Citations

OBJECTIVE: This study investigates temporal trends in the prevalence and incidence of persistent proteinuria among people with adult-onset diabetes (age > or =40 years). RESEARCH DESIGN AND METHODS: The complete community-based medical records of all Rochester, Minnesota, residents with a diagnosis of diabetes or diabetes-like condition from 1945 through 1989 were reviewed to determine whether they met National Diabetes Data Group (NDDG) criteria. All confirmed diabetes cases residing in Rochester on 1 January 1970 (n = 446), 1980 (n = 647), and/or 1990 (n = 940) were identified. The medical records of these prevalence cases were reviewed from the time of the first laboratory urinalysis value to the last visit, death, or 1 April 1992 (whichever came first) for evidence of persistent proteinuria (two consecutive urinalyses positive for protein, with no subsequent negative values). Similarly, the medical records of all 1970-1989 diabetes incidence cases (n = 1,252) were reviewed to investigate temporal changes in 1) the likelihood of having persistent proteinuria before the date NDDG criteria was met, i.e., baseline; 2) the risk of persistent proteinuria after baseline; and 3) the relative risk of mortality associated with persistent proteinuria. RESULTS: The proportion of diabetes prevalence cases with persistent proteinuria on or before the prevalence date declined from 20% in 1970 to 11% in 1980 and 8% in 1990. Among the 1970-1989 diabetes incidence cases, 77 (6%) had persistent proteinuria on or before baseline; the adjusted odds declined by 50% with each 10-year increase in baseline calendar year (P<0.001). Among individuals free of persistent proteinuria at baseline, 136 subsequently developed persistent proteinuria; the estimated 20-year cumulative incidence was 41% (95% CI 31-59); the adjusted risk did not differ as a function of baseline calendar year. Survival of individuals with persistent proteinuria relative to those without was reduced but did not differ by baseline calendar year. CONCLUSIONS: The prevalence of persistent proteinuria among people with adult-onset diabetes in Rochester, Minnesota, declined 60% between 1970 and 1990. The decline appears because of a decrease in the proportion of diabetes incidence cases with persistent proteinuria before baseline rather than secular declines in the risk of persistent proteinuria after baseline or secular increases in the risk of mortality associated with persistent proteinuria. Similarity over time in age and fasting glucose at baseline, and at prevalence dates, is evidence that earlier detection of diabetes is not the sole explanation for the decline.

Abstract Context: Body mass index (BMI) reflects the amount of insulin in the human follicle and may enhance insulin action as a cogonadotropin. Objective: This study examined whether increased adiposity enhances intrafollicular steroidogenesis in normoandrogenic ovulatory women receiving GnRH analog/recombinant human FSH therapy for in vitro fertilization. Design, Setting, and Participants: Study participants were from an institutional practice and comprised 30 normoandrogenic ovulatory women who were lean (n = 17; BMI < 25 kg/m2) or overweight (n = 13; BMI ≥ 25 kg/m2). Women received GnRH analog after basal serum hormone determinations and oral glucose tolerance testing, followed by recombinant human FSH therapy and human chorionic gonadotropin administration when two or more follicles 18 mm or larger in diameter were present. Intervention: Follicle fluid was aspirated at oocyte retrieval from the first follicle of each ovary. Main Outcome Measures: Follicle fluid was assayed for estradiol (E2), progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, insulin, glucose, and lactate. Results: Overweight women had hyperinsulinemia (P = 0.03) with decreased serum SHBG (P = 0.001) and increased serum free testosterone levels (P = 0.02). Elevated intrafollicular insulin levels in overweight women (P = 0.004) were accompanied by normal glucose and lactate levels. Intrafollicular E2 levels were greater in overweight vs. lean women (P = 0.03), whereas the remaining intrafollicular steroid levels were similar in both female groups. Conclusion: In normoandrogenic ovulatory women undergoing in vitro fertilization, increased adiposity elevates insulin and E2 levels in terminally differentiated follicles without altering intrafollicular androgen levels or luteinization. Additional studies are required to determine whether these abnormalities impair oocyte development.

