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Although conservative treatment has shown a good reduction in mortality and morbidity the majority of patients still need definitive surgery to get rid of the disease completely. It is of note that immediate laparotomy in high-risk patients who have a prolonged history or have multiple comorbidities or in organ failure is not advisable as it is associated with higher morbidity and mortality, besides improved postoperative intensive care.We categorized these high-risk patients based on their comorbidities and then performed percutaneous peritoneal lavage to reduce the septic load from the peritoneal cavity before performing the definite procedure.Out of the high-risk patients who survived after the PPD and underwent definitive surgery, 61% survived (n=8/13) while the rest of these, 38.5% expired (n=5).Percutaneous peritoneal drainage initially instituted in high-risk patients to optimize their pre-op condition significantly, improves the outcome and has better results than to operate on such patients straightaway.

BACKGROUND: Viral hepatitis is a global phenomenon, with the disease burden varying on a daily basis. Amongst chronic infections, hepatitis B virus and hepatitis C virus (HCV) are egregiously linked to severe health-related complications, with a worldwide prevalence of 248 million and 71 million respectively. Amongst the developing world, a hand full of countries are exhibiting a gross decline in chronic viral infection prevalence, like Bangladesh. While countries such as India have a consistent prevalence, Pakistan bears one of the largest proportions of chronic viral hepatitis globally with increasing trends shown year-by-year. Various old literature texts have stated an approximate national prevalence rate around 2.6% and 5.3% of hepatitis B and C respectively. OBJECTIVE: The objective of this study was to determine the current seroprevalence rates of chronic viral hepatitis amongst the general population of rural Sindh using a screening program to determine the current disease burden. METHODS: An observational, cross-sectional survey based on a screening program was conducted in 5 districts with a combined population of over 6.5 million. The screening was carried out via the administration of various camps with the assistance of local social workers and welfare organizations. A total of 24,322 individuals met the inclusion criteria and were screened through (HBsAg/HCV) rapid test cassette (WC) Imu-Med one-step diagnostic test. RESULTS: Hepatitis B was found positive in 964 (3.96%) individuals including 421 (43.67%) males and 543 (56.32%) females, while hepatitis C was positive in 2872 (11.80%) individuals including 1474 (51.32%) males and 1398 (48.67%) females. The prevalence amongst the districts varied between 0.97% and 9.06% for hepatitis B, and 1.61% and 29.50% for hepatitis C, respectively. Umerkot was found to be the most prevalent district amongst rural Sindh, while Badin had the least number of seropositive people. The second most prevalent district of the study population was found to be Tando Allahyar followed by Mirpur Khas. The combined seroprevalence of 15.76% was calculated for hepatitis B and C together amongst the five studied districts of rural and peri-urban Sindh. CONCLUSION: The alarmingly high prevalence rates revealed in our study warrant the urgent need to generate multiple effective strategies in the region to enhance awareness amongst the general population regarding screening, prevention, and prompt treatment of the disease. RESUMO CONTEXTO: A hepatite viral é um fenômeno global, com a intensidade da doença variando diariamente. Entre as infecções crônicas, o vírus da hepatite B e o vírus da hepatite C (VHC) estão fortemente ligados a complicações graves relacionadas à saúde, com prevalência mundial de 248 milhões e 71 milhões, respectivamente. Entre o mundo em desenvolvimento, uma quantidade de países está exibindo um declínio bruto na prevalência de infecção viral crônica, tal como Bangladesh. Embora países como a Índia tenham uma prevalência consistente, o Paquistão tem uma das maiores proporções globais de hepatite viral crônica, com tendências crescentes mostradas ano a ano. Vários textos da menos recentes têm declarado uma taxa de prevalência nacional aproximada em torno de 2,6% e 5,3% da hepatite B e C, respectivamente. OBJETIVO: O objetivo deste estudo foi determinar as atuais taxas de soroprevalência da hepatite viral crônica entre a população geral do Sindh rural utilizando um programa de triagem para determinar a carga atual da doença. MÉTODOS: Foi realizada uma pesquisa observacional e transversal baseada em um programa de triagem combinada em cinco distritos com população de mais de 6,5 milhões. A triagem foi realizada por meio da administração de diversos acampamentos com o auxílio de assistentes sociais locais e organizações de assistência social. Um total de 24.322 indivíduos atenderam aos critérios de inclusão e foram examinados através do teste rápido (HBsAg/VHC) Imu-Med em uma etapa. RESULTADOS: Hepatite B positiva foi encontrada em 964 (3,96%) indivíduos incluindo 421 (43,67%) homens e 543 (56,32%) mulheres, enquanto hepatite C foi positiva em 2.872 (11,80%) indivíduos incluindo 1.474 (51,32%) homens e 1.398 (48,67%) mulheres. A prevalência entre os distritos variou entre 0,97% e 9,06% para hepatite B, e 1,61% e 29,50% para hepatite C, respectivamente. Umerkot foi encontrado como o distrito mais prevalente entre Sindh rural, enquanto Badin tinha o menor número de pessoas soropositivas. O segundo distrito mais prevalente da população de estudos foi encontrado como Tando Allahyar, seguido por Mirpur Khas. A soroprevalência combinada de 15,76% foi calculada para hepatite B e C em conjunto entre os cinco distritos estudados do Sindh rural e periurbano. CONCLUSÃO: As taxas de prevalência alarmantemente reveladas em nosso estudo justificam a necessidade urgente de gerar múltiplas estratégias efetivas na região para aumentar a conscientização da população em geral sobre rastreamento, prevenção e tratamento rápido da doença.

The purpose of this case report is to demonstrate the outcomes of reconstruction in small-to-moderate-sized benign tumors of eyelids by using the propeller flap technique. Propeller flaps have been used by plastic surgeons for facial reconstruction and other body parts. However, very few oculoplastic surgeons have utilized this technique in eyelid reconstructive surgeries. We have substantiated this technique and its outcomes in this case report. It is a case series consisted of two patients reporting in the orbit-oculoplastics clinic with suspicious basal cell carcinoma of eyelids, covering less than half of the eyelid. Both the patients underwent tumor excision and reconstruction, with a cutaneous propeller flap supplied by a pedicle. Both the patients recovered well and without any complication. The specimens removed from both the patients were sent for histopathology and the biopsy results revealed both lesions were margin-free basal cell carcinoma. The reconstruction of eyelid defects is challenging due to the small area and cosmetic appearance. Propeller flaps are a reasonable choice of treatment in small to moderately large-sized defects with minimal complications, yet better cosmetic appearance.

Inevitably, along with other healthcare specializations, pediatric surgery was affected by the Coronavirus disease-19 (COVID-19) pandemic. Children were reported to manifest mild to moderate symptoms and mortality was primarily observed in patients aged

