RESUMO
BACKGROUND: Paramethoxymethamphetamine (PMMA) is a ring-substituted amphetamine similar in structure to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), but substantially more toxic. We describe the clinical features of fatal exposures in the provinces of Alberta and British Columbia, Canada. METHODS: We conducted a retrospective case series on deaths in Alberta and BC between June 2011 and April 2012 for which forensic toxicologic analysis was positive for PMMA and the drug was implicated as the primary toxic agent. Data collected included patient demographics, exposure history, clinical features, investigations, therapy provided and postmortem toxicologic findings. RESULTS: A total of 27 PMMA-associated deaths (20 in Alberta, 7 in BC) were reported in the 11-month period. The median age was 24 (range 14-52) years, and 22 (81%) were male. Ten patients were pronounced dead at the scene, and 17 died in hospital. The median time from exposure to death was 17 (range 5-264) hours. The median first-recorded vital signs (and ranges) were: heart rate 160 (86-201) beats/min, blood pressure 89/43 (69/30-162/83) mm Hg, respiratory rate 40 (26-48) breaths/min, oxygen saturation 81% (68%-100%) and temperature 39.4°C (34-43.8°C). Sixteen of the 17 people who died in hospital presented with clinical features consistent with serotonin syndrome. End-organ dysfunction included hepatic (30%) and acute kidney injury (85%), rhabdomyolysis (54%), coagulopathy (61%) and cardiac ischemia (15%). Other drugs identified on toxicologic analysis were MDMA (n = 27), cocaine or its metabolite benzoylecgonine (n = 14) and methamphetamine (n = 12). INTERPRETATION: Exposure to PMMA was characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. In addition to PMMA, multiple synthetic amphetamines were present on toxicologic analysis. When evaluating patients suspected of exposure to sympathomimetic drugs of abuse, clinicians must anticipate multiple clinical effects from the increased release of dopamine, serotonin, norepinephrine and other neurotransmitters.
RESUMO
Failure to understand the risk of false-negative HIV test results during the window period results in anxiety. Patients typically want accurate test results as soon as possible while clinicians prefer to wait until the probability of a false-negative is virtually nil. This review summarizes the median window periods for third-generation antibody and fourth-generation HIV tests and provides the probability of a false-negative result for various days post-exposure. Data were extracted from published seroconversion panels. A 10-day eclipse period was used to estimate days from infection to first detection of HIV RNA. Median (interquartile range) days to seroconversion were calculated and probabilities of a false-negative result at various time periods post-exposure are reported. The median (interquartile range) window period for third-generation tests was 22 days (19-25) and 18 days (16-24) for fourth-generation tests. The probability of a false-negative result is 0.01 at 80 days' post-exposure for third-generation tests and at 42 days for fourth-generation tests. The table of probabilities of falsely-negative HIV test results may be useful during pre- and post-test HIV counselling to inform co-decision making regarding the ideal time to test for HIV.
