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Key Points ChipCytometry was used for multiplex immunophenotyping of human tonsils. It is viable for high-content profiling of cell suspensions and tissue sections. ChipCytometry can identify and localize cell populations and rare cell types., ChipCytometry is a multiplex imaging method that can be used to analyze either cell suspensions or tissue sections. Images are acquired by iterative cycles of immunostaining with fluorescently labeled Abs, followed by photobleaching, which allows the accumulation of multiple markers on a single sample. In this study, we explored the feasibility of using ChipCytometry to identify and phenotype cell subsets, including rare cell types, using a combination of tissue sections and single-cell suspensions. Using ChipCytometry of tissue sections, we successfully demonstrated the architecture of human palatine tonsils, including the B and T cell zones, and characterized subcompartments such as the B cell mantle and germinal center zone, as well as intrafollicular PD1-expressing CD4+ T cells. Additionally, we were able to identify the rare tonsillar T cell subsets, mucosal-associated invariant T (MAIT) and γδ-T cells, within tonsil tissue. Using single-cell suspension ChipCytometry, we further dissected human tonsillar T cell subsets via unsupervised clustering analysis as well as supervised traditional manual gating. We were able to show that PD1+CD4+ T cells are comprised of CXCR5+BCL6high follicular Th cells and CXCR5−BCL6mid pre–follicular Th cells. Both supervised and unsupervised analysis approaches identified MAIT cells in single-cell suspensions, confirming a phenotype similar to that of blood-derived MAIT cells. In this study, we demonstrate that ChipCytometry is a viable method for single-cell suspension cytometry and analysis, with the additional benefit of allowing phenotyping in a spatial context using tissue sections.

Recent attempts to create synthetic Escherichia coli methylotrophs identified that de novo biosynthesis of amino acids, in the presence of methanol, presents significant challenges in achieving autonomous methylotrophic growth. Previously engineered methanol-dependent strains required co-utilization of stoichiometric amounts of co-substrates and methanol. As such, these strains could not be evolved to grow on methanol alone. In this work, we have explored an alternative approach to enable biosynthesis of all amino acids from methanol-derived carbon in minimal media without stoichiometric coupling. First, we identified that biosynthesis of threonine was limiting the growth of our methylotrophic E. coli. To address this, we performed adaptive laboratory evolution to generate a strain that grew efficiently in minimal medium with methanol and threonine. Methanol assimilation and growth of the evolved strain were analyzed, and, interestingly, we found that the evolved strain synthesized all amino acids, including threonine, from methanol-derived carbon. The evolved strain was then further engineered through overexpression of an optimized threonine biosynthetic pathway. We show that the resulting methylotrophic E. coli strain has a methanol-dependent growth phenotype with homoserine as co-substrate. In contrast to previous methanol-dependent strains, co-utilization of homoserine is not stoichiometrically linked to methanol assimilation. As such, future engineering of this strain and successive adaptive evolution could enable autonomous growth on methanol as the sole carbon source. KEY POINTS: • Adaptive evolution of E. coli enables biosynthesis of all amino acids from methanol. • Overexpression of threonine biosynthesis pathway improves methanol assimilation. • Methanol-dependent growth is seen in minimal media with homoserine as co-substrate.

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methylotrophs have proved successful, autonomous methylotrophy, that is, the ability to utilize methane or methanol as sole carbon and energy substrates, has not yet been realized. Here, we address an important limitation of autonomous methylotrophy in E. coli: the inability of the organism to synthesize several amino acids when grown on methanol. We targeted global and local amino acid regulatory networks. Those include removal of amino acid allosteric feedback inhibition (argAH15Y , ilvAL447F , hisGE271K , leuAG462D , proBD107N , thrAS345F , trpES40F ), knockouts of transcriptional repressors (ihfA, metJ); and overexpression of amino acid biosynthetic operons (hisGDCBHAFI, leuABCD, thrABC, trpEDCBA) and transcriptional regulators (crp, purR). Compared to the parent methylotrophic E. coli strain that was unable to synthesize these amino acids from methanol carbon, these strategies resulted in improved biosynthesis of limiting proteinogenic amino acids (histidine, leucine, lysine, methionine, phenylalanine, threonine, tyrosine) from methanol carbon. In several cases, improved amino acid biosynthesis from methanol carbon led to improvements in methylotrophic growth in methanol minimal medium supplemented with a small amount of yeast extract. This study addresses a key limitation currently preventing autonomous methylotrophy in E. coli and possibly other synthetic methylotrophs and provides insight as to how this limitation can be alleviated via global and local regulatory modifications.