Background and objectives Cerebral venous sinus thrombosis (CVST) is a relatively rare and underdiagnosed type of stroke. Rivaroxaban is licensed for venous thromboembolism in patients opting for elective knee and hip replacement surgeries, preventing pulmonary embolism and precluding stroke and systemic embolism in sufferers of non-valvular atrial fibrillation. Beneficial outcomes depicting the efficacious role of rivaroxaban in treating CVST are under study. Materials and methods We performed a prospective observational study in patients diagnosed with CVST in the medicine or neurology unit of a tertiary care hospital in Karachi, Pakistan, between January 2019 and December 2019. The diagnosis of CVST was made by magnetic resonance venography (MRV) in all the cases. Follow-up visits were scheduled at three months and six months, and the occurrence of thrombotic events or bleeding complications was recorded. Follow-up was done by magnetic resonance imaging at three and six months to assess vessel recanalization. Excellent outcome was defined as a modified Rankin Scale (mRS) of 0 or 1. A total of 31 patients were meeting the inclusion criteria and were inducted into the study after informed consent. Results The mean age of the study population was 35.11 ± 8.96 years with 71% females and 29% males. The most prevalent etiology was the pregnancy/postpartum period (52%) followed by antiphospholipid syndrome (23%). The frequent clinical manifestations were headache (84%) followed by vomiting (38%), altered level of consciousness (35%), focal deficit/limb weakness (32%), aphasia (29%), blurring of vision (26%), and seizures (23%). Radiological studies showed that the vessels chiefly occluded in our study were superior sagittal sinus (29%), transverse sinus (23%), sigmoid sinus (16%), jugular vein (9%), and cortical veins (3%). Common features on magnetic resonance imaging (MRI) were cerebral edema (45%), hemorrhage (39%), infarct incidence (32%), and raised intracranial pressure (26%). Clinical outcomes showed 55% of patients had partial recanalization and 39% had complete recanalization after a period of six months of the administration of rivaroxaban. Ninety-three percent (93%) of sufferers recovered excellently according to mRS and only 3% developed recurrent CVST within a span of six months. The frequency of thrombotic events and bleeding complications were reported in 6% of patients, respectively, while mortality reported was also 6%. Conclusion Rivaroxaban has shown promising results in the management of our CVST patients, hence, it further warrants randomized controlled trials of rivaroxaban against conventional treatments to prove its significant role.

Background and objective The term asymptomatic bacteriuria (ASB) refers to the isolation of bacteria in a urine specimen of individuals without any symptoms of urinary tract infection (UTI). Diabetes mellitus (DM) is a disease involving multiple organ systems, characterized by its chronicity and hence endless complications including ASB. This study aimed to determine the characteristics of ASB and antibiotic susceptibility patterns among patients with diabetes. Materials and methods This was a retrospective observational study conducted in a tertiary care hospital. The study included patients with a diagnosis of diabetes with no signs and symptoms of UTI but who still showed the growth of an organism in urine culture. A total of 222 urine cultures were analyzed retrospectively, ensuring that they met the inclusion criteria through non-probability consecutive sampling. Results The mean age of the study participants was 62.89 ± 13.77 years; 76% of them were females, and 61% had a family history of diabetes. The most frequent organisms isolated were Escherichia coli (E. coli), Enterococcus, Klebsiella pneumonia, Pseudomonas aeruginosa, and Enterobacter species. A total of 20 subjects had dual bacterial growth in their cultures, with Enterococcus species (n=17) being the most common organism. Gender, family history of diabetes, levels of hemoglobin A1c (HbA1c), and advanced age were all found significantly associated with ASB. Conclusion Our study is the first of its kind to analyze and examine the risk factors associated with ASB in DM patients, and to identify the pathogens involved, along with assessing their antibiotic resistance profiles.

Background and objectives Chronic liver disease (CLD) encompasses a variety of etiologies, and the infectious causes are mainly hepatitis B and hepatitis C virus. Chronic alcohol abuse and non-alcoholic fatty liver disease also have a major contribution to CLD. The Child-Pugh scoring system indicates the probable prognosis and mortality risk of a patient with cirrhosis. The primary objective of this research is to observe the mortality risks of CLD caused by a variety of etiologies mentioned above. The secondary objective is to determine the biochemical markers that are correlating with the severity of the study groups. Another aim was to determine the Model for End-Stage Liver Disease (MELD) scoring of each study group predicting the severity of disease among the Child-Pugh classification. Materials and methods We broadly classified the etiologies into two study groups: (1) hepatitis B, C associated CLD (hepatitis B, C--CLD) and (2) non-hepatitis B, C associated CLD (non-hepatitis B, C-CLD). This study was conducted as a descriptive, retrospective study involving patients admitted to the Gastroenterology Department at Dow University Hospital between July 2019 and December 2019. All patients who met the inclusion criteria were included in the study in order to document their levels of severity markers of CLD. A total of 167 individuals met the inclusion criteria, and the sampling was done through non-probability consecutive methods. All continuous variables were described as mean and standard deviations, which were then compared using an independent sample t-test. The comparison of categorical data was done either using the chi-square test or Fisher's exact test accordingly. A p-value of

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support (n = 15,001). The most common organ support therapy was invasive mechanical ventilation (n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation (n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy (n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation (n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04323787.

Background and objectives Sleep disorders are prevalent in end-stage renal disease (ESRD) involving the majority of patients undergoing hemodialysis. The main objective of treating sleep disorders in patients of ESRD is to correct subjective and objective sleep quality, decrease fatigue and daytime sleepiness, and enhance daytime functioning. Irrespective of the adverse effects reported, benzodiazepines are widely utilized among patients with sleep disorders in end-stage renal disease. Melatonin is a newer agent being studied for use in hemodialysis patients for improvement of sleep quality. The aim of our observational study is to witness the effectiveness of both benzodiazepine and exogenous melatonin as a treatment of sleep disorders in patients undergoing hemodialysis. Materials and methods We conducted a comparative, observational study in ESRD patients who are on hemodialysis. These patients were selected from attendees of the hemodialysis unit, nephrology department of a tertiary care hospital, including those who were on regular hemodialysis, thrice-weekly in frequency for at least once per year, and taking regular sleep medications for at least three months with frequently reported drug dosages of alprazolam 0.5 mg once daily or melatonin 3 mg once daily (before bedtime). The subjective sleep assessment was done by utilizing four scales, including the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Stanford Sleepiness Scale (SSS). Results A total of 117 hemodialysis-dependent patients met the inclusion criteria, among whom 79 patients were using alprazolam while 38 were using melatonin for their disturbed sleep. The mean age of the study participants was 49.12 ± 12.75, comprising 72 males (61.53%) and 45 females (38.46%). The duration of the diagnosis of chronic kidney disease (CKD), duration of onset of hemodialysis, and estimated glomerular filtration rate (eGFR) was comparable in both groups. Both groups had similar laboratory markers except for higher hemoglobin in the melatonin group (p=0.028) and high parathyroid hormone (PTH) levels in the alprazolam group (p=0.001). PSQI scores were 8.76 ± 3.09 in the alprazolam group and 7.32 ± 2.65 in the melatonin group (p=0.015). In the sub-scores, there were no differences in sleep latency (p=0.481) and daytime dysfunction (p=0.662) while sleep efficiency (p=0.167) and subjective sleep quality (p=0.132) were not statistically significant. The significant differences were lower scores of sleep duration (p=0.040) and sleep disturbance (p=0.003) in the melatonin group. The ESS scores revealed no significant difference in either group (p=0.074). With respect to the ISI and SSS, higher scores were obtained in the alprazolam group. Overall, 89 study participants had reported poor sleep quality, out of which 81% were using alprazolam, and 65% were using melatonin (p=0.071). A total of 50 study participants exhibited excessive daytime sleepiness with 45% of them were using alprazolam and 36% were using melatonin. About 54% of the alprazolam using hemodialysis patients had moderate insomnia while 50% of the melatonin using patients had sub-threshold insomnia (p=0.062). Conclusion As melatonin use has shown better sleep quality and less insomnia severity as compared to alprazolam use in our study, it is postulated that the sleep-wake cycle should be commonly targeted by pharmacological therapy in ESRD.

