Household carbon monoxide (CO) concentrations in a large African city: An unquantified public health burden?

Carbon monoxide (CO) is a poisonous gas produced by incomplete combustion of carbon-based fuels that is linked to mortality and morbidity. Household air pollution from burning fuels on poorly ventilated stoves can lead to high concentrations of CO in homes. There are few datasets available on household concentrations of CO in urban areas of sub-Saharan African countries. CO was measured every minute over 24 h in a sample of homes in Nairobi, Kenya. Data on household characteristics were gathered by questionnaire. Metrics of exposure were summarised and analysis of temporal changes in concentration was performed. Continuous 24-h data were available from 138 homes. The mean (SD), median (IQR) and maximum 24-h CO concentration was 4.9 (6.4), 2.8 (1.0-6.3) and 44 ppm, respectively. 50% of homes had detectable CO concentrations for 847 min (14h07m) or longer during the 24-h period, and 9% of homes would have activated a CO-alarm operating to European specifications. An association between a metric of total CO exposure and self-reported exposure to vapours >15 h per week was identified, however this were not statistically significant after adjustment for the multiple comparisons performed. Mean concentrations were broadly similar in homes from a more affluent area and an informal settlement. A model of typical exposure suggests that cooking is likely to be responsible for approximately 60% of the CO exposure of Nairobi schoolchildren. Household CO concentrations are substantial in Nairobi, Kenya, despite most homes using gas or liquid fuels. Concentrations tend to be highest during the evening, probably associated with periods of cooking. Household air pollution from cooking is the main source of CO exposure of Nairobi schoolchildren. The public health impacts of long-term CO exposure in cities in sub-Saharan Africa may be considerable and should be studied further.

Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PICOG) that maximized discrimination of the predictive model. Patients with higher PICOG have higher predicted relapse risk. The PICOG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PICOG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PICOG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PICOG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PICOG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.

Investigating causal relationships between genetically determined increased risk of attention-deficit/hyperactivity disorder (ADHD) and atopic dermatitis (AD): A Mendelian randomization analysis.

Atopic dermatitis (AD) is a chronic, inflammatory skin condition with a huge disease burden. Attention-deficit/hyperactivity disorder (ADHD) is often diagnosed in children, and is associated with symptoms of inattention, hyperactivity and impulsive behaviour. Observational studies have demonstrated associations between AD and ADHD. However, to date, there has been no formal assessment of causal relationship between the two. We aim to evaluate causal relationships between genetically increased risk of AD and ADHD using Mendelian randomization (MR) approach. Two-sample bi-directional MR was conducted to elucidate potential causal relationships between genetically increased risk of AD and ADHD, using the largest and most recent genome-wide association study datasets for AD and ADHD-EArly Genetics & Lifecourse Epidemiology AD consortium (21 399 cases and 95 464 controls) and Psychiatric Genomics Consortium (20 183 cases and 35 191 controls). Genetically determined increased risk of AD is not associated with ADHD based on genetic information: odds ratio (OR) of 1.02 (95% CI -0.93 to 1.11; p = 0.705). Similarly, genetic determined increased risk of ADHD is not associated with an increased risk of AD: OR of 0.90 (95% CI -0.76 to 1.07; p = 0.236). Horizontal pleiotropy was not observed from the MR-Egger intercept test (p = 0.328) Current MR analysis showed no causal relationship between genetically increased risk of AD and ADHD in either direction in individuals of European descent. Any observed associations between AD and ADHD in previous population studies could possibly be due to confounding lifestyle factors such as psychosocial stress and sleeping habits.

Measurement of SARS-CoV-2 in air and on surfaces in Scottish hospitals.

BACKGROUND: There are still uncertainties in our knowledge of the amount of SARS-CoV-2 virus present in the environment - where it can be found, and potential exposure determinants - limiting our ability to effectively model and compare interventions for risk management. AIM: This study measured SARS-CoV-2 in three hospitals in Scotland on surfaces and in air, alongside ventilation and patient care activities. METHODS: Air sampling at 200 L/min for 20 min and surface sampling were performed in two wards designated to treat COVID-19-positive patients and two non-COVID-19 wards across three hospitals in November and December 2020. FINDINGS: Detectable samples of SARS-CoV-2 were found in COVID-19 treatment wards but not in non-COVID-19 wards. Most samples were below assay detection limits, but maximum concentrations reached 1.7×103 genomic copies/m3 in air and 1.9×104 copies per surface swab (3.2×102 copies/cm2 for surface loading). The estimated geometric mean air concentration (geometric standard deviation) across all hospitals was 0.41 (71) genomic copies/m3 and the corresponding values for surface contamination were 2.9 (29) copies/swab. SARS-CoV-2 RNA was found in non-patient areas (patient/visitor waiting rooms and personal protective equipment changing areas) associated with COVID-19 treatment wards. CONCLUSION: Non-patient areas of the hospital may pose risks for infection transmission and further attention should be paid to these areas. Standardization of sampling methods will improve understanding of levels of environmental contamination. The pandemic has demonstrated a need to review and act upon the challenges of older hospital buildings meeting current ventilation guidance.