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methylotrophs have proved successful, autonomous methylotrophy, i.e. the ability to utilize methane or methanol as sole carbon and energy substrates, has not yet been realized. Here, we address an important limitation of autonomous methylotrophy in E. coli: the inability of the organism to synthesize several amino acids when grown on methanol. By activating the stringent/stress response via ppGpp overproduction, or DksA and RpoS overexpression, we demonstrate improved biosynthesis of proteinogenic amino acids via endogenous upregulation of amino acid synthesis pathway genes. Thus, we were able to achieve biosynthesis of several limiting amino acids from methanol-derived carbon, in contrast to the control methylotrophic E. coli strain. This study addresses a key limitation currently preventing autonomous methylotrophy in E. coli and possibly other synthetic methylotrophs and provides insight as to how this limitation can be alleviated via stringent/stress response activation.

Natural gas and biogas provide an opportunity to harness methane as an industrial feedstock. Bioconversion is a promising alternative to chemical catalysis, which requires extreme operating conditions and exhibits poor specificities. Though methanotrophs natively utilize methane, efforts have been focused on engineering platform organisms like Escherichia coli for synthetic methanotrophy. Here, a synthetic E. coli methanotroph was developed by engineering functional expression of the Methylococcus capsulatus soluble methane monooxygenase in vivo via expression of its cognate GroESL chaperone. Additional overexpression of E. coli GroESL further improved activity. Incorporation of an acetone formation pathway then enabled the conversion of methane to acetone in vivo, as validated via 13C tracing. This work provides the first reported demonstration of methane bioconversion to liquid chemicals in a synthetic methanotroph.

There is great interest in developing synthetic methylotrophs that harbor methane and methanol utilization pathways in heterologous hosts such as Escherichia coli for industrial bioconversion of one-carbon compounds. While there are recent reports that describe the successful engineering of synthetic methylotrophs, additional efforts are required to achieve the robust methylotrophic phenotypes required for industrial realization. Here, we address an important issue of synthetic methylotrophy in E. coli: methanol toxicity. Both methanol, and its oxidation product, formaldehyde, are cytotoxic to cells. Methanol alters the fluidity and biological properties of cellular membranes while formaldehyde reacts readily with proteins and nucleic acids. Thus, efforts to enhance the methanol tolerance of synthetic methylotrophs are important. Here, adaptive laboratory evolution was performed to improve the methanol tolerance of several E. coli strains, both methylotrophic and non-methylotrophic. Serial batch passaging in rich medium containing toxic methanol concentrations yielded clones exhibiting improved methanol tolerance. In several cases, these evolved clones exhibited a > 50% improvement in growth rate and biomass yield in the presence of high methanol concentrations compared to the respective parental strains. Importantly, one evolved clone exhibited a two to threefold improvement in the methanol utilization phenotype, as determined via 13C-labeling, at non-toxic, industrially relevant methanol concentrations compared to the respective parental strain. Whole genome sequencing was performed to identify causative mutations contributing to methanol tolerance. Common mutations were identified in 30S ribosomal subunit proteins, which increased translational accuracy and provided insight into a novel methanol tolerance mechanism. This study addresses an important issue of synthetic methylotrophy in E. coli and provides insight as to how methanol toxicity can be alleviated via enhancing methanol tolerance. Coupled improvement of methanol tolerance and synthetic methanol utilization is an important advancement for the field of synthetic methylotrophy.

