Patterns of use of symptomatic treatments for Alzheimer's disease dementia (AD).

BACKGROUND: Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries. METHODS: The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.S. health plan [US] and UK-Clinical Practice Research Datalink [CPRD GOLD]). This analysis included patients with newly diagnosed AD dementia in 2018-2019, who initiated symptomatic AD drug therapy, with ≥ 1 year baseline period and ≥ 1 year of follow-up. RESULTS: Over median follow-ups of 698 and 645 days, 63% and 65% of AD dementia patients used symptomatic treatments, with 34% and 77% newly initiating therapy, constituting analytic samples of 7637 patients in the US database and 4470 patients in the CPRD, respectively. The median time to the first therapy was 14 days for US and 49 days for CPRD; donepezil ranked the as most frequently used (69% vs 61%), followed by memantine (19% vs 28%) in the US database and CPRD, respectively. Median time on first therapy was 213 and 334 days, and 30% and 12% of patients proceeded to a second treatment in the US and CPRD databases, respectively. CONCLUSION: Approximately two thirds of newly diagnosed AD dementia patients utilized approved symptomatic treatment. Time on first therapy was relatively short (< 1 year) and the majority did not move to a second therapy, highlighting the need for better adherence and persistence to existing AD symptomatic therapies and the need for additional therapies to alleviate the significant burden of AD dementia.

Corifollitropin Alfa Combined With Human Chorionic Gonadotropin in Adolescent Boys With Hypogonadotropic Hypogonadism.

CONTEXT: Adolescent males with hypogonadotropic hypogonadism (HH) have traditionally been treated with exogenous testosterone (T) or human chorionic gonadotropin (hCG) to produce virilization; however, those modalities do not result in growth of the testes and may promote premature maturation and terminal differentiation of Sertoli cells prior to their proliferation, which may impact future fertility. Another option is to use gonadotropins in those individuals to induce testicular growth, proliferation and maturation of Sertoli cells, and production of endogenous T with consequent virilization. OBJECTIVE: We examined the efficacy and safety of corifollitropin alfa (CFA) combined with hCG for the induction of testicular growth and pubertal development in adolescent boys with HH. METHODS: This was a 64-week, multicenter, open-label, single-group study of CFA in adolescent boys, aged 14 to younger than 18 years, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 µg if weight ≤ 60 kg, or 150 µg if weight > 60 kg) given subcutaneously once every 2 weeks, after which they entered a 52-week combined treatment period with CFA, once every 2 weeks, and subcutaneous hCG, twice-weekly (hCG dose adjusted between 500 IU and 5000 IU to keep total T and estradiol levels within protocol-specified ranges). The primary efficacy end point was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound. RESULTS: After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 (95% CI, 7.44-11.97) (arithmetic mean of change from baseline at week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies. CONCLUSION: Treatment of adolescent boys with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased T, and a pubertal growth spurt (EudraCT: 2015-001878-18).

The Burden of Congestion in Patients Hospitalized With Acute Decompensated Heart Failure.

Congestion is associated with adverse outcomes in heart failure (HF) patients. We characterized congestion in patients hospitalized for HF and examined the association between congestion severity at admission and postdischarge outcomes. Using the OPTIMIZE-HF registry linked to Medicare claims, we analyzed patients ≥65 years old hospitalized for HF from 2003 to 2004. Congestion severity was measured using a 15-point scale that scores dyspnea, orthopnea, fatigue, jugular venous pressure, rales, and edema. Patient characteristics and outcomes were described by congestion strata. Proportional hazards models were fit to examine associations between congestion and 1-year outcomes. Congestion scores for the 24,724 patients ranged from 0 to 14, with a median of 5 (Q1, Q3: 3, 7). At baseline, patients with the highest scores (≥7) had the highest rates of recent HF hospitalizations, EF ≤40%, and co-morbidities, including arrhythmias, diabetes mellitus, and renal insufficiency. Adjusting for patient characteristics, a 3-point congestion score increase was positively associated with mortality (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03, 1.09), all-cause rehospitalization (HR 1.02, 95% CI 1.00, 1.04), and HF rehospitalization (HR 1.09, 95% CI 1.06, 1.12), but not emergency department visits (HR 0.99, 95% CI 0.97, 1.01). In conclusion, for patients hospitalized with HF, congestion was associated with rehospitalization and mortality.

The Use of 5-Alpha Reductase Inhibitors to Manage Benign Prostatic Hyperplasia and the Risk of All-cause Mortality.