Duodenal volvulus: a rare cause of small bowel obstruction.

Small bowel volvulus is a rare but life-threatening emergency. Volvulus of the duodenum is even rarer without the presence of predisposing factors. The clinical presentation is vague, including abdominal pain, nausea and vomiting, prompt diagnosis of volvulus therefore relies heavily on radiographs. The treatment options lie between conservative or surgical management, where the decision is influenced by the patient and their presentation. This case is of a 100-year-old female with an extensive surgical and medical background presenting with signs of small bowel obstruction. With the help of imaging, a rare case of duodenal volvulus was diagnosed but managed conservatively due to the patient's background, age and personal wishes.

Healthcare-acquired clusters of COVID-19 across multiple wards in a Scottish health board.

BACKGROUND: Healthcare-acquired COVID-19 has been an additional burden on hospitals managing increasing numbers of patients with SARS-CoV-2. One acute hospital (W) among three in a Scottish healthboard experienced an unexpected surge of COVID-19 clusters. AIM: To investigate possible causes of COVID-19 clusters at Hospital W. METHODS: Daily surveillance provided total numbers of patients and staff involved in clusters in three acute hospitals (H, M and W) and care homes across the healthboard. All clusters were investigated and documented, along with patient boarding, community infection rates and outdoor temperatures from October 2020 to March 2021. Selected SARS-CoV-2 strains were genotyped. FINDINGS: There were 19 COVID-19 clusters on 14 wards at Hospital W during the six-month study period, lasting from two to 42 days (average, five days; median, 14 days) and involving an average of nine patients (range 1-24) and seven staff (range 0-17). COVID-19 clusters in Hospitals H and M reflected community infection rates. An outbreak management team implemented a control package including daily surveillance; ward closures; universal masking; screening; restricting staff and patient movement; enhanced cleaning; and improved ventilation. Forty clusters occurred across all three hospitals before a January window-opening policy, after which there were three during the remainder of the study. CONCLUSION: The winter surge of COVID-19 clusters was multi-factorial, but clearly exacerbated by moving trauma patients around the hospital. An extended infection prevention and control package including enhanced natural ventilation helped reduce COVID-19 clusters in acute hospitals.

The effect of job demands on health and work outcomes: A longitudinal study among Malaysian employees.

The purpose of the current study was to investigate the impact of job demands on health and work outcomes among Malaysian workers. We hypothesized that job demands (i.e., emotional demands and physical demands) would predict future work-related burnout and work engagement, in turn affecting sleep problems and job performance (in-role, extra-role). A longitudinal two-wave survey was conducted among Malaysian workers and valid data from 345 participants were analyzed using structural equation modeling. The results revealed that work-related burnout predicts sleep problems while work engagement increased employees' job performance over time. Overall, the current study highlights the importance of specific job demands (i.e., emotional demands and physical demands) that specifically affect health-related behavior and work-related behavior among workers.

Ambient particulate matter and biomass burning: an ecological time series study of respiratory and cardiovascular hospital visits in northern Thailand.

BACKGROUND: Exposure to particulate matter (PM) emitted from biomass burning is an increasing concern, particularly in Southeast Asia. It is not yet clear how the source of PM influences the risk of an adverse health outcome. The objective of this study was to quantify and compare health risks of PM from biomass burning and non-biomass burning sources in northern Thailand. METHODS: We collected ambient air pollutant data (PM with a diameter of < 10 µm [PM10], PM2.5, Carbon Monoxide [CO], Ozone [O3], and Nitrogen Dioxide [NO2]) from ground-based monitors and daily outpatient hospital visits in Thailand during 2014-2017. Outpatient data included chronic lower respiratory disease (CLRD), ischaemic heart disease (IHD), and cerebrovascular disease (CBVD). We performed an ecological time series analysis to evaluate the association between daily air pollutants and outpatient visits. We used the 90th and 95th percentiles of PM10 concentrations to determine days of exposure to PM predominantly from biomass burning. RESULTS: There was significant intra annual variation in PM10 levels, with the highest concentrations occurring during March, coinciding with peak biomass burning. Incidence Rate Ratios (IRRs) between daily PM10 and outpatient visits were elevated most on the same day as exposure for CLRD = 1.020 (95% CI: 1.012 to 1.028) and CBVD = 1.020 (95% CI: 1.004 to 1.035), with no association with IHD = 0.994 (95% CI: 0.974 to 1.014). Adjusting for CO tended to increase effect estimates. We did not find evidence of an exposure response relationship with levels of PM10 on days of biomass burning. CONCLUSIONS: We found same-day exposures of PM10 to be associated with certain respiratory and cardiovascular outpatient visits. We advise implementing measures to reduce population exposures to PM wherever possible, and to improve understanding of health effects associated with burning specific types of biomass in areas where such large-scale activities occur.