ObjectivesTo assess to which extent the COVID-19 pandemic affected corneal transplantation by virtue of donor selection algorithms in different European countries.DesignSurvey.Setting110 eye banks in 26 European countries.Participants64 eye banks covering 95% of European corneal transplantation activity.InterventionsA questionnaire listing the number of corneas procured and distributed from February to May 2018–2020 was circulated to eye banks.Main outcome measuresThe primary outcome was the number of corneal procurements. Additional outcomes were national algorithms for donor selection, classified according to their stringency (donors with COVID-19 history, suspected for COVID-19, asymptomatic, PCR testing) and the pandemic severity in each country. We calculated Spearman’s correlation coefficient to determine, two by two, the relationship between the 3-month decline in eye banking activity (procurement), the stringency of donor selection algorithm and the grading of pandemic severity (cases and deaths). A partial correlation was run to determine the relationship between decline and stringency while controlling for pandemic severity.ResultsProcurements decreased by 38%, 68% and 41%, respectively, in March, April and May 2020 compared with the mean of the previous 2 years, while grafts decreased, respectively, by 28%, 68% and 56% corresponding to 3866 untreated patients in 3 months. Significant disparities between countries and the decrease in activity correlated with stringency in donor selection independent of pandemic severity.ConclusionsOur data demonstrate significant differences between countries regarding donor screening algorithms based on precautionary principles and, consequently, a decrease in the donor pool, already constrained by a long list of contraindications. Fundamental studies are needed to determine the risk of SARS-CoV-2 transmission by corneal transplantation and guide evidence-based recommendations for donor selection to justify their substantial medical and economic impact.

Methane, the main component of natural gas, can be used to produce methanol which can be further converted to other valuable products. There is increasing interest in using biological systems for the production of fuels and chemicals from methanol, termed methylotrophy. In this work, we have examined methanol assimilation metabolism in a synthetic methylotrophic E. coli strain. Specifically, we applied 13C-tracers and evaluated 25 different co-substrates for methanol assimilation, including amino acids, sugars and organic acids. In particular, co-utilization of threonine significantly enhanced methylotrophy. Through our investigations, we proposed specific metabolic pathways that, when activated, correlated with increased methanol assimilation. These pathways are normally repressed by the leucine-responsive regulatory protein (lrp), a global regulator of metabolism associated with the feast-or-famine response in E. coli. By deleting lrp, we were able to further enhance the methylotrophic ability of our synthetic strain, as demonstrated through increased incorporation of 13C carbon from 13C-methanol into biomass.

Synthetic methylotrophy aims to develop non-native methylotrophic microorganisms to utilize methane or methanol to produce chemicals and biofuels. We report two complimentary strategies to further engineer a previously engineered methylotrophic E. coli strain for improved methanol utilization. First, we demonstrate improved methanol assimilation in the presence of small amounts of yeast extract by expressing the non-oxidative pentose phosphate pathway (PPP) from Bacillus methanolicus. Second, we demonstrate improved co-utilization of methanol and glucose by deleting the phosphoglucose isomerase gene (pgi), which rerouted glucose carbon flux through the oxidative PPP. Both strategies led to significant improvements in methanol assimilation as determined by 13C-labeling in intracellular metabolites. Introduction of an acetone-formation pathway in the pgi-deficient methylotrophic E. coli strain led to improved methanol utilization and acetone titers during glucose fed-batch fermentation.

Emerging Adults (ages 18-25) have the highest prevalence of substance use disorders and rarely receive treatment from the specialty care system. Thus, it is important to have screening instruments specifically developed for emerging adults for use in Screening, Brief Intervention and Referral to Treatment (SBIRT) models. Optimal cutoffs for the widely-used GAIN Short-Screener's (GAIN-SS) Substance Disorder Screener (SDScrY) are not established specifically for emerging adults. Therefore, this study examined the sensitivity and specificity of the SDScrY in predicting emerging adult (ages 18-25) substance use disorders.We analyzed data from emerging adults in a large clinical sample (n=9,808) who completed both the five-item SDScrY (α=0.85) and the full criteria set for DSM-IV Substance Use Disorders. We estimated the sensitivity, specificity and area under the curve to determine optimal cutoffs.Analyses revealed a high correlation between the SDScrY screener and its longer parent scale (r=0.95, p0.001). Sensitivity (83%) and specificity (95%) were highest at a cutoff score of two (AUC=94%) on the SDScrY for any past year substance use disorder. Sensitivity (85%) was also high at a cutoff score of two on the SDScrY for any past year alcohol disorder.The five-item Substance Use Disorder Screener is a sensitive and specific screener for emerging adults, and could be used to identify emerging adults who may benefit from SBIRT interventions.

