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Objective: To provide family physicians with a practical evidence-based approach to management of otitis externa., Sources of Information: The approach described is based on MEDLINE and PubMed literature published between 1993 and 2023., Main Message: Otitis externa is diffuse inflammation of the external auditory canal and typically occurs from moisture exposure and trauma. Management focuses on eliminating infection, pain management, education, and preventing recurrence. The primary treatment of uncomplicated otitis externa is topical. Complicated presentations may require additional systemic therapy., Conclusion: History taking and physical examination can help differentiate among acute, chronic, and necrotizing otitis externa. At-risk populations, typically those who are immunosuppressed, are more likely to develop necrotizing otitis externa and should be carefully monitored., (Copyright © 2024 the College of Family Physicians of Canada.)

A multifactorial risk assessment, correction of hearing impairment, exercise, and an optimized home environment can help prevent imbalance-related falls.

Objective: To provide family physicians with a practical evidence-based approach to the management of patients with hearing loss., Sources of Information: MEDLINE and PubMed databases were searched for English-language hearing loss research, review articles, and guidelines published between 1980 and 2020. Most of the retrieved articles provided level II or III evidence., Main Message: Hearing loss is one of the most common sensory impairments worldwide and causes great detriment to a patient's overall well-being by affecting physical health, finances, social inclusion, and mental health. A robust clinical assessment of hearing loss includes a history and physical examination that effectively characterizes the deficit as conductive, sensorineural, or mixed. Patients presenting with red flags (such as sudden unilateral sensorineural hearing loss) must be urgently referred to otolaryngology-head and neck surgery or immediately assessed in the emergency department. Many nonurgent presentations of hearing loss will also require referral for further audiological assessment, diagnosis, and management., Conclusion: As primary care providers, family physicians are well equipped to manage the psychological concerns associated with hearing loss and to reinforce conservative treatment strategies. Frequently, referral or urgent workup, including imaging, is necessary to confirm a patient's diagnosis and initiate management in order to prevent further complications., (Copyright© the College of Family Physicians of Canada.)

Objective: To provide family physicians with an updated approach to diagnosis and treatment of pharyngitis, detailing key symptoms, methods of investigation, and a summary of common causes., Sources of Information: The approach described is based on the authors' clinical practice and peer-reviewed literature from 1989 to 2018., Main Message: Sore throat caused by pharyngitis is commonly seen in family medicine clinics and is caused by inflammation of the pharynx and surrounding tissues. Pharyngitis can be caused by viral, bacterial, or fungal infections. Viral causes are often self-limiting, while bacterial and fungal infections typically require antimicrobial therapy. Rapid antigen detection tests and throat cultures can be used with clinical findings to identify the inciting organism. Pharyngitis caused by Streptococcus pyogenes is among the most concerning owing to its associated severe complications such as acute rheumatic fever and glomerulonephritis. Hence, careful diagnosis of pharyngitis is necessary to provide targeted treatment., Conclusion: A thorough history is key to diagnosing pharyngitis. Rapid antigen detection tests should be reserved for concerns about antibiotic initiation. Physicians should exercise restraint in antibiotic initiation for pharyngitis, as restraint does not delay recovery or increase the risk of S pyogenes infections., (Copyright© the College of Family Physicians of Canada.)

Objective: To provide family physicians with a practical, evidence-based approach to managing patients with cerumen impaction. Methods: MEDLINE, The Cochrane Library, and the Turning Research Into Practice (TRIP) database were searched for English-language cerumen impaction guidelines and reviews. All such articles published between 1992 and 2018 were reviewed, with most providing level II and III evidence. Results: Cerumen impaction is a common presentation seen in primary care and cerumen removal is one of the most common otolaryngologic procedures performed in general practice. Cerumen impaction is often harmless but can be accompanied by more serious symptoms. Cerumenolytics and irrigation of the ear canal are reasonable first-line therapies and can be used in conjunction or isolation. If irrigation and cerumenolytics are contraindicated, manual removal is appropriate, but the tools necessary are not commonplace in primary care clinics and specialized training may be required to prevent adverse outcomes. Conclusion: Family physicians play a key role in the assessment and management of cerumen impaction and are well equipped to do so. Knowledge of the available techniques for cerumen removal as well as their contraindications ensures that cerumen is removed safely and effectively. When cerumen removal cannot be removed safely in a primary care setting, referral to Otolaryngology-Head and Neck Surgery is appropriate.

