Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

A microprocessor-based spectrum analyser for instructional purposes

This thesis describes the design, construction andtesting of a spectrum analyser unit that is intended for use in ateaching environment. The proposed use of this analyser imposes theconstraints of low cost and simplicity of operation, combined withan adequate, rather than research quality, level of performance.These design criteria have been met by limiting theoperating frequency to 0-1 MHz, and by providing a spurious-freedynamic range of 35 dB. In addition, the cost of the analyser hasbeen reduced by designing it such that an existing oscilloscope isused to display the spectrum. A microprocessor controls both theoverall operation of the analyser and the acquisition and display ofthe spectrum. As a result, a simplified set-up procedure allows aninexperienced operator to achieve the desired display using only oneor two key strokes on a single, front panel keypad.The performance of the instrument has been tested byapplying to it a range of signals of the type commonly encounteredin the teaching of electronics and telecommunications. Theresulting spectra clearly illustrate all relevant features of thisfrequency domain representation of electrical signals and allowquantitative measurements to be made that agree closely withtheoretical values. The potential of the instrument for furtherdevelopment has been investigated and provisions for incorporating arange of future options have been designed into the existinganalyser.The construction of a prototype analyser has verified thefeasibility of producing an instrument to suit the requirements ofthe educational market. It is anticipated that, upon using thisinstrument in undergraduate teaching laboratories, tertiaryinstitutions will be able to give to the teaching of electronics andcommunications a deservedly equal emphasis to both the time andfrequency domains

A Jaw Dropping Case (.pdf)

A 78-year-old woman presented with two months of intermittent diplopia associated with headaches and jaw pain that worsened with chewing

Effect of Primary Prophylactic Antiseizure Medication for Seizure Prevention Following Intracerebral Hemorrhage in the ERICH Study

Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of any stroke subtype and clinicians often administer prophylactic antiseizure medications (ASMs) as a means of preventing post-stroke seizures, particularly following lobar ICH. However, evidence for ASM efficacy in preventing seizures and reducing disability is lacking given limited randomized trials. Herein, we report analysis from a large prospective observational study that evaluates the effect of primary prophylactic ASM administration on seizure occurrence and disability following ICH. Primary analysis was performed on 1630 patients with ICH enrolled in the ERICH study. A propensity score for administration of prophylactic ASM was developed and patients were matched by the closest propensity score (difference < 0.1). McNemar's test was used to compare occurrence of in-hospital seizure and disability, defined by modified Rankin Score (mRS) ≥ 3 at 3 months post ICH. Of the 815 matched pairs of patients treated with primary prophylactic ASM, there was no significant difference in seizure occurrence (p = 0.4631) or disability (p = 0.4653). Subset analysis of 280 matched pairs of patients with primary lobar ICH similarly revealed no significant difference in seizure occurrence (p = 0.1011) or disability (p = 1.00) between prophylactically treated and untreated patients. Although current guidelines do not recommend primary prophylactic ASM following ICH, clinical use remains widespread. Data from the ERICH study did not find an association between administering primary prophylactic ASM and preventing seizures or reducing disability following ICH, thus providing evidence to influence clinical practice and patient care

Deep resequencing of the 1q22 locus in non-lobar intracerebral hemorrhage

ObjectiveGenome-wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases (CSVDs), including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study we performed targeted high-depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown. Methods95,000 base pairs spanning 1q22 , including SEMA4A, SLC25A44 and PMF1 / PMF1-BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and RIFT analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, ChIP-Seq and ChIA-PET databases. Multivariable Mendelian randomization (MVMR) assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at 1q22 could be causally related to ICH risk. ResultsCommon and rare variant analyses prioritized variants in SEMA4A 5'-UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that 1q22 is spatially organized in a single chromatin loop and that the genes therein belong to the same Topologically Associating Domain. ChIP-Seq and ChIA-PET data analysis highlighted the presence of long-range interactions between the SEMA4A -promoter and PMF1 -enhancer regions prioritized by association testing. MVMR analyses demonstrated that PMF1 overexpression could be causally related to non-lobar ICH risk. InterpretationAltered promoter-enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at 1q22 , offering a potential new target for prevention of ICH and CSVD

Deep resequencing of the 1q22 locus in non-lobar intracerebral hemorrhage

OBJECTIVEGenome-wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases (CSVDs), including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study we performed targeted high-depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown. METHODS95,000 base pairs spanning 1q22, including SEMA4A, SLC25A44 and PMF1/PMF1-BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and RIFT analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, ChIP-Seq and ChIA-PET databases. Multivariable Mendelian randomization (MVMR) assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at 1q22 could be causally related to ICH risk. RESULTSCommon and rare variant analyses prioritized variants in SEMA4A 5'-UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that 1q22 is spatially organized in a single chromatin loop and that the genes therein belong to the same Topologically Associating Domain. ChIP-Seq and ChIA-PET data analysis highlighted the presence of long-range interactions between the SEMA4A-promoter and PMF1-enhancer regions prioritized by association testing. MVMR analyses demonstrated that PMF1 overexpression could be causally related to non-lobar ICH risk. INTERPRETATIONAltered promoter-enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at 1q22, offering a potential new target for prevention of ICH and CSVD. This article is protected by copyright. All rights reserved

