intI1 gene abundance from septic tanks in Thailand using validated intI1 primers.

IMPORTANCE: Antimicrobial resistance is a global crisis, and wastewater treatment, including septic tanks, remains an important source of antimicrobial resistance (AMR) genes. The role of septic tanks in disseminating class 1 integron, and by extension AMR genes, in Thailand, where antibiotic use is unregulated remains understudied. We aimed to monitor gene abundance as a proxy to infer potential AMR from septic tanks in Thailand. We evaluated published intI1 primers due to the lack of consensus on optimal Q-PCR primers and the absence of standardization. Our findings confirmed septic tanks are a source of class 1 integron to the environment. We highlighted the significance of intI1 primer choice, in the context of interpretation of risk associated with AMR spread from septic tanks. We recommend the validated set (F3-R3) for optimal intI1 quantification toward the goal of achieving standardization across studies.

The Efficacy of Individualized, Community-Based Physical Activity to Aid Smoking Cessation: A Randomized Controlled Trial.

Objective: The efficacy of individualized, community-based physical activity as an adjunctive smoking cessation treatment to enhance long-term smoking cessation rates was evaluated for the Lifestyle Enhancement Program (LEAP). Methods: The study was a two-arm, parallel-group, randomized controlled trial. All participants (n = 392) received cessation counseling and a nicotine patch and were randomized to physical activity (n = 199; YMCA membership and personalized exercise programming from a health coach) or an equal contact frequency wellness curriculum (n = 193). Physical activity treatment was individualized and flexible (with each participant selecting types of activities and intensity levels and being encouraged to exercise at the YMCA and at home, as well as to use "lifestyle" activity). The primary outcome (biochemically verified prolonged abstinence at 7-weeks (end of treatment) and 6- and 12-months postcessation) and secondary outcomes (7-day point prevalent tobacco abstinence (PPA), total minutes per week of leisure time physical activity and strength training) were assessed at baseline, 7 weeks, 6 months, and 12 months. Results: Prolonged abstinence in the physical activity and wellness groups was 19.6% and 25.4%, respectively, at 7-weeks, 15.1% and 16.6% at 6-months, and 14.1% and 17.1% at 12 months (all between-group P values >0.18). Similarly, PPA rates did not differ significantly between groups at any follow-up. Change from baseline leisure-time activity plus strength training increased significantly in the physical activity group at 7 weeks (P = 0.04). Across treatment groups, an increase in the number of minutes per week in strength training from baseline to 7 weeks predicted prolonged abstinence at 12 months (P ≤ 0.001). Further analyses revealed that social support, fewer years smoked, and less temptation to smoke were associated with prolonged abstinence over 12 months in both groups. Conclusions: Community-based physical activity programming, delivered as adjunctive treatment with behavioral/pharmacological cessation treatment, did not improve long-term quit rates compared to adjunctive wellness counseling plus behavioral/pharmacological cessation treatment. This trial is registered with https://beta.clinicaltrials.gov/study/NCT00403312, registration no. NCT00403312.

A Cross-Sectional Survey of Anesthetic Airway Equipment and Airway Management Practices in Uganda.

BACKGROUND: Anesthesia-related causes contribute to a significant proportion of perioperative deaths, especially in low and middle-income countries (LMICs). There is evidence that complications related to failed airway management are a significant contributor to perioperative morbidity and mortality. While existing data have highlighted the magnitude of airway management complications in LMICs, there are inadequate data to understand their root causes. This study aimed to pilot an airway management capacity tool that evaluates airway management resources, provider practices, and experiences with difficult airways in an attempt to better understand potential contributing factors to airway management challenges. METHODS: We developed a novel airway management capacity assessment tool through a nonsystematic review of existing literature on anesthesia and airway management in LMICs, internationally recognized difficult airway algorithms, minimum standards for equipment, the safe practice of anesthesia, and the essential medicines and health supplies list of Uganda. We distributed the survey tool during conferences and workshops, to anesthesia care providers from across the spectrum of surgical care facilities in Uganda. The data were analyzed using descriptive methods. RESULTS: Between May 2017 and May 2018, 89 of 93 surveys were returned (17% of anesthesia providers in the country) from all levels of health facilities that provide surgical services in Uganda. Equipment for routine airway management was available to all anesthesia providers surveyed, but with a limited range of sizes. Pediatric airway equipment was always available 54% of the time. There was limited availability of capnography (15%), video laryngoscopes (4%), cricothyroidotomy kits (6%), and fiber-optic bronchoscopes (7%). Twenty-one percent (18/87) of respondents reported experiencing a "can't intubate, can't ventilate" (CICV) scenario in the 12 months preceding the survey, while 63% (54/86) reported experiencing at least 1 CICV during their career. Eighty-five percent (74/87) of respondents reported witnessing a severe airway management complication during their career, with 21% (19/89) witnessing a death as a result of a CICV scenario. CONCLUSIONS: We have developed and implemented an airway management capacity tool that describes airway management practices in Uganda. Using this tool, we have identified significant gaps in access to airway management resources. Gaps identified by the survey, along with advocacy by the Association of Anesthesiologists of Uganda, in partnership with the Ugandan Ministry of Health, have led to some progress in closing these gaps. Expanding the availability of airway management resources further, providing more airway management training, and identifying opportunities to support skilled workforce expansion have the potential to improve perioperative safety in Uganda.

