John McGready

Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis.

Although most randomized clinical trials conclude that the addition of continuous peripheral nerve blockade (CPNB) decreases postoperative pain and opioid-related side effects when compared with opioids, studies have included relatively small numbers of patients and the majority failed to show statistical significance during all time periods for reduced pain or side effects. We identified studies primarily by searching Ovid Medline (1966 – May 21, 2004) for terms related to postoperative analgesia with CPNB and opioids. Each article from the final search was reviewed and data were extracted from tables, text, or extrapolated from figures as needed. Nineteen articles, enrolling 603 patients, met all inclusion criteria. Inclusion criteria were a clearly defined anesthetic technique (combined general/regional anesthesia, general anesthesia alone, peripheral nerve block), randomized trial, adult patient population (≥18 yr old), CPNB (or analgesia) used postoperatively (intrapleural catheters were deemed not to be classified as a peripheral nerve catheter), and opioids administered for postoperative analgesia in groups not receiving peripheral nerve block. Perineural analgesia provided better postoperative analgesia compared with opioids (P < 0.001). This effect was seen for all time periods measured for both mean visual analog scale and maximum visual analog scale at 24 h (P < 0.001), 48 h (P < 0.001), and 72 h (mean visual analog scale only) (P < 0.001) postoperatively. Perineural catheters provided superior analgesia to opioids for all catheter locations and time periods (P < 0.05). Nausea/vomiting, sedation, and pruritus all occurred more commonly with opioid analgesia (P < 0.001). A reduction in opioid use was noted with perineural analgesia (P < 0.001). CPNB analgesia, regardless of catheter location, provided superior postoperative analgesia and fewer opioid-related side effects when compared with opioid analgesia.

Characteristics and concordance of autism spectrum disorders among 277 twin pairs

OBJECTIVES To examine patterns of autism spectrum disorder (ASD) inheritance and other features in twin pairs by zygosity, sex, and specific ASD diagnosis. DESIGN Cross-sectional study. SETTING Internet-based autism registry for US residents. PARTICIPANTS Survey results from 277 twin pairs (210 dizygotic [DZ] and 67 monozygotic [MZ]) aged 18 years or younger with at least 1 affected twin. MAIN EXPOSURES Zygosity and sex. OUTCOME MEASURES Concordance within twin pairs of diagnosis, natural history, and results from standardized autism screening. RESULTS Pairwise ASD concordance was 31% for DZ and 88% for MZ twins. Female and male MZ twins were 100% and 86% concordant, respectively, and DZ twin pairs with at least 1 female were less likely to be concordant (20%) than were male-male DZ twin pairs (40%). The hazard ratio for ASD diagnosis of the second twin after a first-twin diagnosis was 7.48 for MZ vs DZ twins (95% confidence interval, 3.8-14.7). Affected DZ individual twins had an earlier age at first parental concern and more frequent diagnoses of intellectual disability than did MZ twins; MZ twins had a higher prevalence of bipolar disorder and Asperger syndrome and higher concordance of the latter. Results of autism screening correlated with parent-reported ASD status in more than 90% of cases. CONCLUSIONS Our data support greater ASD concordance in MZ vs DZ twins. Overall higher functioning, psychiatric comorbidity, and Asperger syndrome concordance among affected MZ vs DZ twins may also suggest differential heritability for different ASDs. For families in which one MZ twin is diagnosed with ASD, the second twin is unlikely to receive an ASD diagnosis after 12 months. In addition, Internet parent report of ASD status is valid.

The Effects of a Small-Dose Naloxone Infusion on Opioid- Induced Side Effects and Analgesia in Children and Adolescents Treated with Intravenous Patient-Controlled Analgesia: A Double-Blind, Prospective, Randomized, Controlled Study

Opioids are frequently associated with side effects such as nausea, vomiting, and pruritus. We hypothesized that a prophylactic, continuous small-dose naloxone infusion would reduce the incidence of opioid-induced side effects without affecting analgesia or opioid consumption. In this prospective, double-blind, randomized, controlled clinical trial, we studied 46 postoperative patients (M:F, 21:25), averaging 14 ± 2.5 yr and 53 ± 17 kg, at the start of morphine IV patient-controlled analgesia. Patients were randomized to either saline (control, n = 26) or naloxone 0.25 &mgr;g · kg−1 · h−1 (n = 20). We found that the incidence and severity of pruritus (77% versus 20%; P < 0.05) and nausea (70% versus 35%; P < 0.05) was significantly more frequent in the placebo group compared with the naloxone group. Morphine consump-tion (1.02 ± 0.41 mg · kg−1 · d−1 versus 1.28 ± 0.61 mg · kg−1 · d−1), pain scores at rest (4 ± 2 versus 3 ± 2), and pain scores with coughing (6 ± 2 versus 6 ± 2) were not different. We conclude that, in children and adolescents, a small-dose naloxone infusion (0.25 &mgr;g · kg−1 · h−1) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion.