Background Abdominal trauma and intra-abdominal sepsis are associated with significant morbidity and mortality. Microcirculation in the gut is disrupted in hemorrhagic and septic shock leading to tissue hypoxia, and the damaged gut acts as a reservoir rich in inflammatory mediators and provides a continual source of inflammation to the systemic circulation leading to sepsis. Sepsis is defined as the presence (probable or documented) of infection together with a systemic inflammatory response to infection. Blood culture is commonly considered to be the preferred approach for diagnosing sepsis, although it is time-consuming, that is, reports are normally available only after 12-48 hours. Procalcitonin levels (PCT) have recently emerged as a promising biomarker in the diagnosis of sepsis. The aim of the present study is to determine the diagnostic accuracy of PCT levels in predicting sepsis in critically ill trauma patients. Methodology This was designed as a validation study conducted in the Indoor Department of General Surgery, Liaquat National Hospital, Karachi. The sample size was calculated by taking the estimated frequency of sepsis in suspected patients at 62.13%, expected sensitivity of PCT at 70.83%, and specificity at 84.21% and the desired precision level of 12% for sensitivity; the calculated sample size was 96. The non-probability consecutive sampling method was used to recruit participants who were diagnosed with sepsis on clinical assessment. Blood culture samples were sent for the enrolled patients and a final diagnosis was made on the blood culture report. PCT levels were measured in these suspected patients on the same day of sending blood culture. Diagnostic accuracy of PCT size was measured using the receiver operating characteristic (ROC) curve. ROC curve was formulated for PCT levels against culture-proven sepsis to determine the ideal cut-off value of PCT levels. Two different cut-offs were determined to obtain the highest sensitivity and highest specificity accordingly. Results A total of 97 individuals met the inclusion criteria with a mean age of 34.89 ± 10.52 years. Mean PCT levels were 0.96 ± 0.59, with a gender predilection towards females (p < 0.001). No age difference was documented among gender (p = 0.655). The mean duration of intensive care unit stay was 11.73 ± 3.56 days. Culture-proven sepsis was identified in 67.0% of the study participants with a higher PCT level (p < 0.001). Among the 52.6% males included in the study, half were reported to have culture-positive sepsis, but among the 47.4% females culture was positive in 87% (p < 0.001). ROC revealed PCT was predictive for culture-positive sepsis at a cut-off value 0.47 ng/mL (p < 0.001), with a sensitivity of 92.3%, specificity of 68.7%, positive predictive value (PPV) of 85.7%, and negative predictive value (NPV) of 81.5%. By increasing the cut-off value to 0.90 ng/mL at area under the curve of 0.816, the specificity increased to 81.3% and sensitivity became 66.2%, with a PPV of 87.8% and NPV of 54.2%. Conclusion Our study determined two cut-values for PCT to predict sepsis, one with the highest sensitivity and the other with better specificity. Other than that, higher PCT levels were significant in female trauma patients. We conclude that PCT is a reliable marker for culture-proven diagnosis of sepsis and may aid physicians/surgeons to promptly manage patients accordingly.

Background and objectives Stone in the biliary tract is one of the most common causes of hospitalization. However, it is difficult to determine the prevalence of gallstones in the general population because they are often asymptomatic. Thus, management lies in the proper clearance of the common bile duct (CBD) along with the removal of the gallbladder, for which it must be diagnosed on time with proper accuracy. Imaging modalities including magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) provide true visualization of choledocholithiasis with comparable sensitivities. The gold standard ERCP is an invasive procedure and may cause complications, such as pancreatitis, perforation, and bleeding. EUS is a minimally invasive procedure to assess the biliary tract using high-frequency sound waves. Until now the EUS has not been addressed much in our local tertiary care setups and this study was conducted to evaluate its accuracy in the diagnosis of choledocholithiasis. The objective of our study is to determine the diagnostic accuracy (specificity and sensitivity) of EUS versus ERCP for the diagnosis of choledocholithiasis. Materials and methods This retrospective study was conducted on patients suspected of having choledocholithiasis undergoing both EUS and ERCP based on their history, clinical symptoms, and laboratory test results including upper abdominal pain, deranged liver function enzymes, and a dilated CBD on radiology. EUS was initially performed for the diagnosis of extrahepatic biliary obstruction followed by one or more of the confirmatory criterion standard tests (including ERCP). In order to reduce the chances of passage of stone resulting in negative analysis, only those patients were included in which both procedures were conducted temporally close together (24-72 hours in most instances). The main outcome measures were diagnostic accuracy with the help of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) using a receiver operating characteristic curve. A total of 123 patients met the inclusion criteria via non-probability consecutive sampling methods. Results The mean age of our study population was 50.30 ± 13.91. We included 63 males (51.2%) and 60 females (48.8%). The most frequent indication for undergoing diagnostic procedures was deranged liver function tests (67.47%). The frequent comorbidities reported were hypertension (29.26%), diabetes (21.95%), chronic liver disease (16.26%), and ischemic heart disease (4.87%). Mean alkaline phosphatase and gamma-glutamyl transferase levels were markedly raised from the baseline in the study population. Post-ERCP complications were also reported in some of the study participants. About 85 patients (69.10%) were diagnosed with choledocholithiasis among the study participants. The diagnostic accuracy of EUS was compared with ERCP revealed an area under the curve (AUC) of 0.930, standard error of 0.031, 95% confidence interval of 0.868-0.991, the sensitivity of 89.5%, specificity of 96.5%, positive predictive value of 91.9%, and negative predictive value of 95.3%. Conclusion It is recommended that ERCP can be selectively conducted or excluded in patients with biliary obstruction in case of EUS negative, thus minimizing the complications and morbidity associated with an invasive procedure, with our results showing a comparative diagnostic accuracy of EUS.

Background and objectives In surgical patients, coronary disease is the main cause of perioperative mortality. The incidence of serious cardiovascular complications is reported as 5% with a probability of 1-2% of death from the cardiac cause in major non-cardiac surgery. B-type natriuretic peptide (BNP) is a sensitive and specific predictor of left ventricular systolic dysfunction and predicts first cardiovascular event and death in the general population. The recent guidelines recommended the use of pro-BNP for independent perioperative prognosis in cardiac patients undergoing non-cardiac surgery. The aim of this study is to assess the predictive value of raised pro-BNP levels in patients who underwent major abdominal surgery and evaluate its relationship with cardiovascular complications and mortality occurring up to 30 days after surgery. Materials and methods We reviewed the medical records of patients undergone surgical procedures in the abdominal region lasting more than two hours, requiring postoperative high dependence or intensive care and an expected hospital stay of at least three days. All types of open or laparoscopic-assisted abdominal or pelvic surgeries that were evaluated for preoperative pro-BNP levels were included in the study. During the postoperative period, all patients were followed for cardiac complications and mortality for 30 days after surgery. Postoperative adverse cardiac events were predefined as angina pectoris, myocardial infarction, cardiogenic dyspnea, acute arrhythmias (atrial fibrillation/flutter, ventricular fibrillation/tachycardia), acute hypertensive event (hypertensive emergency or urgency), congestive heart failure, acute pulmonary edema, or primary cardiac death. While non-cardiac complications were also documented as either pulmonary, septic, postsurgical site infection, and other systemic complications. Subsequently, a survival analysis was done for the discretion of cardiovascular complications and mortality. Results The mean age of the study population was found to be 50.22 ± 14.28 years, mean pro-BNP levels were 909.29 ± 3950.04, and mean days of hospital stay were 7.43 ± 4.49 days. The 30-day postoperative all-cause mortality was found to be 9.8%. Hypertension and diabetes were frequent comorbidities amongst the study population. The mean preoperative pro-BNP levels were found higher in the male gender (p=0.071), also found higher in those with cardiovascular complications (p=0.006) and mortality (p=0.057). Receiver operating characteristic (ROC) analysis showed cardiovascular outcomes with a cut-off value of pro-BNP at 143 pg/ml, AUC of 0.891, at a sensitivity of 91%, positive predictive value (PPV) of 96%, a specificity of 75%, and negative predictive value (NPV) of 58%, while the same for mortality at a cut-off value of 164 pg/ml was found with AUC of 0.815, at a sensitivity of 84%, a specificity of 66%, PPV of 97%, and NPV of 21%. The unadjusted odds ratio for cardiovascular complications was found to be 17.857 (95% CI: 6.56-48.60) while that for mortality was 10.863 (95% Cl: 2.29-51.37). The Kaplan-Meier survival curves showing elevated pro-BNP levels were significantly associated with cardiovascular events, with 30 days mortality at a cut-off value of 164 pg/ml. Conclusion Pro-BNP is a useful marker in postoperative patients for not only predicting cardiovascular outcomes as cited by many previous studies but also mortality.