Methanol is an attractive substrate for biological production of chemicals and fuels. Engineering methylotrophic Escherichia coli as a platform organism for converting methanol to metabolites is desirable. Prior efforts to engineer methylotrophic E. coli were limited by methanol dehydrogenases (Mdhs) with unfavorable enzyme kinetics. We engineered E. coli to utilize methanol using a superior NAD-dependent Mdh from Bacillus stearothermophilus and ribulose monophosphate (RuMP) pathway enzymes from B. methanolicus. Using 13C-labeling, we demonstrate this E. coli strain converts methanol into biomass components. For example, the key TCA cycle intermediates, succinate and malate, exhibit labeling up to 39%, while the lower glycolytic intermediate, 3-phosphoglycerate, up to 53%. Multiple carbons are labeled for each compound, demonstrating a cycling RuMP pathway for methanol assimilation to support growth. By incorporating the pathway to synthesize the flavanone naringenin, we demonstrate the first example of in vivo conversion of methanol into a specialty chemical in E. coli.

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methanol auxotrophs have proved successful, these studies focused on scarce and expensive co-substrates. Here, we engineered E. coli for methanol-dependent growth on glucose, an abundant and inexpensive co-substrate, via deletion of glucose 6-phosphate isomerase (pgi), phosphogluconate dehydratase (edd), and ribose 5-phosphate isomerases (rpiAB). Since the parental strain did not exhibit methanol-dependent growth on glucose in minimal medium, we first achieved methanol-dependent growth via amino acid supplementation and used this medium to evolve the strain for methanol-dependent growth in glucose minimal medium. The evolved strain exhibited a maximum growth rate of 0.15 h-1 in glucose minimal medium with methanol, which is comparable to that of other synthetic methanol auxotrophs. Whole genome sequencing and 13C-metabolic flux analysis revealed the causative mutations in the evolved strain. A mutation in the phosphotransferase system enzyme I gene (ptsI) resulted in a reduced glucose uptake rate to maintain a one-to-one molar ratio of substrate utilization. Deletion of the e14 prophage DNA region resulted in two non-synonymous mutations in the isocitrate dehydrogenase (icd) gene, which reduced TCA cycle carbon flux to maintain the internal redox state. In high cell density glucose fed-batch fermentation, methanol-dependent acetone production resulted in 22% average carbon labeling of acetone from 13C-methanol, which far surpasses that of the previous best (2.4%) found with methylotrophic E. coli Δpgi. This study addresses the need to identify appropriate co-substrates for engineering synthetic methanol auxotrophs and provides a basis for the next steps toward industrial one-carbon bioprocessing.

Our objective was to undertake a systematic review ascertaining the accuracy of using administrative healthcare data to identify epilepsy cases. We searched MEDLINE and Embase from 01/01/1975 to 03/07/2018 for studies evaluating the diagnostic accuracy of routinely collected healthcare data in identifying epilepsy cases. Any disease coding system in use since the International Classification of Diseases, Ninth Revision (ICD-9) was permissible. Two authors independently screened studies, extracted data, and quality-assessed studies. We assessed positive predictive value (PPV), sensitivity, negative predictive value (NPV), and specificity. The primary analysis was a narrative synthesis of review findings. Thirty studies were included, published between 1989 and 2018. Risks of bias were low, high, and unclear in 4, 14, and 12 studies, respectively. Coding systems included ICD-9, ICD-10, and Read Codes, with or without antiepileptic drugs (AEDs). PPVs included ranges of 5.2%-100% (Canada), 32.7%-96.0% (USA), 47.0%-100% (UK), and 37.0%-88.0% (Norway). Sensitivities included ranges of 22.2%-99.7% (Canada), 12.2%-97.3% (USA), and 79.0%-94.0% (UK). Nineteen studies contained at least one algorithm with a PPV >80%. Sixteen studies contained at least one algorithm with a sensitivity >80%. PPV was highest in algorithms consisting of disease codes (ICD-10 G40-41, ICD-9 345) in combination with one or more AEDs. The addition of symptom codes to this (ICD-10 R56; ICD-9 780.3, 780.39) lowered PPV. Sensitivity was highest in algorithms consisting of symptom codes with one or more AEDs. Although using AEDs alone achieved high sensitivities, the associated PPVs were low. Most NPVs and specificities were >90%. We conclude that it is reasonable to use administrative data to identify people with epilepsy (PWE) in epidemiological research. Studies prioritizing high PPVs should focus on combining disease codes with AEDs. Studies prioritizing high sensitivities should focus on combining symptom codes with AEDs. We caution against the use of AEDs alone to identify PWE.