OBJECTIVE: To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. METHODS: We employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. RESULTS: In this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). CONCLUSION: Among men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.

5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS: A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS: In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION: Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.

Prevalence of metabolic syndrome and its components among men with and without clinical benign prostatic hyperplasia: a large, cross-sectional, UK epidemiological study.

OBJECTIVES: To compare the prevalence of metabolic syndrome and the components of metabolic syndrome in men aged ≥50 years with and without clinical benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: This was a cross-sectional study using the UK Clinical Practice Research Datalink (CPRD). Men were selected from the CPRD who were aged ≥50 years and still registered as of 31 December 2011. Cohort 1 included men with clinical BPH, and cohort 2 men without clinical BPH who were matched 1:1 to those in cohort 1 by general practice, year of birth and previous years of available history (1-<2, 2-<3, 3-<4, ≥4 years of available history). The prevalence of metabolic syndrome and its components (for men alive and still registered in the CRPD as of 31 December 2011) was calculated using all available history (lifetime prevalence) and medical history from 2010 and 2011 (current prevalence). Crude odds ratios and 95% confidence intervals for the occurrence of metabolic syndrome and the occurrence of the components of metabolic syndrome were calculated by comparing men with and without BPH. RESULTS: A total of 26.5% of men with clinical BPH had metabolic syndrome compared with 20.9% of matched controls without clinical BPH (absolute difference 5.6%; P < 0.001); men with clinical BPH were therefore significantly more likely to have metabolic syndrome than matched controls without clinical BPH. Significantly greater proportions of men with clinical BPH also had each component of metabolic syndrome compared with matched controls without clinical BPH. The presence of clinical BPH was associated with a 37% increased odds of having metabolic syndrome (for both lifetime prevalence and current prevalence) compared with matched controls without clinical BPH. CONCLUSIONS: There is a significant cross-sectional association between clinical BPH and metabolic syndrome in the UK primary care population.

Association between low muscle mass, functional limitations and hospitalisation in heart failure: NHANES 1999-2004.

BACKGROUND/OBJECTIVES: Muscle mass decreases with age, and heart failure (HF) patients may experience greater reductions due to pathophysiological processes associated with this disease. Reduced muscle mass may predispose HF patients to functional limitations and increased morbidity and mortality. This study estimated the associations between HF, low muscle mass (LMM), functional limitations and hospitalisation, as well as the combined effect of HF and LMM on these outcomes in a nationally representative sample. DESIGN: A cross-sectional survey. SETTING: the National Health and Nutrition Examination Survey 1999-2004. SUBJECTS: A total of 402 HF (weighted 3,994,205) and 7,061 non-HF participants (weighted 91,058,850), ≥45 years with dual-energy X-ray absorptiometry measurements. METHODS: the 20th percentile of the sex-specific distribution of lean appendicular mass residuals from linear regression with height and fat mass as predictors, served as the LMM cut-point. Logistic regression provided adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association of HF and LMM with functional limitations and hospitalisation. RESULTS: There were statistically significant adjusted associations between HF and limitations in household chores, walking one-fourth of a mile and hospitalisation (OR (95% CI): 2.5 (1.7 -3.8), 1.9 (1.2 -3.0) and 1.6 (1.1 -2.4), respectively). LMM was significantly associated with limitations in household chores and walking one-fourth of a mile (OR (95% CI): 1.5 (1.2, 1.9) and 1.4 (1.2, 1.7), respectively). Interaction between HF and LMM was noted for the associations with functional limitations. CONCLUSIONS: This hypothesis-generating study found a synergistic interaction between HF and LMM; the presence of LMM increased the negative effects of HF. HF patients may experience increased disease burden due to LMM.

Dietary patterns are associated with metabolic syndrome in adult Samoans.

