabilitation program. The rehabilitation process is difficult, and it can be frustrating to have to rebuild your muscles and learn to walk again after your injury. Your knee will likely feel stiff for some time as you work to regain normal range of motion.The following rehabilitation schedule is an example of one that your team may recommend:First phase — During the first two weeks after surgery, the goal is to increase your range of motion (flexing and extending the knee), maintain strength, minimize the development of scar tissue, and eliminate swelling. Most people begin to walk without crutches by the end of the first week. You should apply ice and elevate your knee daily to minimize swelling.Exercises during this phase should include those discussed above. Surgeons differ in their approach to rehabilitation during the first several weeks after surgery (when the graft is at greatest risk of damage). It is important to listen carefully to instructions about which exercises to do and which to avoid. Especially early in the rehabilitation process, more exercise is not always better.Second phase — Between the third and twelfth weeks after surgery, the goal is to improve range of motion, strength, walking, and balance. Most people are allowed to walk or use an exercise bike for 15 to 20 minutes per day. When possible, walking or running in a pool with a floating belt can be helpful.You will likely do many of the exercises discussed above (see 'Non-surgical rehabilitation' above) The following exercises may also be recommended.●Quarter squats – Stand 18 to 24 inches from a wall. Lean back against the wall. Bend both knees slightly (the buttocks should not be lower than the knees), keeping your back straight (picture 7). Hold for five seconds then slowly stand up straight. Rest as needed. Repeat 10 to 15 times (one set). Perform a total of three sets. To increase the difficulty, bend your knees more deeply, hold for a longer time, and increase the speed.Alternately, use an exercise ball to perform squats. Stand up straight, holding the ball between your back and the wall. Slowly bend the knees and lower your back (roll the ball down the wall). Hold for a count of five. Stand up. Repeat 10 to 15 times.●Bridges – Lie on your back on the floor. Keep the feet on the floor and bend both knees. Place the hands about 12 inches to the side of the body (on the floor). Lift the buttocks six to eight inches off the floor (picture 8). Hold for five seconds, then slowly release. Rest as needed. Repeat 10 to 15 times (one set). Perform a total of three sets.To increase the difficulty, keep your right foot on the floor and lift your left foot off the floor, keeping the left leg straight. Raise the buttocks using the right foot to support your lower body. Switch sides. Repeat 10 to 15 times (one set). Perform a total of three sets.●Single-leg calf raises – Stand behind a chair, holding onto the chair. Lift the foot on your non-injured side off the floor so that you are standing on your injured leg. Slowly rise up and stand on the ball of your foot and toes (picture 9). Hold for five seconds then slowly roll down onto your entire foot. Rest as needed. Repeat 10 to 15 times (one set). Increase the difficulty of this exercise by rising higher, holding longer, or moving up and down more quickly. Perform a total of three sets.●Step ups – Use a stair climber or steps, step up first with your injured leg. Continue for 10 to 15 minutes per day.●Balance – Use a wobble board or balance disk to improve your knee strength and balance ability.If a wobble board or balance disk is not available, try balancing on your affected leg while lifting the unaffected leg off the ground; do not hold onto any support (picture 10). Hold this position for a count of five to 10. Rest and repeat 10 to 15 times. To increase the difficulty, raise your unaffected leg into the air.Third phase — Four or more months after surgery, the difficulty and intensity of the exercises described above should be continued. In addition, you will likely be able to resume exercises that include jumping and landing.●Lunge – Stand with your feet together. Step the right foot approximately 36 inches in front of the body. The right knee should be over the right ankle and the left calf should be parallel to the floor (picture 11). Hold for five seconds. Step the right foot back so that the feet are together. Rest as needed. Repeat with the left leg. Repeat 10 to 15 times (one set). Perform a total of three sets.You will likely be able to resume some low-risk activities at this point, including jogging in a straight line, swimming (kick lightly), and biking on the road. As your strength and ability improve, running and other activities can be restarted as well.Return to sports — Most people who have surgical reconstruction of the ACL have a good outcome.In general, athletes can return to sports once the reconstructed knee has had sufficient time to heal and demonstrates strength, balance, and function roughly equal to the uninjured knee (assuming the uninjured knee is healthy). This generally occurs by about 8 to 12 months after surgery but can vary depending upon the sport and the person's compliance with the rehabilitation program. Waiting at least 10 months before returning to sports may reduce the risk of re-injuring the knee; in some cases, it is necessary to wait even longer to allow for full healing.There is no specific set of criteria that guarantees that a person is completely ready to return to sports after an ACL repair. Effective criteria should include some functional assessment that reflects the demands of the sport to which you are returning. It's essential to follow all of your doctor's and physical therapist's instructions and not try to do too much too soon. Even if you feel like you are ready to return to sports, your body might not be. Sticking with your rehabilitation program will maximize your chances of a complete recovery and reduce your risk of reinjury.ANTERIOR CRUCIATE LIGAMENT INJURY PREVENTION — Several expert organizations, including the American Academy of Orthopaedic Surgeons and the American College of Sports Medicine, agree that programs to prevent anterior cruciate ligament (ACL) injury are beneficial, particularly for female athletes. Many experts also believe that any athlete who is at high-risk for an ACL injury (eg, American football players, skiers) should participate in a prevention program.An analysis of ACL injury prevention programs noted the following:●Programs that incorporated high-intensity jumping exercises reduced injury rates.