Background: This systematic review of epilepsy mortality systematic reviews evaluates comparative risks, causes, and risk factors for all-cause mortality in people with epilepsy (PWE) to specifically establish the burden of epilepsy related deaths. Methods: MEDLINE and Embase were searched from conception to 26/12/2018 for systematic reviews evaluating all-cause mortality in PWE of any age. Independent study selection, data extraction and quality assessment were performed. Deaths were separated into epilepsy-related and unrelated using a recently published classification system. Outcomes included standardized mortality ratio (SMR) and mortality rate (MR) in a primary analysis of comparative risks, causes, and risk factors for all-cause and epilepsy-related mortality. A narrative synthesis of review findings was used to present results, including from a secondary analysis individual epilepsy-related death risk factors. Results: Six moderate/high-quality systematic reviews were included in the primary analysis, evaluating 103 observational studies. All-cause mortality remained similarly high between 1950–present (median SMR range 2.2– 3.4). Africa had the highest SMR (median 5.4, range 2.6–7.2). SMRs were also higher for children < 18 years (median 7.5, range 3.1–22.4) than adults (median 2.6, range 1.3–8.7), and for epilepsy-related (median 3.8, range 0.0–82.4,) than unrelated causes (median 1.7, range 0.7–17.6). Structural brain disease conferred the greatest risk for all-cause mortality (SMR range 24.0–41.5). Common epilepsy-related causes included alcohol, drowning, pneumonia, and suicide. In secondary analysis of nine additional systematic reviews, epilepsy-related death risk factors were reported for sudden unexpected death in epilepsy, drowning and suicide. Conclusions: Premature all-cause mortality remains a major problem in PWE globally, particularly in children and young adults, with most being epilepsy-related and potentially preventable. SUDEP is only one of several other common and important epilepsy-related causes of death.

Background Technology-assisted intervention and prevention strategies present opportunities for substance use–related research with emerging adults (EAs) and their peers. Emerging adulthood is a developmentally distinct period in which individuals between the ages of 18 and 29 years undergo unique emotional, cultural, developmental, and biological changes as they transition into adulthood. Crowdsourcing, or gathering feedback from a large group within web-based communities, offers researchers a unique and cost-effective way to obtain large amounts of information in a short period. Objective This paper presents market feedback obtained via Amazon’s Mechanical Turk from EAs (N=458) on the acceptability and utility of brief intervention scripts for a smartphone app currently under development. The mobile app, Harbor, teaches friends of EAs with substance use problems effective and supportive strategies for helping their friend make changes in their substance use behavior. Methods We examined feedback on the wording of the intervention scripts and estimated the market size of EAs who may use this app. Furthermore, we calculated correlations between script ratings and measures of personal risky drinking (ie, Alcohol Use Disorder Identification Test) and the participants’ use of confrontational, enabling, or supportive behaviors with an existing friend. Results Approximately half of our sample (208/458, 45.4%) indicated that they had a close friend for whom they had concerns about their substance use, suggesting a potentially high demand for an app such as Harbor. Initial findings suggest that peers who engage in less enabling behaviors with friends who have a substance use problem exhibited lower risky drinking behaviors overall (r206=−0.501; P Conclusions There exists a demonstrated level of desirability and acceptability among EAs for a mobile app such as Harbor. EAs who wish to engage in more supportive behaviors with their friends who engage in substance use and who are amenable to assisting their friends with sobriety likely would use and benefit from this app.

Purpose The purpose of the present study was to investigate the relationship between subcortical nuclei volume and cognition in children with post-convulsive status epilepticus (CSE). Methods Structural T1-weighted magnetic resonance imaging (MRI) scans (Siemens Avanto, 1.5 T) and neuropsychological assessments (full-scale intelligence quotient (FSIQ) and Global Memory Scores (GMS)) were collected from subjects at a mean 8.5 years post-CSE (prolonged febrile seizures (PFS), n = 30; symptomatic/known, n = 28; and other, n = 12) and from age- and sex-matched healthy controls (HC). Subjects with CSE were stratified into those with lower cognitive ability (LCA) (CSE +, n = 22) and those without (CSE −, n = 48). Quantitative volumetric analysis using Functional MRI of the Brain Software Library (FSL) (Analysis Group, FMRIB, Oxford) provided segmented MRI brain volumes. Univariate analysis of covariance (ANCOVA) was performed to compare subcortical nuclei volumes across subgroups. Multivariable linear regression was performed for each subcortical structure and for total subcortical volume (SCV) to identify significant predictors of LCA (FSIQ