Purpose Despite widespread popular use of complementary and alternative medicine (CAM) therapies, a rigorous evidence base about their efficacy for cancer-related pain is lacking. This is a systematic review of randomized controlled trials (RCTs) evaluating CAM therapies for cancer-related pain. Methods RCTs using CAM interventions for cancer-related pain were abstracted using Medline, EMBASE, CINAHL, AMED, and Cochrane database. Results Eighteen trials were identified (eight poor, three intermediate, and seven high quality based on Jadad score), with a total of 1,499 patients. Median sample size was 53 patients, and median intervention duration was 45 days. All studies were from single institutions, four had sample size justification, and none reported any adverse effects. Seven trials reported significant benefit for the following CAM therapies: acupuncture (n = 1), support groups (n = 2), hypnosis (n = 1), relaxation/imagery (n = 2), and herbal supplement/HESA-A (n = 1, but study was of low quality without control data). Seven studies reported immediate postintervention or short-term benefit of the following CAM interventions: acupuncture (n = 2), music (n = 1), herbal supplement/Ai-Tong-Ping (n = 1), massage (n = 1), and healing touch (n = 2). Four studies reported no benefit of CAM interventions (music, n = 2; massage, n = 2) in reducing cancer pain compared with a control arm. Conclusion There is paucity of multi-institutional RCTs evaluating CAM interventions for cancer pain with adequate power, duration, and sham control. Hypnosis, imagery, support groups, acupuncture, and healing touch seem promising, particularly in the short term, but none can be recommended because of a paucity of rigorous trials. Future research should focus on methodologically strong RCTs to determine potential efficacy of these CAM interventions.

There is little consensus on what constitutes adequate health insurance coverage. The concept of a lack of adequate coverage, or underinsurance, is a matter of ongoing debate. A measure of adequate coverage is of critical importance as the nature of health insurance products evolves. Changes to health coverage include more direct out-of-pocket spending by consumers and a reduction of covered benefits. This article updates and extends an earlier review of underinsurance measurement published in 1993. We present a conceptual approach to measuring underinsurance and provide a review of the empirical findings obtained from the application of these approaches. A discussion of the limitations in the selection of a measurement approach includes a review of the extant data sources used. We recommend a national effort to develop a consistent approach to monitor changes in the economic and structural dimensions of health insurance coverage with a concerted effort to define and measure underinsurance.

Background— Congenital long-QT syndrome (LQTS) is a primary arrhythmogenic syndrome stemming from perturbed cardiac repolarization. LQTS, which affects ≈1 in 3000 persons, is 1 of the most common causes of autopsy-negative sudden death in the young. Since the sentinel discovery of cardiac channel gene mutations in LQTS in 1995, hundreds of mutations in 8 LQTS susceptibility genes have been identified. All 8 LQTS genotypes represent primary cardiac channel defects (ie, ion channelopathy) except LQT4, which is a functional channelopathy because of mutations in ankyrin-B. Approximately 25% of LQTS remains unexplained pathogenetically. We have pursued a “final common pathway” hypothesis to elicit novel LQTS-susceptibility genes. With the recent observation that the LQT3-associated, SCN5A -encoded cardiac sodium channel localizes in caveolae, which are known membrane microdomains whose major component in the striated muscle is caveolin-3, we hypothesized that mutations in caveolin-3 may represent a novel pathogenetic mechanism for LQTS. Methods and Results— Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, we performed open reading frame/splice site mutational analysis on CAV3 in 905 unrelated patients referred for LQTS genetic testing. CAV3 mutations were engineered by site-directed mutagenesis and the molecular phenotype determined by transient heterologous expression into cell lines that stably express the cardiac sodium channel hNa v 1.5. We identified 4 novel mutations in CAV3 -encoded caveolin-3 that were absent in >1000 control alleles. Electrophysiological analysis of sodium current in HEK293 cells stably expressing hNa v 1.5 and transiently transfected with wild-type and mutant caveolin-3 demonstrated that mutant caveolin-3 results in a 2- to 3-fold increase in late sodium current compared with wild-type caveolin-3. Our observations are similar to the increased late sodium current associated with LQT3-associated SCN5A mutations. Conclusions— The present study reports the first CAV3 mutations in subjects with LQTS, and we provide functional data demonstrating a gain-of-function increase in late sodium current.