●Programs that analyzed athletes’ movements and provided direct feedback about proper positioning and movement reduced injury rates.●Programs that incorporated strength training reduced injury rates, although strength training alone did not.●Balance training alone is unlikely to reduce injury rates, although it may enhance other prevention techniques.●Athletes must participate in prevention training at least two times per week for a minimum of six consecutive weeks to accrue benefit.Prevention programs are usually tailored to a particular sport and should initially be taught and supervised by a knowledgeable athletic trainer, physical therapist, or comparable professional (ACL injury prevention sports tips). Use of external braces or other devices has not been shown to reduce the risk of ACL tears and is not recommended for prevention.WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.Patient level information — UpToDate offers two types of patient education materials.The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Patient education: Anterior cruciate ligament tear (The Basics) Patient education: Knee pain (The Basics) Patient education: Using crutches (The Basics)Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon. Patient education: Knee pain (Beyond the Basics) Patient education: Total knee replacement (Beyond the Basics)Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading. Anterior cruciate ligament injury Approach to the adult with unspecified knee pain Knee bursitis Medial (tibial) collateral ligament injury of the knee Meniscal injury of the knee Overview of running injuries of the lower extremity Patella fractures Patellofemoral pain Proximal tibial fractures in adults Proximal tibial fractures in childrenThe following organizations also provide reliable health information.●National Library of Medicine(https://medlineplus.gov/ency/article/007208.htm, available in Spanish)●American Academy of Orthopaedic Surgeons(orthoinfo.aaos.org/topic.cfm?topic=A00549)●American Physical Therapy Association(http://www.apta.org/)This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circ*mstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof.The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms ©2023 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.Topic 707 Version 23.0

CloseIntermediate- and long-acting medications for children with attention deficit hyperactivity disorderIntermediate- and long-acting medications for children with attention deficit hyperactivity disorder Medication United States trade name (generic availability) Description of release and duration of action Initial dose* Dose advancement Maximum dose (per day) Methylphenidate Methylphenidate ER10, 20, mg tablets Metadate ER (generic available) Delayed onset with continuous release over 3 to 8 hours. May require twice daily dosing and/or use with immediate-release methylphenidate. Tablet must be swallowed whole. 10 mg Increments of 10 mg per day every 3 to 7 days ≤50 kg: 60 mg >50 kg: 100 mg¶ Methylphenidate ER chewable tablets20 mg (scored), 30 mg (scored), 40 mg (not scored) Quillichew ER Continuous release over 6 to 8 hours with duration of action up to 13 hours. 20 mg Increments of 10 mg, 15 mg, or 20 mg per day every 7 days 60 mg Methylphenidate XR-ODT8.6, 17.3, 25.9 mg tablets as methylphenidate base (equivalent to 10, 20, 30 mg of methylphenidate hydrochloride)Δ Cotempla XR-ODT 25% immediate-release and 75% extended-release for duration of action up to 12 hours. Whole tablet must be dissolved on tongue; should be taken consistently either with or without food.◊ 17.3 mg Increments of 8.6 to 17.3 mg per day every 7 days 51.8 mg Methylphenidate ER18, 27, 36, 54 mg tablets Concerta (generic available) 20% immediate-release and 80% continuous-release over 10 to 12 hours by osmotic delivery. Tablet must be swallowed whole. 18 mg Increments of 9 to 18 mg per dose every 3 to 7 days <13 years: 54 mg ≥13 years: 72 mg Methylphenidate LA10, 20, 30, 40 mg capsules Ritalin LA (generic available except 10 mg) 50% immediate-release and 50% delayed-release over 8 to 12 hours (bimodal). Capsule may be swallowed whole or opened and contents sprinkled over a spoonful of cold applesauce and swallowed immediately; capsule or contents should not be crushed or chewed. 10 or 20 mg Increments of 10 or 20 mg per dose every 3 to 7 days ≤50 kg: 60 mg >50 kg: 100 mg¶ Methylphenidate CD10, 20, 30, 40, 50, 60 mg capsules Generic available 30% immediate-release and 70% delayed-release over 8 to 12 hours (bimodal). Capsule may be swallowed whole or opened and contents sprinkled over a spoonful of cold applesauce and swallowed immediately; capsule or contents should not be crushed or chewed. 20 mg Increments of 10 mg per dose every 3 to 7 days ≤50 kg: 60 mg >50 kg: 100 mg¶ Methylphenidate XR10, 15, 20, 30, 40, 50, 60 mg capsules Aptensio XR (generic available) 40% immediate release and 60% controlled release for duration of action of 12 hours. Capsule may be swallowed whole or opened and contents sprinkled over a spoonful of cold applesauce and swallowed immediately; capsule or contents should not be crushed or chewed. 10 mg Increments of 10 mg every 7 days 60 mg Methylphenidate XR25, 35, 45, 55, 70, 85 mg capsules Adhansia XR 20% immediate-release and 80% controlled release for duration of action of 16 hours Capsule may be swallowed whole or opened and contents sprinkled over a spoonful of cold applesauce or yogurt and swallowed immediately; capsule or contents should not be crushed or chewed. 25 mg Increments of 10 to 15 mg every 5 days 85 mg Methylphenidate XR oral suspension5 mg/mL Quillivant XR 20% immediate-release and 80% extended-release for duration of action up to 12 hours. 20 mg Increments of 10 mg every 7 days 60 mg Methylphenidate extended release capsules20, 40, 60, 80, 100 mg capsules Jornay PM <5% of total drug is available within the first 10 hours after administration. Peak concentration occurs 14 hours after dose with gradual decline thereafter. Capsules may be swallowed whole or opened and the contents sprinkled over a spoonful of cold applesauce; capsule or contents should not be crushed or chewed. 20 mg per day in the evening (adjust timing to optimize tolerability and efficacy) Increments of 20 mg per day every 7 days 100 mg Methylphenidate patch§10, 15, 20, 30 mg patch Daytrana Onset 2 hours after application of patch and continuous release over 9 to 12 hours. 