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Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma. METHODS: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician’s diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes. RESULTS: A genome-wide significant association was identified between baseline FEV(1)/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10(−8) in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10(−6)). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV(1) (P = 3.3 × 10(−3)), postbronchodilator (PB) FEV(1) (7.3 × 10(−3)), and PB FEV(1)/FVC ratio (P = 2.7 × 10(−3)). The identified baseline FEV(1)/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR. CONCLUSIONS: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Study Objective We used electronic health record data to define frequency of inadequate intraoperative neuromuscular blockade (NMB). Design Retrospective observational study using electronic health record data. Setting Operating room in a tertiary care academic hospital. Patients A total of 129,209 adult patients with American Society of Anesthesiologists physical status 1 to 5 undergoing general anesthesia in an outpatient or inpatient setting who received nondepolarizing NMB. We excluded patients intubated before arrival to the operating room, patients undergoing a liver transplant or cardiac surgery, and patients who remained intubated at the end of the operation. Interventions None. Measurements The primary outcomes were inadequate NMB defined by (1) documentation of patient movement and (2) documentation of surgical request for additional NMB, followed by NMB agent administration. Main Results A total of 1261 patients (1.0%) demonstrated either intraoperative movement (369 or 0.29%) or prompted surgical request for additional NMB agent (921 or 0.71%). Trend analysis showed a variation in the annual rate of inadequate NMB, with an increase from 2004 to 2013 for criteria 1 and 2. Conclusions Nearly 1% of all general anesthetic procedures involving NMB exhibit inadequate relaxation resulting in procedural interruption. These data suggest that current use of neuromuscular blocking drugs and NMB monitoring expose patients to inadequate blockade. The risk of this phenomenon warrants further study.

Study objective Muscular tone that inhibits anesthetic or surgical care characterizes insufficient neuromuscular block. The incidence of insufficient neuromuscular block is unknown, therefore we developed novel electronic search strategies to identify occurrences of insufficient neuromuscular block. Our primary goal was to determine the incidence of intraoperative insufficient neuromuscular block in abdominal and neurovascular surgery. Our secondary goal was to assess factors independently associated with insufficient block. Design Retrospective cohort. Setting Operating rooms in a tertiary care center. Patients Adults having abdominal, laparoscopic, and interventional neurovascular procedures under general anesthesia with endotracheal intubation between April 2005 and February 2013. Measurements An expert panel of anesthesiologists used a Delphi process to develop criteria to identify insufficient intraoperative neuromuscular block. 10 final criteria were agreed upon and used to determine the incidence of insufficient neuromuscular block. Main results 48,315 surgeries met our inclusion requirements. Intraoperative insufficient neuromuscular block was identified in 13,538 cases, representing 28% (95% CI: 27.6%, 28.4%) of the operations. Younger age, male sex, type of surgery, longer duration of surgery, pre-existing conditions, and use of volatile anesthetics were independently associated with insufficient block after Bonferroni correction. Conclusion Our results suggest that episodes of insufficient block occur in over a quarter of operations that are generally thought to require muscle relaxation. Without neuromuscular monitoring, it is difficult to separate inadequate anesthesia from inadequate neuromuscular block, and both presumably contributed in many cases.

Obstructive sleep apnea (OSA) is a prevalent condition that is associated with early postoperative respiratory complications (PRCs). As the majority of patients with OSA are undiagnosed, preoperative screening remains the most efficient method to identify suspected OSA.This retrospective study was performed on patients undergoing anesthesia in a single academic medical center. We assigned OSA risk class retrospectively to all patients in the study by using the Perioperative Sleep Apnea Prediction (PSAP) score. We evaluated the relationship between PSAP categories and early postoperative invasive airway placement after adjusting for several preoperative and intraoperative factors (including surgical risk) previously associated with PRC occurrence.A total of 108,479 patients were included in the final analysis with an incidence of PRC was 0.3% (n = 280). High PSAP score was associated with postoperative intubation (adjusted odds ratio, 2.3; 95% confidence interval, 1.5-3.7). Several risk factors reflecting anesthetic agents, neuromuscular blocking agents, and opioids were also independently associated with early PRC.We report that suspected OSA based on the PSAP score is independently associated with increased risk of early PRC. Specific anesthetic agents are independently associated with early PRC, pointing to the potential for examining risk modification through these exposures in future studies.

