Ayush Malhotra

SummarySon preference has been considered as a determinant of women's risk of intimate partner violence experience in India, although quantitative evidence from large nationally representative studies testing this relationship is limited. This study examines the association between husband's son preference, sex composition of children and risk of physical and sexual IPV victimization among wives. Information was collected for 26,284 couples in the nationally representative 2005–2006 National Family Health Survey of India. The exposures were husband's son preference measured as husband's desire for one or more sons greater than the number of daughters and sex composition of the household: only sons, only daughters and mixed. Outcome included past year physical and/or sexual IPV. The results showed that husband's reported son preference and sex composition of children were not associated with risk for IPV victimization in the models adjusted for socio-demographic factors. The findings from this first population-based study of socio-cultural norms around son preference and married Indian women's risk for IPV victimization indicate that cultural preference for sons does not influence women's risk for IPV victimization.

Copyright © 2015 by the Society of Criti. Objective: Global lung stress varies considerably with low tidal volume ventilation for acute respiratory distress syndrome. High stress despite low tidal volumes may worsen lung injury and increase risk of death. No widely available parameter exists to assess global lung stress. We aimed to determine whether the volume delivered during a recruitment maneuver is inversely associated with lung stress and mortality in acute respiratory distress syndrome. Design: Substudy of an acute respiratory distress syndrome clinical trial on esophageal pressure-guided positive end-expiratory pressure titration. Setting: U.S. academic medical center. Patients: Forty-two patients with acute respiratory distress syndrome in whom airflow, airway pressure, and esophageal pressure were recorded during the recruitment maneuver. Interventions: A single recruitment maneuver was performed before initiating protocol-directed ventilator management. Recruitment maneuvers consisted of a 30-second breath hold at 40 cm H2O airway pressure under heavy sedation or paralysis. VRM was calculated by integrating the flow-time waveform during the maneuver. End-inspiratory stress was defined as the transpulmonary pressure during end-inspiratory pause of a tidal breath and tidal stress as the transpulmonary pressure difference between end-inspiratory and end-expiratory pauses. Measurements and Main Results: VRM ranged between 7.4 and 34.7 mL/kg predicted body weight. Lower VRM predicted high end-inspiratory and tidal lung stress. After adjusting for Pao2/Fio2 and either driving pressure, tidal volume, or plateau pressure and positive end-expiratory pressure, VRM remained independently associated with both end-inspiratory and tidal stress. In unadjusted analysis, low VRM predicted increased risk of death. VRM remained significantly associated with mortality after adjusting for study arm. Conclusions: Low VRM independently predicts high lung stress and may predict risk of death in patients with acute respiratory distress syndrome.

© 2015 Wolters Kluwer Health, Inc. PURPOSE: Prior research has shown a significant relationship between 6-minute walking distance and health-related quality of life in patients with chronic obstructive pulmonary disease. However, few studies have examined this relationship above and below the 350-m threshold that prognosticates survival and whether serum biomarkers could provide insight into the causes of quality-of-life differences above and below this threshold. METHODS: Measures of lung function, 6MWD, and HRQOL were compared in patients with COPD. Differences in HRQOL domains and serum biomarkers were compared in patients whose 6MWD were > or 350 m, surfactant protein D levels were associated with higher SF-36 scores in general pain, vitality, and social functioning. CONCLUSIONS: In COPD, there is an association between 6MWD and the physical domains of the SF-36 and SGRQ in those patients walking 350 m are not related to systemic inflammation. The association between interleukin 8 with nonphysical domains in patients with 6MWD < 350 m suggests that inflammation may play a larger role in the perceptive domain than previously recognized.

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 cases and 1/3,971 controls from the initial cohort, and in 9/2,645 cases and 1/2,420 controls of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia ) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders. Head circumference was larger in patients with the microdeletion than in patients with the microduplication. © 2009 Nature America, Inc. All rights reserved.

