Molnupiravir Use Among Patients with COVID-19 in Real-World Settings: A Systematic Literature Review.

INTRODUCTION: Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective was to conduct a systematic literature review (SLR) of evidence on the effectiveness of MOV in reducing the risk of severe COVID-19 outcomes in real-world outpatient settings. METHODS: The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and using pre-determined population, intervention, comparison, outcome, time, and study design inclusion criteria. Eligible studies were published between January 1, 2021, and March 10, 2023, and evaluated the real-world effectiveness of MOV compared to no treatment in reducing the risk of severe COVID-19 outcomes among outpatients ≥ 18 years of age with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. RESULTS: Nine studies from five countries were included in the review. The size of the MOV-treated group ranged from 359 to 7818 individuals. Omicron variants of SARS-CoV-2 were dominant in all study periods. Most studies noted differences in the baseline characteristics of the MOV-treated and untreated control groups, with the treated groups generally being older and with more comorbidities. Eight studies reported that treatment with MOV was associated with a significantly reduced risk of at least one severe COVID-19 outcome in at least one age group, with greater benefits consistently observed among older age groups. CONCLUSIONS: In this SLR study, treatment with MOV was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the MOV-treated and control groups may have led to underestimation of the effectiveness of MOV in many observational studies. Real-world studies published to date thus provide additional evidence supporting the continued benefits of MOV in non-hospitalized adults with COVID-19.

COVID-19 continues to be a major source of morbidity and mortality. Throughout the pandemic, many countries authorized various therapies for the treatment of individuals presenting with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Some of these therapies have since been rendered ineffective due to the emergence of Omicron variants in late 2021. The objective of the current study was to conduct a systematic literature review to assess real-world evidence on the effectiveness of molnupiravir, including effectiveness against COVID-19 caused by Omicron variants, to supplement the findings of the MOVe-OUT clinical trial and further inform on the potential clinical benefit and utility of this antiviral agent. Nine studies were included in the systematic literature review. We found that treatment with molnupiravir was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the molnupiravir-treated and control groups may have led to underestimation of the effectiveness of molnupiravir in many observational studies. In summary, real-world effectiveness studies provide additional evidence supporting the continued benefits of molnupiravir in non-hospitalized adults with COVID-19.

Factors Associated With Decision to Use and Dosing of Sugammadex in Children: A Retrospective Cross-Sectional Observational Study.

BACKGROUND: Sugammadex was initially approved for reversal of neuromuscular blockade in adults in the United States in 2015. Limited data suggest sugammadex is widely used in pediatric anesthesia practice however the factors influencing use are not known. We explore patient, surgical, and institutional factors associated with the decision to use sugammadex versus neostigmine or no reversal, and the decision to use 2 mg/kg vs 4 mg/kg dosing. METHODS: Using data from the Multicenter Perioperative Outcomes Group (MPOG) database, an EHR-derived registry, we conducted a retrospective cross-sectional study. Eligible cases were performed between January 1, 2016 and December 31, 2020, for children 0 to 17 years at US hospitals. Cases involved general anesthesia with endotracheal intubation and administration of rocuronium or vecuronium. Using generalized linear mixed models with institution and anesthesiologist-specific random intercepts, we measured the importance of a variety of patient, clinician, institution, anesthetic, and surgical risk factors in the decision to use sugammadex versus neostigmine, and the decision to use a 2 mg/kg vs 4 mg/kg dose. We then used intraclass correlation statistics to evaluate the proportion of variance contributed by institution and anesthesiologist specifically. RESULTS: There were 97,654 eligible anesthetics across 30 institutions. Of these 47.1% received sugammadex, 43.1% received neostigmine, and 9.8% received no reversal agent. Variability in the choice to use sugammadex was attributable primarily to institution (40.4%) and attending anesthesiologist (27.1%). Factors associated with sugammadex use (compared to neostigmine) include time from first institutional use of sugammadex (odds ratio [OR], 1.08, 95% confidence interval [CI], 1.08-1.09, per month, P < .001), younger patient age groups (0-27 days OR, 2.59 [2.00-3.34], P < .001; 28 days-1 year OR, 2.72 [2.16-3.43], P < .001 vs 12-17 years), increased American Society of Anesthesiologists [ASA] physical status (ASA III: OR, 1.32 [1.23-1.42], P < .001 ASA IV OR, 1.71 [1.46-2.00], P < .001 vs ASA I), neuromuscular disease (OR, 1.14 (1.04-1.26], P = .006), cardiac surgery (OR, 1.76 [1.40-2.22], P < .001), dose of neuromuscular blockade within the hour before reversal (>2 ED95s/kg OR, 4.58 (4.14-5.07], P < .001 vs none), and shorter case duration (case duration <60 minutes OR, 2.06 [1.75-2.43], P < .001 vs >300 minutes). CONCLUSIONS: Variation in sugammadex use was primarily explained by institution and attending anesthesiologist. Patient factors associated with the decision to use sugammadex included younger age, higher doses of neuromuscular blocking agents, and increased medical complexity.

