Is Zolpidem Associated with Increased Risk of Fractures in the Elderly with Sleep Disorders? A Nationwide Case Cross-Over Study in Taiwan

Background

We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly.

Design of study

Case-crossover design.

Methods and Materials

Elderly enrollees (n = 6010) in Taiwan’s National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures.

Results

After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant.

Conclusion

Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.     

Is Socioeconomic Status of the Rearing Environment Causally Related to Obesity in the Offspring?

We attempt to elucidate whether there might be a causal connection between the socioeconomic status (SES) of the rearing environment and obesity in the offspring using data from two large-scale adoption studies: (1) The Copenhagen Adoption Study of Obesity (CASO), and (2) The Survey of Holt Adoptees and Their Families (HOLT). In CASO, the SES of both biological and adoptive parents was known, but all children were adopted. In HOLT, only the SES of the rearing parents was known, but the children could be either biological or adopted. After controlling for relevant covariates (e.g., adoptee age at measurement, adoptee age at transfer, adoptee sex) the raw (unstandardized) regression coefficients for adoptive and biological paternal SES on adoptee body mass index (BMI: kg/m²) in CASO were -.22 and -.23, respectively, both statistically significant (p = 0.01). Controlling for parental BMI (both adoptive and biological) reduced the coefficient for biological paternal SES by 44% (p = .034) and the coefficient for adoptive paternal SES by 1%. For HOLT, the regression coefficients for rearing parent SES were -.42 and -.25 for biological and adoptive children, respectively. Controlling for the average BMI of the rearing father and mother (i.e., mid-parental BMI) reduced the SES coefficient by 47% in their biological offspring (p≤.0001), and by 12% in their adoptive offspring (p = .09). Thus, despite the differing structures of the two adoption studies, both suggest that shared genetic diathesis and direct environmental transmission contribute about equally to the association between rearing SES and offspring BMI.     

Does the Duration and Time of Sleep Increase the Risk of Allergic Rhinitis? Results of the 6-Year Nationwide Korea Youth Risk Behavior Web-Based Survey

Allergic rhinitis (AR) is the most common chronic disorder in the pediatric population. Although several studies have investigated the correlation between AR and sleep-related issues, the association between the duration and time of sleep and AR has not been analyzed in long-term national data. This study investigated the relationship between sleep time and duration and AR risk in middle- and high-school students (adolescents aged 12–18). We analyzed national data from the Korea Youth Risk Behavior Web-based Survey by the Korea Centers for Disease Control and Prevention from 2007–2012. The sample size was 274,480, with an average response rate of 96.2%. Multivariate logistic regression analyses were conducted to determine the relationship between sleep and AR risk. Furthermore, to determine the best-fitted model among independent variables such as sleep duration, sleep time, and the combination of sleep duration and sleep time, we used Akaike Information Criteria (AIC) to compare models. A total of 43,337 boys and 41,665 girls reported a diagnosis of AR at baseline. The odds ratio increased with age and with higher education and economic status of the parents. Further, students in mid-sized and large cities had stronger relationships to AR than those in small cities. In both genders, AR was associated with depression and suicidal ideation. In the analysis of sleep duration and sleep time, the odds ratio increased in both genders when sleep duration was <7 hours, and when the time of sleep was later than 24∶00 hours. Our results indicate an association between sleep time and duration and AR. This study is the first to focus on the relationship between sleep duration and time and AR in national survey data collected over 6 years.     

Duration of Adulthood Overweight,Obesity, and Cancer Risk in the Women’s Health Initiative: A Longitudinal Study from the United States

BackgroundHigh body mass index (BMI) has become the leading risk factor of disease burden in high-income countries. While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women.ConclusionsIn summary, this study showed that a longer duration of overweight and obesity is associated with an increased risk of developing several forms of cancer. Furthermore, the degree of overweight experienced during adulthood seemed to play an important role in the risk of developing cancer, especially for endometrial cancer. Although the observational nature of our study precludes inferring causality or making clinical recommendations, our findings suggest that reducing overweight duration in adulthood could reduce cancer risk and that obesity prevention is important from early onset. If this is true, health care teams should recognize the potential of obesity management in cancer prevention and that excess body weight in women is important to manage regardless of the age of the patient.     