Multiscale depth of anaesthesia prediction for surgery using frontal cortex electroencephalography.

Hypnotic and sedative anaesthetic agents are employed during multiple medical interventions to prevent patient awareness. Careful titration of agent dosing is required to avoid negative side effects; the accuracy thereof may be improved by Depth of Anaesthesia Monitoring. This work investigates the potential of a patient specific depth monitoring prediction using electroencephalography recorded neural oscillation from the frontal lobe of 10 patients during sedation, where a comparison of the prediction accuracy was made across five different approaches to post-processing; Noise Assisted-Empirical Mode Decomposition, the Raw Signal, Linear Series Decomposition Learner, Deep Wavelet Scattering and Deep Learning features. These methods towards anaesthesia depth prediction were investigated using the Bispectral Index as ground truth, where it was seen that the Raw Signal, enhanced feature set and a low complexity classification model (Linear Discriminant Analysis) provided the best classification accuracy, in the region of 85.65 % ±10.23 % across the 10 subjects. Subsequent work in this area would now build on these results and validate the best performing methods on a wider cohort of patients, investigate means of continuous DoA estimation using regressions, and also feature optimisation exercises in order to further streamline and reduce the computation complexity of the designed model.

Deploying an In Vitro Gut Model to Assay the Impact of the Mannan-Oligosaccharide Prebiotic Bio-Mos on the Atlantic Salmon (Salmo salar) Gut Microbiome.

Alpha mannose-oligosaccharide (MOS) prebiotics are widely deployed in animal agriculture as immunomodulators as well as to enhance growth and gut health. Their mode of action is thought to be mediated through their impact on host microbial communities and their associated metabolism. Bio-Mos is a commercially available prebiotic currently used in the agri-feed industry, but studies show contrasting results of its effect on fish performance and feed efficiency. Thus, detailed studies are needed to investigate the effect of MOS supplements on the fish microbiome to enhance our understanding of the link between MOS and gut health. To assess Bio-Mos for potential use as a prebiotic growth promoter in salmonid aquaculture, we have modified an established Atlantic salmon in vitro gut model, SalmoSim, to evaluate its impact on the host microbial communities. The microbial communities obtained from ceca compartments from four adult farmed salmon were inoculated in biological triplicate reactors in SalmoSim. Prebiotic treatment was supplemented for 20 days, followed by a 6-day washout period. Inclusion of Bio-Mos in the media resulted in a significant increase in formate (P = 0.001), propionate (P = 0.037) and 3-methyl butanoic acid (P = 0.024) levels, correlated with increased abundances of several, principally, anaerobic microbial genera (Fusobacterium, Agarivorans, Pseudoalteromonas). DNA metabarcoding with the 16S rDNA marker confirmed a significant shift in microbial community composition in response to Bio-Mos supplementation with observed increase in lactic acid producing Carnobacterium. In conjunction with previous in vivo studies linking enhanced volatile fatty acid production alongside MOS supplementation to host growth and performance, our data suggest that Bio-Mos may be of value in salmonid production. Furthermore, our data highlights the potential role of in vitro gut models to complementin vivo trials of microbiome modulators. IMPORTANCE In this paper we report the results of the impact of a prebiotic (alpha-MOS supplementation) on microbial communities, using an in vitro simulator of the gut microbial environment of the Atlantic salmon. Our data suggest that Bio-Mos may be of value in salmonid production as it enhances volatile fatty acid production by the microbiota from salmon pyloric ceca and correlates with a significant shift in microbial community composition with observed increase in lactic acid producing Carnobacterium. In conjunction with previous in vivo studies linking enhanced volatile fatty acid production alongside MOS supplementation to host growth and performance, our data suggest that Bio-Mos may be of value in salmonid production. Furthermore, our data highlights the potential role of in vitro gut models to augment in vivo trials of microbiome modulators.