Objective: To provide family physicians with an updated approach to the diagnosis and management of Ménière disease (MD), detailing the natural course of MD and describing how to initiate medical therapy while awaiting consultation with otolaryngology-head and neck surgery., Sources of Information: The approach is based on the authors' clinical practices and review articles from 1989 to 2018. Most of the cited studies provided level II or III evidence., Main Message: Ménière disease is an uncommon disorder of the inner ear causing vertigo attacks with associated unilateral hearing loss, tinnitus, and aural fullness. It has a degenerative course that often results in permanent sensorineural hearing loss. On average, MD stabilizes with no further vestibular attacks by about 8 years after the onset of symptoms; however, this is highly variable. Vertigo symptoms can be controlled through a combination of dietary salt restriction, stress reduction, and medical therapy (betahistine, diuretics, or both). These can be initiated by family physicians before consultation with otolaryngology-head and neck surgery. Symptoms refractory to such strategies can be treated using nonablative, and occasionally ablative, therapies., Conclusion: A thorough history is key to the approach to and management of MD and permits differentiating MD from other vestibular and nonvestibular conditions., (Copyright© the College of Family Physicians of Canada.)

Introduction: Extracorporeal membrane oxygenation-assisted CPR (ECPR) is an evolving adjunct for resuscitation of OHCA patients. The primary objective of this systematic review was to assess survival-to-hospital discharge with good neurologic recovery after OHCA among patients treated with ECPR compared to conventional CPR (CCPR)., Methods: A systematic search of MEDLINE ® and EMBASE ® electronic databases was performed from inception until July 2016 to identify studies reporting ECPR use in adults with OHCA and survival outcomes., Results: Of the 1512 citations identified, 75 studies met our inclusion criteria (63 case series and 12 cohort studies). Among case series, 0 to 71.4% of patients treated with ECPR survived to discharge with a good neurologic outcome. Subgroup analysis of the cohort studies demonstrated survival-to-hospital discharge with good neurologic recovery in the ECPR group ranging from 8.3 to 41.6% compared to 1.5 to 9.1% in the CCPR group. Five cohort studies adjusted for confounders, 3 of which demonstrated significantly increased adjusted odds ratios of survival among the ECPR-treated patients. Due to significant heterogeneity (I 2  = 63%, p = 0.03), pooling of outcomes and a meta-analysis were not conducted., Conclusion: Although a trend towards improved survival with good neurologic outcome was reported in controlled, low-risk of bias cohort studies, a preponderance of low quality evidence may ascribe an optimistic effect size of ECPR on survival among OHCA patients. Our confidence in a clinically relevant difference in outcomes compared to current standards of care for OHCA remains weak. In this state of equipoise, high quality RCT data is urgently needed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

First, determine whether the sensation the patient is experiencing is dizziness or true vertigo. Then eliminate ominous causes from the array of benign ones.

Some β-blockers are efficiently removed from the circulation by hemodialysis ("high dialyzability") whereas others are not ("low dialyzability"). This characteristic may influence the effectiveness of the β-blockers among patients receiving long-term hemodialysis. To determine whether new use of a high-dialyzability β-blocker compared with a low-dialyzability β-blocker associates with a higher rate of mortality in patients older than age 66 years receiving long-term hemodialysis, we conducted a propensity-matched population-based retrospective cohort study using the linked healthcare databases of Ontario, Canada. The high-dialyzability group (n=3294) included patients initiating atenolol, acebutolol, or metoprolol. The low-dialyzability group (n=3294) included patients initiating bisoprolol or propranolol. Initiation of a high- versus low-dialyzability β-blocker was associated with a higher risk of death in the following 180 days (relative risk, 1.4; 95% confidence interval, 1.1 to 1.8; P<0.01). Supporting this finding, we repeated the primary analysis in a cohort of patients not receiving hemodialysis and found no significant association between dialyzability and the risk of death (relative risk, 1.0; 95% confidence interval, 0.9 to 1.3; P=0.71). β-Blocker exposure was not randomly allocated in this study, so a causal relationship between dialyzability and mortality cannot be determined. However, our findings should raise awareness of this potentially important drug characteristic and prompt further study., (Copyright © 2015 by the American Society of Nephrology.)