Pulmonary lung involvement in adult-onset Still’s disease (AOSD) can be classified into two categories: with or without acute respiratory distress syndrome. Interstitial fibrosis in AOSD is rare, occurring in less than 5% of cases. Here, the authors present a case of a 40-year-old male of Asian descent with a past history of hyperthyroidism who presented with fever, shortness of breath associated with cough, sore throat, diffuse arthralgias, pink-coloured rash, and hepatomegaly. Laboratory investigations revealed leukocytosis, abnormal liver function tests, negative antinuclear antibodies, and negative rheumatoid factor. Chest X-ray showed bilateral basal infiltrates, while high-resolution CT chest scan confirmed the diagnosis of interstitial lung disease in association with ASOD. This case suggested a direct association of AOSD and interstitial lung disease, but autoimmune pathogenesis is the only link synchronising both diseases and the exact mechanism of direct involvement is ambiguous.

Background and objectives Chronic kidney disease (CKD) share a common pathophysiology with non-alcoholic fatty liver disease (NAFLD). This study aims to identify the lipid derangements in patients of CKD and to associate them with radiological evidence of NAFLD. Material and methods A cross-sectional observational study was performed in a tertiary care hospital, to include all chronic kidney disease patients (n=238) through non-probability consecutive sampling. The criteria for inclusion were baseline estimated Glomerular filtration rate (eGFR) below 60 ml/min/1.73m2 for at least three months and chronic renal parenchymal changes on ultrasound. Two study groups were identified based on ongoing hemodialysis, while two further study groups were identified based on radiological evidence of fatty liver disease. Results The mean age of the study population was 48.52 ± 9.44 years with no difference amongst hemodialysis status, females elder than males (p= 0.027), those with fatty liver were much younger (p=0.014), and the most common age group below 50 years (p=0.005) among the fatty liver group. Radiological evidence of NAFLD was found amongst two-third of the study group with the status of hemodialysis indifferent among the study population (p=0.436). The mean values amongst fatty liver versus non-fatty liver groups revealed high creatinine, alanine transaminase (ALT), high-density lipoprotein (HDL), triglycerides (TG), and very-low-density lipoprotein (VLDL) in the fatty liver group, low-density lipoprotein (LDL) and total cholesterol (TC) were indifferent amongst the groups, while LDL/HDL ratio was higher in the non-fatty liver group. Conclusion A significantly higher HDL was found in fatty liver associated with CKD as compared to the non-fatty liver group.

We are presenting a case of pericardial tumor in an elderly female patient who presented with low-grade fever, purpuric rashes all over the body, grittiness in the eyes, and dry mouth with decreased oral intake, night sweats, weight loss, chest pain, and dyspnea. She was diagnosed with Sjögren’s syndrome secondary to systemic lupus erythematosus (SLE) with positive anti-nuclear antibody (ANA), anti-double-stranded DNA (anti-ds-DNA), and anti-Sjögren's-syndrome-related antigen A autoantibodies (SS-A/Ro) antibodies. Computerized tomography scan of the chest with contrast showed multiple calcified mediastinal lymph nodes and a well-defined solid cystic lesion adjacent to the left atrial appendage in favor of a pericardial tumor with minimal pericardial effusion. Biopsy could not be done due to the risk of cardiac tamponade and pneumothorax secondary sensitive location of the tumor. The patient was referred to the oncology and cardiothoracic surgery department for an opinion regarding resection of the tumor and further palliative management. This case is unique in a way that the current literature does not associate SLE with pericardial tumor, while our patient had no other primary malignancy or secondary metastasis ruled out on a positron emission tomography (PET) scan.

Pakistan had an epidemic of dengue fever with a yearly prevalence of 0.4-0.5/100,000 reported. In the current epidemics of dengue, utilization of Carica papaya leaves earned popularity in treating thrombocytopenia.Our main objective was to determine the course and duration of recovery of thrombocytopenia in patients with dengue infection who were using papaya extracts and compare them to those who did not receive papaya extracts during the hospital stay. The study included all the patients with a diagnosis of dengue infection via serology, with the exclusion of all patients who were transfused with platelets during the hospital stay, or had a known chronic or autoimmune thrombocytopenic illness. ICU admissions and mortalities were also excluded from the study population. Platelet counts of study groups were monitored and compared at Day 1, 4 and 7 with one group using papaya extracts alongside intravenous hydration administered in both study and control groups. There was no significant difference in the length of hospital stay between the two groups, no added benefit in the doubling time of platelets. Although many studies are supporting the role of papaya extracts in increasing platelet counts on a molecular level, its role in attaining recovery from acute thrombocytopenic conditions like dengue viral fever is still ambiguous and lack clinical evidence in our study.

Background and objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. The disease mainly affects the respiratory system of the patient, in particular, the lungs, which leads to patients presenting with acute respiratory distress syndrome and acute respiratory failure, with 5-15% of patients requiring observation in the intensive care unit (ICU) with respiratory support in the form of ventilation. This study was aimed at identifying the role of biochemical markers in the risk stratification of invasive and non-invasive ventilation of hospitalized COVID-19 patients. Materials and methods The study was conducted as a prospective, observational study of all admitted COVID-19 patients. A comparative analysis was performed of the survivors who were on invasive versus (vs) non-invasive ventilation and the non-survivors similarly. After computing the descriptive statistics, a multinomial logistic regression model was applied to obtain an unadjusted odds ratio (OR) at 95% confidence interval (CI), with Hosmer-Lemeshow (HL) goodness-of-fit test used to predict the fitness of the data. Kaplan-Meier survival curves were obtained for each of the laboratory investigations predicting survival along with the intensive care stay and invasive ventilation. A log-rank test was carried out to compare the survival distributions. Results A total of 373 included patients in the study had a mean age of 52.78 ± 15.76 years with females younger than males, and indifference amongst invasive vs non-invasively ventilated (p=0.821). Females were slightly more prone to invasive ventilation (p=0.097). Overall, 39% of the subjects did not need respiratory support, while 13% were on a ventilator, 16% on bilevel positive airway pressure/continuous positive airway pressure (BiPAP/CPAP), and 31% on supplemental oxygen therapy. Among the laboratory markers, mean hemoglobin was evidently lower in the invasive group, leukocytosis and thrombocytopenia were present in both invasively ventilated and non-surviving patients, while neutrophilia and lymphocytopenia were statistically indifferent among the mode of ventilation. Elevated urea, creatinine, and sodium were also significantly deranged laboratory markers amongst the invasively ventilated group. C-reactive protein (CRP) and lactate dehydrogenase (LDH) were elevated significantly in the invasive group, while serum ferritin was more frequently raised in the non-invasively ventilated group. Procalcitonin (PCT) was significantly associated with invasive ventilation as opposed to the non-invasive group. D-dimer was equally raised in both the groups at admission but significantly elevated in the invasive group at discharge. A multinomial regression model signified D-dimer (OR: 16.301), hypernatremia (OR: 12.738), creatinine (OR: 12.589), urea (OR: 12.576), and LDH (OR: 12.245) most significantly associated with death, while those for invasive ventilation were D-dimer (OR: 8.744), hypernatremia (OR: 4.532), PCT (OR: 3.829), neutrophilia (OR: 3.804), leukocytosis (OR: 3.330), and serum urea (OR: 3.312). Kaplan-Meier curves conclude total leucocyte count (TLC), neutrophils, lymphocytes, urea, creatinine, sodium, CRP, LDH, PCT, and D-dimer all significantly contributing to an early death. Conclusion The most significant marker for mortality was D-dimer, followed by serum sodium, urea/creatinine, LDH, ICU stay, and invasive ventilation.