10 mg§ Increments of 5 mg per dose every 3 to 7 days 30 mg Dexmethylphenidate Dexmethylphenidate XR5, 10, 15, 20, 25, 30, 35, 40 mg capsules Focalin XR (generic available) 50% immediate-release and 50% delayed-release over 10 to 12 hours (bimodal). Capsule may be swallowed whole or opened and contents sprinkled over a spoonful of cold applesauce and swallowed immediately; capsule or contents should not be crushed or chewed. 5 mg Increments of 5 mg per dose every 3 to 7 days 40 mg Serdexmethylphenidate-dexmethylphenidate26.1/5.2, 39.2/7.8, 52.3/10.4 mg capsules Azstarys 70% serdexmethylphenidate (dexmethylphenidate prodrug) and 30% dexmethylphenidate (immediate release). Peak dexmethylphenidate concentration occurs approximately 2 hours after the dose (onset of action within 1 hour), with gradual decline thereafter for duration of action of up to 13 hours. Capsule may be swallowed whole or opened and contents sprinkled over 2 tablespoons of applesauce or into 50 mL of water and consumed within 10 minutes of mixing. Age 6 to 12 years:39.2/7.8 mg Increase or decrease by 13.1/2.6 mg after one week 52.3/10.4 mg Age ≥13 years:39.2/7.8 mg Increase to 52.3/10.4 after 1 week Amphetamines Dextroamphetamine-amphetamine ER5, 10, 15, 20, 25, 30 mg capsules¥ Adderall XR (generic available) Combination of immediate- and continuous-release over 10 to 12 hours. 5 mg Increments of 5 mg per dose every 3 to 7 days ≤50 kg: 40 mg >50 kg: 60 mg‡ Dextroamphetamine-amphetamine ER12.5, 25, 37.5, 50 mg capsules¥† Mydayis Combination of immediate- and two different delayed-release beads for duration up to 16 hours. Capsule may be swallowed whole or sprinkled over a spoonful of cold applesauce and swallowed immediately; capsule or contents should not be crushed or chewed. 12.5 mg Increments of 12.5 mg every 7 days 13 through 17 years: 25 mg ≥18 years: 50 mg Amphetamine EROral suspension 2.5 mg amphetamine as base per mL¥ 5, 10, 15, and 20 mg tablets Dyanavel XR Combination of immediate- and extended-release for duration of action up to 13 hours. Tablets may be chewed or swallowed whole 2.5 or 5 mg Increments of 2.5 to 10 mg per day every 4 to 7 days 20 mg Amphetamine ERODT 3.1, 6.3, 9.4, 12.5, 15.7, 18.8 mg as base¥ Adzenys XR-ODT Combination of 50% immediate- and 50% extended-release; levels are comparable to dextroamphetamine-amphetamine ER capsules when equivalent doses are used.¥ 6.3 mg Increments of 3.1 or 6.3 mg per day every 7 days 6 to 12 years: 18.8 mg ≥13 years: 12.5 mg Dextroamphetamine SR5, 10, 15 mg capsules Generic extended release available (Dexedrine Spansule brand is no longer available) Combination of immediate- and continuous-release over 8 to 12 hours. May require dividing dose twice daily. 5 mg Increments of 5 mg per day every 3 to 7 days ≤50 kg: 40 mg >50 kg: 60 mg‡Dextroamphetamine patch§4.5, 9, 13.5, 18 mg per 9 hour patches Xelstrym Strength is amount of dextroamphetamine released from patch over 9 hours Onset 2 hours after application of patch; continuous release from application site over 9 to 12 hours 4.5 mg§ Increments of 4.5 mg per day every 7 days 18 mg Lisdexamfetamine10, 20, 30, 40, 50, 60, 70 mg capsules 10, 20, 30, 40, 50, 60 mg chewable tablets Vyvanse Prodrug converted to dextroamphetamine in bloodstream with an effect over approximately 10 hours. Capsule may be opened and dissolved in water or juice for immediate use. Chewable tablets must be chewed completely before swallowing. 20 mg Increments of 10 or 20 mg per day every 3 to 7 days 70 mg Nonstimulants Selective norepinephrine reuptake inhibitors Atomoxetine10, 18, 25, 40, 60, 80, 100 mg capsules Strattera (generic available) At least 10 to 12 hours. 0.5 mg/kg per day for minimum of 3 days Increase to 1.2 mg/kg per day after a minimum of 3 days (maximum 100 mg per day) Lesser of 1.4 mg/kg or 100 mg Viloxazine ER100, 150, 200 mg capsules Qelbree Lasts throughout the day. Capsule may be swallowed whole or opened and contents sprinkled over a teaspoonful of applesauce and swallowed immediately and without chewing; neither the capsule nor contents should be crushed or chewed. Age 6 to 11:100 mg Increments of 100 mg weekly 400 mg Age 12 to 17:200 mg Increments of 200 mg weekly Alpha-2 adrenergic agonists Guanfacine ER**1, 2, 3, 4 mg tablets Intuniv (generic available) At least 10 to 12 hours. 1 mg per day Increments of 1 mg per day at no less than weekly intervals ≤12 years: 4 mg >12 years: 7 mg¶¶ER: extended release; XR: extended release; ODT: orally disintegrating tablet; LA: long-acting; CD: controlled dispense; SR: sustained release.* Suggested doses for initiating treatment with long-acting stimulant medications for treatment of children aged ≥6 years.¶ This maximum dose exceeds the US Food and Drug Administration (FDA)-approved maximum dose; careful monitoring for adverse effects is warranted.Δ Cotempla XR-ODT strengths are expressed by the manufacturer as methylphenidate base. Most other methylphenidate product doses are expressed as methylphenidate hydrochloride salt. Cotempla XR-ODT dose needs to be converted to methylphenidate hydrochloride for comparison with other methylphenidate products.◊ Although the prescribing information indicates that Cotempla XR-ODT should be taken consistently with or without food, we suggest that it be taken consistently with food – given the general stimulant effect of appetite suppression.§ Patch is applied 2 hours before needed effect and worn for a total of 9 hours. Doses for the methylphenidate and dextroamphetamine patches are not equivalent to those for the oral preparations.¥ Amphetamine ER oral suspension and ODT strengths reflect milligrams of amphetamine base, whereas dextroamphetamine-amphetamine ER capsule strengths reflect milligrams of dextroamphetamine-amphetamine salts. These cannot be substituted on an mg-per-mg basis. Refer to UpToDate content related to dose equivalents of stimulants for attention deficit hyperactivity disorder in children.‡ Doses above 40 mg per day total are rarely necessary and warrant close monitoring.† Mydayis is not approved by the FDA for children <13 years.** Immediate-release form cannot be substituted mg-for-mg for ER form due to pharmaco*kinetic differences. Discontinuation requires dose tapering to prevent rebound increase in blood pressure.¶¶ The typical maximum dose for this age group is 4 mg/day; a maximum dose of 7 mg/day may be used for adolescents >12 years who weigh >58.5 kg (120 pounds), but the 7 mg dose may be associated with somnolence.Data from:Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007; 46:894.Drugs for ADHD. Med Lett Drugs Ther 2020; 62:9.Wender EH. Managing stimulant medication for attention-deficit/hyperactivity disorder. Pediatr Rev 2001; 22:183.Prepared with additional data from the US Food and Drug Administration approved product information, available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed on March 29, 2022).Graphic 77580 Version 31.0