Background: Intravenous acyclovir-induced acute kidney injury (AKI) from drug crystallization in the renal tubules is described in case reports, review articles, and drug prescribing manuals. Similarly, AKI from oral acyclovir is described in case reports, but the risk in routine practice is unknown., Study Design: Retrospective population-based cohort study., Setting & Participants: We studied a large cohort of older patients in Ontario, Canada, receiving new outpatient prescriptions from 1997 to 2011 for oral acyclovir or valacyclovir (which is metabolized to acyclovir). The comparison drug was famciclovir, an antiviral used for indications similar to acyclovir, but with no known renal toxicity., Predictor: Outpatient prescription for oral acyclovir, valacyclovir, or famciclovir., Outcomes: The primary outcome was hospital admission with AKI in the 30 days after the initial prescription., Measurements: We assessed the primary outcome with health care diagnostic codes. In a subpopulation, we assessed AKI using available laboratory serum creatinine measurements., Results: 76,269 patients received acyclovir or valacyclovir and 84,646 received famciclovir. On average, patients were aged 76 [IQR, 71-81] years and prescription duration was 7 days. Acyclovir or valacyclovir use was not associated with a higher risk of hospital admission with AKI (209 [0.27%] events with acyclovir or valacyclovir vs 238 [0.28%] events with famciclovir [relative risk, 0.97; 95% CI, 0.81-1.17]). Results were consistent in adjusted analyses, in all subgroups, and in the subpopulation with laboratory measurements., Limitations: Diagnostic codes had high specificity but low sensitivity and underestimated the incidence of AKI. Only a limited number of patients (n = 2,729) had serum creatinine values available., Conclusions: In this population-based study of older adults, oral acyclovir use was not associated with a higher risk of AKI compared to famciclovir., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To define geographical regions (forward sortation areas; FSAs) in Southwestern Ontario, Canada from which patients would reliably present to a hospital with linked laboratory data if they developed adverse events related to medications dispensed in outpatient pharmacies., Design: Descriptive research., Setting: Forty-five hospitals in Southwestern Ontario, Canada, from 2003 to 2009., Participants: Patients aged 66 years and older who received an outpatient prescription for any drug and presented to the emergency department in the subsequent 120 days., Main Outcome Measure: The proportion of patients in a given FSA presenting to an emergency department at a hospital with linked laboratory data versus a hospital without linked laboratory data. To be included in the catchment area at least 90% of emergency department visits in an FSA must have occurred at laboratory-linked hospitals in a given year., Results: Over the study period, there were 649 713 emergency department visits by patients with recent prescription claims from pharmacies in 1 of 118 FSAs. In total, 141 302 of these patients presented to an emergency department at a laboratory-linked hospital. For the year 2003, 12 FSAs met our criteria to be in the catchment area and this number grew to 25 FSAs by the year 2009., Conclusions: The relevant geographical regions for hospitals with linked laboratory data have been successfully identified. Studies can now be conducted using these well-defined areas to obtain reliable information on the incidence and absolute risk of presenting to hospital with laboratory abnormalities in older adults dispensed commonly prescribed medications in outpatient pharmacies.