The role of shear dynamics in biofilm formation.

There is growing evidence that individual bacteria sense and respond to changes in mechanical loading. However, the subtle responses of multispecies biofilms to dynamic fluid shear stress are not well documented because experiments often fail to disentangle any beneficial effects of shear stress from those delivered by convective transport of vital nutrients. We observed the development of biofilms with lognormally distributed microcolony sizes in drinking water on the walls of flow channels underflow regimes of increasing complexity. First, where regular vortices induced oscillating wall shear and simultaneously enhanced mass transport, which produced the thickest most extensive biofilms. Second, where unsteady uniform flow imposed an oscillating wall shear, with no enhanced transport, and where the biomass and coverage were only 20% smaller. Finally, for uniform steady flows with constant wall shear where the extent, thickness, and density of the biofilms were on average 60% smaller. Thus, the dynamics of shear stress played a significant role in promoting biofilm development, over and above its magnitude or mass transfer effects, and therefore, mechanosensing may prevail in complex multispecies biofilms which could open up new ways of controlling biofilm structure.

Validating Flow Cytometry as a Method for Quantifying Bdellovibrio Predatory Bacteria and Its Prey for Microbial Ecology.

Bdellovibrio bacteriovorus is a predatory, Gram-negative bacteria that feeds on many pathogenic bacteria and has been investigated as a possible solution for mitigating biofilms in different fields. The application depends on more fundamental ecological studies into the dynamics between Bdellovibrio and their prey. To do so requires an accurate, reliable, and, preferably rapid, way of enumerating the cells. Flow cytometry (FCM) is potentially a rapid, accurate, and inexpensive tool for this, but it has yet to be validated in the enumeration of Bdellovibrio. In this study, we developed a protocol to measure the number of Bdellovibrio in samples of various densities using FCM and compared the results with those of other methods: optical density (OD), PFU assay (PFU), and quantitative PCR (qPCR). We observed a strong correlation between values obtained using FCM and PFU (ρ = 0.923) and FCM and qPCR (ρ = 0.987). Compared to optical density there was a much weaker correlation (ρ = 0.784), which was to be expected given the well-documented uncertainty in converting optical density (OD) to cell numbers. The FCM protocol was further validated by demonstrating its ability to distinguish and count mixed populations of Bdellovibrio and the prey Pseudomonas. Thus, the accuracy of FCM as well as its speed and reproducibility make it a suitable alternative for measuring Bdellovibrio cell numbers, especially where many samples are required to capture the dynamics of predator-prey interactions. IMPORTANCE The rise of antibiotic resistance and the unwanted growth of bacteria is a universally growing problem. Predatory bacteria can be used as a biological alternative to antibiotics because they grow by feeding on other bacteria. To apply this effectively requires further study and a deeper understanding of the forces that drive a prey population to elimination. Initially, such studies require more reliable methods to count these cells. Flow cytometry (FCM) is potentially a rapid, accurate, and inexpensive tool for this, but it has yet to be validated for predatory bacteria. This study develops a protocol to count the predatory bacteria Bdellovibrio bacteriovorus and its Pseudomonas prey using FCM and compare the results with those of other methods, demonstrating its ability for studies into B. bacteriovorus predation dynamics. This could lead to the use of B. bacteriovorus for killing bacterial biofilms in fields, such as drinking water and agriculture.

A novel approach to baseline water quality assessment at local and catchment scale: a case study from Berambadi, India.