CloseComparison of drugs used to treat attention deficit hyperactivity disorder in childrenComparison of drugs used to treat attention deficit hyperactivity disorder in children   Advantages Disadvantages Comments Short-acting stimulants Extensive data efficacy and safety. Generic formulations available. Flavored oral suspension and chewable tablet available for methylphenidate. Orally disintegrating tablet available for amphetamine. Must be taken 2 to 3 times per day if full-day coverage is desired.   Long-acting stimulants Can be dosed once per day (can avoid administration at school). Side effects may extend later in the day. Increased cost. Fewer generic options. Short-acting stimulant can be added in PM for afternoon boost when needed. Single-pulse sustained release (eg, Metadate ER) Generic formulations available.   Must be swallowed whole. Preferably taken 30 to 45 minutes before meal. Extended release oral suspension (Dyanavel XR), extended-release chewable tablet (eg, Quillichew ER, Dyanavel XR), or orally disintegrating tablet (Adzenys XR-ODT, Cotempla XR-ODT) May be used for children who have difficulty swallowing pills. These preparations are flavored and may be more palatable. No generic options. Increased cost. May be taken with or without food.* Do not mix oral suspensions with food or other liquids before taking. Sustained release bead preparations (eg, Ritalin LA, Focalin XR, Adderall XR, Metadate CD, Aptensio XR, Adhansia XR, Mydayis¶) Approximates a twice-per-day or 3-times-per-day dosing schedule. Can be sprinkled into soft foods for children who have difficulty swallowing pills. Generic formulations are available for some products.   The beads should not be chewed. Some products should not be taken with antacids or other drugs that decrease gastric acidity. Ingestion with a high-fat meal may delay time of onset and increase peak concentration. Methylphenidate HCl extended-release capsules (Jornay PM) Designed to deliver drug in the early morning. Lasts throughout the day, using delayed-release and extended-release technology. No generic options. Increased cost. Initiate dosing at 8:00 PM. Adjust the timing of administration between 6:30 PM and 9:30 PM to optimize efficacy and tolerability the next morning and throughout the day. May be taken with or without food. May be taken whole, or the capsule may be opened, and the entire contents sprinkled onto applesauce (to be consumed immediately and entirely without chewing). Prodrug coformulated with immediate release (serdexmethylphenidate-dexmethylphenidate [Azstarys]) Fast onset (from immediate-release dexmethylphenidate) and duration that lasts throughout the day (from serdexmethylphenidate [dexmethylphenidate prodrug]). Can be sprinkled over applesauce or into water for children who have difficulty swallowing pills. No generic options. May be taken with or without food. May be taken whole or the capsule may be opened and the entire contents sprinkled onto applesauce or into water (to be consumed within 10 minutes). Osmotic release (eg, Concerta) Approximates a 3-times-per-day dosing schedule. Generic formulations available. Children with decreased GI absorption or intestinal resection may not receive the full benefit. Capsule should not be opened or chewed. Capsule is passed through the GI tract and into the stool intact. Patch (Daytrana, Xelstrym) Can be used for patients who cannot take oral medications. Patch must be applied 2 hours before needed effect. Associated with application site reactions (including permanent loss of pigmentation with Daytrana). No generic options. Increased cost. Early removal of the patch permits controlled duration (effects last approximately 2 to 3 hours after patch is removed). Prodrug (Lisdexamfetamine [Vyvanse]) May have lower risk for abuse. Capsules can be opened and mixed with water for children who have difficulty swallowing capsules. Chewable tablet available. No generic options. Increased cost.   Selective norepinephrine reuptake inhibitors Can be dosed once per day. Lower potential for abuse than stimulants. Not a controlled substance. May be less efficacious than stimulants. Potential increased risk of suicidal ideation. "Drug holidays" are not an option. Concomitant use or use within 14 days after discontinuing monoamine oxidase inhibitor is contraindicated. Atomoxetine Generic formulation available. More time to steady state (up to 2 weeks for initial response; up to 8 weeks for maximal effect). Taking with food may prevent nausea. Requires dosing adjustment if administered with agents that inhibit the cytochrome P450 2D6 (CYP2D6) enzyme. Viloxazine ER capsules Earlier onset than atomoxetine (initial response may occur within 1 week; up to 5 weeks for maximal effect). Capsule may be opened and contents sprinkled over a teaspoonful of applesauce for children who have difficulty swallowing capsules. No generic option. May be taken with or without food. Strong CYP1A2 inhibitor; concomitant administration of sensitive substrates is contraindicated; other CYP1A2 substrates may require dosing adjustments. Extended release alpha-2-adrenergic agonists Not a controlled substance. May also treat coexisting conditions (eg, sleep disorders, tic disorders). Generic formulations available. May be less efficacious than stimulants. More time to steady state (up to two weeks for initial response). "Drug holidays" are not an option. Must be swallowed whole, not crushed or chewed. May lead to hypotension and orthostasis.ER: extended release; XR: extended release; ODT: orally disintegrating tablets; LA: long-acting; CD: controlled dispense; HCl: hydrochloride; GI: gastrointestinal.* Although the prescribing information indicates that Cotempla XR-ODT should be taken consistently with or without food, we suggest that it be taken consistently with food – given the general stimulant effect of appetite suppression.