The incidence rate of hepatic decompensation was higher in patients with human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) triple infection than in those with HIV/HCV coinfection (24.1 vs 10.8 events per 1000 person-years; hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.12-3.18). Compared with HIV/HCV-infected patients, the rate of decompensation was increased among HIV/HBV/HCV-infected patients receiving no anti-HBV therapy (HR, 2.48; 95% CI, 1.37-4.49) but not among those who did receive such therapy (HR, 1.09; 95% CI, .40-2.97).

Background Postoperative respiratory complications (PRCs) are associated with significant morbidity, mortality, and hospital costs. Obstructive sleep apnea (OSA), often undiagnosed in the surgical population, may be a contributing factor. Thus, we aimed to develop and validate a score for preoperative prediction of OSA (SPOSA) based on data available in electronic medical records preoperatively. Methods OSA was defined as the occurrence of an OSA diagnostic code preceded by a polysomnography procedure. A priori defined variables were analyzed by multivariable logistic regression analysis to develop our score. Score validity was assessed by investigating the score’s ability to predict non-invasive ventilation. We then assessed the effect of high OSA risk, as defined by SPOSA, on PRCs within seven postoperative days and in-hospital mortality. Results A total of 108,781 surgical patients at Partners HealthCare hospitals (2007–2014) were studied. Predictors of OSA included BMI >25 kg*m−2 and comorbidities, including pulmonary hypertension, hypertension, and diabetes. The score yielded an area under the curve of 0.82. Non-invasive ventilation was significantly associated with high OSA risk (OR 1.44, 95% CI 1.22–1.69). Using a dichotomized endpoint, 26,968 (24.8%) patients were identified as high risk for OSA and 7.9% of these patients experienced PRCs. OSA risk was significantly associated with PRCs (OR 1.30, 95% CI 1.19–1.43). Conclusion SPOSA identifies patients at high risk for OSA using electronic medical record-derived data. High risk of OSA is associated with the occurrence of PRCs. Electronic supplementary material The online version of this article (doi:10.1186/s12871-017-0361-z) contains supplementary material, which is available to authorized users.

INTRODUCTION:The clinical importance of postoperative episodic hypoxemia is still unclear, and therefore largely under-studied. As a result, there is limited understanding of its relationship with early postoperative respiratory complications (PRC, defined as intubation within three days of surgery) and hospital resource utilization. MATERIALS AND METHODS:This single center study was performed using a retrospective observational design. We described population based definitions of desaturation from continuous SpO2 monitoring data captured in the post anesthesia care unit (PACU), namely median SpO2 in PACU, duration of desaturation below median, nadir desaturation, and length of oxygen therapy relative to PACU duration. These measures were evaluated against the occurrence of early PRC in logistic regression models. Measures that were independently associated with early PRC were accepted as the primary study exposures. Stratified logistic regression models were planned if significant interaction occurred with high risk surgical procedures. Models were adjusted by including several patient conditions, procedural, and anesthesia risk factors. Propensity matching on desaturation occurrence was planned to evaluate the relationship with postoperative resource utilization. RESULTS:Among 125,740 patients included in the univariate analyses, 351 patients (0.3%) developed early PRC. Nadir desaturation 60 min) to 3.04 (>90 min); p

