Peripheral Nerve Blockade for Open Inguinal Hernia Repair in a Patient With Severe Cardiopulmonary Disease.

Patients with severe cardiopulmonary morbidity present a unique challenge to peri- and intraoperative providers. Inducing general anesthesia in this patient population poses the risk of adverse events that could lead to poor surgical outcomes, prolonged debilitation, or death. Therefore, it is important that anesthesiologists become comfortable with preoperative evaluation as well as alternative strategies to providing surgical anesthesia. This case report details the clinical course of a patient with severe cardiopulmonary morbidity who underwent open inguinal hernia repair without oral or intravenous sedation after receiving multi-level paravertebral blocks in addition to isolated ilioinguinal and iliohypogastric nerve blocks. This medically challenging case provides educational value regarding preoperative evaluation, pertinent anatomy and innervation, and the importance of patient-centered care and communication.

The link between cutaneous inflammation and cognitive impairment.

Cognitive impairment is a symptom of neurological disorders, including dementia and Alzheimer's disease; and mild cognitive impairment can be a precursor of both disorders. Aged humans and animal models with other systemic disorders, such as cardiovascular diseases and diabetes, display a higher incidence of cognitive decline. Epidemiological studies have shown that the incidence of cognitive impairment also is higher in subjects with certain inflammatory skin disorders, including psoriasis and chronic eczematous dermatitis. Chronologically aged individuals exhibit increased cutaneous inflammation and elevated circulating cytokine levels, linked to alterations in epidermal function, which itself can induce cutaneous inflammation. Conversely, strategies that improve epidermal function can lower cytokine levels in both the skin and circulation. Thus, it seems likely that epidermal dysfunction could contribute, at least in part, to the development of chronic low-grade inflammation, also termed 'inflammaging', in the elderly. The evidence of cognitive impairment in patients with inflammatory dermatoses suggests a link between cutaneous inflammation and cognitive impairment. Because of the pathogenic role of epidermal dysfunction in ageing-associated cutaneous inflammation, improvements in epidermal function could be an alternative approach for mitigation of the ageing-associated decline in cognitive function.

Responding to Mycobacterium chimaera heater-cooler unit contamination: international and national intersectoral collaboration coordinated in the state of Queensland, Australia.

BACKGROUND: The index case of Mycobacterium chimaera infection in a patient following open cardiac surgery in the state of Queensland, Australia prompted a centralized coordinated response to mitigate the risk. AIM: To describe the public health response to M. chimaera contamination of heater-cooler units (HCUs) and patient infection. METHODS: A public health sector strategy was developed with national and international consultation to respond to the threat of HCUs contaminated with M. chimaera. Data linkage of non-tuberculous mycobacterium notifications and selected procedures was undertaken where potential use of HCUs was identified through hospitalization records. Water sampling and testing protocols were standardized. Public disclosure and patient notification were undertaken. FINDINGS: A single case of disseminated M. chimaera infection in a patient has been diagnosed to date in Queensland, Australia. Ten of 12 (83%) LivaNova Stockert 3T HCUs from five hospitals tested positive for M. chimaera. In total, 5650 patients were notified by post of their potential risk of exposure. Use of the telehealth call centre was modest. M. chimaera was also found in extracorporeal membrane oxygenation heater units produced by two other device manufacturers, four of which tested positive prior to commissioning for use. CONCLUSIONS: Rapid international collaboration optimized the Queensland Health response to potential M. chimaera exposure during cardiac surgery. State-wide collaboration ensured a transparent, consistent approach to contacting patients and informing the public of the potential risk. A framework for ongoing risk management, clinical awareness and laboratory diagnosis was established. No further cases of M. chimaera infection have been identified in Queensland.

Hyak mortality monitoring system: innovative sampling and estimation methods - proof of concept by simulation.

Traditionally health statistics are derived from civil and/or vital registration. Civil registration in low- to middle-income countries varies from partial coverage to essentially nothing at all. Consequently the state of the art for public health information in low- to middle-income countries is efforts to combine or triangulate data from different sources to produce a more complete picture across both time and space - data amalgamation. Data sources amenable to this approach include sample surveys, sample registration systems, health and demographic surveillance systems, administrative records, census records, health facility records and others. We propose a new statistical framework for gathering health and population data - Hyak - that leverages the benefits of sampling and longitudinal, prospective surveillance to create a cheap, accurate, sustainable monitoring platform. Hyak has three fundamental components: Data amalgamation: A sampling and surveillance component that organizes two or more data collection systems to work together: (1) data from HDSS with frequent, intense, linked, prospective follow-up and (2) data from sample surveys conducted in large areas surrounding the Health and Demographic Surveillance System (HDSS) sites using informed sampling so as to capture as many events as possible;Cause of death: Verbal autopsy to characterize the distribution of deaths by cause at the population level; andSocioeconomic status (SES): Measurement of SES in order to characterize poverty and wealth. We conduct a simulation study of the informed sampling component of Hyak based on the Agincourt HDSS site in South Africa. Compared with traditional cluster sampling, Hyak's informed sampling captures more deaths, and when combined with an estimation model that includes spatial smoothing, produces estimates of both mortality counts and mortality rates that have lower variance and small bias.