Association Between Body Mass Index and Functional Outcomes in Patients With Intracerebral Hemorrhage

Evidence of the so-called "obesity paradox," which refers to the protective effect and survival benefit of obesity in patients with spontaneous intracerebral hemorrhage (ICH), remains controversial. This study aims to determine the association between body mass index (BMI) and functional outcomes in patients with ICH and whether it is modified by race/ethnicity. Included individuals were derived from the Ethnic/Racial Variations of Intracerebral Hemorrhage study, which prospectively recruited 1,000 non-Hispanic White, 1,000 non-Hispanic Black, and 1,000 Hispanic patients with spontaneous ICH. Only patients with available BMI were included. The primary outcome was 90-day mortality. Secondary outcomes were mortality at discharge, modified Rankin Scale (mRS), Barthel Index, and self-reported health status measures at 90 days. Associations between BMI and ICH outcomes were assessed using univariable and multivariable logistic, ordinal, and linear regression models, as appropriate. Sensitivity analyses after excluding frail patients and by patient race/ethnicity were performed. A total of 2,841 patients with ICH were included. The median age was 60 years (interquartile range 51-73). Most patients were overweight (n = 943; 33.2%) or obese (n = 1,032; 36.3%). After adjusting for covariates, 90-day mortality was significantly lower among overweight and obese patients than their normal weight counterparts (adjusted odds ratio [aOR] = 0.71 [0.52-0.98] and aOR = 0.70 [0.50-0.97], respectively). Compared with patients with BMI <25 kg/m , those with BMI ≥25 kg/m had better 90-day mRS (aOR = 0.80 [CI 0.67-0.95]), EuroQoL Group 5-Dimension (EQ-5D) (aβ = 0.05 [0.01-0.08]), and EQ-5D VAS (aβ = 3.80 [0.80-6.98]) scores. These differences persisted after excluding withdrawal of care patients. There was an inverse relationship between BMI and 90-day mortality (aOR = 0.97 [0.96-0.99]). Although non-Hispanic White patients had significantly higher 90-day mortality than non-Hispanic Black and Hispanic (26.6% vs 19.5% vs 18.0%, respectively; < 0.001), no significant interactions were found between BMI and race/ethnicity. No significant interactions between BMI and age or sex for 90-day mortality were found, whereas for 90-day mRS, there was a significant interaction with age ( = 0.004). We demonstrated that a higher BMI is associated with decreased mortality, improved functional outcomes, and better self-reported health status at 90 days, thus supporting the paradoxical role of obesity in patients with ICH. The beneficial effect of high BMI does not seem to be modified by race/ethnicity or sex, whereas age may play a significant role in patient functional outcomes

Risk Factors Associated With Mortality and Neurologic Disability After Intracerebral Hemorrhage in a Racially and Ethnically Diverse Cohort

Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and most survivors experience significant disability. To assess primary patient risk factors associated with mortality and neurologic disability 3 months after ICH in a large, racially and ethnically balanced cohort. This cohort study included participants from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, which prospectively recruited 1000 non-Hispanic White, 1000 non-Hispanic Black, and 1000 Hispanic patients with spontaneous ICH to study the epidemiological characteristics and genomics associated with ICH. Participants included those with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Analyses were completed in November 2021. Patient demographic and clinical characteristics as well as hospital event and imaging variables were examined, with characteristics meeting P < .20 considered candidates for a multivariate model. Elements included in the ICH score were specifically analyzed. Individual characteristics were screened for association with 3-month outcome of neurologic disability or mortality, as assessed by a modified Rankin Scale (mRS) score of 4 or greater vs 3 or less under a logistic regression model. A total of 25 characteristics were tested in the final model, which minimized the Akaike information criterion. Analyses were repeated removing individuals who had withdrawal of care. A total of 2568 patients (mean [SD] age, 62.4 [14.7] years; 1069 [41.6%] women and 1499 [58.4%] men) had a 3-month outcome determination available, including death. The final logistic model had a significantly higher area under the receiver operating characteristics curve (C = 0.88) compared with ICH score alone (C = 0.76; P < .001). Among characteristics associated with neurologic disability and mortality were larger log ICH volume (OR, 2.74; 95% CI, 2.36-3.19; P < .001), older age (OR per 1-year increase, 1.04; 95% CI, 1.02-1.05; P < .001), pre-ICH mRS score (OR, 1.62; 95% CI, 1.41-1.87; P < .001), lobar location (OR, 0.22; 95% CI, 0.16-0.30; P < .001), and presence of infection (OR, 1.85; 95% CI, 1.42-2.41; P < .001). The findings of this cohort study validate ICH score elements and suggest additional baseline and interim patient characteristics were associated with variation in 3-month outcome