Background and objective COVID-19 is a highly disseminating viral disease imparted by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which was declared a global pandemic by the World Health Organization. In our study, we aimed to describe the clinical characteristics of the first 100 hospitalized patients of confirmed COVID-19 in a developing country. Materials and methods The study included all the admitted patients (n = 100) having COVID-19 polymerase chain reaction (PCR) positive, and evaluated clinical profiles and characteristics of the patients linking to disease severity. Results Out of the 100 patients, 67 were in the ward, 33 were in ICU, 78 of them recovered, while 22 deaths reported. The mean age was 52.58 ± 15.68, with most frequent comorbidities are diabetes and hypertension while frequent symptoms are fever and dry cough. Bilateral lower zone patchy infiltrates are frequent chest radiographic findings. Amongst the patients admitted in ICU, there were significant differences in the total leukocyte count (P = 0.001), neutrophils and lymphocytes (P =< 0.001), monocytes (P = 0.027), urea (P =< 0.001), creatinine (P = 0.002), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) increasing with disease severity, lymphocyte-to-monocyte ratio (LMR) and lymphocyte-to-C‐reactive protein ratio (LCR) decreasing with mortalities. Gamma-glutamyl transferase (GGT) followed by aspartate aminotransferase (AST) are frequent hepatic derangements, while C-reactive protein (CRP) levels predicting ICU admission with area under the curve (AUC): 0.806, positive predictive value (PPV): 85.1% and lactate dehydrogenase (LDH) predicting mortality with AUC: 0.877, PPV: 97.3%, while NLR (AUC: 0.806, PPV: 95.8%) for mortality and neutrophils (AUC: 0.773, PPV: 87.5%) for ICU patients. Conclusion A number of factors are linked with disease severity and mortality along with dynamic changes of the laboratory investigations during hospital stay affecting prognosis.

Background and objectives Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are rapidly spreading, posing a serious threat to the health of people worldwide, resulting in the World Health Organization officially declaring it a pandemic. There are several biochemical markers linked with predicting the severity of coronavirus disease. This study aims to identify the most effective predictive biomarker such as C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), procalcitonin (PCT), and D-dimer, among others, in predicting the clinical outcome of the disease. Materials and methods This study was conducted as a retrospective, observational, multi-centric study, including all admitted COVID-19 positive patients only. The disease outcome was followed along with the hospital course of every patient at the time of analysis. Baseline laboratory investigations of all patients were monitored both at admission and discharge. A comparative analysis was done between the survivors (n=263) and non-survivors (n=101). Statistical analysis was conducted using IBM SPSS Statistics for Windows Version 25 (Armonk, NY: IBM Corp.). Results Of 364 patients, 65.7% were in the isolation ward, and 34.3% were in the intensive care unit; 72.3% of patients survived, while 27.7% of patients died. The mean age of the study population was 52.6 ± 15.8 years with female patients significantly younger than male patients (p=0.001) and 50 to 75 years being the most common age group (p=0.121). Among the survivors versus non-survivors of COVID-19, there were significant differences in total leukocyte count (p

We present a case of a male diabetic patient with one of the most well-known major complications of diabetes mellitus (DM), i.e., diabetic ketoacidosis (DKA). The finding of euglycemic DKA, or DKA with blood glucose levels of less than 200 mg/dL, is a rare occurrence especially in patients with type II DM. He presented with hypotension and increased anion gap metabolic acidosis on a background of keto diet for weight loss and recent use of sodium-glucose linked transporter inhibitors. He was successfully managed with dextrose water, insulin infusion, and potassium replacement. A ketogenic diet consists of high fat, low carbohydrate, and adequate protein regimen that sends the body into a state of starvation in which high glucagon and low insulin levels lead to the activation of other counter-regulatory hormones, such as epinephrine and cortisol, that causes a rise in the level of free fatty acids in the blood increasing ketone body production. Rarely, sodium-glucose linked transport inhibitors can also cause DKA, with euglycemia instead of hyperglycemia. The finding of plasma glucose levels within normal range prompted patients to maintain and sometimes even lower their insulin dose; even their providers were often misled by the euglycemia that resulted in delayed diagnosis and treatment. Thus, it is imperative to stay aware of the possible clinical presentations in order to intervene in a timely manner and prevent further progression and complications.

A 30-year-old Asian male with a significant history of deep vein thrombosis and family history positive for pulmonary embolism presented with complaints of fever, nonradiating epigastric pain, and a sense of abdominal fullness. After the initial workup, ultrasonography of the whole abdomen was carried out which showed thrombus formation in the portal vein. A CT scan of the abdomen was performed, which showed findings suggestive of mesenteric panniculitis. Keeping the significant family history and imaging findings in mind, the clotting and thrombin profiles were analysed and came back positive for the factor V Leiden gene (homozygous). A CT angiogram was performed to demonstrate extensive thrombosis throughout the abdominal vasculature with cavernous transformation. It is asserted that the chronic thrombosis on a background of factor V mutation led towards chronic inflammation of the mesentery. To the authors’ knowledge it is the first reported case of mesenteric panniculitis in a patient with factor V homozygous gene mutation.

Objective: To compare the outcome in terms of post-operative pain in cases where ilio-inguinal nerve is sectioned electively with those where nerve is preserved during hernioplasty for primary inguinal hernia. Study Design: Randomized Controlled Trial. Settings: Surgical Units of Allied & DHQ hospital, Faisalabad Pakistan. Duration: 1 year from Jan 2017 to Dec 2017. Methodology: Approval from ethical review committee was obtained and patients from OPD based on the inclusion criteria were enrolled after informed consent. They were randomly divided into two groups. Patients in Group A had their ilio-inguinal nerve excised whereas it was preserved in patients in Group B. These procedures were performed by senior surgeons. Follow up was done by preserving patients’ telephone numbers in protocol proforma. Pain was assessed after 1 month of the procedure. Whole information was added on a Performa. Results: The study showed, mean age in Group A was 28.58+3.29 years and 33.8+8.35 years in Group B. 85% of patients(n=34) in Group A were males and 15%(n=6) were females whereas 77.5%(n=31) in Group B were males and 22.5%(n=9) were females. Frequency of post-operative pain in both groups was calculated and it was found that 32.5% of the patients (n=13) in Group A and 57.5% (n=23) in Group B had pain. On the other hand, 67.5% of patients (n=27) in Group A and 42.5% (n=17) in Group B had no pain (p value =0.024). This demonstrates a clear difference between the two study groups. Conclusion: In the nutshell that the outcome in terms of frequency of post-operative pain is significantly better in cases where ilio-inguinal nerve is sectioned as compared with those where nerve is preserved during hernioplasty for inguinal hernia.

Background & Objectives: COVID-19 is a global pandemic, also affecting Pakistan with its first case reported on 26th February 2020. Since then, it has been a total of 217,809 positive cases and 4473 deaths in Pakistan so far. Deranged liver function enzymes levels are prominently detected extra-pulmonary clinical manifestation of COVID-19 reported by at least one-half of the patients. Our study aimed to evaluate these derangements in our population. Methods: A retrospective, observational study was conducted to include all the admitted patients having COVID-19 positive, and evaluated those for derangements of liver function enzymes (n=77). The statistical analysis was conducted to compare those derangements amongst the disease severity, prognostic markers, and death. Results: Out of the 77 patients, 55 were admitted in the ward, 22 were in ICU, 61 of them recovered, while 16 deaths reported. The most deranged liver enzyme was found out to be Gamma-glutamyl transferase (51.94%), followed by Aspartate transferase (41.55%), Alanine transferase (28.57%), and Alkaline phosphatase (14.28%). Total bilirubin was deranged in only 10 patients, however, direct bilirubin was above the normal range in 33 patients, while indirect component in only 4 patients. Increased direct bilirubin, Aspartate aminotransferase, and Gamma-glutamyl transferase were associated with increased mortality, increased ICU admissions, increased neutrophils, lymphocytopenia, leukocytosis, and neutrophil to lymphocyte ratio>3, while Alanine aminotransferase and Alkaline phosphatase were not associated with the above factors. Conclusion: The deranged values of liver function enzymes in COVID-19 are correlated with an increased number of ICU admissions, mortalities as well as prognostic markers.

