Surgical management of inflammatory bowel disease: A low prevalence, developing country perspective

OBJECTIVE: To determine the outcomes of surgical management of inflammatory bowel disease. METHODS: The retrospective case series was conducted at Aga Khan University Hospital, Karachi, and comprised medical record of adult patients operated between January 1986 and December 2010 for inflammatory bowel disease. Outcomes consisted of complications till last follow-up and 30-day mortality (disease or procedure related). Functional status of patients with ileal pouch was determined via telephone. SPSS 16 was used to analyse data. RESULTS: Of the 36 patients whose records were reviewed, 21(58%) were males, and body mass index was less than 23 in 34(91%). A total of 27(75%) patients underwent elective surgery for their condition. Ileal pouch was formed in 9(25%). Overall mortality was 14(38.8%). Overall incidence of complications was 26(72%), with wound infection being the most common early morbidity in 11(30.5%). Late morbidity included pouchitisin 4/9 (44.9%) and strictures 2/36 (5.5%).On telephonic follow-up, 6 of the remaining 7patients (85%) with ileal pouch were satisfied with the functional results of the procedure. CONCLUSIONS: The retrospective case series represents results from a developing country with low prevalence of inflammatory boweldisease and hence limited experience

Pancreaticoduodenectomy: A developing country perspective

Objective: To review retrospectively, the resultsof Whipple\u27s procedure from 1986 to December 2009 at the Aga Khan University Hospital. Methods: Patient\u27s case notes were reviewed to extract information related to demographics, clinical and laboratory data, operative procedure and post operative period. Surgical mortality was defined as death within 30 days of procedure. Results: Hundred and twenty one patients underwent a successful pancreaticoduodenectomy during this period. There were 78 males and 43 females. Most presented with clinical features of obstructive jaundice. Perioperative evaluation in the majority included an abdominal ultrasound and contrast enhanced CT scan. A preoperative ERCP was performed in 64 (53%) patients and a stent was placed in 32 (26%). Stent related sepsis was noted in 8 patients (25%). Eighty four (69%) patients underwent a standard resection, 31% had a pylorus preserving procedure. The commonest pathology was adeno-carcinoma located in the pancreatic head or periampullary area. Post operative morbidity was noted in 54% of patients, the commonest being chest infection (20%) followed by delayed gastric emptying and pancreatic anastomotic leak. There were 12 perioperative deaths giving a surgical mortality of 10%. Conclusion: To our understanding this is the largest series of consecutive pancreaticoduodenectomies reported in Pakistan. Our morbidity and mortality rates compare favourably with international centers of similar yearly case volume. There is a need to establish regional centers to effectively manage complex disease conditions and improve the standard of care offered to our patients

Building Resilience Against ViolencE (BRAVE): protocol of a parenting intervention for mothers and fathers with post-traumatic stress disorder in Pakistan

Abstract Background Prevalence of post-traumatic stress disorder (PTSD) is high in Pakistan both due to natural disasters and ongoing conflicts. Offspring of trauma survivors are at increased risk for mental and physical illnesses. Parental PTSD has been linked to troubled parent–child relationships, behaviour problems, trauma symptoms, and depression in children. This study aims to explore the acceptability, feasibility and indications of the effectiveness of group learning through play plus trauma-focused cognitive behaviour therapy (LTP Plus TF-CBT) for parents experiencing PTSD. Methods/Design This is a two-arm pilot cluster randomised controlled trial (RCT). We aim to recruit 300 parents with a diagnosis of PTSD. The screening will be done using the Impact of Event Scale-Revised. Diagnosis of PTSD will be confirmed using the Clinician-Administered PTSD Scale-5 (CAPS-5). Union Councils from Peshawar and Karachi will be randomised into either group LTP Plus TF CBT arm or treatment as usual (TAU). The intervention includes 12 sessions of LTP Plus TF-CBT delivered weekly in the first 2 months and then fortnightly in a group setting by trained psychologists. The groups will be co-facilitated by the community health workers (CHWs). Parents will be assessed at baseline and 4th month (end of the intervention), using the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder (GAD-7) Scale, Client Service Receipt Inventory (CSRI), and Ages and Stages Questionnaire (ASQ-3) Discussion This trial would help build an understanding of the acceptability, feasibility and indications of the effectiveness of a low-cost parenting intervention

The Pakistan risk of myocardial infarction study: A resource for the study of genetic, lifestyle and other determinants of myocardial infarction in south Asia

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Characterization of Aortic Valve Interstitial Cells Responsible for Elastogenesis