Impact of type 2 diabetes on hospitalization and mortality in people with malignancy.

AIM: To compare the characteristics of and outcomes for people with malignancies with and without a co-diagnosis of diabetes. METHODS: Emergency department and hospital discharge data from a single centre for the period between 1 January 2015 and 31 December 2017 were used to identify people with a diagnosis of a malignancy and diabetes. Multivariate Cox regression models were used to estimate the effect of diabetes on all-cause mortality. A truncated negative binomial regression model was used to assess the impact of diabetes on length of hospital inpatient stay. Prentice-Williams-Peterson total time models were used to assess the effect of diabetes on number of emergency department re-presentations and inpatient re-admissions. RESULTS: Of 7004 people identified with malignancies, 1195 (17.1%) were also diagnosed with diabetes. A diagnosis of diabetes was associated with a greater number of inpatient re-admissions [adjusted hazard ratio 1.13 (95% CI 1.03, 1.24)], a greater number of emergency department re-presentations [adjusted hazard ratio 1.13 (95% CI 1.05, 1.22)] and longer length of stay [adjusted incidence rate ratio 1.14 (95% CI 1.04, 1.25)]. A co-diagnosis of diabetes was also associated with a 48% increased risk of all-cause mortality [adjusted hazard ratio 1.48 (95% CI 1.22-1.76)]. CONCLUSIONS: People with malignancies and diabetes had significantly more emergency department presentations, more inpatient admissions, longer length of hospital stay and higher rates of all-cause mortality compared to people with a malignancy without diabetes.

Rectal varices due to chronic inferior mesenteric vein thrombosis caused by external compression in a large hiatus hernia containing the pancreas.

A 79-year-old woman presented with a large fresh rectal bleed. Computed tomography revealed that she had a large type IV hiatus hernia, which contained the stomach and pancreas. Compression of the inferior mesenteric vein and splenic vein had led to thrombosis within these vessels and retrograde flow within the inferior mesenteric vein. This had led to the formation of portosystemic rectal varices. Ectopic varices occasionally form in the rectum, often in the context of liver cirrhosis. At the time of writing, ours is the first reported case of portosystemic rectal varices formulated in response to obstruction of vessels within a hiatus hernia.

Association of size-fractionated indoor particulate matter and black carbon with heart rate variability in healthy elderly women in Beijing.

Associations between size-fractionated indoor particulate matter (PM) and black carbon (BC) and heart rate variability (HRV) and heart rate (HR) in elderly women remain unclear. Twenty-nine healthy elderly women were measured for 24-hour HRV/HR indices. Real-time size-fractionated indoor PM and BC were monitored on the same day and on the preceding day. Mixed-effects models were applied to investigate the associations between pollutants and HRV/HR indices. Increases in size-fractionated indoor PM were significantly associated with declines in power in the high-frequency band (HF), power in the low-frequency band (LF), and standard deviation of all NN intervals (SDNN). The largest decline in HF was 19% at 5-minute moving average for an interquartile range (IQR) increase (24 µg/m3 ) in PM0.5 . The results showed that smaller particles could lead to greater reductions in HRV indices. The reported associations were modified by body mass index (BMI): Declines in HF at 5-minute average for an IQR increase in PM0.5 were 34.5% and 1.0% for overweight (BMI ≥25 kg/m2 ) and normal-weight (BMI <25 kg/m2 ) participants, respectively. Moreover, negative associations between BC and HRV indices were found to be significant in overweight participants. Increases in size-fractionated indoor PM and BC were associated with compromised cardiac autonomic function in healthy elderly women, especially overweight ones.

Bilateral central retinal vein occlusion in a pregnant lady.

We report a rare case of central retinal vein occlusion (CRVO) in pregnancy. There was dramatic deterioration of vision in both eyes through pregnancy despite repeated attempts of laser treatment and systemically controlled diabetes. Significant improvement was noted postpartum. Pregnancy is an aggravated factor of bilateral CRVO.

Genetics of ancestry-specific risk for relapse in acute lymphoblastic leukemia.