Secular Trends in Prevalence and Risk Factors of Obesity in Infants and Preschool Children in 9 Chinese Cities, 1986–2006

Introduction

No prevalence/trends were reported in Chinese infants and preschool children at the national level in this historical period of 1980s–2000s. The objectives of this paper were to present the 20-year trends in prevalence and risk factors of obesity in children below 7 years.

Methods

Data obtained from a series of three sequential national surveys performed using the same design in the same 9 cities in 1986, 1996 and 2006. Weight and height (length <3 years) were measured using unified procedures at each period. Obesity was defined as a weight-for-height ≥120% of median of the NCHS/WHO international reference. A population-based paired matching case-control study was employed for screening risk factors.

Results

In 1986, there was no substantial obesity epidemic, but the overall obesity prevalence reached 3.4% (boys 4.1% and girls 2.7%) in 2006, rising by 2.8 times between 1986 and 2006. Reversed gender difference, relatively higher prevalence in preschool age and more rapid increase in the second 10-year were three very obvious characteristics in China, e.g. prevalence of boys 9.9% and girls 4.9% in 2006 and increasing rate of boys 0.45 percentage points per year (pp/y) and girls 0.21 pp/y at 6–7 years groups, 0.17 pp/y of the second 10-year higher 1-fold than previous.

Conclusions

China has been moving into the alarming epidemic of childhood obesity. Effort should be immediately made to prevent further deterioration. High birth weight, high parental BMI and several behavioral and family-related factors were identified and had important practical value for obesity intervention.     

What Is the Optimal Threshold at Which to Recommend Breast Biopsy?

Background

A 2% threshold, traditionally used as a level above which breast biopsy recommended, has been generalized to all patients from several specific situations analyzed in the literature. We use a sequential decision analytic model considering clinical and mammography features to determine the optimal general threshold for image guided breast biopsy and the sensitivity of this threshold to variation of these features.

Methodology/Principal Findings

We built a decision analytical model called a Markov Decision Process (MDP) model, which determines the optimal threshold of breast cancer risk to perform breast biopsy in order to maximize a patient’s total quality-adjusted life years (QALYs). The optimal biopsy threshold is determined based on a patient’s probability of breast cancer estimated by a logistic regression model (LRM) which uses demographic risk factors (age, family history, and hormone use) and mammographic findings (described using the established lexicon–BI-RADS). We estimate the MDP model''s parameters using SEER data (prevalence of invasive vs. in situ disease, stage at diagnosis, and survival), US life tables (all cause mortality), and the medical literature (biopsy disutility and treatment efficacy) to determine the optimal “base case” risk threshold for breast biopsy and perform sensitivity analysis. The base case MDP model reveals that 2% is the optimal threshold for breast biopsy for patients between 42 and 75 however the thresholds below age 42 is lower (1%) and above age 75 is higher (range of 3–5%). Our sensitivity analysis reveals that the optimal biopsy threshold varies most notably with changes in age and disutility of biopsy.

Conclusions/Significance

Our MDP model validates the 2% threshold currently used for biopsy but shows this optimal threshold varies substantially with patient age and biopsy disutility.     

A Polymorphism in the Chitotriosidase Gene Associated with Risk of Mycetoma Due to Madurella mycetomatis Mycetoma–A Retrospective Study

BackgroundMadurella mycetomatis is the most prevalent causative agent of eumycetoma in Sudan, an infection characterized by the formation of grains. Many patients are exposed to the causative agent, however only a small number develop infection. M. mycetomatis contains chitin in its cell wall, which can trigger the human immune system. Polymorphisms in the genes encoding for the chitin-degrading enzymes chitotriosidase and AMCase were described, resulting in altered chitinase activity. We investigated the association between 4 of these polymorphisms and the incidence of M. mycetomatis mycetoma in a Sudanese population.MethodologyPolymorphisms studied in 112 eumycetoma patients and 103 matched controls included a 24-bp insertion in the chitotriosidase gene (rs3831317), resulting in impaired chitinase activity and single nucleotide polymorphism (SNP) in the AMCase gene (rs61756687), resulting in decreased AMCase activity. Also, a SNP (rs41282492) and a 10-bp insertion in the 5’UTR region of the AMCase gene (rs143789088) were studied, both resulting in increased AMCase activity. DNA was isolated from blood and genotypes were determined using PCR-RFLP.ConclusionDecreased chitotriosidase activity was associated with increased risk of M. mycetomatis mycetoma.     

Is There a Benefit to Extending the Duration of Helicobacter pylori Sequential Therapy to 14 Days?