Optimal design and maintenance are necessary for the sustainability of wastewater treatment systems. In this study, we present the outcome of a novel approach to baseline assessment conducted prior to the design and deployment of a decentralized wastewater treatment system at a school in rural India. The baseline water quality monitoring protocol was deployed to assess (a) the quality and quantity of wastewater (greywater and blackwater) flows from the school and (b) the status of surface water and groundwater quality in the catchment. Hourly greywater flows and water quality trends were monitored across four seasons at the school. Average freshwater consumption at the school was 518 ± 322 L/day for hand washing and 287 ± 97 L/day for cooking meals. Greywater generation showed high hourly variations in COD levels. Greywater generated from hand wash and kitchen sources contributed to 110 g/day and 96 g/day of BOD5 respectively and 214 g/day and 141 g/day of COD respectively. Based on additional data from a self-reporting sanitation survey, the organic contaminant load generated from the toilet was estimated to be 1.5 ± 0.1 kg COD/day. At the catchment scale, both groundwater and surface water quality were monitored seasonally to assess the impact of raw sewage and stormwater inputs. Compared with borewells, high nitrate-N levels (> 10 mg/L) were observed in the village hand pump samples throughout the year. Maximum nitrate-N (16 mg/L) and fecal coliforms (3.9 log MPN/100 mL) levels were observed in surface waters during monsoons, indicating the impact of sewage and surface runoff on water quality. The proposed approach is useful to estimate data on freshwater use and wastewater generation at the school and hence to make the case for, and design of, a sustainable water management intervention.

SalmoSim: the development of a three-compartment in vitro simulator of the Atlantic salmon GI tract and associated microbial communities.

BACKGROUND: The aquaculture sector now accounts for almost 50% of all fish for human consumption and is anticipated to provide 62% by 2030. Innovative strategies are being sought to improve fish feeds and feed additives to enhance fish performance, welfare, and the environmental sustainability of the aquaculture industry. There is still a lack of knowledge surrounding the importance and functionality of the teleost gut microbiome in fish nutrition. In vitro gut model systems might prove a valuable tool to study the effect of feed, and additives, on the host's microbial communities. Several in vitro gut models targeted at monogastric vertebrates are now in operation. Here, we report the development of an Atlantic salmon gut model, SalmoSim, to simulate three gut compartments (stomach, pyloric caecum, and midgut) and associated microbial communities. RESULTS: The gut model was established in a series of linked bioreactors seeded with biological material derived from farmed adult marine-phase salmon. We first aimed to achieve a stable microbiome composition representative of founding microbial communities derived from Atlantic salmon. Then, in biological triplicate, the response of the in vitro system to two distinct dietary formulations (fishmeal and fishmeal free) was compared to a parallel in vivo trial over 40 days. Metabarcoding based on 16S rDNA sequencing qPCR, ammoniacal nitrogen, and volatile fatty acid measurements were undertaken to survey the microbial community dynamics and function. SalmoSim microbiomes were indistinguishable (p = 0.230) from their founding inocula at 20 days and the most abundant genera (e.g., Psycrobacter, Staphylococcus, Pseudomonas) proliferated within SalmoSim (OTUs accounting for 98% of all reads shared with founding communities). Real salmon and SalmoSim responded similarly to the introduction of novel feed, with majority of the taxa (96% Salmon, 97% SalmoSim) unaffected, while a subset of taxa (e.g., a small fraction of Psychrobacter) was differentially affected across both systems. Consistent with a low impact of the novel feed on microbial fermentative activity, volatile fatty acid profiles were not significantly different in SalmoSim pre- and post-feed switch. CONCLUSION: By establishing stable and representative salmon gut communities, this study represents an important step in the development of an in vitro gut system as a tool for the improvement of fish nutrition and welfare. The steps of the system development described in this paper can be used as guidelines to develop various other systems representing other fish species. These systems, including SalmoSim, aim to be utilised as a prescreening tool for new feed ingredients and additives, as well as being used to study antimicrobial resistance and transfer and fundamental ecological processes that underpin microbiome dynamics and assembly. Video abstract.

Drift dynamics in microbial communities and the effective community size.

The structure and diversity of all open microbial communities are shaped by individual births, deaths, speciation and immigration events; the precise timings of these events are unknowable and unpredictable. This randomness is manifest as ecological drift in the population dynamics, the importance of which has been a source of debate for decades. There are theoretical reasons to suppose that drift would be imperceptible in large microbial communities, but this is at odds with circumstantial evidence that effects can be seen even in huge, complex communities. To resolve this dichotomy we need to observe dynamics in simple systems where key parameters, like migration, birth and death rates can be directly measured. We monitored the dynamics in the abundance of two genetically modified strains of Escherichia coli, with tuneable growth characteristics, that were mixed and continually fed into 10 identical chemostats. We demonstrated that the effects of demographic (non-environmental) stochasticity are very apparent in the dynamics. However, they do not conform to the most parsimonious and commonly applied mathematical models, where each stochastic event is independent. For these simple models to reproduce the observed dynamics we need to invoke an 'effective community size', which is smaller than the census community size.