The prevalence of metabolic syndrome has reached epidemic levels in the Samoan Islands. In this cross-sectional study conducted in 2002-2003, dietary patterns were described among American Samoan (n = 723) and Samoan (n = 785) adults (> or =18 y) to identify neo-traditional and modern eating patterns and to relate these patterns to the presence of metabolic syndrome using Adult Treatment Panel III criteria. The neo-traditional dietary pattern, similar across both polities, was characterized by high intake of local foods, including crab/lobster, coconut products, and taro, and low intake of processed foods, including potato chips and soda. The modern pattern, also similar across both polities, was characterized by high intake of processed foods such as rice, potato chips, cake, and pancakes and low intake of local foods. The neo-traditional dietary pattern was associated with significantly higher serum HDL-cholesterol in American Samoa (P-trend = 0.05) and a decrease in abdominal circumference in American Samoa and Samoa (P-trend = 0.004 and 0.01, respectively). An inverse association was found with metabolic syndrome, although it did not reach significance (P = 0.23 in American Samoa; P = 0.13 in Samoa). The modern pattern was significantly positively associated with metabolic syndrome in Samoa (prevalence ratio = 1.21 for the fifth compared with first quintile; 95% CI: 0.93.1.57; P-trend = 0.05) and with increased serum triglyceride levels in both polities (P < 0.05). Reduced intake of processed foods high in refined grains and adherence to a neo-traditional eating pattern characterized by plant-based fiber, seafood, and coconut products may help to prevent growth in the prevalence of metabolic syndrome in the Samoan islands.

Does genetic variation in the Delta6-desaturase promoter modify the association between alpha-linolenic acid and the prevalence of metabolic syndrome?

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with protection against components of the metabolic syndrome, but the role of alpha-linolenic acid (ALA), the metabolic precursor of EPA and DHA, has not been studied. The Delta(6)-desaturase enzyme converts ALA into EPA and DHA, and genetic variation in the Delta(6)-desaturase gene (FADS2) may affect this conversion. OBJECTIVES: We hypothesize that high ALA is associated with a lower prevalence of the metabolic syndrome and that genetic variation in FADS2 modifies this association. DESIGN: We studied 1815 Costa Rican adults. Adipose tissue ALA was used as a biomarker of intake, and metabolic syndrome was identified with the definition from the National Cholesterol Education Program, Adult Treatment Panel III. Prevalence ratios (PRs) and 95% CIs were estimated from binomial regression models, and the likelihood ratio was used to test for effect modification. RESULTS: High concentrations of adipose tissue ALA were associated with lower PRs of the metabolic syndrome compared with low ALA (0.81; 95% CI: 0.66, 1.00, for the comparison between the highest and the lowest quintiles; P for trend < 0.02). Higher concentrations of adipose tissue ALA were associated with a lower PR among homozygote (0.67; 95% CI: 0.53, 0.86) and heterozygote (0.84; 95% CI: 0.72, 0.99) carriers of the FADS2 T allele, but not among homozygote carriers of the deletion variant allele (0.99; 95% CI: 0.78, 1.27; P for interaction: 0.08). CONCLUSIONS: Elevated ALA concentrations in adipose tissue are associated with lower prevalence of the metabolic syndrome. A lack of association among homozygote carriers of the FADS2 deletion allele suggests that this association may be due in part to the conversion of ALA into EPA.

Adiponectin and type 2 diabetes in Samoan adults.

OBJECTIVE: Previous studies have established an association between adiponectin and type 2 diabetes. It is unclear whether adiponectin will be useful among Samoan Islanders, characterized by markedly elevated levels of obesity, in differentiating those at risk of developing type 2 diabetes. METHODS: Cross-sectional, genetic epidemiology study of obesity in American Samoa and Samoa 2002-2003 (n = 1,599). Logistic regression provided adjusted odds ratios and 95% confidence intervals for the association between adiponectin, diabetes, and prediabetes (impaired fasting glucose). RESULTS: There is a significant decreasing trend in the odds of diabetes and prediabetes across increasing quintiles of adiponectin with an OR of 2.8 (95% CI: 1.6, 5.0) and 2.9 (95% CI: 1.5, 5.7), respectively, in the lowest relative to the highest quintile of adiponectin (P-for-trend = 0.004 and 0.001). CONCLUSIONS: Adiponectin is an important correlate, independent of other risk factors, of the pathogenesis of type 2 diabetes among Samoan islanders and may help distinguish those at higher risk of developing this disease.

Comparison of 3 methods for identifying dietary patterns associated with risk of disease.

Reduced rank regression and partial least-squares regression (PLS) are proposed alternatives to principal component analysis (PCA). Using all 3 methods, the authors derived dietary patterns in Costa Rican data collected on 3,574 cases and controls in 1994-2004 and related the resulting patterns to risk of first incident myocardial infarction. Four dietary patterns associated with myocardial infarction were identified. Factor 1, characterized by high intakes of lean chicken, vegetables, fruit, and polyunsaturated oil, was generated by all 3 dietary pattern methods and was associated with a significantly decreased adjusted risk of myocardial infarction (28%-46%, depending on the method used). PCA and PLS also each yielded a pattern associated with a significantly decreased risk of myocardial infarction (31% and 23%, respectively); this pattern was characterized by moderate intake of alcohol and polyunsaturated oil and low intake of high-fat dairy products. The fourth factor derived from PCA was significantly associated with a 38% increased risk of myocardial infarction and was characterized by high intakes of coffee and palm oil. Contrary to previous studies, the authors found PCA and PLS to produce more patterns associated with cardiovascular disease than reduced rank regression. The most effective method for deriving dietary patterns related to disease may vary depending on the study goals.