Sleep is an important part of one’s daily routine and sleeping less than 6 hours at night is considered decreased somnolence. The frequency of obesity is shooting up worldwide, mainly in developed countries. Obesity has become a very grave root cause of health issues in our society. Our study aims to find out the association between obesity and sleep, and the frequency of poor sleep quality among normal weight-bearing and overweight individuals. It was conducted as a cross-sectional, observational, questionnaire-based survey, a total of 380 subjects were randomly selected from the community. Sleep quality was compared among both the groups using standard validated scale questionnaire for sleep quality (Pittsburg Sleep Quality Index). Our study found out that out of 380 individuals who were being inquired 228 (60%) individuals were normal weight-bearing and 68 (30%) were overweight. Sleep quality was found to be impaired in 120 (52%) of normal-weight individuals as compared to 36 (45%) overweight individuals, although mean PSQI was higher in overweight’s (p=0.008). We further found that self-reported sleep duration was not different in normal as well as overweight individuals. The rate of poor sleep quality was found equal among male and female overweight individuals. It is concluded that sleep quality is dependent on various factors including sleep awareness, sleep hygiene, environment, and other factors that should be taken into account also regardless of the weight of the person. We also recommend that working on awareness regarding the importance of sleep and helping parents to establish an appropriate sleep routine for young children may be useful in preventing obesity.

Hepatocellular carcinoma is ranked as the sixth most common cancer globally. It also accounts for the second leading determinant of cancer-related mortalities worldwide. In the present day, transarterial chemoembolization (TACE) is the treatment modality of preference for high burden hepatocellular carcinoma. Our study aims to report the efficacy of TACE and alterations in laboratory parameters in patients of hepatocellular carcinoma before and after undergoing TACE in lieu with size >3 cm or 3cm tumor size (p=0.050). After TACE, bilirubin levels were remarkably improved in 3cm tumor size. Serum creatinine worsened in 3 cm tumor size, and SGPT was indifferent in 3cm tumor size. Mean meld score was found improved in both the study groups however, greater improvements were seen in >3cm tumor size group. Downstaging of child-pugh classes was statistically significant in both the study groups (p

Osteogenesis Imperfecta (OI) is a genetic disorder of bone fragility. In most cases, genetic testing is not usually done either due to a lack of availability or unaffordability. In our study, we looked for a rare gene variant in a patient with Osteogenesis Imperfecta type 1. Our patient who was a 6-month-old baby boy presented to us with multiple bone fractures, blue sclera, umbilical hernia with the absence of dentinogenesis Imperfecta, and hypercalcemia. A gene sequencing came out to be COL1A1 positive having a nucleotide change of glycine acid mutation replaced by serine, which was a unique feature in a patient of OI, and as Glycine was critical for COL1A1 gene, its replacement leads to the patient presented as a homozygous case of OI. OI is usually diagnosed on a history of recurrent spontaneous fractures and characteristic features like blue sclera, short stature, and deformities of long bones or spine.

Purpose of the study: Outbreaks of infectious diseases are known to have significant psychological effects not only on the general population but on health care workers as well. The COVID-19 pandemic also has been a challenge for Healthcare workers across the globe when it comes to their mental health. Study design: This is an observational cross-sectional study, carried out amongst the frontline doctors of COVID-19 units, by a well-structured questionnaire using Google Forms. The two scales used measure anxiety and depression among the healthcare workers were the Hamilton anxiety scale (HAM-A), and the hospital anxiety and depression scale (HADS). Results: The mean age of all the participants in the study was 25.40 ± 1.61, including 57% house officers/interns and 43% medical residents/postgraduate trainees. Both the anxiety and depression scales were significantly higher in house officers as compared to their senior doctors (residents/postgraduate trainees). According to HAM-A, 62% of respondents were in the mild category, 20% mild to moderate, 5% moderate to severe, while 14 respondents (13%) were in severe anxiety category. The HAM-A (P=0.078) and HADS for anxiety was significantly higher in females (P=0.001), while HADS for depression was statistically indifferent among the gender. The means of all scales got improved after the postings in Corona wards. The duration of practice also had an inverse correlation observed with all the studied scales. Conclusion: Depression and anxiety were seen quite higher in our population of health care workers with significant improvements that were observed after completing the rotations of corona units.

Thrombotic thrombocytopenic purpura (TTP) is a hematological disorder with an incidence of around 6.5 cases per million every year. It is characterized by the clot formation in blood vessels and resulting thrombocytopenia due to widespread utilization in the process. Other clinical features include hemolytic anemia, neurological abnormalities, fever, and renal failure. The cause can be either congenital or acquired secondary to infections, the use of certain drugs, and autoimmune disorders. On the other hand, Dengue fever is a viral infection that can result in multiple systemic complications including disrupted coagulation, renal dysfunction, and inflammation in the liver, brain, and myocardial pathology. In this case report, we present a rare presentation of thrombotic thrombocytopenic purpura in a patient with dengue fever. The mortality rate, in untreated cases, has been reported by up to 90%. With timely diagnosis and management with plasmapheresis, this can be reduced to 10-20%. Currently, it is important to control such an unknown outbreak of Dengue fever, as it is a serious health care issue of disease control and prevention in Pakistan.

This is a cross-sectional study conducted to determine the frequency and spectrum of bleeding disorders in different regions of Pakistan and to improve facilities to cure them. Samples were collected from different regions of Pakistan. There bleeding presentation and history of the family were recorded. 435 patients were selected from the different regions of Pakistan; 318 male (73%) and 117 female (26%). Laboratory analysis included Prothrombin time, Activated partial thromboplastin time, Bleeding time, platelet counts and fibrinogen assay were performed. According to their results, vWF:Ag, vWF:RCo, inhibitor screening, Bethesda test, urea clot solubility test, and platelet aggregation test were performed to diagnosed bleeding disorders in patients. Out of 435 patients, 283 constitute CBD, 80 diagnosed with RBD, and 72 remain undiagnosed. Patients diagnosed with 52% hemophilia A, 1.4% with its inhibitor, 8.4% with hemophilia B, 0.35% with its inhibitor, 3.88% with VWD, 33.5%with its type III. A rare bleeding disorder is diagnosed in 80 subjects with 20% fibrinogen, 16.25% FXIII, 15% FVII, 11.25% FV, 10% vitamin k dependent factors, 8.25% GT, 5% FXII and epinephrine, 2.5% FII and FX and 1.25% FV + FVIII, BSS and FXI deficiencies. Clinical bleeding episodes varied in patients with respect to its deficiencies include gum bleeding, menorrhagia, hematoma, bruises, umbilical cord bleeding, hemorrhagia, and hemarthrosis. Study shows that hemophilia A is more frequent than hemophilia B. vWD type III has a higher prevalence. In RBD, fibrinogen deficiency is the most common, followed by FXIII, FVII, and FV respectively.

In the new Coronavirus Disease 2019 (COVID-19) pandemic, cancer patients are considered a particularly susceptible population. We compared the type and magnitude of COVID-19 clinical manifestations among cancer patients in our center to non-cancer COVID-19 affected patients including 99 patients (28 cancer patients and 71 non-cancer patients). Hepatocellular carcinoma, breast carcinoma, and leukemia were the most common cancers. Diabetes and hypertension were prevalent comorbidities. Dyspnea, cough, fatigue, myalgia and diarrhea were statistically indifferent in both groups. Fatigue was more pronounced in cancer patients [OR: 2.573(1.025-6.460), p = 0.041] along with early onset of bilateral patchy consolidation [HR: 3.127(1.197-5.851), p = 0.032].

