The secular trends in male:female ratio at birth in postwar industrialized countries.

Finnish investigators [Vartiainen et al. Environmental Chemicals and Changes in Sex Ratio: Analysis Over 250 Years in Finland. Environ Health Perspect 107:813-815 (1999)] presented the sex ratio of all newborn babies from 1751 to 1997 in order to evaluate whether Finnish long-term data are compatible with the hypothesis that the decrease in the ratio of male to female births after World War I and World War II in industrial countries is caused by environmental factors. They found an increase in the proportion of males from 1751 to 1920, which was interrupted by peaks in male births during World War I and World War II and followed by a decrease thereafter, similar to the trends in many other countries. The turning point of male proportion, however, preceded the period of industrialization and introduction of pesticides and hormonal drugs. Thus, a causal association between these environmental exposures and this decrease is unlikely. In addition, none of the various family parameters (e.g., paternal age, maternal age, age difference in parents, birth order) could explain the historical time trends. Vartiainen et al. concluded that at present it is unknown how these historical trends could be mediated. The postwar secular decline of the male:female ratio at birth is not an isolated phenomenon and parallels the decline of perinatal morbidity and mortality, congenital anomalies, and various constitutional diseases. This parallelism indicates a common etiology and may be caused by reduction of conceptopathology, as a correlate to increasing socioeconomic development. An inverted dose response or the dose-response fallacy due to vanishing male conceptuses explains the low sex ratios before World War I and World War II in newborns from black parents and from the lowest socioeconomic classes

The efficacy of two bupivacaine hydrochloride injection products

No Abstract

Clinical problems with the performance of euthanasia and physician-assisted suicide in The Netherlands

BACKGROUND AND METHODS: The characteristics and frequency of clinical problems with the performance of euthanasia and physician-assisted suicide are uncertain. We analyzed data from two studies of euthanasia and physician-assisted suicide in The Netherlands (one conducted in 1990 and 1991 and the other in 1995 and 1996), with a total of 649 cases. We categorized clinical problems as technical problems, such as difficulty inserting an intravenous line; complications, such as myoclonus or vomiting; or problems with completion, such as a longer-than-expected interval between the administration of medications and death. RESULTS: In 114 cases, the physician's intention was to provide assistance with suicide, and in 535, the intention was to perform euthanasia. Problems of any type were more frequent in cases of assisted suicide than in cases of euthanasia. Complications occurred in 7 percent of cases of assisted suicide, and problems with completion (a longer-than-expected time to death, failure to induce coma, or induction of coma followed by awakening of the patient) occurred in 16 percent of the cases; complications and problems with completion occurred in 3 percent and 6 percent of cases of euthanasia, respectively. The physician decided to administer a letha

Physician-assisted death in psychiatric practice in the Netherlands

BACKGROUND: In 1994 the Dutch Supreme Court ruled that in exceptional instances, physician-assisted suicide might be justifiable for patients with unbearable mental suffering but no physical illness. We studied physician-assisted suicide and euthanasia in psychiatric practice in the Netherlands. METHODS: In 1996, we sent questionnaires to 673 Dutch psychiatrists - about half of all such specialists in the country - and received 552 responses from the 667 who met the study criteria (response rate, 83 percent). We estimated the annual frequencies of requests for physician-assisted suicide by psychiatrists and actual instances of assistance. RESULTS: Of the respondents, 205 (37 percent) had at least once received an explicit, persistent request for physician-assisted suicide and 12 had complied. We estimate there are 320 requests a year i

Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol

Background: To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. Methods/Design: We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. Discussion: The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases

Dyadic interventions for community-dwelling people with dementia and their family caregivers: a systematic review.

Background: In this review, we study the effects of dyadic psychosocial interventions focused on community-dwelling people with dementia and their family caregivers, and the relationship of the effects with intervention components of programs. Methods: A search from January 2005 to January 2012 led to 613 hits, which we reviewed against our inclusion criteria. We added studies from 1992 to 2005 reviewed by Smits et al. (Smits, C. H. M., De Lange, J., Droes, R.-M., Meiland, F., Vernooij-Dassen, M. and Pot, A. M. (2007). Effects of combined intervention programs for people with dementia living at home and their caregivers: a systematic review. International Journal of Geriatric Psychiatry, 22, 1181-1193). We assessed the methodological quality of 41 programs with the Cochrane criteria and two items of the Oxford Centre of Evidence-based Medicine guidelines. Results: Studies of moderate to high quality concerning 20 different dyadic psychosocial programs for people with dementia and caregivers were included. Nineteen of these programs show significant effects on the patient with dementia, the caregiver, or both. Due to differences in the programs and the studies, this study does not provide an unequivocal answer about which programs are most effective. Programs with intervention components that actively train one or more specific functional domains for the person with dementia and/or the caregiver seem to have a beneficial impact on that domain, although there are exceptions. Reasons can be found in the program itself, the implementation of the program, and the study design. Conclusions: Dyadic psychosocial programs are effective, but the outcomes for the person with dementia and the caregiver vary. More attention is needed for matching the targeted functional domains, intervention components, and delivery characteristics of a program with the needs of the person with dementia and the family caregiver. Copyright © International Psychogeriatric Association 2013