© 2015 Elsevier Ltd. Obstructive sleep apnoea is a common disease that is now more widely recognised because of the rise in prevalence and the increasingly compelling data that shows major neurocognitive and cardiovascular sequelae. At the same time, the clinical practice of sleep medicine is changing rapidly, with novel diagnostics and treatments that have established a home-based management approach. We review the most recent insights and discoveries in obstructive sleep apnoea, with a focus on diagnostics and therapeutics. As will be discussed, management of obstructive sleep apnoea could soon transition from a so-called one size fits all approach to an individualised approach.

© 2014 Elsevier B.V. Obstructive sleep apnea is an underdiagnosed common public health concern causing deleterious effects on metabolic and cardiovascular health. Although much has been learned regarding the pathophysiology and consequences of OSA in the past decades, the molecular mechanisms associated with such processes remain poorly defined. The advanced high-throughput proteomics-based technologies have become a fundamental approach for identifying novel disease mediators as potential diagnostic and therapeutic targets for many diseases, including OSA. Here, we briefly review OSA pathophysiology and the technological advances in proteomics and the first results of its application to address critical issues in the OSA field.

© 2015 Canadian Cardiovascular Society. Sleep-disordered breathing is one of the most common comorbidities in people with congestive heart failure. Although SDB has major cardiometabolic consequences, the attributable risk of SDB in asymptomatic CHF patients remains unclear. Whether early intervention using positive airway pressure would improve the prognosis in CHF patients is uncertain. As yet, there is insufficient evidence that routine polysomnography screening is cost-effective for asymptomatic CHF patients. Careful clinical risk evaluation and thoughtful use of limited-channel home sleep testing should be considered before the application of routine polysomnography in all CHF patients.

Background We have previously demonstrated that severity of obstructive sleep apnea as measured by the apnea-hypopnea index is a significant independent predictor of readily-computed time-domain metrics of short-term heart rate variability. Methods We aimed to assess time-domain HRV measured over 5-min while awake in a trial of obese subjects undergoing one of two OSA therapies: weight-loss surgery for BMI 43.7 [42.0, 51.4] kg/m2, and AHI 18.1 [16.3, 67.5] events/h) or continuous positive airway pressure. Polysomnography was followed by electrocardiography during wakefulness; measurements were repeated at 6 and 12-18 months post-intervention. Results Despite similar measurements at baseline, subjects who underwent surgery exhibited greater improvement in short-term HRV than those who underwent CPAP. Conclusions Our data suggest a possible divergence in autonomic function between the effects of weight loss resulting from bariatric surgery, and the amelioration of obstructive respiratory events resulting from CPAP treatment. Randomized studies are necessary before clinical recommendations can be made. © 2014 Elsevier Inc. All rights reserved.

Copyright © 2015 by the American Thoracic Society. Rationale: A low respiratory arousal threshold is a physiological trait involved in obstructive sleep apnea pathogenesis. Trazodone may increase arousal threshold without compromising upper airway muscles, which should improve OSA. Objectives: We aimed to examine how trazodone alters OSA severity and arousal threshold. We hypothesized that trazodone would increase the arousal threshold and improve the apnea/hypopnea index in selected patients with OSA. Methods: Subjects were studied on two separate nights in a randomized crossover design. Fifteen unselected subjects with OSA underwent a standard polysomnogram plus an epiglottic catheter to measure the arousal threshold. Subjects were studied after receiving trazodone and placebo, with 1 week between conditions. The arousal threshold was calculated as the nadir pressure before electrocortical arousal from approximately 20 spontaneous respiratory events selected randomly. Measurements and Main Results: Compared with placebo, trazodone resulted in a significant reduction in AHI, without worsening oxygen saturation or respiratory event duration. Trazodone was not associated with a significant change in the non-REM arousal threshold compared with placebo. In subgroup analysis, responders to trazodone spent less time in N1 sleep and had an accompanying reduction in arousal index, whereas nonresponders were not observed to have a change in sleep parameters. Conclusions: These findings suggest that trazodone could be effective therapy for patients with OSA without worsening hypoxemia. Future studies should focus on underlying mechanisms and combination therapies to eliminate OSA.