Background: Foam cell formation by intimal smooth muscle cells (SMCs) inhibits the elaboration of extracellular matrix, which is detrimental to plaque stabilization. In the present study, we examined the lipoproteins and receptors involved in human SMC foam cell formation and investigated the ability of 24(S),25-epoxycholesterol [24(S),25-EC], an oxysterol agonist of the liver X receptor, to attenuate SMC foam cell formation., Methods and Results: Incubation of human internal thoracic SMCs with atherogenic lipoproteins demonstrated that low-density lipoprotein (LDL), but not oxidized or acetylated LDL, was the primary lipoprotein taken up, resulting in marked cholesteryl ester deposition (6-fold vs 1.8-fold; P<0.05; n=4). Exposure of SMCs to exogenous or endogenously synthesized 24(S),25-EC attenuated LDL uptake (-90% and -47% respectively; P<0.05; n=3) through decreased sterol regulatory element-binding protein-2 expression (-30% and -17%, respectively; P<0.001; n=3), decreased LDL receptor expression (-75% and -40%, respectively; P<0.05; n=3) and increased liver X receptor-mediated myosin regulatory light chain interacting protein expression (7- and 3-fold, respectively; P<0.05; n=4). Furthermore, exogenous 24(S),25-EC increased adenosine triphosphate-binding cassettes A1- and G1-mediated cholesterol efflux to apolipoprotein AI (1.9-fold; P<0.001; n=5) and high-density lipoprotein(3) (1.3-fold; P<0.05; n=5). 24(S),25-EC, unlike a nonsteroidal liver X receptor agonist, T0901317, did not stimulate sterol regulatory element-binding protein-1c-mediated fatty acid synthesis or triglyceride accumulation. 24(S),25-EC preserved the assembly of fibronectin and type I collagen by SMCs., Conclusions: The oxysterol 24(S),25-EC prevented foam cell formation in human SMCs by attenuation of LDL receptor-mediated LDL uptake and stimulation of cholesterol efflux, restoring the elaboration of extracellular matrix. In contrast to T0901317, 24(S),25-EC prevented the development of a triglyceride-rich foam cell phenotype. (J Am Heart Assoc. 2012;1:e000810 doi: 10.1161/JAHA.112.000810.).

Orlistat is an inhibitor of gastric and pancreatic lipase with proven efficacy in the augmentation and maintenance of weight loss. Although its use has been limited by troublesome but benign gastrointestinal side effects, it has more recently been associated with acute kidney injury (AKI). In this review, we summarize orlistat's benefits and drawbacks and discuss the body of evidence supporting its role as a cause of AKI. Although we cannot yet draw an unequivocal causal link between orlistat and AKI, there is enough evidence to include orlistat exposure in the clinical assessment of patients with AKI.

Liver X receptor (LXR) activation represents a mechanism to prevent macrophage foam cell formation. Previously, we demonstrated that partial inhibition of oxidosqualene:lanosterol cyclase (OSC) stimulated synthesis of the LXR agonist 24(S),25-epoxycholesterol (24(S),25-epoxy) and enhanced ABCA1-mediated cholesterol efflux. In contrast to a synthetic, nonsteroidal LXR activator, TO-901317, triglyceride accumulation was not observed. In the present study, we determined whether endogenous 24(S),25-epoxy synthesis selectively enhanced expression of macrophage LXR-regulated cholesterol efflux genes but not genes that regulate fatty acid metabolism. THP-1 human macrophages incubated with the OSC inhibitor (OSCi) RO0714565 (15 nM) significantly reduced cholesterol synthesis and maximized synthesis of 24(S),25-epoxy. Endogenous 24(S),25-epoxy increased ABCA1, ABCG1, and APOE mRNA abundance and consequently increased cholesterol efflux to apoAI. In contrast, OSCi had no effect on LXR-regulated genes LPL (lipoprotein lipase) and FAS (fatty acid synthase). TO-901317 (>or=10 nM) significantly enhanced expression of all genes examined. OSCi and TO-901317 increased the mRNA and precursor form of SREBP-1c, a major regulator of fatty acid and triglyceride synthesis. However, conversion of the precursor to the active form (nSREBP-1c) was blocked by OSCi-induced 24(S),25-epoxy but not by TO-901317 (>or=10 nm), which instead markedly increased nSREBP-1c. Disruption of nSREBP-1c formation by 24(S),25-epoxy accounted for diminished FAS and LPL expression. In summary, endogenous synthesis of 24(S),25-epoxy selectively up-regulates expression of macrophage LXR-regulated cholesterol efflux genes without stimulating genes linked to fatty acid and triglyceride synthesis.