Sustainable water resources through harvesting rainwater and the effectiveness of a low-cost water treatment.

Increases in world population and climate change are some of the pressures affecting water resources for current and future water availability. The variability in water availability can reduce agricultural yields, food supplies and potentially leads to malnutrition and spread of diseases in water-poor countries. Even some water-rich countries can experience prolonged periods of dry weather, causing a drop in water reservoirs levels, forcing more restricted water resources management. Rainwater harvesting is one key option in adapting to water shortage and future demands that may alleviate the pressure on existing water resources. This work evaluates a roof top rainwater harvesting system (RWHS) installed as part of a decentralised wastewater treatment system designed to enable a circular economy by providing a more reliable water supply system in a remote public school in rural India. The effectiveness of the RWHS in reducing the pressure on a groundwater supply was assessed along with the physical, chemical and microbial characteristics of the stored rainwater over time. Further, the application of a low-cost primary treatment to make the harvested water safe to use for multiple purposes was investigated. The results revealed that the harvested water was of acceptable quality at the start of collection, however, microbial abundance increased when the rainwater was stored for a long time without treatment. Thus, a chlorine dosing regimen for the RWHS was designed based on laboratory and field experiments. The results also demonstrated that the low-cost chlorination process was effective in the field in reducing microbial abundance in the stored water for more than 30 days. However, as the residual chlorine level was reduced with time to <0.2 mg/l in the storage vessel, the microbial abundance increased, albeit to a much lower level that meets the Indian bathing water standards. The results provide evidence that installed RWHS has reduced the pressure on existing water supply at the school by up to 25% of the water that used for washing and flushing with no treatment, and with regular chlorination, greater savings and multiple uses of the stored rainwater can be achieved.

Growth and Break-Up of Methanogenic Granules Suggests Mechanisms for Biofilm and Community Development.

Methanogenic sludge granules are densely packed, small, spherical biofilms found in anaerobic digesters used to treat industrial wastewaters, where they underpin efficient organic waste conversion and biogas production. Each granule theoretically houses representative microorganisms from all of the trophic groups implicated in the successive and interdependent reactions of the anaerobic digestion (AD) process. Information on exactly how methanogenic granules develop, and their eventual fate will be important for precision management of environmental biotechnologies. Granules from a full-scale bioreactor were size-separated into small (0.6-1 mm), medium (1-1.4 mm), and large (1.4-1.8 mm) size fractions. Twelve laboratory-scale bioreactors were operated using either small, medium, or large granules, or unfractionated sludge. After >50 days of operation, the granule size distribution in each of the small, medium, and large bioreactor sets had diversified beyond-to both bigger and smaller than-the size fraction used for inoculation. Interestingly, extra-small (XS; <0.6 mm) granules were observed, and retained in all of the bioreactors, suggesting the continuous nature of granulation, and/or the breakage of larger granules into XS bits. Moreover, evidence suggested that even granules with small diameters could break. "New" granules from each emerging size were analyzed by studying community structure based on high-throughput 16S rRNA gene sequencing. Methanobacterium, Aminobacterium, Propionibacteriaceae, and Desulfovibrio represented the majority of the community in new granules. H2-using, and not acetoclastic, methanogens appeared more important, and were associated with abundant syntrophic bacteria. Multivariate integration (MINT) analyses identified distinct discriminant taxa responsible for shaping the microbial communities in different-sized granules.

Community-based physical activity as adjunctive smoking cessation treatment: Rationale, design, and baseline data for the Lifestyle Enhancement Program (LEAP) randomized controlled trial.

Despite advances in behavioral and pharmacological treatment for tobacco use and dependence, quit rates remain suboptimal. Increasing physical activity has shown some promise as a strategy for improving cessation outcomes. However, initial efficacy studies focused on intensive, highly structured exercise programs that may not be applicable to the general population of smokers. We describe the rationale and study design and report baseline participant characteristics from the Lifestyle Enhancement Program (LEAP), a two-group, randomized controlled trial. Adult smokers who engaged in low levels of leisure time physical activity were randomly assigned to treatment conditions consisting of an individualized physical activity intervention delivered by health fitness instructors in community-based exercise facilities or an equal contact wellness control. All participants received standard cognitive behavioral smoking cessation counseling combined with nicotine replacement therapy. The primary outcomes are seven-day point prevalence abstinence at seven weeks, six- and 12 months. Secondary outcomes include self-reported physical activity, dietary intake, body mass index, waist circumference, percent body fat, and nicotine withdrawal symptoms. Participants consist of 392 sedentary smokers (mean [standard deviation] age = 44.6 [10.2] = years; 62% female; 31% African American). Results reported here provide information regarding experiences recruiting smokers willing to change multiple health behaviors including smoking and physical activity.