Background and Aims: Ten‐day sequential therapy with a proton‐pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori (H. pylori) eradication rates between 90 and 94% (i.e., Grade B success). It has been suggested that prolonging the duration of therapy might improve the treatment success. We tested whether prolonging treatment duration to 14‐days would improve the results to 95% or greater eradication. Methods: This was a multi‐center, single site, pilot study in which H. pylori‐infected patients received a 14‐day sequential therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, clarithromycin, and metronidazole for 7 days). H. pylori status was assessed 8 weeks after therapy. Success was defined as achieving 95% or greater eradication by per‐protocol (PP) analysis. Results: One hundred and twenty‐three subjects received the 14‐day sequential therapy. The eradication rate was 93.9% (95% confidence interval [CI], 89.5–98.3%) by PP and 91.9% (95% CI, 87.1–96.7%) by intention‐to‐treat analysis. Adverse events were experienced by 21.1%; compliance of 90% or greater was 95.9%. Conclusions: Extending sequential therapy to 14 days did not result in improving the treatment outcome to 95% or greater.     

Is Using the Strengths and Difficulties Questionnaire in a Community Sample the Optimal Way to Assess Mental Health Functioning?

An important characteristic of a screening tool is its discriminant ability or the measure’s accuracy to distinguish between those with and without mental health problems. The current study examined the inter-rater agreement and screening concordance of the parent and teacher versions of SDQ at scale, subscale and item-levels, with the view of identifying the items that have the most informant discrepancies; and determining whether the concordance between parent and teacher reports on some items has the potential to influence decision making. Cross-sectional data from parent and teacher reports of the mental health functioning of a community sample of 299 students with and without disabilities from 75 different primary schools in Perth, Western Australia were analysed. The study found that: a) Intraclass correlations between parent and teacher ratings of children’s mental health using the SDQ at person level was fair on individual child level; b) The SDQ only demonstrated clinical utility when there was agreement between teacher and parent reports using the possible or 90% dichotomisation system; and c) Three individual items had positive likelihood ratio scores indicating clinical utility. Of note was the finding that the negative likelihood ratio or likelihood of disregarding the absence of a condition when both parents and teachers rate the item as absent was not significant. Taken together, these findings suggest that the SDQ is not optimised for use in community samples and that further psychometric evaluation of the SDQ in this context is clearly warranted.     

Independent Effects of Sleep Duration and Body Mass Index on the Risk of a Work-Related Injury: Evidence From the US National Health Interview Survey (2004–2010)

Fatigue has been linked to adverse safety outcomes, and poor quality or decreased sleep has been associated with obesity (higher body mass index, BMI). Additionally, higher BMI is related to an increased risk for injury; however, it is unclear whether BMI modifies the effect of short sleep or has an independent effect on work-related injury risk. To answer this question, the authors examined the risk of a work-related injury as a function of total daily sleep time and BMI using the US National Health Interview Survey (NHIS). The NHIS is an in-person household survey using a multistage, stratified, clustered sample design representing the US civilian population. Data were pooled for the 7-yr survey period from 2004 to 2010 for 101 891 “employed” adult subjects (51.7%; 41.1?±?yrs of age [mean?±?SEM]) with data on both sleep and BMI. Weighted annualized work-related injury rates were estimated across a priori defined categories of BMI: healthy weight (BMI: <25), overweight (BMI: 25–29.99), and obese (BMI: ≥30) and also categories of usual daily sleep duration: <6, 6–6.99, 7–7.99, 8–8.99, and ≥9?h. To account for the complex sampling design, including stratification, clustering, and unequal weighting, weighted multiple logistic regression was used to estimate the risk of a work-related injury. The initial model examined the interaction among daily sleep duration and BMI, controlling for weekly working hours, age, sex, race/ethnicity, education, type of pay, industry, and occupation. No significant interaction was found between usual daily sleep duration and BMI (p?=?.72); thus, the interaction term of the final logistic model included these two variables as independent predictors of injury, along with the aforementioned covariates. Statistically significant covariates (p?≤?.05) included age, sex, weekly work hours, occupation, and if the worker was paid hourly. The lowest categories of usual sleep duration (<6 and 6–6.9?h) showed significantly (p?≤?.05) elevated injury risks than the referent category (7–8?h sleep), whereas sleeping >7–8?h did not significantly elevate risk. The adjusted injury risk odds ratio (OR) for a worker with a usual daily sleep of <6?h was 1.86 (95% confidence interval [CI]: 1.37–2.52), and for 6–6.9?h it was 1.46 (95% CI: 1.18–1.80). With regards to BMI, the adjusted injury risk OR comparing workers who were obese (BMI: ≥30) to healthy weight workers (BMI: <25) was 1.34 (95% CI: 1.09–1.66), whereas the risk in comparing overweight workers (BMI: 25–29.99) to healthy weight risk was elevated, but not statistically significant (OR?=?1.08; 95% CI: .88–1.33). These results from a large representative sample of US workers suggest increase in work-related injury risk for reduced sleep regardless of worker's body mass. However, being an overweight worker also increases work-injury risk regardless of usual daily sleep duration. The independent additive risk of these factors on work-related injury suggests a substantial, but at least partially preventable, risk. (Author correspondence: david.lombardi@libertymutual.com)     