¶ Mydayis is not approved by the US Food and Drug Administration for children <13 years.Data from:Daughton JM, Kratochvil CJ. Review of ADHD pharmacotherapies: Advantages, disadvantages, and clinical pearls. J Am Acad Child Adolesc Psychiatry 2009; 48:240.Harpin VA. Medication options when treating children and adolescents with ADHD: Interpreting the NICE guidance 2006. Arch Dis Child Educ Pract Ed 2008; 93:58.Drugs for ADHD. Med Lett Drugs Ther 2015; 57:37.Wigal SB. Efficacy and safety limitations of attention deficit hyperactivity disorder pharmacotherapy in pediatric patients. J Pediatr 2009; 154:S13.US Food and Drug Administration. FDA drug safety communication: FDA reporting permanent skin color changes associated with use of Daytrana patch (methylphenidate transdermal system) for treating ADHD. Available at: www.fda.gov/Drugs/DrugSafety/ucm452244.htm (Accessed on June 30, 2015).Cutler AJ, Suzuki K, Starling B, et al. Efficacy and safety of dextroamphetamine transdermal system for the treatment of attention-deficit/hyperactivity disorder in children and adolescents: Results from a pivotal phase 2 study. J Child Adolesc Psychopharmacol 2022; 32:89.Prepared with additional information from US Food and Drug Administration approved product information. Available at: www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (Accessed on March 29, 2022).Graphic 80151 Version 29.0

The tropomyosin receptor kinase (TRK) family of transmembrane receptor proteins (TRKA, TRKB, and TRKC) is encoded by the neurotrophic tyrosine receptor kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3, respectively). All three TRK proteins can become targets of structural rearrangement caused by an NTRK

The introduction of non-resectoscopic endometrial ablation (NREA) techniques has greatly increased the use of endometrial ablation as a therapeutic option for patients with abnormal uterine bleeding. NREA is performed with a device that is inserted into the uterine cavity and delivers energy to unif

CloseDosing recommendations for antiviral agents for the treatment of influenza in children and adolescents[1-3]Dosing recommendations for antiviral agents for the treatment of influenza in children and adolescents[1-3] Drug/formulation Dosing recommendations Oseltamivir (Tamiflu)* 30 mg capsule 45 mg capsule 75 mg capsule6 mg/mL suspension¶ 1 through 12 years Children ≥12 months should receive approximately 4 mg/kg per day orally divided into 2 doses for a 5-day treatment course ≤15 kg >15 to 23 kg >23 to 40 kg >40 kg 60 mg/day orally divided into 2 doses for 5 days 90 mg/day orally divided into 2 doses for 5 days 120 mg/day orally divided into 2 doses for 5 days 150 mg/day orally divided into 2 doses for 5 days ≥13 years 150 mg/day orally divided into 2 doses for 5 days Baloxavir (Xofluza)Δ 40 mg tablet80 mg tablet 2 mg/mL oral suspension ≥5 years Weight <20 kg (oral suspension) – 2 mg/kg orally as a single dose Weight 20 to <80 kg (oral suspension or tablet) – 40 mg orally as a single dose Weight ≥80 kg (oral suspension or tablet) – 80 mg orally as a single dose Peramivir (Rapivab)* 200 mg in 20 mL (10 mg/mL) in a single-use vial 6 months through 12 years 12 mg/kg per dose IV as a single dose (maximum dose 600 mg) ≥13 years 600 mg IV as a single dose Zanamivir (Relenza)◊ 5 mg per inhalation (Diskhaler) ≥7 years 2 inhalations (10 mg total per dose) twice daily for 5 days§This table is meant for use with UpToDate content related to treatment of seasonal influenza in children. The choice of agent for treatment may vary with the age of the child and susceptibility patterns of circulating strains. Refer to UpToDate content for additional details, including indications for treatment and dosing recommendations for oseltamivir in infants younger than 1 year.IV: intravenously.* Dose adjustment is necessary for patients with renal insufficiency.¶ When dispensing the oral suspension of oseltamivir, providers and pharmacists must take care to provide a dosing device that matches the units of measure on the prescription.Δ Baloxavir is available in Japan for the treatment of influenza in children <12 years of age who weigh at least 10 kg. Refer to Japanese prescribing information for dosing information for children <12 years of age.◊ Zanamivir is not recommended for the treatment of hospitalized patients, because of limited data in patients with severe influenza. Zanamivir inhalation powder should not be reconstituted in any liquid formulation and is not recommended for use in nebulizers or mechanical ventilators.§ Two doses should be administered on day 1, provided that the doses can be spaced at least 2 hours apart.References:American Academy of Pediatrics. Non-HIV antiviral Drugs. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.930.Rapivab (peramivir injection) for intravenous use. US Food & Drug Administration (FDA) approved product information. Revised January 2021. US Food & Drug Administration. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm (Accessed on February 3, 2021).Xofluza (baloxavir marboxil) prescribing information. US Food and Drug Administration (FDA) approved product information. Revised August 2022. Available online at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm (Accessed on August 16, 2022).Graphic 70571 Version 25.0

Patients undergoing chemotherapy for cancer using conventional cytotoxic agents, molecularly targeted agents, and immunotherapeutic agents, require careful assessment of liver function both prior to and during therapy. Potential interactions between the liver and chemotherapy fall into two categorie

CloseDeltoid injection siteDeltoid injection siteThe arm should be completely exposed and lifted slightly out to the side (which causes the subdeltoid bursa to slide under the acromion). Identify the shoulder tip (acromion) and the deltoid tuberosity (ie, the site of insertion of the deltoid). Draw an imaginary inverted triangle between the acromion and the deltoid tuberosity. The correct injection site is in the middle one-third of this triangle (ie, in the center of the deltoid muscle, midway between the acromion and the deltoid tuberosity).Adapted from:Administration of vaccines. In: The Australian Immunisation Handbook, 10th ed. Available at: https://immunisationhandbook.health.gov.au/vaccination-procedures/administration-of-vaccines (Accessed on September 30, 2019).Wadman M. Vaccines on trial. Science 2017; 356:370.Graphic 114648 Version 4.0

