Lee L. Lanza

Mortality in current and former users of clozapine

Clozapine (Clozaril®), a tricyclic dibenzodiazepine, causes fewer extrapyramidal side effects than do other antipsychotic drugs. Because it can induce agranulocytosis, however, clozapine is indicated only for schizophrenia that is not responsive to other therapies. To describe the drugs effects on

Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture.

OBJECTIVE: Depot medroxyprogesterone acetate (DMPA) reversibly reduces bone mineral density. To estimate the extent to which DMPA might increase fracture risk, we undertook a retrospective cohort study of fractures in DMPA users and users of non-DMPA contraceptives, using the General Practice Research Database. METHODS: Eligible women were aged younger than 50 years at the qualifying first contraceptive prescription. The DMPA users were classified by DMPA exposure (cumulative and time of last dose) based on prescription records. All incident fractures were included; fracture incidence and risk factors before starting contraceptive use (DMPA or other) also were estimated. RESULTS: We identified 11,822 fractures in 312,395 women during 1,722,356 person-years of follow-up. Before contraceptive use started, DMPA users had higher fracture risk than nonusers (incidence rate ratio 1.28, 95% confidence interval [CI] 1.07–1.53). After DMPA started, crude fracture incidence was 9.1 per 1,000 person-years for DMPA users and 7.3 for nonusers (crude incidence rate ratio 1.23, 95% CI 1.16–1.30). Fracture risk in DMPA users did not increase after starting DMPA (incidence rate ratio after or before 1.08, 95% CI 0.92–1.26). There was little confounding by age or other factors that could be measured. Fracture incidence was 9.4 per 1,000 person-years in low-exposure DMPA users, and 7.8 per 1,000 in high-exposure DMPA users. The DMPA users had higher fracture risk than nonusers at the start of contraceptive use, with no discernible induction period. CONCLUSION: Although DMPA users experienced more fractures than nonusers, this association may be the result of confounding by a pre-existing higher risk for fractures in women who chose DMPA for contraception. LEVEL OF EVIDENCE: II

Toxic shock syndrome, contraceptive methods, and vaginitis

To elucidate further the etiology of toxic shock syndrome, we assessed the effects of certain contraceptive methods and recent history of vaginal infection on the incidence of toxic shock syndrome, with confounding effects of other risk factors controlled. We found a strong but imprecise positive association between toxic shock syndrome and tubal ligation (rate ratio = 7.9, 90% confidence interval 1.4 to 42.7). We also observed a negative association with oral contraceptives (rate ratio = 0.49, 90% confidence interval 0.22 to 1.1) and a positive association with a recent history of vaginitis (rate ratio = 2.1, 90% confidence interval 1.2 to 3.9).

Estimated Risks of Fatal Events Associated with Acetaminophen, Ibuprofen, and Naproxen Sodium Used for Analgesia

Objective: We assessed the net effect on risk of death for within-label use of acetaminophen and the two nonaspirin alternative oral non-prescription analgesics available in the U.S. (ibuprofen and naproxen sodium) in relation to upper gastrointestinal hemorrhage, liver failure, and renal failure. Methods: For each drug we obtained estimates of recent general-population prevalence of use and the number of deaths in the US from acute liver injury, acute renal failure, and gastrointestinal hemorrhage for the years 2006-2008 in the population age 20 years or older. We searched the literature and reviewed all informative epidemiologic studies to obtain estimates of the relative risks for each analgesic-endpoint combination. From the estimates of prevalence, relative risk and total one-year risk for the U.S. population, we back-calculated the risk among unexposed, using it as a benchmark from which we could obtain the change in absolute risk related to using each analgesic. Results: Under most assumptions for the relative risks among the different analgesics, acetaminophen use carried the smallest absolute increase in risk, the best estimate being about 35 deaths per million in one year. The comparable estimated increased risk of death related to use of ibuprofen or naproxen sodium was 64 deaths for ibuprofen and 118 deaths for naproxen sodium per million person-years respectively. Conclusions: When non-prescription analgesics are used according to labeled instructions, acetaminophen use appears likely to be associated with smaller combined risks for upper gastrointestinal hemorrhage, liver disease, and renal disease than is use of ibuprofen or naproxen sodium.

Incidence of pelvic inflammatory disease among women treated for gonorrhea or chlamydia.

Background—No estimate exists of the incidence of pelvic inflammatory disease (PID) after the occurrence of a recent bout of sexually transmitted disease (STD).

Comment on journal review of ‘Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture’

We thank Dr Curry for an accurate summary1 of our study entitled ‘Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture’.2 Nevertheless, we do not recommend more selective use of depot medroxyprogesterone acetate (DMPA) on account of fracture risk, as we believe that this recommendation would reduce access to an effective, safe contraceptive without actually reducing fracture risk. As we reported, in those subjects with at least 6 months of pre-DMPA medical history (176 pre-treatment fractures …