How do Different Indices of Obesity Correlate with Cardiometabolic Disease Risk Factors in Multiethnic Youths?

ObjectiveTo investigate the relationship between cardiometabolic disease risk factors (CDRFs) among ethnic minorities and anthropometric factors including body mass index z score, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in Hispanic and non-Hispanic black youths originating primarily from Central America, South America, and the Caribbean.MethodsClinical data of 167 young persons 2 to 19 years of age encountered in an outpatient pediatric endocrinology clinic were analyzed. The CDRFs included fasting insulin and glucose, homeostasis model assessment of insulin resistance (HOMA-IR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), high-density lipoprotein cholesterol, triglycerides, cardiac C-reactive protein (CRP), and apolipoproteins.ResultsFor both the non-Hispanic black and the Hispanic youths, WC was significantly correlated with SBP (r = 0.63; P < .001 and r = 0.50; P < .001, respectively), DBP (r = 0.61; P < .001 and r = 0.47; P < .001, respectively), and cardiac CRP (r = 0.76; P < .001 and r = 0.26; P = .026, respectively). Similarly, WHTR was significantly correlated with SBP, DBP, and cardiac CRP for the non-Hispanic black study subjects, whereas SBP (r = 0.22; P = .01), DBP ( r = 0.34; P < .001), fasting insulin ( r = 0.43; P < .001), HOMA-IR (r = 0.38; P < .001), apolipoprotein A-I (r = 0.30; P = .01), and CRP (r = 0.44; P < .001) were significantly correlated for the Hispanic group. For both groups, body mass index z score was not consistently correlated with CDRFs, and waist-to-hip ratio was not significantly correlated with any CDRFs, except for apolipoprotein B in non-Hispanic black youths.ConclusionOur study shows that WC and WHTR may be useful anthropometric factors for better identification of ethnic minority youths at risk for adult-onset cardiometabolic disease. (Endocr Pract. 2009;15:403-409)     

Ambulatory Blood Pressure Monitoring: Importance of Sampling Rate and Duration—48 Versus 24 Hours—on the Accurate Assessment of Cardiovascular Risk