Background Using electronic health record data, we hypothesized that larger reversal doses are used for patients with deeper levels of neuromuscular blockade (NMB) as evidenced by the last recorded TOF measurement. We also examined if dosing regimens reflect current practice guidelines of using ideal body weight (IBW) for NMB agents and total body weight (TBW) for neostigmine. Methods This is a retrospective observational study of adult, ASA 1–4 patients who underwent general anaesthesia and received non-depolarizing NMB agents between 01/01/2004 and 12/31/2013. For the primary outcome, percentages of cases receiving neostigmine and median doses administered for each subjective train-of-four (TOF) category were calculated. Secondary analyses evaluated associations between NMB dosing and neostigmine administration based on Body Mass Index (BMI) categories. Results A total of 135,633 cases met inclusion criteria for the study. There was no clinically significant difference in median neostigmine dosing based on last TOF count prior to reversal administration: 37.5 mcg/kg for TOF of 4/4 vs. 37.9 mcg/kg for TOF of 0/4 for the total neostigmine dose. Significantly higher number of patients with lower TOF counts received additional neostigmine administration: 5.7 % for 0/4 vs. 1.5 % for 4/4 TOF counts. The median times to extubation following neostigmine administration were clinically similar across TOF count categories. The median doses for neostigmine based on TBW decreased with higher BMI categories and were significantly different between the lowest and highest categories: 42.8 mcg/kg vs 30.8 mcg/kg for total doses (p 40.

This article describes experiments that explore the possibility of using an optical tracking device input to remotely control dual-arm robots. We propose using the Leap Motion controller as an alternative to using joysticks, this allows for more intuitive 6-DOF control where only one hand is needed to control each robot arm. We affixed two end effectors to a Baxter research robot, a standard electric gripper, and an AR10 robotic hand. The standard electric gripper was controlled via pinch gestures and all five fingers and thumb were controlled on the AR10 robotic hand using finger movement from the Leap. Some simple tests were performed and the results indicate that in lifting standard objects the standard electric gripper had a higher success rate. The main problem with the hand appeared to be due to the absence of any touch or force feedback to the operator, as the user became more comfortable with the system the better their performance became. This leads us to believe that the use of a robotic hand could be improved with a training program.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of invasive surgical site infection (SSI) in the USA. Antimicrobial prophylaxis for SSI typically includes a cephalosporin. Vancomycin is used to provide MRSA coverage, but the timing of administration is challenging. Linezolid is an attractive agent for SSI prophylaxis, particularly for the prevention of SSI due to MRSA.We developed a decision-analytic model to evaluate linezolid use for cardiothoracic SSI prophylaxis. A theoretical cohort of 10,000 cardiothoracic surgery patients was followed through 2 stages: (1) occurrence of SSI, and (2) mortality after SSI. All patients were administered cefuroxime, vancomycin, or linezolid between 1 and 180 min prior to surgical incision. SSIs were categorized into 3 pathogen categories: (1) methicillin-susceptible Gram-positive, (2) methicillin-resistant Gram-positive, and (3) other organisms. The most effective strategy resulted in the fewest SSIs. Assumptions for antibiotic effectiveness, impact of administration time, and pathogens were based on the published literature.Compared with cefuroxime, there was a 1% increase in the total number of SSIs in the linezolid group (mean SSI increase = 7), while there was a 12% increase in the vancomycin group (mean SSI increase = 86). Linezolid prophylaxis resulted in fewer SSIs due to methicillin-resistant Gram-positive infections (n = 108) compared with cefuroxime (n = 200, 46% reduction in the linezolid group) and vancomycin (n = 119, 9% reduction in the linezolid group).This simulation indicates that linezolid may offer benefits for SSI prophylaxis over existing prophylactic agents, particularly for the prevention of SSI due to Gram-positive methicillin-resistant pathogens.

What is known Warfarin is a potent anti-coagulant with many drug-drug interactions, including antimicrobials. There is limited data on the frequency of prescription of high-risk antimicrobials to patients on warfarin.