Bioreactor Scalability: Laboratory-Scale Bioreactor Design Influences Performance, Ecology, and Community Physiology in Expanded Granular Sludge Bed Bioreactors.

Studies investigating the feasibility of new, or improved, biotechnologies, such as wastewater treatment digesters, inevitably start with laboratory-scale trials. However, it is rarely determined whether laboratory-scale results reflect full-scale performance or microbial ecology. The Expanded Granular Sludge Bed (EGSB) bioreactor, which is a high-rate anaerobic digester configuration, was used as a model to address that knowledge gap in this study. Two laboratory-scale idealizations of the EGSB-a one-dimensional and a three- dimensional scale-down of a full-scale design-were built and operated in triplicate under near-identical conditions to a full-scale EGSB. The laboratory-scale bioreactors were seeded using biomass obtained from the full-scale bioreactor, and, spent water from the distillation of whisky from maize was applied as substrate at both scales. Over 70 days, bioreactor performance, microbial ecology, and microbial community physiology were monitored at various depths in the sludge-beds using 16S rRNA gene sequencing (V4 region), specific methanogenic activity (SMA) assays, and a range of physical and chemical monitoring methods. SMA assays indicated dominance of the hydrogenotrophic pathway at full-scale whilst a more balanced activity profile developed during the laboratory-scale trials. At each scale, Methanobacterium was the dominant methanogenic genus present. Bioreactor performance overall was better at laboratory-scale than full-scale. We observed that bioreactor design at laboratory-scale significantly influenced spatial distribution of microbial community physiology and taxonomy in the bioreactor sludge-bed, with 1-D bioreactor types promoting stratification of each. In the 1-D laboratory bioreactors, increased abundance of Firmicutes was associated with both granule position in the sludge bed and increased activity against acetate and ethanol as substrates. We further observed that stratification in the sludge-bed in 1-D laboratory-scale bioreactors was associated with increased richness in the underlying microbial community at species (OTU) level and improved overall performance.

Risk factors for atrial fibrillation and their population burden in postmenopausal women: the Women's Health Initiative Observational Study.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in women. Large studies evaluating key AF risk factors in older women are lacking. We aimed to identify risk factors for AF in postmenopausal women and measure population burden of modifiable risk factors. DESIGN: Prospective observational study. SETTING: The Women's Health Initiative (WHI) Observational Study. PATIENTS: 93 676 postmenopausal women were followed for an average of 9.8 years for cardiovascular outcomes. After exclusion of women with prevalent AF or incomplete data, 8252 of the remaining 81 892 women developed incident AF. MAIN OUTCOME MEASURES: Incident AF was identified by WHI-ascertained hospitalisation records and diagnosis codes from Medicare claims. Multivariate Cox hazard regression analysis identified independent risk factors for incident AF. RESULTS: Age, hypertension, obesity, diabetes, myocardial infarction and heart failure were independently associated with incident AF. Hypertension and overweight status accounted for 28.3% and 12.1%, respectively, of the population attributable risk. Hispanic and African-American participants had lower rates of incident AF (HR 0.58, 95% CI 0.47 to 0.70 and HR 0.59, 95% CI 0.53 to 0.65, respectively) than Caucasians. CONCLUSIONS: Caucasian ethnicity, traditional cardiovascular risk factors and peripheral arterial disease were independently associated with higher rates of incident AF in postmenopausal women. Hypertension and overweight status accounted for a large proportion of population attributable risk. Measuring burden of modifiable AF risk factors in older women may help target interventions.

Prescribing for co-workers: practices and attitudes of faculty and residents.