Patient: Female, 67 Final Diagnosis: IVC filter perforation through duodenum Symptoms: Abdominal pain Medication: — Clinical Procedure: Esophagogastroduodenoscopy Specialty: Gastroenterology and Hepatology Objective: Challenging differential diagnosis Background: The number of IVC filter-related complications has increased with their growing utilization; however, IVC filter perforation of the duodenum is rare. It can manifest with nonspecific abdominal pain, gastrointestinal bleeding, cava-duodenal fistula, or small bowel obstruction. Case Report: A 67-year-old female presented with several years of right upper quadrant abdominal pain which was exacerbated by movement and food intake. She had a history of hepatic steatosis, cholecystectomy, and multiple DVTs with inferior vena cava filter placement. Physical exam was unremarkable. Laboratory tests demonstrated elevated alkaline phosphatase and transaminases. Esophagogastroduodenoscopy revealed a thin metallic foreign body embedded in the duodenal wall and protruding into the duodenal lumen with surrounding erythema and edema, but no active hemorrhage. Further evaluation with non-contrast CT scan revealed that one of the prongs of her IVC filter had perforated through the vena cava wall into the adjacent duodenum. Exploratory laparotomy was required for removal of the IVC filter and repair of the vena cava and duodenum. Her post-operative course was uneventful. Conclusions: In patients with history of IVC filter placement with non-specific abdominal pain, a high clinical suspicion of IVC filter perforation of the duodenum should be raised, as diagnosis may be challenging. CT scan and EGD are valuable in the diagnosis. Excellent outcomes have been reported with open surgical filter removal. Low retrieval rates of IVC filters have led to increased complications; hence, early removal should be undertaken as clinically indicated.

ObjectivesAssess the impact of selective prohibition and seizure of novel psychoactive substances (NPS) supply on NPS use prevalence within psychiatric admissions and evaluate demographic characteristics of current NPS users.DesignA 6-month retrospective cross-sectional analysis of discharge letters between 1 October 2015 and 31 March 2016.SettingGeneral psychiatry inpatients and intensive home treatment team (IHTT) community patients at a psychiatric hospital in a Scottish city.ParticipantsAll participants were between the ages of 18 and 65 years. After application of exclusion criteria, 473 discharge letters of general psychiatry patients were deemed suitable for analysis and 264 IHTT patient discharge letters were analysed.InterventionsA nationwide temporary class drug order (TCDO) was placed on 10 April 2015 reclassifying methylphenidate-related compounds as class B substances. On 15 October 2015, local forfeiture orders were granted to trading standards permitting the seizure of NPS supplies.Primary and secondary outcome measuresThe primary outcome measure was to determine the prevalence of NPS use in two cohorts. Second, demographic features of patients and details regarding their psychiatric presentation were analysed.ResultsThe prevalence of NPS use in general psychiatry and IHTT patients was 6.6% and 3.4%, respectively. Inpatients using NPS compared with non-users were more likely to be men (OR 2.92, 95% CI 1.28 to 6.66, P=0.009), have a forensic history (OR 5.03, CI 2.39 to 10.59, PConclusionsCompared with previous work, psychiatric inpatient NPS use has fallen. NPS continue to be used by a demographic previously described resulting in presentations consistent with a drug-induced psychosis and at times requiring detention under the Mental Health Act. Further research is required to evaluate the effectiveness of the recent prohibition of all NPS.

IgG deficiency can predispose to recurrent pyogenic infections. The association of IgG deficiency withClostridium difficileinfection has been infrequently reported in the literature. We present a case of a middle-age woman with multiple hospitalizations for recurrentC. difficilein a short span of time which prompted consideration of a possible fecal transplant. On evaluation, she was found to have low total IgG, with subclass analysis revealing low IgG1 and IgG3. She was started on monthly infusions of immunoglobulins and one year after her last episode ofC. difficileshe has not had any recurrence. The role of immunoglobulin infusion in the treatment of recurrentC. difficileis controversial, with some studies revealing no clear evidence of benefit. Our case report suggests that the patients who have underlying IgG deficiency may benefit from immunoglobulin, as this can significantly reduce the incidence of recurrent infections and hence save the healthcare costs.