Supplemental Digital Content is available in the text., IMPORTANCE: At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES: To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES: Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS: Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE: Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

Background: Recurrent overt or occult gastrointestinal (GI) bleeding is a serious complication of von Willebrand Disease (VWD) and is the most common cause of hospitalization for patients with VWD. Data from the VWD Prophylaxis Network (VPN) emphasized the importance of prophylaxis in minimizing bleeding episodes in VWD; however, the management of GI bleeding in these patients remains challenging. Despite the availability of von Willebrand factor (VWF) replacement therapy, GI bleeding may be refractory and require the use of multiple treatment approaches. Currently, there are limited published data and no consensus regarding the most effective treatment for GI bleeding in patients with VWD. Aims: To describe the natural history of treatment and management of GI bleeds in patients with VWD, stratified by those patients who have a history of GI bleeding that precedes this chart review versus patients who experienced their first GI bleed within the 5 years of this chart review. Outcomes following the use of VWF replacement products and adjuvant therapy, including recombinant VWF were collected. Methods: This ongoing retrospective, multicenter, observational chart review (abstraction initiated 2019) will include up to 20 patients from 6 US centers with confirmed congenital VWD with ≥1 GI bleed within the last 5 years. Demographics and clinical information, including potential etiology, treatment regimens, will be gathered from patient records on all recorded GI bleeds within the last 5 years. Clinical effectiveness will be defined by treatment response, change in duration of treatment, or time to bleed resolution across treatment cohorts (e.g., prophylaxis vs on-demand; recombinant VWF [rVWF] vs plasma-derived VWF [pdVWF]), at the time of a GI bleed and for any subsequent period of prophylactic treatment to prevent GI bleed recurrence. Data will be analyzed descriptively. Results: To date, data on 37 bleeds in 13 patients with Type 1 (23%), Type 2 (46%) or Type 3 (31%) VWD have been abstracted; 54% were female, mean (±SD) age was 53.9 (22.0) years, 85% had ≥1 recorded GI-specific morbidity, 6 patients (46%) had no history of prior GI bleeding. Three patients (23%) were on regular prophylaxis using pdVWF-factor VIII (FVIII) concentrates at initial GI bleed presentation. All were receiving Humate-P; dose was not recorded for 2 patients and 1 patient received 50 IU/kg. Out of 37 bleeding episodes, 9 (24%) occurred in patients during VWF prophylaxis, of which 7 occurred in 1 patient. Among the 7 patients with a previous history of GI bleeding, 1 was on a prophylactic regimen prior to the initial GI bleeding episode. None of the patients without a history of GI bleeding were on a prophylactic regimen at the initiation of the chart review; 1 patient was receiving prophylaxis at the time the fourth bleed was documented. On-demand treatment for GI bleeding included aminocaproic acid, tranexamic acid, pdVWF-FVIII concentrates, rFVIII, rVWF, corticosteroids, polypectomy, and thalidomide. After resolution of the GI bleeding episode, in 17/37 bleeding events, prophylactic treatment continued (either as part of the final treatment regimen to resolve the bleed and sustained prophylaxis, or after the final treatment regimen purely as prophylaxis). At the conclusion of data collection for the current patients, 4 out of 6 without a GI bleeding history, and 1 out of 7 with a GI bleeding history, were receiving prophylaxis. Conclusions: Data from this retrospective chart review are the first to describe prophylactic regimens prior to and after GI bleeding, in VWD patients with and without a GI bleeding history. More patients with congenital VWD and a history of GI bleeding were treated with prophylaxis following GI bleeds, compared to patients without a history of GI bleeds. These data describe the role of prophylaxis in management of GI bleeding and add to existing data from the VPN describing a modest reduction of GI bleeding in some patients on prophylaxis. These data underscore the continuing unmet need of the successful management of GI bleeding in VWD. Further data will be collected, and additional analyses performed to determine if this trend persists in a larger sample of patients with VWD. Disclosures Roberts: uniQure:Consultancy;Takeda:Consultancy, Research Funding, Speakers Bureau;Pfizer:Consultancy;Novo Nordisk:Consultancy, Speakers Bureau;Sanofi:Consultancy, Speakers Bureau;Octapharma:Consultancy, Speakers Bureau.Escobar:National Hemophilia Foundation:Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda:Consultancy, Membership on an entity's Board of Directors or advisory committees;Sanofi:Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer:Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech, Inc.:Consultancy, Membership on an entity's Board of Directors or advisory committees;Novo Nordisk:Consultancy, Membership on an entity's Board of Directors or advisory committees.Acharya:Novonordisk, BPL:Membership on an entity's Board of Directors or advisory committees.Hwang:Takeda:Honoraria;Shire:Honoraria.Wang:Bioverativ Inc:Honoraria;CSL Behring:Honoraria;Biomarin:Honoraria;Genentech:Honoraria;Takeda:Honoraria;Bayer:Honoraria.Hale:Takeda Pharmaceutical Company Limited:Current Employment.Oladapo:Takeda:Current Employment, Current equity holder in publicly-traded company.Asghar:HCD Economics:Current Employment.

Introduction Severe hemophilia A (SHA) is characterized by spontaneous (non-trauma related) bleeding episodes into the joint space and muscle tissue, leading to progressive joint deterioration and chronic pain. Chronic joint damage is most often associated with severe hemophilia, however more recent research has illustrated that people with moderate hemophilia A (MHA) also experience hemophilic arthropathy and functional impairment. The need to measure joint health in children as well as adults, is underscored by findings from the Joint Outcome Continuation Study, which found that FVIII prophylaxis was insufficient to protect joints from damage, from childhood through adolescence in severe HA (Warren et al., 2020). The objective of this analysis is to gain a more patient-centric understanding of the clinical, economic and humanistic burden associated with 'Problem Joints', a measure of joint morbidity developed in consultation with an expert panel to overcome limitations with existing measures, in people with MHA and SHA. Methods A descriptive cohort analysis was conducted, utilizing retrospective, cross-sectional real-world data from the 'Cost of Haemophilia in Europe: a Socioeconomic Survey' (CHESS Paeds and CHESS II), studies of adult and pediatric persons with hemophilia. The analysis population is comprised of children (17 and below) with MHA or SHA in CHESS Paeds, and adults aged 20 and over with MHA or SHA in CHESS II. To account for the possibility that persons aged 18 or 19 in CHESS II may have participated in CHESS Paeds, these individuals were excluded from the analysis. Physician-reported clinical outcome data and patient/caregiver-reported quality of life were analyzed. A problem joint (PJ) is defined as having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e. chronic synovitis and/or hemophilic arthropathy). Analyses were stratified by number of PJs: none, 1 PJ, and 2+ PJs. We report retrospective data of the 12 months prior to study enrollment, on annualized bleeding rate (ABR), prevalence of target joints (TJ), as defined by the International Society on Thrombosis and Haemostasis, and EQ-5D-/5L/Y/Proxy score. Results are presented as mean (standard deviation) or N (%). Results Among 785 participants (N = 464 SHA; N = 321 MHA) in CHESS Paeds, mean age and BMI were 10.33 (4.63) and 22.50 (17.07), respectively. Of 493 participants (aged 20 and above) in CHESS II (N = 298 SHA; N = 195 MHA), the mean age and BMI were 38.61 (14.06) and 24.55 (2.92), respectively. Current inhibitor to FVIII replacement was more prevalent in children than in adults (10% vs. 5%). In CHESS II, approximately 40% of people with MHA and 49% with SHA had one or more PJs, respectively [1 PJ (23% vs. 28%); 2+ PJs (16% vs. 21%)]. In CHESS Paeds, approximately 14% of children with MHA and 18% with SHA had at least one PJ, respectively [1 PJ (9% vs. 14%); 2+ PJs (5% vs. 3%)]. TJs were less prevalent with MHA in comparison to SHA, in both adults (24% vs. 45%) and children (13% vs. 22%). Clinical burden was higher among both children and adults with PJs compared to those with no PJs. ABR correlates with the number of PJs, in those with MHA and SHA in CHESS II (Figure 1). Similarly, PJs were associated with higher ABR across MHA and SHA in CHESS Paeds (Figure 2). Hemophilia-related hospitalizations were higher in both adult and pediatric participants with PJs. In CHESS II, MHA with no PJs had fewer [0.73 (1.23)] hospitalizations compared to having those with 1 PJ [1.38 (1.11)] or 2+ PJs [1.28 (1.25)]. Similarly, children with MHA with 2+ PJs had 1.60 (1.92) hemophilia-related hospitalizations, compared to 1.38 (1.92) with 1 PJ and 0.71 (1.14) with no PJs. PJs were associated with impaired quality of life. In CHESS II, MHA and SHA EQ-5D-5L values in persons with no PJs were 0.81 (0.19) and 0.79 (0.18), respectively, compared to 0.65 (0.16) and 0.62 (0.23) with 1 PJ, and 0.65 (0.14) and 0.51 (0.33) in with 2+ PJs. A similar trend was observed in EQ-5D-Y and EQ-5D-proxy scores in CHESS Paeds. Conclusions Data from CHESS Paeds and CHESS II demonstrate an association between chronic joint damage, as measured by the 'problem joint' definition, and worsening clinical and quality of life outcomes, across both MHA and SHA. Further analyses will seek to expand upon the initial results presented here, to investigate the wider elements of burden associated with compromised long-term joint health. Disclosures McLaughlin: BioMarin: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Roche/Chugai: Speakers Bureau; Takeda: Speakers Bureau. Hermans:Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; WFH: Other; EAHAD: Other; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; LFB: Consultancy, Speakers Bureau. Asghar:HCD Economics: Current Employment. Burke:HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Nissen:GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Aizenas:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Dhillon:HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara:F. Hoffmann-La Roche Ltd: Consultancy; HCD Economics: Current Employment, Current equity holder in private company.