BACKGROUND: Physicians sometimes are asked by co-workers for prescriptions to deal with their medical problems. These "hallway" requests typically occur outside a formal doctor-patient relationship.There are professional guidelines on serving as physician for family members and friends, but no guidelines address writing prescriptions for co-workers. The frequency of these requests and the factors physicians consider in responding to them have not been examined. OBJECTIVES: To obtain data on the frequency of these requests and physicians' attitudes and practices in responding to them, and to explore the ethical considerations in writing prescriptions for co-workers. DESIGN: A survey was administered to all physician faculty and residents in an academic department of internal medicine. The questions included whether the respondent had ever been asked for a prescription by a co-worker and how often the respondent had received such requests and written such prescriptions in the previous three months. Respondents also were asked to rate how likely they would be to write such a prescription in 15 hypothetical scenarios. RESULTS: Of the 113 respondents who completed surveys, 68 percent reported having been asked for a prescription by a co-worker. Among those who had ever been asked, 59 percent had been asked one or more times during the previous three months and 88 percent had ever written such a prescription. Also, 88 percent of all respondents stated they were "very likely" or "likely" to write the prescription in one or more of the hypothetical scenarios. CONCLUSIONS: Most physicians in our sample had been asked for prescriptions by co-workers, and most had written such prescriptions. Many respondents indicated a willingness to write such prescriptions in a variety of scenarios, despite the absence of a formal doctor-patient relationship. Further discussion of the ethical considerations in writing prescriptions for co-workers is needed.

Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition study.

BACKGROUND: The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. METHODS AND RESULTS: The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02-1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04-1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11-1.93). PR interval was not associated with increased all-cause mortality. CONCLUSIONS: We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.

A comparison of rectilinear and truncated exponential biphasic waveforms in elective cardioversion of atrial fibrillation: a prospective randomized controlled trial.

BACKGROUND: Several different biphasic waveforms are used clinically, but few studies have compared their efficacy. The two main waveforms are the biphasic rectilinear (BR) and biphasic truncated exponential (BTE) waveforms, both of which have important differences, particularly at the extremes of transthoracic impedance. OBJECTIVE: To compare the efficacy of two commonly used defibrillation waveforms in the elective cardioversion of atrial fibrillation. METHODS: In a prospective randomized controlled study, sequential adult patients undergoing elective cardioversion for AF were recruited. Patients were randomized to receive synchronized defibrillation using either a BR or BTE waveform, both using a 50J, 100J, 150J, 200J, 200J selected energy escalating protocol. Failure to cardiovert after the fifth shock was classed as failed defibrillation. The power of this study was 80% with 5% significance level to detect a difference of 20% or greater between groups. Survival analysis was used to compare the total energy delivered to achieve successful cardioversion between groups. RESULTS: A total of 202 patients were recruited, of which data are complete for 199 (100 BR; 99 BTE). Median number of shocks to achieve cardioversion was 2 for the BR waveform and 3 for the BTE waveform (P = 0.059). In the BR waveform group, 95/100 (95.0%) achieved sinus rhythm. In the BTE waveform group, 90/99 (90.9%) achieved sinus rhythm and this group required on average 117.1J more energy to achieve the outcome compared to the BR waveform group (P = 0.838). CONCLUSIONS: BR and BTE waveforms show similar high efficacy in the elective cardioversion of atrial fibrillation.

Lifestyle intervention improves heart rate recovery from exercise in adults with type 2 diabetes: results from the Look AHEAD study.

The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT) and (2) to determine the independent and combined effects of weight loss and fitness changes upon HRR. In 4503 participants (45-76 years) who completed 1 year of intervention, HRR was measured after a submaximal GXT to compare the influence of (ILI) with (DSE) upon HRR. Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (P < 0.001) while mean fitness increased in ILI by 20.9% versus 5.8% in DSE (P < 0.001). At Year 1, all exercise and HRR variables in ILI improved (P < 0.0001) versus DSE: heart rate (HR) at rest was lower (72.8 ± 11.4 versus 77.7 ± 11.7 b/min), HR range was greater (57.7 ± 12.1 versus 53.1 ± 12.4 b/min), HR at 2 minutes was lower (89.3 ± 21.8 versus 93.0 ± 12.1 b/min), and HRR was greater (41.25 ± 22.0 versus 37.8 ± 12.5 b/min). Weight loss and fitness gain produced significant separate and independent improvements in HRR.

Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial.

BACKGROUND: By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort. METHODS: Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50-79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00000611. FINDINGS: After a median follow-up of 11·8 years (IQR 9·1-12·9), the use of oestrogen for a median of 5·9 years (2·5-7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62-0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61-1·02) and post-intervention phase effects (0·75, 0·51-1·09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13-0·91; p=0·03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39-0·97; p=0·04). INTERPRETATION: Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer. FUNDING: US National Heart, Lung, and Blood Institute; Wyeth.