Introduction In an increasingly digital age for healthcare around the world, administrative data have become rich and accessible tools for potentially identifying and monitoring population trends in diseases including epilepsy. However, it remains unclear (1) how accurate administrative data are at identifying epilepsy within a population and (2) the optimal algorithms needed for administrative data to correctly identify people with epilepsy within a population. To address this knowledge gap, we will conduct a novel systematic review of all identified studies validating administrative healthcare data in epilepsy identification. We provide here a protocol that will outline the methods and analyses planned for the systematic review. Methods and analysis The systematic review described in this protocol will be conducted to follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and Embase will be searched for studies validating administrative data in epilepsy published from 1975 to current (01 June 2018). Included studies will validate the International Classification of Disease (ICD), Ninth Revision (ICD-9) onwards (ie, ICD-9 code 345 and ICD-10 codes G40–G41) as well as other non-ICD disease classification systems used, such as Read Codes in the UK. The primary outcome will be providing pooled estimates of accuracy for identifying epilepsy within the administrative databases validated using sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curves. Heterogeneity will be assessed using the I2 statistic and descriptive analyses used where this is present. The secondary outcome will be the optimal administrative data algorithms for correctly identifying epilepsy. These will be identified using multivariable logistic regression models. 95% confidence intervals will be quoted throughout. We will make an assessment of risk of bias, quality of evidence, and completeness of reporting for included studies. Ethics and dissemination Ethical approval is not required as primary data will not be collected. Results will be disseminated in peer-reviewed journals, conference presentations and in press releases. PROSPERO registration CRD42017081212.

The importance of employment in society is unmistakable, but for many people sustained employment remains elusive. The unemployment rate for individuals with disabilities is staggering, and the consequences of being unemployed affects those individuals, their families, and society. The effects of performance feedback delivered via covert audio coaching on the job performance of supported employees were examined in this investigation. A multiple baseline design across employees and work tasks was used to evaluate the effects of the intervention on work performance. Supported employees made substantial improvements on their work performance, and the improvements maintained for 4 to 5 weeks following the removal of the intervention. The results have implications for the use of covert audio coaching in employment and other settings.

Side effects can limit opioid dosage and reduce quality of life. The purpose of this systematic review was to assess the management of opioid side effects in the context of cancer pain management or, in the event that no evidence was available for cancer pain, for chronic noncancer pain. The side effects studied were constipation, pruritus, nausea and vomiting, myoclonus, sedation, respiratory depression, and delirium. Opioid rotation to manage side effects was also studied. For each side effect, we searched MEDLINE and the Cochrane Controlled Trials Register and identified 657 possible titles for inclusion. Of these, 67 studies met inclusion criteria for analysis. The lack of well-designed, randomized controlled trials and the heterogeneity of populations and study designs made the drawing of firm conclusions difficult and precluded performance of meta-analysis. The type, strength, and consistency of evidence for available interventions to manage opioid side effects vary from strong (eg, on the use of naloxone to reverse respiratory depression or constipation) to weak (eg, changing from the oral to epidural route of morphine administration to manage sedation). Well-designed trials in the specified populations are required to furnish clinicians with secure evidence on managing opioid side effects successfully.

A 63 year old female presented to the emergency department with a several month history of intermittent right upper quadrant abdominal pain, early satiety with loss of appetite, and an unintentional weight loss of 8. She underwent a battery of tests that returned negative and subsequently sent for Computed tomographic angiography (CTA) of the abdomen revealing luminal stenosis of the proximal 1 cm of the celiac axis estimating 90% occlusion and a patent SMA and IMA with, typical for median arcuate ligament syndrome. The symptoms, diagnosis, and treatment options are discussed. Keywords: Median arcuate ligament syndrome (MALS); postprandial pain; unintentional weight loss (Published: 25 November 2014) Citation: Journal of Community Hospital Internal Medicine Perspectives 2014, 4 : 25083 - http://dx.doi.org/10.3402/jchimp.v4.25083