Concerns have been raised over the use of different manufacturers' versions of A-rated antiepileptic drug (AED) formulations in epilepsy patients.To estimate the association between acute epilepsy exacerbations and switching between different A-rated AEDs.A nested case-control study was conducted using pharmacy and medical claims data from January 1, 2005 through December 31, 2007. 18-65-year-olds who had an epilepsy diagnosis and received AED therapy during 2005 were eligible for study. Cases were defined as individuals with a documented exacerbation of epilepsy in the form of a 2006 or 2007 inpatient or emergency room claim for epilepsy. Controls were from the same population and matched on baseline epilepsy diagnosis and follow-up time since January 1, 2006. The exposure was a switch between A-rated AEDs in the 90 days prior to the matching date. Conditional logistic regression was used to estimate the odds of an epilepsy exacerbation after a switch controlling for important covariates.A total of 34 216 individuals were eligible for study, of whom 2949 cases were matched to 8847 controls. The unadjusted odds ratio (OR) between a switch and an epilepsy exacerbation was 1.51 (95% CI: 1.29-1.76). After adjusting for potential confounders, the odds ratio was 1.08 (95% CI: 0.91-1.29). Treatment with three or more AEDs or a change in outpatient diagnosis from baseline resulted in ORs of 2.96 (95% CI: 2.48-3.49) and 2.53 (95% CI: 2.28-2.82), respectively.After addressing potential confounders, no evidence that A-rated switching was associated with increased acute exacerbations of epilepsy was found. Study limitations include potentially incomplete identification of seizures, no information on indication for medication use, and limited information on duration and severity of disease. This study provides additional insight into the relationship between A-rated AED switching and acute exacerbations of epilepsy.

Background The United States is moving toward active drug safety surveillance using sources such as administrative claims and electronic medical records, but use of these data for studying teratogenicity has been challenging, as they typically do not allow for the easy identification of pregnancies. Our goal was to develop and validate an algorithm for the identification of pregnancies in the general practice research database (GPRD) that could be used to study pregnancy outcomes. Methods The algorithm identified pregnancies in women 15–45-year-old that were pregnant between 1 January 1987 and 31 December 2006. We identified live births, stillbirths, and spontaneous and elective terminations within a woman's record. We validated the algorithm using the additional clinical details maternity (ACDM) file and de-identified free-text records. Results We analyzed 16 035 394 records from 3 093 927 individuals and identified 383 184 women who had a total of 580 356 pregnancies. There were 415 221 full-term live births, 3080 pre- or post-term births, 1834 multi-fetus deliveries, 86 408 spontaneous abortions or miscarriages, 72 164 elective terminations, and 1649 stillbirths or fetal deaths. A marker of pregnancy care was identifiable for 86.3% of the 580 356 pregnancies. The internal validation steps indicated that the algorithm produced consistent results with the ACDM file. Conclusions We were successful in identifying a large number of pregnancies in the GPRD. Our use of a hierarchical approach to identify pregnancy outcomes builds upon the methods suggested in previous work, while implementing additional steps to minimize potential misclassification of pregnancy outcomes. Copyright © 2009 John Wiley & Sons, Ltd.

Introduction Obstructive sleep apnoea (OSA), the most common type of sleep-disordered breathing, is associated with significant immediate and long-term morbidity, including fragmented sleep and impaired daytime functioning, as well as more severe consequences, such as hypertension, impaired cognitive function and reduced quality of life. Perioperatively, OSA occurs frequently as a consequence of pre-existing vulnerability, surgery and drug effects. The impact of OSA on postoperative respiratory complications (PRCs) needs to be better characterised. As OSA is associated with significant comorbidities, such as obesity, pulmonary hypertension, myocardial infarction and stroke, it is unclear whether OSA or its comorbidities are the mechanism of PRCs. This project aims to (1) develop a novel prediction score identifying surgical patients at high risk of OSA, (2) evaluate the association of OSA risk on PRCs and (3) evaluate if pharmacological agents used during surgery modify this association. Methods Retrospective cohort study using hospital-based electronic patient data and perioperative data on medications administered and vital signs. We will use data from Partners Healthcare clinical databases, Boston, Massachusetts. First, a prediction model for OSA will be developed using OSA diagnostic codes and polysomnography procedural codes as the reference standard, and will be validated by medical record review. Results of the prediction model will be used to classify patients in the database as high, medium or low risk of OSA, and we will investigate the effect of OSA on risk of PRCs. Finally, we will test whether the effect of OSA on PRCs is modified by the use of intraoperative pharmacological agents known to increase upper airway instability, including neuromuscular blockade, neostigmine, opioids, anaesthetics and sedatives. Ethics and dissemination The Partners Human Research Committee approved this study (protocol number: 2014P000218). Study results will be made available in the form of manuscripts for publication and presentations at national and international meetings.