Importance of case age in the purported association between phylogenetics and hemolytic uremic syndrome in Escherichia coli O157:H7 infections.

Escherichia coli O157:H7 is the largest cause of hemolytic uremic syndrome (HUS). Previous studies proposed that HUS risk varies across the E. coli O157:H7 phylogenetic tree (hypervirulent clade 8), but the role of age in the association is unknown. We determined phylogenetic lineage of E. coli O157:H7 isolates from 1160 culture-confirmed E. coli O157:H7 cases reported in Washington State, 2004-2015. Using generalised estimating equations, we tested the association between phylogenetic lineage and HUS. Age was evaluated as an effect modifier. Among 1082 E. coli O157:H7 cases with both phylogenetic lineage and HUS status (HUS n = 76), stratified analysis suggested effect modification by age. Lineages IIa and IIb, relative to Ib, did not appear associated with HUS in children 0-9-years-old. For cases 10-59-years-old, lineages IIa and IIb appeared to confer increased risk of HUS, relative to lineage Ib. The association reversed in ⩾60-year-olds. Results were similar for clade 8. Phylogenetic lineage appears to be associated with HUS risk only among those ⩾10-years-old. Among children <10, the age group most frequently affected, lineage does not explain progression to HUS. However, lineage frequency varied across age groups, suggesting differences in exposure and/or early disease manifestation.

Association of meteorological and geographical factors and risk of initial Pseudomonas aeruginosa acquisition in young children with cystic fibrosis.

Initial infection with the sentinel respiratory pathogen in children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa), is generally with environmental strains of this ubiquitous organism. The purpose of this study was to evaluate the associations between meteorological and geographical factors and risk of initial Pa acquisition in young children with CF. Using the U.S. Cystic Fibrosis Foundation Patient Registry from 2003 to 2009, 3463 patients met inclusion criteria, of which 48% (n = 1659) acquired Pa during follow-up. From multivariable Weibull regression, increased risk of Pa acquisition was associated with increasing temperature [hazard ratio (HR) per 1 °C: 1·13; 95% confidence interval (CI) 1·08-1·13], dew point (HR per 1 °C: 1·10, 95% CI 1·07-1·13), rainfall (HR per cm: 1·10, 95% CI 1·07-1·12), latitude (HR per 1 °C northing: 1·15, 95% CI 1·11-1·20), longitude (HR per 1 °C easting: 1·01, 95% CI 1·01-1·02) and elevation (HR per 100 m: 1·05, 95% CI 1·03-1·07). These results suggest that environmental factors may play a previously unrecognized role in the aetiology of initial Pa acquisition.

Feelings of worthlessness during a single complicated major depressive episode predict postremission suicide attempt.

OBJECTIVE: To establish which symptoms of major depressive episode (MDE) predict postremission suicide attempts in complicated single-episode cases. METHOD: Using the nationally representative two-wave National Epidemiologic Survey on Alcohol and Related Conditions data set, we identified wave 1 lifetime single-episode MDE cases in which the episode remitted by the beginning of the wave 2 three-year follow-up period (N = 2791). The analytic sample was further limited to 'complicated' cases (N = 1872) known to have elevated suicide attempt rates, defined as having two or more of the following: suicidal ideation, marked role impairment, feeling worthless, psychomotor retardation, and prolonged (>6 months) duration. RESULTS: Logistic regression analyses showed that, after controlling for wave 1 suicide attempt which significantly predicted postremission suicide attempt (OR = 10.0), the additional complicated symptom 'feelings of worthlessness' during the wave 1 index episode significantly and very substantially predicted postremission suicide attempt (OR = 6.96). Neither wave 1 psychomotor retardation nor wave 1 suicidal ideation nor any of the other wave 1 depressive symptoms were significant predictors of wave 2 suicide attempt. CONCLUSION: Among depressive symptoms during an MDE, feelings of worthlessness is the only significant indicator of elevated risk of suicide attempt after the episode has remitted, beyond previous suicide attempts.

DSM-5, psychiatric epidemiology and the false positives problem.