Objective To compare the efficacy and adverse effects of using bronchial blockers (BBs) and double-lumen endobronchial tubes (DLTs). Design Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing BBs and DLTs. Setting Hospital units undertaking thoracic surgery Participants Patients undergoing thoracic surgery requiring lung isolation. Interventions BBs and DLTs. Measurements and Main Results A systematic literature search was conducted for RCTs comparing BBs and DLTs using Google Scholar, Ovid Medline, and Cochrane library databases up to October 2013. Inclusion criteria were RCTs comparing BBs and DLTs, intubation carried out by qualified anesthesiologists or trainee specialists, outcome measures relating to either efficacy or adverse effects. Studies that were inaccessible in English were excluded. Mantel-Haenszel fixed-effect meta-analysis of recurring outcome measures was performed using RevMan 5 software. The search produced 39 RCTs published between 1996 and 2013. DLTs were quicker to place (mean difference: 51 seconds, 95% confidence intervals [CI] 8-94 seconds; p = 0.02) and less likely to be incorrectly positioned (odds ratio [OR] 2.70; 95% CI 1.18-6.18, p = 0.02) than BBs. BBs were associated with fewer patients having a postoperative sore throat (OR 0.39, 95% CI: 0.23-0.68, p = 0.0009), less hoarseness (OR: 0.43,95%, CI 0.24-0.75, p = 0.003), and fewer airway injuries (OR 0.40, 95% CI 0.21-0.75, p = 0.005) than DLTs. Conclusion While BBs are associated with a lower incidence of airway injury and a lower severity of injury, DLTs can be placed quicker and more reliably.

A 73 year old man presented to his primary care physician with sudden onset dysphagia to solids and liquids. He urgently completed a barium swallow study showing what was believed to be a coin. Endoscopic removal subsequently revealed it was a lithium battery. Consequences and management of lithium battery ingestion are discussed. Keywords: dysphagia; lithium; battery (Published: 29 September 2014) Citation: Journal of Community Hospital Internal Medicine Perspectives 2014, 4 : 25156 - http://dx.doi.org/10.3402/jchimp.v4.25156

Emphysematous gastritis (EG) is a rare cause of abdominal pain, which should be differentiated from gastric emphysema. It is hypothesized to result from air-producing microorganisms in patients with underlying predisposing factors. Because of the non-specific presentation of EG, it is diagnosed radiographically. CT scan is the diagnostic modality of choice that typically reveals irregular, mottled appearance of the air in the thickened gastric wall and in the portal vein in the liver. We report a rare case of EG in a male with a history of diabetes mellitus who presented to the emergency department with diarrhea, nausea, vomiting, and epigastric pain. On examination, he was hypotensive and had mild tenderness in the epigastrium. Laboratory tests revealed leukocytosis, elevated lactate, anion gap metabolic acidosis, and acute kidney injury. A non-contrast CT abdomen revealed findings consistent with EG. Even though mortality rate in access of 60% have been reported without prompt surgical intervention in EG, recent literature suggests favorable prognosis with conservative measures in patients without an overt surgical indication. Our patient was also managed conservatively with IV antibiotics and gradual advancement of diet and had complete resolution of symptoms over the ensuing few days. The factors that correlate with a poor prognosis include elevated serum lactate, serum creatinine, and concomitant pneumatosis in small bowel and colon.Keywords: emphysematous gastritis; epigastric pain; lactate; metabolic acidosis; CT scan; mortality(Published: 1 September 2015)Citation: Journal of Community Hospital Internal Medicine Perspectives 2015, 5: 28010 - http://dx.doi.org/10.3402/jchimp.v5.28010

While generally safe, the most feared complication of colonoscopy is perforation of the colon, occurring in nearly 1 in 1,000 procedures, and is more common when polypectomy is performed and electrocautery is used. Less commonly known is the post-polypectomy electrocoagulation syndrome, a transmural burn of the colon which mimics the signs and symptoms of perforation as well as the time course, but follows a benign course and can be treated conservatively.Keywords: tubulovillous polyp; snare polypectomy; transmural burn; post-polypectomy electrocoagulation syndrome(Published: 19 October 2015)Citation: Journal of Community Hospital Internal Medicine Perspectives 2015, 5: 29147 - http://dx.doi.org/10.3402/jchimp.v5.29147