To assess the short-term direct medical costs and effectiveness associated with achieving recommended glycaemic goals using commonly prescribed first-line oral antihyperglycaemic medications in type 2 diabetes mellitus.A literature-based, decision-tree model was developed to project the number of patients achieving glycosylated haemoglobin values of7% on oral therapies and the associated costs over a 3-year timeframe. For each first-line strategy, patients could progress to combination therapy using two or more agents prior to the introduction of insulin. The overall cost of treatment included costs (2001/2002 values; US dollars) of comprehensive medical care, laboratory tests, patient education, drug therapy, home glucose monitoring and adverse events.At 3 years, the overall cost of treatment for the various first-line strategies was 6,106 US dollars for glipizide gastrointestinal therapeutic system, 6,727 US dollars for metformin immediate release, 6,826 US dollars for metformin extended release, 7,141 US dollars for glibenclamide (glyburide)/metformin, 7,759 US dollars for rosiglitazone and 9,298 US dollars for repaglinide. Costs of comprehensive routine medical care ranged from approximately 1,538-2,128 US dollars in year 1 and from approximately 952-1,543 US dollars in subsequent years, for controlled and uncontrolled patients, respectively. Adverse events represented1%, and drug therapies represented approximately 50%, of the overall cost, respectively. Substantial cost differences between the strategies were seen within the first year. Regardless of first-line therapy, patients progressed quickly to combination therapies, with effectiveness among the agents being similar.Short-term costs required to provide comprehensive diabetes care and achieve glycemic goals can be substantial. The model suggests a sulphonylurea strategy may provide similar effectiveness with cost savings over other agents and should be considered when selecting an initial drug therapy in newly diagnosed patients with type 2 diabetes mellitus.

AIM Sustained virologic response (SVR) can be attained with boceprevir plus peginterferon alfa and ribavirin (PR) in up to 68% of patients, and short duration therapy is possible if plasma HCV RNA levels are undetectable at treatment week 8 (TW8 response). We have developed predictive models for SVR, and TW8 response using data from boceprevir clinical trials. METHODS Regression models were built to predict TW8 response and SVR. Separate models were built for TW8 and SVR using baseline variables only, and compared to models with baseline variables plus HCV RNA change after 4 weeks of PR (TW4 delta). Predictive accuracy was assessed by c-statistics, calibration curves, and decision curve analyses. Nomograms were developed to create clinical decision support tools. Models were externally validated using independent data. RESULTS The models that included TW4 delta produced the best discrimination ability. The predictive factors for TW8 response (n = 856) were TW4 delta, race, platelet count and ALT. The predictive factors for SVR (n = 522) were TW4 delta, HCV-subtype, gender, BMI, RBV dose and platelet count. The discrimination abilities of these models were excellent (C-statistics = 0.88, 0.80 respectively). Baseline models for TW8 response (n = 444) and SVR (n = 197) had weaker discrimination ability (C-statistic = 0.76, 0.69). External validation confirmed the predictive accuracy of the week 4 models. CONCLUSIONS Models incorporating baseline and treatment week 4 data provide excellent prediction of TW8 response and SVR, and support the clinical utility of the lead-in phase of PR. The nomograms are suitable for point-of-care use to inform individual patient and physician decision-making.