The revision effort leading to the publication of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was flawed in process, goals and outcome. The revision process suffered from lack of an adequate public record of the rationale for changes, thus shortchanging future scholarship. The goals, such as dimensionalising diagnosis, incorporating biomarkers and separating impairment from diagnosis, were ill-considered and mostly abandoned. However, DSM-5's greatest problem, and the target of the most vigorous and sustained criticism, was its failure to take seriously the false positives problem. By expanding diagnosis beyond plausible boundaries in ways inconsistent with DSM-5's own definition of disorder, DSM-5 threatened the validity of psychiatric research, including especially psychiatric epidemiology. I present four examples: increasing the symptom options while decreasing the diagnostic threshold for substance use disorder, elimination of the bereavement exclusion from major depression, allowing verbal arguments as evidence of intermittent explosive disorder and expanding attention-deficit/hyperactivity disorder to adults before addressing its manifest false positives problems.

Detecting signals in pharmacogenomic genome-wide association studies.

In a common pharmacogenomic scenario, outcome measures are compared for treated and untreated subjects across genotype-defined subgroups. The key question is whether treatment benefit (or harm) is particularly strong in certain subgroups, and therefore the statistical analysis focuses on the interaction between treatment and genotype. However, genome-wide analysis in such scenarios requires careful statistical thought as, in addition to the usual problems of multiple testing, the marker-defined sample sizes, and therefore power, vary across the individual genotypes being evaluated. The variability in power means that the usual practice of using a common P-value threshold across tests has difficulties. The reason is that the use of a fixed threshold, with variable power, implies that the costs of type I and type II errors vary across tests in a manner that is implicit rather than dictated by the analyst. In this paper we discuss this problem and describe an easily implementable solution based on Bayes factors. We pay particular attention to the specification of priors, which is not a straightforward task. The methods are illustrated using data from a randomized controlled clinical trial in which homocysteine levels are compared in individuals receiving low and high doses of folate supplements and across marker subgroups. The method we describe is implemented in the R computing environment with code available from http://faculty.washington.edu/jonno/cv.html.

HIBAG--HLA genotype imputation with attribute bagging.

Genotyping of classical human leukocyte antigen (HLA) alleles is an essential tool in the analysis of diseases and adverse drug reactions with associations mapping to the major histocompatibility complex (MHC). However, deriving high-resolution HLA types subsequent to whole-genome single-nucleotide polymorphism (SNP) typing or sequencing is often cost prohibitive for large samples. An alternative approach takes advantage of the extended haplotype structure within the MHC to predict HLA alleles using dense SNP genotypes, such as those available from genome-wide SNP panels. Current methods for HLA imputation are difficult to apply or may require the user to have access to large training data sets with SNP and HLA types. We propose HIBAG, HLA Imputation using attribute BAGging, that makes predictions by averaging HLA-type posterior probabilities over an ensemble of classifiers built on bootstrap samples. We assess the performance of HIBAG using our study data (n=2668 subjects of European ancestry) as a training set and HLA data from the British 1958 birth cohort study (n≈1000 subjects) as independent validation samples. Prediction accuracies for HLA-A, B, C, DRB1 and DQB1 range from 92.2% to 98.1% using a set of SNP markers common to the Illumina 1M Duo, OmniQuad, OmniExpress, 660K and 550K platforms. HIBAG performed well compared with the other two leading methods, HLA*IMP and BEAGLE. This method is implemented in a freely available HIBAG R package that includes pre-fit classifiers for European, Asian, Hispanic and African ancestries, providing a readily available imputation approach without the need to have access to large training data sets.

Predictive validation of single-episode uncomplicated depression as a benign subtype of unipolar major depression.

OBJECTIVE: To evaluate the predictive validity of a proposed benign major depressive disorder (MDD) subtype, single-episode 'uncomplicated MDD', defined as MDD that remits within 6 months and lacks severe impairment, psychotic ideation, suicidal ideation, psychomotor retardation, and feeling worthless. METHOD: Using two-wave National Epidemiologic Survey on Alcohol and Related Conditions data, four groups differing in wave 1 lifetime MDD history (no history [n = 27 609]; single-episode uncomplicated [n = 418]; other single-episode [n = 1943]; multiple episode [n = 2473]) were evaluated for 3-year follow-up rates of major depressive episode (MDE), generalized anxiety disorder (GAD), and suicide attempt. RESULTS: Follow-up rates for no-MDD-history, single-episode uncomplicated MDD, other single-episode MDD, and multiple-episode MDD, respectively, were depressive episode 6.1%, 6.9%, 19.5%, 27.1%; GAD 2.7%, 4.3%, 7.8%, 11.2%; and suicide attempt 0.3%, 0.1%, 0.8%, 1.7%. For all validators, 3-year rates for single-episode uncomplicated cases were not significantly different from no-MDD-history rates, but significantly lower than both single- and multiple-episode other-MDD rates. Mild MDD, defined by having only five or six symptoms, did not yield similarly benign results; logistic regression showed 'uncomplicated' provides incremental validity over 'mild' in explaining validator rates. Validator differences were not explainable by treatment-rate differences. CONCLUSION: Single-episode uncomplicated MDD is a benign subtype lacking typical MDD negative sequelae. The planned DSM-5.1 revision should reinstitute an extended bereavement exclusion applied to all stressors.

