Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

BACKGROUND: Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. PRESENTATION: We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. IMPLICATIONS: We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. TESTING: Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis

Influenza A Viruses from Wild Birds in Guatemala Belong to the North American Lineage

The role wild bird species play in the transmission and ecology of avian influenza virus (AIV) is well established; however, there are significant gaps in our understanding of the worldwide distribution of these viruses, specifically about the prevalence and/or significance of AIV in Central and South America. As part of an assessment of the ecology of AIV in Guatemala, we conducted active surveillance in wild birds on the Pacific and Atlantic coasts. Cloacal and tracheal swab samples taken from resident and migratory wild birds were collected from February 2007 to January 2010.1913 samples were collected and virus was detected by real time RT-PCR (rRT-PCR) in 28 swab samples from ducks (Anas discors). Virus isolation was attempted for these positive samples, and 15 isolates were obtained from the migratory duck species Blue-winged teal. The subtypes identified included H7N9, H11N2, H3N8, H5N3, H8N4, and H5N4. Phylogenetic analysis of the viral sequences revealed that AIV isolates are highly similar to viruses from the North American lineage suggesting that bird migration dictates the ecology of these viruses in the Guatemalan bird population

Pharmacologic Treatment of Knee Osteoarthritis in Athletic Women

There is a greater incidence of anterior cruciate ligament tears due to noncontact sports injuries in women compared with men. Anterior cruciate ligament tears are associated with accelerated development of knee osteoarthritis (OA), which is also more prevalent in women than in men. This article considers therapeutic modalities that are best suited for athletic women with knee OA. Clinical data on the safety and efficacy of pharmacotherapies for knee OA, including acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), and topical NSAIDs, are discussed, with attention paid to special considerations for women who participate in athletic activity. Adverse events associated with the use of acetaminophen and oral NSAIDs place potential limits on the dose and duration of therapy and may be of greater concern in female athletes than in other patient groups. Topical NSAIDs, which effect relief through the same mechanism of action as oral NSAIDs, produce dramatically lower systemic NSAID exposure compared with oral NSAIDs and are associated with a lower incidence of systemic adverse events. These findings, along with additional future studies, may have particular relevance to the choice of the most effective treatment options for athletic women with OA of the knee

Clinical replicability of rehabilitation interventions in randomized controlled trials reported in main journals is inadequate

Objective: The objective of this study was to study if randomized controlled trials (RCTs) in rehabilitation (a field where complex interventions prevail) published in main journals include all the details needed to replicate the intervention in clinical practice (clinical replicability). Study Design and Setting: Forty-seven rehabilitation clinicians of 5 professions from 7 teams (Belgium, Italy, Malaysia, Pakistan, Poland, Puerto Rico, the USA) reviewed 76 RCTs published by main rehabilitation journals exploring 14 domains chosen through consensus and piloting. Results: The response rate was 99%. Inter-rater agreement was moderate/good. All clinicians considered unanimously 12 (16%) RCTs clinically replicable and none not replicable. At least one \u201cabsent\u201d information was found by all participants in 60 RCTs (79%), and by a minimum of 85% in the remaining 16 (21%). Information considered to be less well described (8\u201319% \u201cperfect\u201d information) included two providers (skills, experience) and two delivery (cautions, relationships) items. The best described (50\u201379% \u201cperfect\u201d) were the classic methodological items included in CONSORT (descending order: participants, materials, procedures, setting, and intervention). Conclusion: Clinical replicability must be considered in RCTs reporting, particularly for complex interventions. Classical methodological checklists such as CONSORT are not enough, and also Template for Intervention Description and Clinical replication do not cover all the requirements. This study supports the need for field-specific checklists