Global methylmercury exposure from seafood consumption and risk of developmental neurotoxicity: a systematic review

OBJECTIVE To examine biomarkers of methylmercury (MeHg) intake in women and infants from seafood-consuming populations globally and characterize the comparative risk of fetal developmental neurotoxicity. METHODS A search was conducted of the published literature reporting total mercury (Hg) in hair and blood in women and infants. These biomarkers are validated proxy measures of MeHg, a neurotoxin found primarily in seafood. Average and high-end biomarkers were extracted, stratified by seafood consumption context, and pooled by category. Medians for average and high-end pooled distributions were compared with the reference level established by a joint expert committee of the Food and Agriculture Organization (FAO) and the World Health Organization (WHO). FINDINGS Selection criteria were met by 164 studies of women and infants from 43 countries. Pooled average biomarkers suggest an intake of MeHg several times over the FAO/WHO reference in fish-consuming riparians living near small-scale gold mining and well over the reference in consumers of marine mammals in Arctic regions. In coastal regions of south-eastern Asia, the western Pacific and the Mediterranean, average biomarkers approach the reference. Although the two former groups have a higher risk of neurotoxicity than the latter, coastal regions are home to the largest number at risk. High-end biomarkers across all categories indicate MeHg intake is in excess of the reference value. CONCLUSION There is a need for policies to reduce Hg exposure among women and infants and for surveillance in high-risk populations, the majority of which live in low-and middle-income countries.

Effect of temperature on cystic fibrosis lung disease and infections: A replicated cohort study

Background Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF). Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown. Methods Multivariate regression was used to assess correlation between specific environmental factors, the presence of pulmonary pathogens, and variation in lung function using subjects enrolled in the U.S. CF Twin and Sibling Study (CFTSS: n = 1378). Significant associations were tested for replication in the U.S. CF Foundation Patient Registry (CFF: n = 16439), the Australian CF Data Registry (ACFDR: n = 1801), and prospectively ascertained subjects from Australia/New Zealand (ACFBAL: n = 167). Results In CFTSS subjects, the presence of Pseudomonas aeruginosa (OR = 1.06 per °F; p<0.001) was associated with warmer annual ambient temperatures. This finding was independently replicated in the CFF (1.02; p<0.001), ACFDR (1.05; p = 0.002), and ACFBAL (1.09; p = 0.003) subjects. Warmer temperatures (−0.34 points per °F; p = 0.005) and public insurance (−6.43 points; p<0.001) were associated with lower lung function in the CFTSS subjects. These findings were replicated in the CFF subjects (temperature: −0.31; p<0.001; insurance: −9.11; p<0.001) and similar in the ACFDR subjects (temperature: −0.23; p = 0.057). The association between temperature and lung function was minimally influenced by P. aeruginosa. Similarly, the association between temperature and P. aeruginosa was largely independent of lung function. Conclusions Ambient temperature is associated with prevalence of P. aeruginosa and lung function in four independent samples of CF patients from two continents.

Quantification of the Relative Contribution of Environmental and Genetic Factors to Variation in Cystic Fibrosis Lung Function

OBJECTIVE To assess the relative contributions of environmental and genetic factors to variation in cystic fibrosis (CF) lung disease. STUDY DESIGN Genetic and environmental contributions were quantified by use of intrapair correlations and differences in CF-specific forced expiratory volume in 1 second measures from 134 monozygous twins and 272 dizygous twins and siblings while in different living environments (ie, living with parents vs living alone), as well as by use of intraindividual differences in pulmonary function from a separate group of 80 siblings. RESULTS Pulmonary function among monozygous twins was more similar than among dizygous twin and sibling pairs, regardless of living environment, affirming the role of genetic modifiers in CF pulmonary function. Regression modeling revealed that genetic factors account for 50% of pulmonary function variation, unique environmental or stochastic factors (36%), and shared environmental factors (14%; P < .0001). The intraindividual analysis produced similar estimates for the contributions of the unique and shared environment. The shared environment effects appeared primarily because of living with a sibling with CF (P = .003), rather than factors within the parental household (P = .310). CONCLUSIONS Genetic and environmental factors contribute equally to pulmonary function variation in CF. Environmental effects are dominated by unique and stochastic effects rather than common exposures.