ClosePatient education: Back pain in children and adolescents (Beyond the Basics)Patient education: Back pain in children and adolescents (Beyond the Basics)Author:Peter A Nigrovic, MD Section Editor:Suzanne C Li, MD, PhD Deputy Editor:Mary M Torchia, MDLiterature review current through: Nov 2022. | This topic last updated: Aug 02, 2021.Please read the Disclaimer at the end of this page.BACK PAIN OVERVIEW — Back pain occurs commonly in children and adolescents, affecting up to 50 percent of children by age 18 to 20 years. The pain may be sharp and shooting, burning, or aching, and may be felt anywhere in the back.Although back pain may be a sign of a more concerning problem, especially in children younger than 10 years, most episodes of back pain in children are not serious and resolve without treatment.This topic will review the most common causes of back pain in children, treatments that can be tried at home, and a guide to when the child should see their health care provider. Back pain in adults is discussed separately. (See"Patient education: Low back pain in adults (Beyond the Basics)".)BACK PAIN CAUSES — The most common cause of low back pain in children is muscle sprain and strain. This can occur while playing, from carrying a heavy backpack, or after a fall.Less common causes include abnormalities in the spinal bones (vertebrae), infections, arthritis, and, rarely, cancer. (See"Back pain in children and adolescents: Causes".)WHEN TO SEEK HELP — Contact your child's health care provider if your child has one or more of the following:●Back pain that is severe, occurs at night or wakes the child from sleep, or worsens over time●Back pain accompanied by fever (temperature >100.4°F or 38°C)●Back pain accompanied by weight loss●Back pain in a child under five years of age●Leg weakness, walking with a limp, or refusing to walk●Back pain that developed after a recent injury●Past history of cancer or tuberculosis●Change in bowel or bladder control (eg, new accidents)●Back pain that prevents the child from participating in normal activities●Back pain that is accompanied by morning stiffness lasting more than 30 minutesBACK PAIN DIAGNOSIS — To determine the most likely cause of a child's back pain, the health care provider will ask questions and will perform a physical examination. Blood tests and x-rays or other imaging tests are not always needed, especially if the back pain began recently. (See"Back pain in children and adolescents: Evaluation".)BACK PAIN TREATMENT — If your child has back pain but has none of the warning signs described above (see 'When to seek help' above), it is reasonable to try some home treatments initially. However, if the child's pain does not improve, call the child's health care provider.Pain medications — Nonprescription pain medications, such as acetaminophen (sample brand name: Tylenol) or ibuprofen (sample brand names: Advil, Motrin) may help to reduce a child's back pain. These medications are particularly helpful for back pain caused by overuse, strains, and sprains.These medications should be given according to the child's weight, rather than age.Heat — Applying heat can help with back pain during the first few days after overuse or an injury. You may use a heating pad, hot water bottle, or other hot pack. Be careful to avoid burning the skin with a pack or pad that is too hot.Remaining active — Staying active can help to relieve muscle spasms and prevents weakening of the muscles. On the other hand, back pain caused by overexertion may not improve without rest. Thus, high-impact activities (running, jumping, or other activities that cause pain) should be avoided while the child has pain. It is fine for the child to continue with regular day-to-day activities and light exercise that does not cause pain.Bed rest is not recommended. Children who prefer to remain completely inactive should be evaluated by a health care provider.Stretching and strengthening exercises — As the pain begins to improve, your child's health care provider may recommend specific stretching and strengthening exercises. A physical therapist can help to design a program tailored to your child.Activities such as walking, swimming, bicycling, and other low-impact activities are also recommended. The child should temporarily avoid activities that involve twisting or bending, are high impact, or that make the back hurt more.WHERE TO GET MORE INFORMATION — Your child's health care provider is the best source of information for questions and concerns related to your child's medical problem.This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients and caregivers, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.Patient level information — UpToDate offers two types of patient education materials.The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Patient education: Low back pain in adults (The Basics) Patient education: Scoliosis (The Basics)Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon. Patient education: Low back pain in adults (Beyond the Basics)Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading. Evaluation of the child with a limp Back pain in children and adolescents: Causes Adolescent idiopathic scoliosis: Clinical features, evaluation, and diagnosis Back pain in children and adolescents: Evaluation Overview of the causes of limp in children Spondyloarthritis in children Adolescent idiopathic scoliosis: Management and prognosisThe following organizations also provide reliable health information.●American Academy of Orthopaedic Surgeons(http://orthoinfo.aaos.org/topic.cfm?topic=A00036)●Kidshealth.org(https://www.kidshealth.org/en/parents/backpack.html)[1-3]Backpack safety. American Academy of Pediatrics. Available at: www.aap.org/publiced/BR_Backpack.htm (Accessed on March 30, 2009).Diepenmaat AC, van der Wal MF, de Vet HC, Hirasing RA. Neck/shoulder, low back, and arm pain in relation to computer use, physical activity, stress, and depression among Dutch adolescents. Pediatrics 2006; 117:412.Pellisé F, Balagué F, Rajmil L, et al. Prevalence of low back pain and its effect on health-related quality of life in adolescents. Arch Pediatr Adolesc Med 2009; 163:65.This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circ*mstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof.The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms ©2023 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.Topic 1192 Version 14.0References1 : Backpack safety. American Academy of Pediatrics. Available at: www.aap.org/publiced/BR_Backpack.htm (Accessed on March 30, 2009).2 : Neck/shoulder, low back, and arm pain in relation to computer use, physical activity, stress, and depression among Dutch adolescents.3 : Prevalence of low back pain and its effect on health-related quality of life in adolescents.