The purpose of this study is to investigate 1-year adherence rates to aromatase inhibitors (AI) and to determine risk factors for non-adherence among commercially insured post-menopausal breast cancer patients. A retrospective cohort of 13,593 commercially insured breast cancer patients with a prescription claim for an AI therapy (exemestane, anastrozole, and letrozole) in 2006 were identified using the MarketScan® Commercial Claims and Encounters Database. Adherence was calculated by the medication possession ratio (MPR) for a 1-year period following the initial claim in 2006. The main outcome variable was non-adherence (

The United States is moving toward active drug safety surveillance using sources such as administrative claims and electronic medical records, but use of these data for studying teratogenicity has been challenging, as they typically do not allow for the easy identification of pregnancies. Our goal was to develop and validate an algorithm for the identification of pregnancies in the general practice research database (GPRD) that could be used to study pregnancy outcomes.The algorithm identified pregnancies in women 15-45-year-old that were pregnant between 1 January 1987 and 31 December 2006. We identified live births, stillbirths, and spontaneous and elective terminations within a woman's record. We validated the algorithm using the additional clinical details maternity (ACDM) file and de-identified free-text records.We analyzed 16,035,394 records from 3,093,927 individuals and identified 383,184 women who had a total of 580,356 pregnancies. There were 415,221 full-term live births, 3080 pre- or post-term births, 1834 multi-fetus deliveries, 86,408 spontaneous abortions or miscarriages, 72 164 elective terminations, and 1649 stillbirths or fetal deaths. A marker of pregnancy care was identifiable for 86.3% of the 580,356 pregnancies. The internal validation steps indicated that the algorithm produced consistent results with the ACDM file.We were successful in identifying a large number of pregnancies in the GPRD. Our use of a hierarchical approach to identify pregnancy outcomes builds upon the methods suggested in previous work, while implementing additional steps to minimize potential misclassification of pregnancy outcomes.

Background The General Practice Research Database (GPRD) has been used to identify associations between pregnancy medication exposures and birth defects, but experts have argued that databases such as this one cannot provide detailed information for the valid identification of complicated congenital anomalies. Our objective was to determine if the GPRD could be used to identify cases of neural tube defects (NTDs). Methods First, we created algorithms for anencephaly, encephalocele, meningocele, and spina bifida and used them to identify potential cases. We used the algorithms to identify 217 potential NTD cases in either a child's or a mother's record. We validated cases by querying general practitioners (GPs) via questionnaire. Where cases of NTD were identified in the mother's record, in addition to confirming the diagnosis, we asked the GPs if the diagnosis was for the mother or that of her fetus or offspring. Results Two hundred seventeen cases were identified, and 165 GP questionnaires were returned. We validated an NTD diagnosis for 117 cases, giving our algorithms a positive predictive value (PPV) of 0.71. The PPVs varied by NTD type: 0.81 for anencephaly, 0.83 for cephalocele, 0.64 for meningocele, and 0.47 for spina bifida. Conclusions Our identification algorithm was useful in identifying three of the four types of NTDs studied. Additional information is necessary to accurately identify cases of spina bifida. Copyright © 2008 John Wiley & Sons, Ltd.

Misuse of antibiotic therapy can have a profound negative impact both on individuals and on the community. The objective of this meta-analysis was to estimate the prevalence of antibiotic misuse in terms of non-compliance with therapy or reuse of leftover antibiotics in the community. Of 2848 screened articles, 46 contained the required information on the number of participants, the number compliant/using leftovers and the measurement technique. Mean compliance with antibiotics was 62.2% (95% confidence interval (CI), 56.4-68.0%) and mean use of leftover antibiotics was 28.6% (95% CI, 21.8-35.4%). Although variation in the methods resulted in substantial heterogeneity in the estimates, results were generally consistent by region and measurement technique. Patient education and simpler antibiotic regimens should be encouraged to promote responsible use of antibiotic therapy.