The relationship between alcohol use, eating habits and weight change in college freshmen.

PURPOSE: This study aims to improve understanding of how alcohol consumption in college freshmen affects eating patterns before, during, and after drinking, as well as its relation to body weight change. METHODS: Two hundred eighty-two college freshmen (61% female; 59% Caucasian) completed measures of alcohol use, measured body mass index (BMI), and eating and activity habits before, during and following drinking episodes. Students were categorized by drinking status (non-drinker, low-risk, and moderate/high-risk) in order to explore group differences. RESULTS: Seventy-five percent of the sample reported past-month alcohol consumption, with 65% (N=134) of these categorized as "low-risk" drinkers and 35% (N=72) as "moderate-risk" drinkers. Moderate-risk drinkers were more likely than low-risk drinkers to report increases in appetite after drinking, with nearly half of students reporting overeating and making unhealthy food choices following drinking. Moderate-risk drinkers also demonstrated significant increases in 1st semester BMI change, relative to non-drinkers and low-risk drinkers. CONCLUSIONS: Eating patterns for a significant number of college students are altered before, during, and following drinking episodes, which related to change in freshman year BMI.

Telithromycin use and spontaneous reports of hepatotoxicity.

BACKGROUND AND OBJECTIVE: Recent reports have described cases of telithromycin-related hepatotoxicity. The objective of this study is to quantify the effect of telithromycin use on the risk of hepatotoxicity. METHODS: We conducted a spontaneous-report case-control study of hepatotoxicity in telithromycin recipients using reports from the US FDA Adverse Event Reporting System. Reports from between 1 January 2005 and 30 June 2005 were examined. Cases included reports of patients with abnormal liver function tests, hepatocellular damage and hepatic impairment, while patients with reported conditions with similar reporting probabilities were considered as controls. The primary outcome measure of the analysis was the reporting odds ratio (ROR) evaluating the a priori hypothesis that telithromycin use confers an elevated risk of hepatotoxicity relative to other agents. RESULTS: A total of 2219 cases and 20,667 controls were identified. We estimated an ROR for hepatotoxicity associated with telithromycin compared with other agents of 1.82 (95% CI 1.12, 2.96) after controlling for age and gender, approximating an 82% excess risk in users of telithromycin relative to users of other agents. CONCLUSIONS: This analysis is the first to specifically quantify the effect of telithromycin on the risk of hepatotoxicity. Telithromycin use may increase the risk of hepatotoxicity by >80%. Biases inherent in spontaneous reports include under-reporting of events and differential or time-varying reporting due to enhanced clinician awareness. Future studies should employ alternative data sources because of the inherent limitations of passive surveillance systems.

Recovery from relapse among successful weight maintainers.

BACKGROUND: Little is known about the natural history of weight change among persons who are successful at losing weight. OBJECTIVE: This study evaluated the occurrence of weight regain and recovery among 2400 persons in the National Weight Control Registry (NWCR) who had lost an average (+/- SD) of 32.1 +/- 17.8 kg and had kept it off for 6.5 +/- 8.1 y. DESIGN: Participants were evaluated prospectively over 2 y. RESULTS: The mean reported weight change from entry into the NWCR to 2 y later was 3.8 +/- 7.6 kg. At year 2, 96.4% of the sample remained > or =10% below their maximum lifetime weight. However, small regains were common, and few persons were able to re-lose weight after any weight regain. Of the participants who gained any weight between baseline and year 1 (n = 1483; 65.7%), only 11.0% returned to their baseline weight or below at year 2. Of the participants who relapsed, which was defined as a weight regain of > or =5% at year 1 (n = 575, or 25.5% of the sample), only 4.7% returned to their baseline weight or below at year 2, and only 12.9% re-lost at least half of their year 1 gain by year 2. Logistic regression showed that recovery was related to gaining less at year 1 and to smaller increases in depressive symptoms between baseline and year 1. CONCLUSION: Although successful weight losers continued to maintain a large percentage of their weight losses over 2 y, recovery from even minor weight regain was uncommon.