Copyright © 2014 by the American Thoracic Society. Rationale: A low respiratory arousal threshold is one of several traits involved in obstructive sleep apnea pathogenesis and may be a therapeutic target; however, there is no simple way to identify patients without invasive measurements. Objectives: To determine the physiologic determinates of the ArTH and develop a clinical tool that can identify patients with low ArTH. Methods: Anthropometric data were collected in 146 participants who underwent overnight polysomnography with an epiglottic catheter to measure the ArTH. The ArTH was measured from up to 20 non-REM and REM respiratory events selected randomly. Multiple linear regression was used to determine the independent predictors of the ArTH. Logistic regression was used to develop a clinical scoring system. Measurements and Main Results: Nadir oxygen saturation as measured by pulse oximetry, apnea-hypopnea index, and the fraction of events that were hypopneas were independent predictors of the ArTH 1. A score of 2 or above correctly predicted a low arousal threshold in 84.1% of participants with a sensitivity of 80.4% and a specificity of 88.0%, a finding that was confirmed using leave-one-out cross-validation analysis. Conclusions: Our results demonstrate that individuals with a low ArTH can be identified from standard, clinically available variables. This finding could facilitate larger interventional studies targeting the ArTH.

© 2015, Springer Science+Business Media New York. Background and Aims: Nonalcoholic fatty liver disease and obstructive sleep apnea are growing in prevalence in the USA. Existing data on the relationship between OSA and NAFLD are conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis. Using a robust definition of NASH in a large, well-characterized cohort, we sought to evaluate whether OSA was associated with NASH and advanced fibrosis. Methods: Two hundred and thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5 % macrovesicular steatosis, lobular inflammation, and hepatocyte ballooning. NAFLD activity score was also determined for each subject. Results: Subjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA. OSA was associated with the presence of NASH, and this remained significant after adjusting for age, gender, race, and diabetes mellitus. Steatosis grade, lobular inflammation grade, NAS score, and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment. Conclusions: OSA is associated with elevated aminotransferase levels, the presence of NASH, and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH.

The upper airway is often modeled as a Starling resistor, which predicts that flow is independent of inspiratory effort during flow limitation. However, while some obstructive sleep apnea patients exhibit flat, Starling resistor-like flow limitation, others demonstrate considerable negative effort dependence, defined as the percent reduction in flow from peak to mid-inspiration. We hypothesized that the variability in NED could be due to differences in phasic pharyngeal muscle activation between individuals. Therefore, we induced topical pharyngeal anesthesia to reduce phasic pharyngeal muscle activation to see if it increased NED.Twelve subjects aged 50±10 years with a BMI of 35±6kg/m2 and severe OSA were studied. NED and phasic genioglossus muscle activity of flow limited breaths were determined before and after pharyngeal anesthesia with lidocaine. Pharyngeal anesthesia led to a 33% reduction in EMGGG activity, but NED worsened only by 3.6±5.8%.In conclusion, phasic EMGGG had little effect on NED. This finding suggests that individual differences in phasic EMGGG activation do not likely explain the variability in NED found among OSA patients. © 2014.

Copyright © 2015 by the American Thoracic Society. Rationale: When obstructive sleep apnea and chronic obstructive pulmonary disease coexist in the so-called "overlap" syndrome,a high risk formortalityandmorbidity hasbeenreported.There is controversy about the prevalence of OSA in people affected by COPD. Objectives: The purpose of this study was to investigate objective meaures of sleep-disordered breathing in patients with moderate to severe COPD to test the hypothesis that COPD is associated with an increased prevalence of OSA. Methods: Fifty-four patients with moderate to severe COPD were enrolled prospectively. Twenty patients were on supplemental oxygen at baseline. Exercise tolerance; questionnaires related to symptoms, sleep, and quality of life; and home polysomnography were obtained. Measurements and Main Results: Forty-four patients had full polysomnography suitable for analysis. OSA was present in 29 subjects. Sleep efficiency was poor in 45% of subjects. Conclusions: OSA is highly prevalent in patients with moderate to severe COPD referred to pulmonary rehabilitation. Sleep quality is also poor among this selected group. These patients have greaterthan- expected sleep-disordered breathing, which could be an important contributory factor to morbidity and mortality. Pulmonary rehabilitation programs should consider including a sleep assessment in patients with moderate to severe COPD and interventions when indicated to help reduce the impact of OSA in COPD.