INTRODUCTION Severe hemophilia A ( Recent commentary has identified a number of patient-important and patient-relevant outcomes that have been understudied, namely the challenges faced by people living with hemophilia to participate in the labor force. The socio-economic impact of hemophilia is comparatively less well understood than clinical outcomes and therapy-related costs. Under-employment and under-utilization have long-term consequences to individuals' job prospects and psychosocial health, as well as an economic cost to the society. The objective of the analysis is to compare labor market participation, among people with severe hemophilia from the US and the general population. This analysis draws on household data derived from the 2019 Current Population Survey (CPS), and on patient-reported data from a patient-centric study conducted in 2019 of people with severe hemophilia, in the US: the 'Cost of Severe Hemophilia Across the US: A Socioeconomic Survey' (CHESS US+). METHODS A patient-centric framework informed the design of CHESS US+ a retrospective (12 months prior to study enrollment), cross-sectional dataset of adults with severe hemophilia in the US. Conducted in 2019, the study used a patient-completed questionnaire to collect data on patient-relevant clinical, economic, and humanistic outcomes. This analysis examines labor market participation (full-time, part-time, unemployed), and corresponding general population data derived from the 2019 Current Population Survey (CPS). Data on the general population were sourced from the 2019 CPS 'Employment status of the civilian noninstitutional population'. Persons 'not in the labor force' in the 2019 CPS and retired persons in CHESS US+ were not included in the analysis. We present data on the civilian labor force, in CHESS US+ and in the 2019 CPS. Results are presented as mean (standard deviation) or N (%). RESULTS Of 356 patients profiled in the CHESS US+ study, 97 (27%) had severe hemophilia B and 257 (73%) had severe hemophilia A. Mean age and weight (kg) of the cohort was 34.99 (12.15) and 85.71 (22.81), respectively. The labor force participation rates of non-retired people with severe hemophilia in CHESS US+ (N = 340) and the general population (161,458) are described in Table 1. Examining aggregate data on employment status observed a higher proportion of people with severe hemophilia in part-time employment (24.4% vs. 15.7%). Differences in the labor force participation of people living with severe hemophilia compared to the general population were most pronounced in the full-time employment rate and the unemployment rate. Compared to 80.7% of the general population (Table 1), only 53.5% of people with severe hemophilia in CHESS US+ had a full-time job. Moreover, the unemployment rate (Table 1) in the 2019 CPS compared with the rate observed in CHESS US+ (3.7% vs. 22.1%) provides a stark contrast in the employment experiences of people living with severe hemophilia relative to the general population. CONCLUSIONS This analysis of CHESS US+ illustrates the impact of severe hemophilia on labor force participation. People with severe hemophilia were more likely than the general population to be unemployed, or in part-time employment. A notable contrast was observed in the rate of full-time employment and unemployment, among the general population compared to people living with severe hemophilia. These data illustrate the need to quantify the impact of hemophilia using a holistic approach that considers the cost of involuntary illness-related part-time and unemployment. Disclosures Asghar: HCD Economics: Current Employment. Burke:HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy; University of Chester: Current Employment. Misciattelli:Freeline: Current Employment, Current equity holder in publicly-traded company. Kar:Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan:HCD Economics: Current Employment; uniQure: Consultancy. O'Hara:F. Hoffmann-La Roche Ltd: Consultancy; HCD Economics: Current Employment, Current equity holder in private company.

INTRODUCTION Severe hemophilia, i.e., The ability of people living with hemophilia to participate in the labor force, without barriers to job choice or working hours, is a key outcome in the drive to achieve health equity. The objective of the analysis is to examine the relationship between adherence and the labor force participation of people with severe hemophilia in the US. METHODS This analysis draws data from a patient-reported study, the 'Cost of Severe Hemophilia Across the US: A Socioeconomic Survey' (CHESS US+). Conducted in 2019, the CHESS US+ study is a cross-sectional patient-centered study of adults with severe hemophilia in the US. A patient-completed questionnaire collected data on clinical, economic, and humanistic outcomes, for a 12-month retrospective period. This analysis examines labor force participation and employment status (full-time, part-time, unemployed, retired) and chronic pain categorized by 'none', low-level ('1-5'), and high-level ('6-10'). The analysis was stratified by adherence to treatment, self-reported on a 1-10 scale, from "not at all" to "fully", categorized into low (1-6), moderate (7-9) and full (10) adherence. Results are presented as mean (standard deviation) or N (%). RESULTS The analysis comprised 356 people with severe hemophilia A (73%) and B (27%) who participated in CHESS US+ study. In Table 1, the baseline characteristics of the study population are stratified by full adherence (N = 119), moderate adherence (N=134) and low adherence (N=103). Having no chronic pain was most prevalent in the full adherence group (37.7%), compared to moderate (8.3%) or low (13.9%) adherence cohorts. Chronic pain, both low- and high-levels were least prevalent among people with full adherence. Moreover, people with low adherence were disproportionately more likely to have high-levels of chronic pain relative to moderate adherence or full adherence (Table 1). Unemployment, however, was highest in full adherence (21.1%), and people with full adherence were also least likely to be in full-time employment (42%). The full-time employment rate decreased as adherence declined from full to moderate (Table 1), and was comparable in people with low adherence (57.3%) or moderate adherence (54.5%). CONCLUSIONS This analysis of CHESS US+ examined the complex relationship between labor market outcomes and adherence to treatment, among adults with severe hemophilia in the US. Adherence was associated with lower rates of chronic pain, representing the importance of achieving an optimal treatment strategy. Nonetheless, patients achieving optimal adherence were less likely to be in full-time employment, and more likely to be part-time or unemployed, comparatively. Together, these data characterize a trade-off in clinical outcomes versus workforce participation, and suggest that the goal of achieving health equity may currently still be unmet. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar:HCD Economics: Current Employment. Misciattelli:Freeline: Current Employment, Current equity holder in publicly-traded company. Kar:Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan:uniQure: Consultancy; HCD Economics: Current Employment. Dhillon:HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.