The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single-nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort. 224 SNPs were associated with rapid drug clearance or drug resistance, and 32 were replicated in the independent cohort. The adverse risk associated with black and Hispanic ancestries was attenuated by addition of the 4 SNPs most strongly associated with relapse in these populations (for blacks: model without SNPs hazard ratio (HR)=2.32, P=2.27 × 10-4, model with SNPs HR=1.07, P=0.79; for Hispanics: model without SNPs HR=1.7, P=8.23 × 10-5, model with SNPs HR=1.31, P=0.065). Relapse SNPs associated with asparaginase resistance or allergy were overrepresented among SNPs associated with relapse in the more asparaginase intensive treatment arm (20/54 in Capizzi-methorexate arm vs 8/54 in high-dose methotrexate arm, P=0.015). Inherited genetic variation contributes to race-specific and treatment-specific relapse risk.

Genome-Wide Study Links PNPLA3 Variant With Elevated Hepatic Transaminase After Acute Lymphoblastic Leukemia Therapy.

Remission induction therapy for acute lymphoblastic leukemia (ALL) includes medications that may cause hepatotoxicity, including asparaginase. We used a genome-wide association study to identify loci associated with elevated alanine transaminase (ALT) levels after induction therapy in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols. Germline DNA was genotyped using arrays and exome sequencing. Adjusting for age, body mass index, ancestry, asparaginase preparation, and dosage, the PNPLA3 rs738409 (C>G) I148M variant, previously associated with fatty liver disease risk, had the strongest genetic association with ALT (P = 2.5 × 10-8 ). The PNPLA3 rs738409 variant explained 3.8% of the variability in ALT, and partly explained race-related differences in ALT. The PNPLA3 rs738409 association was replicated in an independent cohort of 2,285 patients treated on Children's Oncology Group protocol AALL0232 (P = 0.024). This is an example of a pharmacogenetic variant overlapping with a disease risk variant.

Inhibition of the Gab2/PI3K/mTOR signaling ameliorates myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations.

Activating mutations, such as E76K and D61Y, in PTPN11 (SHP2), a protein tyrosine phosphatase implicated in multiple cell signaling processes, are associated with 35% of patients with juvenile myelomonocytic leukemia (JMML), an aggressive childhood myeloproliferative neoplasm (MPN). Here we show that the interaction between leukemia-associated mutant Shp2 and Gab2, a scaffolding protein important for cytokine-induced PI3K/Akt signaling, was enhanced, and that the mTOR pathway was elevated in Ptpn11E76K/+ leukemic cells. Importantly, MPN induced by the Ptpn11E76K/+ mutation was markedly attenuated in Ptpn11E76K/+/Gab2-/- double mutant mice-overproduction of myeloid cells was alleviated, splenomegaly was diminished and myeloid cell infiltration in nonhematopoietic organs was decreased in these double mutants. Excessive myeloid differentiation of stem cells was also normalized by depletion of Gab2. Acute leukemia progression of MPN was reduced in the double mutant mice and, as such, their survival was much prolonged. Furthermore, treatment of Ptpn11E76K/+ mice with Rapamycin, a specific and potent mTOR inhibitor, mitigated MPN phenotypes. Collectively, this study reveals an important role of the Gab2/PI3K/mTOR pathway in mediating the pathogenic signaling of the PTPN11 gain-of-function mutations and a therapeutic potential of Rapamycin for PTPN11 mutation-associated JMML.

Anterior segment imaging-based subdivision of subjects with primary angle-closure glaucoma.

PurposeThe purpose of this study was to identify whether it was possible to subdivide subjects with primary angle-closure glaucoma (PACG) based on anterior segment optical coherence tomography (ASOCT) imaging, and to determine the characteristics of such subgroups.MethodsWe evaluated 210 subjects with PACG. All subjects underwent gonioscopy and ASOCT imaging. Customized software was used to measure ASOCT parameters. An agglomerative hierarchical clustering method was first used to determine the optimum number of parameters to be included in the determination of subgroups. Then, the best number of subgroups was determined using Akaike Information Criterion (AIC) and Gaussian Mixture Model (GMM) methods.ResultsThe mean age of the subjects was 67.9 years, and 53.3% were female. Following the hierarchical clustering, four parameters (iris area, anterior chamber depth (ACD), anterior chamber width (ACW), and lens vault (LV)) were chosen to be representative of related parameters. The optimal number of subgroups using GMM analysis and AIC was 3. Subgroup 1 (N=89; 42.4%) was characterized by a large iris area, subgroup 2 (N=24; 11.4%) by a large LV and a shallow ACD, whereas subgroup 3 (N=97; 46.2%) displayed only intermediate values across iris area, LV, and ACD.ConclusionsWe identified three distinct subgroups of PACG subjects based on ASOCT imaging.