Biomedical Science Ph.D. Career Interest Patterns by Race/Ethnicity and Gender.

Increasing biomedical workforce diversity remains a persistent challenge. Recent reports have shown that biomedical sciences (BMS) graduate students become less interested in faculty careers as training progresses; however, it is unclear whether or how the career preferences of women and underrepresented minority (URM) scientists change in manners distinct from their better-represented peers. We report results from a survey of 1500 recent American BMS Ph.D. graduates (including 276 URMs) that examined career preferences over the course of their graduate training experiences. On average, scientists from all social backgrounds showed significantly decreased interest in faculty careers at research universities, and significantly increased interest in non-research careers at Ph.D. completion relative to entry. However, group differences emerged in overall levels of interest (at Ph.D. entry and completion), and the magnitude of change in interest in these careers. Multiple logistic regression showed that when controlling for career pathway interest at Ph.D. entry, first-author publication rate, faculty support, research self-efficacy, and graduate training experiences, differences in career pathway interest between social identity groups persisted. All groups were less likely than men from well-represented (WR) racial/ethnic backgrounds to report high interest in faculty careers at research-intensive universities (URM men: OR 0.60, 95% CI: 0.36–0.98, p = 0.04; WR women: OR: 0.64, 95% CI: 0.47–0.89, p = 0.008; URM women: OR: 0.46, 95% CI: 0.30–0.71, p<0.001), and URM women were more likely than all other groups to report high interest in non-research careers (OR: 1.93, 95% CI: 1.28–2.90, p = 0.002). The persistence of disparities in the career interests of Ph.D. recipients suggests that a supply-side (or “pipeline”) framing of biomedical workforce diversity challenges may limit the effectiveness of efforts to attract and retain the best and most diverse workforce. We propose incorporation of an ecological perspective of career development when considering strategies to enhance the biomedical workforce and professoriate through diversity.

Peripherally inserted central catheters: a randomized, controlled, prospective trial in pediatric surgical patients.

Peripherally-inserted central catheters (PICCs) are long-term IV catheters used for drug and fluid administration, blood sampling, or hyperalimentation. The short-term use of PICCs in postoperative patients has not been studied. In this randomized, controlled trial, patients received either a PICC or peripheral IV catheter (PIV). Our outcome measures were patient and parent satisfaction with care, complications of the venous access devices, number of postoperative venipunctures, and cost-effectiveness of use. Satisfaction was significantly more frequent in the PICC group (P < 0.05), and there were significantly fewer postoperative needle punctures in the PICC group compared with the PIV group (P < 0.05). Minor complications were common in the PIV group; major complications were uncommon in both groups. PICCs are more expensive, but better satisfaction can make them a cost-effective option. Additionally, insertion during surgical preparation time in the operating room (OR) means that cost is not increased by adding anesthesiologist and OR time. Anesthesiologists should consider placing PICCs in patients requiring more than 4 days of in-hospital postoperative care, especially if frequent blood sampling or IV access is required.

Weight for age charts for children with achondroplasia

To develop accurate weight for age charts for individuals with achondroplasia. These novel weight for age, gender‐specific growth curves for achondroplasia patients from birth through 16 years were constructed from a longitudinal, retrospective, single observer cohort study of 334 individuals with achondroplasia. Weight for age data from 301 subjects in this achondroplasia cohort, constituting 1,964 total weight measurements, are presented in these weight for age curves. Percentiles (5, 25, 50, 75, 95th) were estimated across the age continuum by gender, using a 1 month window (±0.5 months) around each time point of interest. Percentiles were smoothed using a quadratic, penalized smoother by a semi‐parametric model approach. Raw weight data from the achondroplasia cohort are compared to that of average stature children presented in the current CDC growth curves, divided into 0–36 months and 2–16 years. There was overlap of birth weight between achondroplasia and average stature infants. This statistical modeling method can be applied to other anthropometric parameters collected from this achondroplasia cohort (e.g., length, BMI), other skeletal dysplasia diagnoses, and to syndromic, non‐skeletal dysplasia diagnoses which may benefit from standardization of weight for age.

Career Development among American Biomedical Postdocs

This study reports results from a national survey examining the career development of biomedical postdocs. Findings point to the need for enhanced career development programs earlier in the training process and interventions that are sensitive to distinctive patterns of interest development across social identity groups.