CloseSuggested doses of low molecular weight heparins in adult patients with a high body mass index (BMI)Suggested doses of low molecular weight heparins in adult patients with a high body mass index (BMI)   VTE treatment VTE prophylaxis Product labeling on use in patients with a high BMI Enoxaparin*Use standard treatment dosing (ie, 1 mg/kg every 12 hours based on TBW).¶ Once-daily dosing regimens of enoxaparin are not recommended.[1]BMI 30 to 39 kg/m2: Use standard prophylaxis dosing (ie, 30 mg every 12 hours or 40 mg once daily).[2] Some experts use weight-based dosing (ie, 0.5 mg/kg based on TBW once or twice daily, depending upon level of VTE risk).Δ[3,4] BMI ≥40 kg/m2: Empirically increase standard prophylaxis dose by 30% (ie, from 30 mg every 12 hours to 40 mg every 12 hours).◊[2] Some experts use weight-based dosing (ie, 0.5 mg/kg based on TBW once or twice daily, depending upon level of VTE risk).Δ[3-7] High VTE-risk bariatric surgery with BMI ≤50 kg/m2: 40 mg every 12 hours.§[8,9] High VTE-risk bariatric surgery with BMI >50 kg/m2: 60 mg every 12 hours.§[9]Safety and efficacy of prophylactic doses in patients with obesity (BMI >30 kg/m2) has not been fully determined, and there is no consensus for dose adjustment. Observe carefully for signs and symptoms of VTE.[10] Marginal increase observed in mean anti-factor Xa activity using TBW and 1.5 mg/kg once-daily dosing in healthy persons with obesity (BMI 30 to 48 kg/m2) compared with healthy persons with lower BMI.[10] DalteparinUse standard treatment dosing (ie, 200 units/kg once daily based on TBW for the first month, followed by 150 units/kg TBW once daily for subsequent months).¶¥ May consider using 100 units/kg based on TBW every 12 hours for patients weighing ≥90 kg.[11] The labeled indication in the United States for adult patients is extended treatment of cancer-associated VTE.[12]BMI 30 to 39 kg/m2: Use standard prophylaxis dosing (ie, 5000 units once daily).[2] BMI ≥40 kg/m2: Empirically increase standard prophylaxis dose by 30% (ie, from 5000 units once daily to 6500 units once daily).Δ◊[2] Cancer-associated VTE treatment: Use TBW-based dosing for patients weighing up to 99 kg. Use a maximum dose of 18,000 units per day for patients weighing ≥99 kg.¶¥[12] Nadroparin (not available in the United States) Use standard treatment dosing (ie, 171 anti-factor Xa units/kg once daily based on TBW or 86 units/kg every 12 hours based on TBW).¶‡BMI 30 to 39 kg/m2: For orthopedic surgery, use weight-based dosing (ie, 38 anti-factor Xa units/kg once daily based on TBW increasing on postoperative day 4 to 57 anti-factor Xa units/kg once daily); for general surgery use standard fixed dosing (ie, 2850 anti-factor Xa units once daily); for medically ill patients use standard fixed dosing (ie, 5700 anti-factor Xa units once daily provided TBW >70 kg).[2] BMI ≥40 kg/m2: For orthopedic surgery, use weight-based dosing (ie, 38 anti-factor Xa units/kg once daily based on TBW increasing on postoperative day 4 to 57 anti-factor Xa units/kg once daily); for general surgery, empirically increase fixed dose by ~30% (ie, increase from 2850 to 3800 anti-factor Xa units once daily); for medically ill patients, empirically increase fixed dose by ~30% (ie, increase from 5700 to 7400 anti-factor Xa units once daily provided TBW >70 kg).Δ◊[2]Safety and efficacy of LMWHs in high-weight (ie, >120 kg) patients has not been fully determined. Individualized clinical and laboratory monitoring is recommended (Canada product monograph).[13] VTE treatment: Use TBW-based dosing for patients weighing up to 100 kg. Use a maximum dose of 17,100 anti-Xa units per day for patients weighing >100 kg.¶‡[13] Tinzaparin (not available in the United States) Use standard treatment dosing (ie, 175 anti-factor Xa units/kg once daily based on TBW).¶BMI 30 to 39 kg/m2: For orthopedic surgery, use weight-based prophylaxis dosing (ie, 50 or 75 anti-factor Xa units/kg based on TBW once daily); for general surgery and medically ill patients, use standard fixed dosing (ie, 3500 or 4500 anti-factor Xa units once daily depending upon level of VTE risk).[2] BMI ≥40 kg/m2: For orthopedic surgery, use weight-based prophylaxis dosing (ie, 50 or 75 anti-factor Xa units/kg based on TBW once daily); for general surgery and medically ill patients, empirically increase fixed dose by 30% (ie, increase from 3500 to 4500 anti-factor Xa units once daily or from 4500 to 6000 anti-factor Xa units once daily depending on level of VTE risk).Δ◊[2] Moderate to high VTE-risk bariatric surgery, extended postoperative prophylaxis regimen: According to a protocol evaluated at one center: Beginning on postoperative day 1: 75 units/kg based on TBW once daily for 10 days; patients weighing <110 kg received 4500 units once daily; patients weighing ≥160 kg received 14,000 units once daily.Δ§[14] Safety and efficacy in patients weighing >120 kg has not been fully determined. Individualized clinical and laboratory monitoring is recommended (Canada product monograph).