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.

Contribution of Comorbid Conditions to the Diagnosis of Insomnia: A Database Study in a Commercially Insured Population.

ABSTRACT: Insomnia is a common sleep disorder characterized as dissatisfaction with sleep quantity or quality resulting in distress or impairment of social, occupational, or other daily functioning. It is unknown if there are medical conditions that have strong associations with insomnia but are unrecognized in previous literature. In this cross-sectional study based on IBM Marketscan Research Databases, we measured insomnia and 78 medical conditions in patients with 2-year continuous enrollment during 2018-2019. We selected important comorbidities associated with insomnia for eight age-sex groups and built logistic regression models to measure the associations. The prevalence of diagnosed insomnia increased with age, from <0.4% in the age group 0-17 to 4%-5% in the age group ≥65. Females had a higher prevalence of insomnia than males. Anxiety and depression were two important comorbidities across all age-sex subgroups. Most odds ratios of comorbidities remained significant after adjusting for other comorbidities in regression models. We did not find any new medical conditions that had strong associations with insomnia but were unrecognized in previous literature. The findings can help physicians use comorbidities to identify patients with high risk of insomnia.

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).

Unintended pregnancy in users of nomegestrol acetate and 17ß-oestradiol (NOMAC-E2) compared with levonorgestrel-containing combined oral contraceptives: final results from the PRO-E2 study.

OBJECTIVE: To assess and compare the risk of unintended pregnancy in NOMAC-E2 users with levonorgestrel-containing COC (COCLNG) users in clinical practice. STUDY DESIGN: In this observational study, new users1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (contraceptive failures per 100 women-years [WY]), crude hazard ratios (HRcrude) and adjusted hazard ratios (HRadj). RESULTS: Overall, 44,559 and 46,754 users were recruited to the NOMAC-E2 and COCLNG user cohorts, respectively. There were 64 unintended pregnancies in NOMAC-E2 users (0.15 per 100 WY; 95% CI, 0.11-0.19) and 200 in COCLNG users (0.41 per 100 WY; 95% CI, 0.35-0.47). The unintended pregnancy risk was statistically significantly lower in the NOMAC-E2 cohort (p<.0001) compared to the COCLNG user cohort. The HRadj of NOMAC-E2 vs COCLNG was 0.45 (95% CI, 0.34-0.60; adjusted for age, body mass index, gravidity, COC user status, education level). CONCLUSIONS: NOMAC-E2 demonstrated superior contraceptive effectiveness compared to COCLNG, likely due to the comparatively short hormone-free interval and possibly reinforced by the long half-life of NOMAC.

Prospective controlled cohort study on the safety of a monophasic oral contraceptive containing nomegestrol acetate (2.5mg) and 17ß-oestradiol (1.5mg) (PRO-E2 study): risk of venous and arterial thromboembolism.

OBJECTIVE: To assess and compare the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in NOMAC-E2 users with levonorgestrel-containing combined oral contraceptive (COCLNG) users. STUDY DESIGN: This large, prospective, observational active surveillance study used a non-inferiority design. New users of NOMAC-E2 and COCLNG were recruited in 12 countries in Australia, Europe, and Latin America. Women were followed up directly and self-reported outcomes of interest were validated via treating physicians. The main outcome of interest was VTE, specifically deep venous thrombosis of the lower extremities (DVT) and pulmonary embolism (PE). Secondary outcomes included all VTE and ATE. Data on confounders were captured and independent blinded adjudication assessed the classification of events. Incidence rates, crude (HRcrude), and adjusted (HRadj) hazard ratios were calculated. RESULTS: A total of 101,498 women (49,598 NOMAC-E2 users and 51,900 COCLNG users) were enrolled and followed for up to 2 years (144,901 WY of observation). NOMAC-E2 users had a higher mean age (31.0 ± 8.63 years) than COCLNG users (29.3 ± 8.53 years) but other baseline characteristics were similar between the cohorts. The main analysis comparing the risk of DVT of the lower extremities and PE in NOMAC-E2 users versus COCLNG users yielded an HRadj of 0.59 (95% CI, 0.25-1.35) (adjusted for age, BMI, family history of VTE, and current duration of use). The risk of all VTE and ATE was not higher in NOMAC-E2 users compared with COCLNG users. CONCLUSION(S): NOMAC-E2 use was not associated with a higher risk of VTE or ATE compared with COCLNG.

Association Between an Acute, Drug-Induced Decrease in High-Density Lipoprotein Cholesterol Levels and Risk of Cardiovascular Events.