The treatment of stable paediatric forearm fractures using a cast that may be removed at home: comparison with traditional management in a randomised controlled trial.

We investigated whether, in the management of stable paediatric fractures of the forearm, flexible casts that can be removed at home are as clinically effective, cost-effective and acceptable to both patient and parent as management using a cast conventionally removed in hospital. A single-centre randomised controlled trial was performed on 317 children with a mean age of 9.3 years (2 to 16). No significant differences were seen in the change in Childhood Health Assessment Questionnaire index score (p = 0.10) or EuroQol 5-Dimensions domain scores between the two groups one week after removal of the cast or the absolute scores at six months. There was a significantly lower overall median treatment cost in the group whose casts were removed at home (£150.88 (sem 1.90) vs £251.62 (sem 2.68); p < 0.001). No difference was seen in satisfaction between the two groups (p = 0.48).

Season is associated with Pseudomonas aeruginosa acquisition in young children with cystic fibrosis.

Pseudomonas aeruginosa, the principal respiratory pathogen in cystic fibrosis (CF) patients, is ubiquitous in the environment. Initial P. aeruginosa isolates in CF patients are generally environmental in nature. However, little information regarding seasonality of P. aeruginosa acquisition is available. We conducted a retrospective study to evaluate the seasonality of initial P. aeruginosa acquisition in young children with CF in the USA using the Cystic Fibrosis Foundation National Patient Registry from 2003 to 2009. Additionally, we assessed whether seasonal acquisition varied by climate zone. A total of 4123 children met inclusion criteria and 45% (n = 1866) acquired P. aeruginosa during a mean 2.0 years (SD 0.2 years) of follow up. Compared with winter, increased P. aeruginosa acquisition was observed in summer (incidence rate ratio (IRR): 1.22; 95% CI: 1.07-1.40) and autumn (IRR: 1.34; 95% CI: 1.18-1.52), with lower acquisition observed in spring (IRR: 0.81; 95% CI: 0.70-0.94). Seasonal variations in P. aeruginosa acquisition rates in the temperate and continental climate zones were similar to those in the overall cohort. In contrast, no significant seasonal effect was observed in the dry climate zone. In a corresponding analysis, no seasonal difference was observed in the rate of acquisition of Staphylococcus aureus, another common CF respiratory pathogen. These results provide preliminary support that climatic factors may be associated with initial P. aeruginosa acquisition in CF patients. Investigation and identification of specific risk factors, as well as awareness of seasonal variation, could potentially inform clinical recommendations including increased awareness of infection control and prevention strategies.

Can the DSM's major depression bereavement exclusion be validly extended to other stressors? Evidence from the NCS.

OBJECTIVE: To evaluate whether the DSM's distinction between uncomplicated (normal) vs. complicated (disordered) bereavement-related depressive episodes can be validly extended to non-bereavement stressor-related depression (SRD). Previous findings supporting the uncomplicated/complicated SRD distinction's discriminant validity were criticized as tautological because of definitional biases (e.g., 'uncomplicated' requires brief duration, yet duration was a validator). We tested whether uncomplicated/complicated SRD validator differences are tautological or real. METHOD: Using National Comorbidity Survey data, we compared uncomplicated SRDs, complicated SRDs, and endogenous/psychotic MDD on levels of eight pathology validators. We identified definitional biases affecting six validators, and corrected them by deleting the biasing definitional components and recalculating validator levels. RESULTS: After correction of biases, uncomplicated SRDs had significantly lower pathology levels than both complicated SRDs and endogenous/psychotic MDD on seven of eight validators, disconfirming the tautology hypothesis. Regression analysis revealed that 'uncomplicated' cannot be equated with 'mild'. Extending the 'uncomplicated' durational threshold from 2 to 6 months yielded equal or stronger discriminant validity, suggesting the arbitrariness of the current durational criterion. CONCLUSION: Uncomplicated SRDs' lower pathology levels are because of real syndromal differences, not definitional tautologies. The uncomplicated/complicated distinction has discriminant validity when extended to non-bereavement SRDs as an indicator of normality vs. disorder.