[15]All doses shown are for patients with normal kidney function and are for subcutaneous administration. For dose adjustment due to kidney impairment, refer to Lexicomp monographs.Generally, anti-factor Xa monitoring is not recommended, but it can be considered for patients with BMI ≥40 kg/m2 who are unstable, experience unexpected thromboembolic or bleeding complications, or require prolonged VTE treatment.VTE: venous thromboembolism; TBW: total body weight, also known as actual body weight; LMWH: low molecular weight heparin; FDA: Food and Drug Administration.* Conversion: 1 mg enoxaparin is approximately equal to 100 international units enoxaparin.¶ The 2018 American Society of Hematology (ASH) guidelines and other expert reviews suggest against dose reduction or use of a maximum dose for VTE treatment in patients with a high BMI citing consequences of therapeutic failure and lack of correlation between anti-factor Xa concentrations and increased bleeding risk.[2,16]Δ Rounding of the dose may be necessary depending on product detail. Refer to Lexicomp monograph included with UpToDate.◊ An empiric dose increase of approximately 30% for fixed prophylactic doses of LMWH for VTE prophylaxis for patients with a high BMI is based on clinical experience, expert opinion, and analysis of pharmacodynamic and clinical outcomes data.[2]§ An optimal approach to thromboprophylaxis in bariatric surgery patients has not been established; there is considerable variability in approach among surgeons and programs. For additional information refer to UpToDate topics on bariatric surgery and institutional protocols.¥ According to the US FDA approved dalteparin prescribing information, a fixed dose of 18,000 units per day is recommended for patients weighing ≥99 kg who are being treated for cancer-associated VTE.[12] However, guidelines suggest that dalteparin dose should be based on TBW.[2,15] Capped dalteparin dose of 18,000 units per day is not recommended.‡ According to the Canadian approved nadroparin product monograph, a fixed dose of 17,100 units per day is recommended for patients weighing more than 100 kg.[13] However, guidelines suggest that nadroparin dose should be based on TBW.[2,16] Capped nadroparin dose of 17,100 units per day is not recommended.References:Merli G, Spiro TE, Olsson CG, et al. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med 2001; 134:191.Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: Available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 2009; 43:1064.Rondina MT, Wheeler M, Rodgers GM, et al. Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-ill patients. Thromb Res 2010; 125:220.Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e24S.Freeman A, Horner T, Pendleton RC, Rondina MT. Prospective comparison of three enoxaparin dosing regimens to achieve target anti-factor Xa levels in hospitalized, medically ill patients with extreme obesity. Am J Hematol 2012; 87:740.Parikh S, Jakeman B, Walsh E, et al. Adjusted-dose enoxaparin for VTE prevention in the morbidly obese. J Pharm Technol 2015; 31:282.Bickford A, Majercik S, Bledsoe J, et al. Weight-based enoxaparin dosing for venous thromboembolism prophylaxis in the obese trauma patient. Am J Surg 2013; 206:847.Scholten DJ, Hoedema RM, Scholten SE. A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg 2002; 12:19.Borkgren-Okonek MJ, Hart RW, Pantano JE, et al. Enoxaparin thromboprophylaxis in gastric bypass patients: Extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis 2008; 4:625.Enoxaparin sodium. United States prescribing information. Revised April 2020. Available at: https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=de6fb917-a94a-41ea-9d7d-937d4080ffcd&type=pdf (Accessed on November 22, 2021).Al-Yaseen E, Wells PS, Anderson J, et al. The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients. J Thromb Haemost 2005; 3:100.Dalteparin sodium injection. United States prescribing information. Revised September 2021. Available at: https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=23527b8b-9b28-4e6d-9751-33b143975ac7&type=pdf (Accessed on November 22, 2021).Nadroparin calcium injection. Canada product monograph. Revised September 2019. Available at: https://pdf.hres.ca/dpd_pm/00053484.PDF (Accessed on January 14, 2022).Tseng EK, Kolesar E, Handa P, et al. Weight-adjusted tinzaparin for the prevention of venous thromboembolism after bariatric surgery. J Thromb Haemost 2018; 16:2008.Tinzaparin sodium injection. Canada product monograph. Revised May 2017. Available at: https://pdf.hres.ca/dpd_pm/00040736.PDF (Accessed on November 22, 2021).Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: Optimal management of anticoagulation therapy. Blood Adv 2018; 27:3257.Graphic 65464 Version 18.0

Snakebites account for significant morbidity and mortality worldwide, especially in South and Southeast Asia, sub-Saharan Africa, and Latin America [1]. Venomous snakes are widely distributed around the world and clinical effects from envenomation can overlap to a great degree even among different c