Independent prospective studies have found that ambulatory blood pressure (BP) monitoring (ABPM) is more closely correlated with target organ damage and cardiovascular disease (CVD) risk than clinic BP measurement. This is based on studies in which BP was sampled every 15–30?min for ≤24?h, without taking into account that reproducibility of any estimated parameter from a time series to be potentially used for CVD risk assessment might depend more on monitoring duration than on sampling rate. Herein, we evaluated the influence of duration (48 vs. 24?h) and sampling rate of BP measurements (form every 20–30?min up to every 2?h) on the prognostic value of ABPM-derived parameters. We prospectively studied 3344 subjects (1718 men/1626 women), 52.6?±?14.5 yrs of age, during a median follow-up of 5.6 yrs. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or ≥1 of them at bedtime. At baseline, BP was measured at 20-min intervals from 07:00 to 23:00?h and at 30-min intervals at night for 48?h, and physical activity was simultaneously monitored every min by wrist actigraphy to accurately derive the awake and asleep BP means. Identical assessment was scheduled annually and more frequently (quarterly) if treatment adjustment was required. ABPM profiles were modified to generate time series of identical 48-h duration but with data sampled at 1- or 2-h intervals, or shorter, i.e., first 24?h, time series with data sampled at the original rate (daytime 20-min intervals/nighttime 30-min intervals). Bland-Altman plots indicated that the range of individual differences in the estimated awake and asleep systolic (SBP) and diastolic BP (DBP) means between the original and modified ABPM profiles was up to 3-fold smaller for data sampled every 1?h for 48?h than for data sampled every 20–30?min for the first 24?h. Reduction of ABPM duration to just 24?h resulted in error of the estimated asleep SBP mean, the most significant prognostic marker of CVD events, in the range of ?21.4 to +23.9?mm Hg. Cox proportional-hazard analyses adjusted for sex, age, diabetes, anemia, and chronic kidney disease revealed comparable hazard ratios (HRs) for mean BP values and sleep-time relative BP decline derived from the original complete 48-h ABPM profiles and those modified to simulate a sampling rate of one BP measurement every 1 or 2?h. The HRs, however, were markedly overestimated for SBP and underestimated for DBP when the duration of ABPM was reduced from 48 to only 24?h. This study on subjects evaluated prospectively by 48-h ABPM documents that reproducibility in the estimates of prognostic ABPM-derived parameters depends markedly on duration of monitoring, and only to a lesser extent on sampling rate. The HR of CVD events associated with increased ambulatory BP is poorly estimated by relying on 24-h ABPM, indicating ABPM for only 24?h may be insufficient for proper diagnosis of hypertension, identification of dipping status, evaluation of treatment efficacy, and, most important, CVD risk stratification. (Author correspondence: rhermida@uvigo.es)     

A Taxonomic Signature of Obesity in the Microbiome? Getting to the Guts of the Matter

Obesity is an important and intractable public health problem. In addition to the well-known risk factors of behavior, diet, and genetics, gut microbial communities were recently identified as another possible source of risk and a potential therapeutic target. However, human and animal-model studies have yielded conflicting results about the precise nature of associations between microbiome composition and obesity. In this paper, we use publicly available data from the Human Microbiome Project (HMP) and MetaHIT, both surveys of healthy adults that include obese individuals, plus two smaller studies that specifically examined lean versus obese adults. We find that inter-study variability in the taxonomic composition of stool microbiomes far exceeds differences between lean and obese individuals within studies. Our analyses further reveal a high degree of variability in stool microbiome composition and diversity across individuals. While we confirm the previously published small, but statistically significant, differences in phylum-level taxonomic composition between lean and obese individuals in several cohorts, we find no association between BMI and taxonomic composition of stool microbiomes in the larger HMP and MetaHIT datasets. We explore a range of different statistical techniques and show that this result is robust to the choice of methodology. Differences between studies are likely due to a combination of technical and clinical factors. We conclude that there is no simple taxonomic signature of obesity in the microbiota of the human gut.     

Lifelong Obesity in a Polygenic Mouse Model Prevents Age- and Diet-Induced Glucose Intolerance– Obesity Is No Road to Late-Onset Diabetes in Mice

Aims/Hypothesis

Visceral obesity holds a central position in the concept of the metabolic syndrome characterized by glucose intolerance in humans. However, until now it is unclear if obesity by itself is responsible for the development of glucose intolerance.

Methods

We have used a novel polygenic mouse model characterized by genetically fixed obesity (DU6) and addressed age- and high fat diet-dependent glucose tolerance.

Results

Phenotype selection over 146 generations increased body weight by about 2.7-fold in male 12-week DU6 mice (P<0.0001) if compared to unselected controls (Fzt:DU). Absolute epididymal fat mass was particularly responsive to weight selection and increased by more than 5-fold (P<0.0001) in male DU6 mice. At an age of 6 weeks DU6 mice consumed about twice as much food if compared to unselected controls (P<0.001). Absolute food consumption was higher at all time points measured in DU6 mice than in Fzt:DU mice. Between 6 and 12 weeks of age, absolute food intake was reduced by 15% in DU6 mice (P<0.001) but not in Fzt:DU mice. In both mouse lines feeding of the high fat diet elevated body mass if compared to the control diet (P<0.05). In contrast to controls, DU6 mice did not display high fat diet-induced increases of epididymal and renal fat. Control mice progressively developed glucose intolerance with advancing age and even more in response to the high fat diet. In contrast, obese DU6 mice did neither develop a glucose intolerant phenotype with progressive age nor when challenged with a high fat diet.

Conclusions/Interpretation

Our results from a polygenic mouse model demonstrate that genetically pre-determined and life-long obesity is no precondition of glucose intolerance later in life.