The aortic valve (AoV) controls unidirectional blood distribution from the left ventricle of the heart to the aorta for systemic circulation. During the systolic and diastolic phases, AoV leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance based on the arrangement of collagen, elastin, and glycosaminoglycans. The ECM structure is generated and maintained by valvular interstitial cells (VICs), which reside within the leaflets. VICs are a heterogeneous population of cells that are derived from a mixture of developmental precursors. Mainly, VICs arise from endocardial and neural crest cells that migrate into the cardiac cushions during development. The contribution of these diverse populations to the formation of the ECM microarchitecture has not been established. Relatively little is known about the regulation of elastic fibers, though elastin abnormalities result in congenital AoV defects and elastin degradation initiates AoV diseases. The present study showed for the first time the relationship of pigment presence in the mouse AoV with elastic fiber patterning. To establish the timing of elastin (Eln) expression in the mouse AoV, RT-qPCR was performed and found that Elnpeaks at late embryogenesis (E17.5) and early postnatal stages but remains at low levels in adulthood. Confocal microscopy of AoVs from mutant mice revealed that elastic fibers were almost completely missing in Kitwv/wv mice that have no pigment and were more abundant and disoriented in K5-Edn3 transgenic hyperpigmented mice. Additionally, by combining RNAscope with immunofluorescence, I found that VICs that co-express the melanocyte-specific marker Tyrosinaseand alpha-smooth muscle actin (aSMA) express Elnindicating they are responsible for elastin production. Furthermore, by lineage tracing using the Wnt1-Cre system, I found that these cells are not exclusively derived from the neural crest suggesting a contribution of a third lineage other than the known two. Moreover, using atomic force microscopy I found that the pigment affects the mechanical stiffness of the AoV leaflet, where those from K5-Edn3 have higher overall stiffness when compared to those from Kitwv/wv and wild type mice. Despite a striking phenotype, these mice live normally and have no overt cardiac differences. In conclusion, the present study showed that pigment is necessary for the proper patterning of the mouse AoV leaflets and contribute to its biomechanical properties. The results also indicated that Elnproducing cells have a unique melanocytic and smooth muscle cell phenotype and are not derived from the neural crest

Emerging indications for percutaneous cholecystostomy for the management of acute cholecystitis--a retrospective review.

Acute cholecystitis is a frequent cause of general surgical admissions with a mortality risk that is related to the age of the Patient. Percutaneous cholecystostomy (PC) has been used as a bridging technique while awaiting resolution of sepsis. We evaluated the outcome of our study population following percutaneous cholecystostomy for acute cholecystitis due to benign etiologies. Methods: Retrospective review of Patients undergoing PC from January 1988 to December 2008. Patients were reviewed for demographic features, co-morbidity, resolution of symptoms, hospital stay, outcome, complications and ASA class. Results: 62 Patients underwent PC for acute cholecystitis. 49 Patients had calculous cholecystitis. 61% (n = 38) were ≥ 60 years old. 92% had resolution of symptoms within 48 h, and 8% had partial or no resolution. 84% had a decline in total leucocyte counts. The mean hospital stay was 10.6 days and 30-day mortality was 15%. 69% Patients had no post-procedure complication. Of the remainder, 1 Patient had post-procedure hemorrhage and the remaining developed complications that included pneumonia, hypotension and vasovagal reactions. The duration of drainage ranged from 1 to 3 months. 3 Patients underwent emergency cholecystectomy during the same admission, 20 Patients underwent interval cholecystectomy. 22 Patients had no further intervention and had no recurrent symptoms, of these 73% (n = 16) had calculous cholecystitis. In this sub-group of non-operated Patients, 76% were ASA III & IV. Conclusions: PC is a low risk management option for high risk Patients with acute cholecystitis. It can be used as a temporizing measure while awaiting resolution of sepsis and optimization of co-morbidities, or as a definitive therapeutic option for acalculous cholecystitis. We also conclude that it has a good potential to be used as a definitive therapy for high risk (ASAIII & IV) Patients with acute calculous cholecystitis

Effect of rectal washout on local recurrence of rectal cancer in the era of total mesorectal excision: Meta-analysis

Introduction: Presence of intraluminal viable cancer cells implanting into the anastomosis has been proposed as a potential cause for developing local recurrence in patients undergoing anterior resection for rectal cancer. Rectal washout has been proposed as a method to prevent this from happening. There have been conflicting reports in literature regarding the effect of rectal washout on local recurrence. We aim to look at the role of rectal washout in preventing local recurrence of rectal cancer in patients undergoing total or tumor-specific mesorectal excision (TME).Materials and methods: A literature review of studies evaluating the role of rectal washout on rectal cancer local recurrence was performed using PubMed, Scopus, EMBASE and non-English language literature search using CiNii (Japanese) and CNKI (Chinese). Inclusion criteria were use of TME, comparison of rectal washout with no washout, and evaluation of local recurrence as outcome.Results: Four studies were identified according to inclusion criteria. The meta-analysis showed a protective effect of rectal washout on local recurrence (OR 0.45 95% CI 0.45-0.75). However, one of the studies included had more than 90% weightage. Excluding this study from analysis showed no difference on local recurrence with rectal washout (OR 0.94, 95% CI 0.37-2.36).Conclusion: The effect of rectal washout on rectal cancer local recurrence in patients who undergo TME is questionable and needs to be evaluated further by prospective studies

Studying the Impact of Composition of Personal Empowerment on Beneficiaries of Microcredit

The current study aimed to study the impact of dimensions of personal empowerment and microcredit upon the worth of life of women borrowers. This research originated to unlock the potential of a dimension of personal empowerment by way of social political and cultural awareness that has a significant role in improving the quality of life of women. While its dimension of freedom of movement found insignificant due to the prevailed strict patriarchal system, whereas substantial outcomes in respect of contrary to economic decision making illustrated the rigid socio-cultural norms of Pakistan. Therefore, for the sake of strengthening the business purpose, it is necessary that stepping the freedom of movement that leads to the quality of life of women