The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Characteristics of BCR-ABL rearrangement variants in Pakistani patients with chronic myeloid leukemia and acute lymphocytic leukemia

Background: A reciprocal translocation between the long arms of chromosome 9 and 22 [t (9;22) (q 34; q 1.1)] results in the formation of a fusion hybrid gene also called Philadelphia chromosome encodes proteins with a constitutively activated tyrosine kinase activity [1,2]. These proteins being leukemogenic result in Chronic Myeloid leukemia (CML) and Acute lymphoid leukemia (ALL). Breakage in the long arms of chromosome 9 (ABL1 gene) can occur anywhere within a \u3e 300-kb segment at the 5’end of the gene [1]. Site of breakage in chromosome 22 (BCR gene) can occur in different regions within a 5.8kb region known as the major breakpoint cluster region (M-bcr), spanning 5 exons previously known as b1 to b5 but now as exon 12 to 16 [1]. In CML, the breakpoint in the BCR gene mostly (95%) falls within the major break point cluster region with b2a2 at 40 % and b3a2 at 55% [1].Methods: The number of reported patients was 686 over a period of 2 years and 10 months (from October 2016 to July 2019). Males comprised 58% of the total while females were 42%. The male to female ratio was 1.4:1. The tested patients were divided into 3 major groups according to their age i.e. x \u3c 20, 20\u3ex\u3c50 and x \u3e 50.The mean age was 40.2 years.Results: Out of the tested 686 patients, 303 were reported to have the BCRABL1 transcript off which 54.2% were males and 45.9% were females. The ratio of patients diagnosed with Chronic Myeloid Leukemia to Acute Lymphoid leukemia was 9.8:1. 9% of the patients had the mutation e1a2 while 32% had b2a2 and 59% were reported with b3a2.Conclusions: We conclude that the distribution of BCR/ABL transcript types in patients with CML and ALL differs from most, but not all other populations studied. Currently there are no data from studies of CML and ALL in analyzing a comparable number of cases. The underlying mechanism and causes for the sex-depending distribution of the BCR/ABL transcript types remains open to speculation

Age–sex differences in the global burden of lower respiratory infections and risk factors, 1990–2019: results from the Global Burden of Disease Study 2019

Summary Background The global burden of lower respiratory infections (LRIs) and corresponding risk factors in children older than 5 years and adults has not been studied as comprehensively as it has been in children younger than 5 years. We assessed the burden and trends of LRIs and risk factors across all age groups by sex, for 204 countries and territories. Methods In this analysis of data for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we used clinician-diagnosed pneumonia or bronchiolitis as our case definition for LRIs. We included International Classification of Diseases 9th edition codes 079.6, 466–469, 470.0, 480–482.8, 483.0–483.9, 484.1–484.2, 484.6–484.7, and 487–489 and International Classification of Diseases 10th edition codes A48.1, A70, B97.4–B97.6, J09–J15.8, J16–J16.9, J20–J21.9, J91.0, P23.0–P23.4, and U04–U04.9. We used the Cause of Death Ensemble modelling strategy to analyse 23 109 site-years of vital registration data, 825 site-years of sample vital registration data, 1766 site-years of verbal autopsy data, and 681 site-years of mortality surveillance data. We used DisMod-MR 2.1, a Bayesian meta-regression tool, to analyse age–sex-specific incidence and prevalence data identified via systematic reviews of the literature, population-based survey data, and claims and inpatient data. Additionally, we estimated age–sex-specific LRI mortality that is attributable to the independent effects of 14 risk factors. Findings Globally, in 2019, we estimated that there were 257 million (95% uncertainty interval [UI] 240–275) LRI incident episodes in males and 232 million (217–248) in females. In the same year, LRIs accounted for 1·30 million (95% UI 1·18–1·42) male deaths and 1·20 million (1·07–1·33) female deaths. Age-standardised incidence and mortality rates were 1·17 times (95% UI 1·16–1·18) and 1·31 times (95% UI 1·23–1·41) greater in males than in females in 2019. Between 1990 and 2019, LRI incidence and mortality rates declined at different rates across age groups and an increase in LRI episodes and deaths was estimated among all adult age groups, with males aged 70 years and older having the highest increase in LRI episodes (126·0% [95% UI 121·4–131·1]) and deaths (100·0% [83·4–115·9]). During the same period, LRI episodes and deaths in children younger than 15 years were estimated to have decreased, and the greatest decline was observed for LRI deaths in males younger than 5 years (–70·7% [–77·2 to –61·8]). The leading risk factors for LRI mortality varied across age groups and sex. More than half of global LRI deaths in children younger than 5 years were attributable to child wasting (population attributable fraction [PAF] 53·0% [95% UI 37·7–61·8] in males and 56·4% [40·7–65·1] in females), and more than a quarter of LRI deaths among those aged 5–14 years were attributable to household air pollution (PAF 26·0% [95% UI 16·6–35·5] for males and PAF 25·8% [16·3–35·4] for females). PAFs of male LRI deaths attributed to smoking were 20·4% (95% UI 15·4–25·2) in those aged 15–49 years, 30·5% (24·1–36·9) in those aged 50–69 years, and 21·9% (16·8–27·3) in those aged 70 years and older. PAFs of female LRI deaths attributed to household air pollution were 21·1% (95% UI 14·5–27·9) in those aged 15–49 years and 18·2% (12·5–24·5) in those aged 50–69 years. For females aged 70 years and older, the leading risk factor, ambient particulate matter, was responsible for 11·7% (95% UI 8·2–15·8) of LRI deaths. Interpretation The patterns and progress in reducing the burden of LRIs and key risk factors for mortality varied across age groups and sexes. The progress seen in children younger than 5 years was clearly a result of targeted interventions, such as vaccination and reduction of exposure to risk factors. Similar interventions for other age groups could contribute to the achievement of multiple Sustainable Development Goals targets, including promoting wellbeing at all ages and reducing health inequalities. Interventions, including addressing risk factors such as child wasting, smoking, ambient particulate matter pollution, and household air pollution, would prevent deaths and reduce health disparities

Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019

Background: Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings: In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation: Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Funding: Bill & Melinda Gates Foundation