BACKGROUND AND OBJECTIVE: The literature describing the long-term effect of an acute, drug-induced decrease in high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) risk is limited. We aimed to further explore this potential association. METHODS: A retrospective cohort study was conducted using the Clinical Practice Research Datalink (CPRD) between 2006 and 2014. The study enrolled patients who initiated statin therapy for a short term, to identify patients with an acute, short-term decrease in HDL levels rather than to assess sustained treatment. HDL-C measurements were assessed within 9 months before and after statin initiation and patients were followed up for up to 5 years for CV events, comparing those with a decrease in HDL-C with those with constant HDL-C levels. The primary composite endpoint of major adverse cardiac events (MACE) was defined as CV death, myocardial infarction, revascularisation, and hospitalised ischaemic stroke. We estimated crude and propensity score weighted 5-year cumulative risk differences and hazard ratios (HR) comparing both groups. RESULTS: A total of 17,543 patients (HDL-C decrease group, n = 6454; HDL-C constant group, n = 11,089) were included in the study. The 5-year cumulative incidence of MACE in the HDL-C constant cohort was 5.91%. The corresponding risk differences for HDL-C decrease versus the constant group was 1.23% (95% confidence interval [CI] 0.28-2.18) and the HR was 1.20 (95% CI 1.04-1.39). This was mainly driven by an increased risk in ischaemic stroke (HR 1.44, 95% CI 1.08-1.90) and CV death (HR 1.23, 95% CI 0.93-1.63). CONCLUSION: Patients with a short-term, drug-induced decrease in HDL-C had a moderately increased long-term risk of CV events compared with those with constant HDL-C levels. TRIAL REGISTRATION NUMBER: 207595 (GlaxoSmithKline Trial registry; https://www.gsk-studyregister.com/ ).

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.

Pruritus Is Common and Undertreated in Patients With Primary Biliary Cholangitis in the United Kingdom.

BACKGROUND AND AIMS: Little is known about the prevalence or treatment of pruritus associated with primary biliary cholangitis (PBC). We analyzed data from patients with PBC recruited from all clinical centers in the United Kingdom (UK) to characterize the prevalence, severity, progression, and treatment of pruritus. METHODS: We performed cross-sectional and longitudinal studies of patients in the UK-PBC cohort to assess trajectories of pruritus. Data on pruritus frequency, severity, and therapy were collected via paper questionnaires completed by 2194 patients at their initial assessment in 2011 and then again in 2014 and 2017. Self-reported treatment data were validated against the prescription record of PBC cohort in the Clinical Practice Research Datalink, a primary care database. We defined persistent pruritus as itch that occurs frequently or all the time and severe pruritus as PBC-40 pruritus domain scores of 12 or more, throughout their disease course. Latent class mixed models were used to study pruritus trajectories and identify factors associated with high pruritus. RESULTS: At initial assessment, 1613 (73.5%) patients had experienced pruritus at some point since their development of PBC-persistent pruritus was reported by 34.5% of the patients and severe pruritus by 11.7%. Only 37.4% of patients with persistent pruritus and 50% with severe pruritus reported ever receiving cholestyramine. Frequencies of rifampicin use were 11% in patients with persistent pruritus and 23% in patients with severe pruritus. Comparison of 2011 and 2014 surveys (comprising 1423 patients) showed consistent self-reported data on pruritus. Proportions of patients in the UK-PBC cohort treated with cholestyramine or naltrexone (37.4% and 4.4%) did not differ significantly from proportions treated in the Clinical Practice Research Datalink cohort (30.4% and 4.4%) (P = .07 for cholestyramine and P = .32 for naltrexone). Latent class mixed models (n = 1753) identified 3 different groups of pruritus. Multivariable analysis identified younger age at diagnosis and higher level of alkaline phosphatase at 12 months after diagnosis as factors significantly associated with persistent high pruritus. CONCLUSIONS: In a large national cohort study of patients with PBC, we found a high prevalence of pruritus and inadequate guideline-recommended therapy. Patient-reported data used to determine pruritus prevalence and treatment are reliable. Younger age and levels of higher alkaline phosphatase were associated with persistent pruritus. We need to increase awareness and management of pruritus in PBC in the UK.

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.

Holiday weight management by successful weight losers and normal weight individuals.

This study compared weight control strategies during the winter holidays among successful weight losers (SWL) in the National Weight Control Registry and normal weight individuals (NW) with no history of obesity. SWL (n = 178) had lost a mean of 34.9 kg and had kept > or = 13.6 kg off for a mean of 5.9 years. NW (n = 101) had a body mass index of 18.5-24.9 kg/m(2). More SWL than NW reported plans to be extremely strict in maintaining their usual dietary routine (27.3% vs. 0%) and exercise routine (59.1% vs. 14.3%) over the holidays. Main effects for group indicated that SWL maintained greater exercise, greater attention to weight and eating, greater stimulus control, and greater dietary restraint, both before and during the holidays. A Group x Time interaction indicated that, over the holidays, attention to weight and eating declined significantly more in SW than in NW. More SWL (38.9%) than NW (16.7%) gained > or = 1 kg over the holidays, and this effect persisted 1 month later (28.3% and 10.7%, respectively). SWL worked harder than NW did to manage their weight, but they appeared more vulnerable to weight gain during the holidays.