Split Dosage Weekly Regimen of Oral Methotrexate is Associated With Improved Side Effect Profile in Rheumatoid Arthritis Patients: A Quasi-Experimental Study.

Background and objectives: Methotrexate (MTX) is globally used by physicians to treat patients with Rheumatoid Arthritis (RA). Previously conducted researches indicate prevalent side effects associated with conventional once-weekly dosage amongst a population sample of patients consuming MTX. The objectives of our study were to find out whether there is a difference between the two studied regimens in efficacy and adverse effects of methotrexate. Materials and methods: Study participants were recruited from the outpatient rheumatology department after ethical approval and informed patient consent. Disease activity was assessed at baseline with various reliable and validated scales (SDAI, PAS, DAS-28 among others) after the propensity score-matched 1:1 among the two groups. One group continued their once-weekly regimen (group A), while the other group had their dosage of oral MTX split into alternate days per week (group B). The propensity-matched groups of 123 patients each were included in the final analysis. Results: The most frequently reported side effect was decreased appetite, followed by gastritis, nausea, headache, and vomiting. Within the two groups, no significant differences were found in disease activity scales. The only considerable difference was mean corpuscular volume (MCV) being higher in Group A (p = 0.0128). Comparison of side effect profile at 6 months after intervention showed improved gastritis (63.4 vs 41.5%), nausea (51.2% vs 35.8%), appetite (74.0% vs 60.2%) and hepatotoxicity (14.6% vs 5.7%) in Group B. Conclusion: An alternate-day regimen may prove more beneficial to the patient's compliance due to fewer side effects and similar efficacy to the conventional dosage.

Hematological Indices Predicting the Severity of Acute Pancreatitis Presenting to the Emergency Department: A Retrospective Analysis.

Introduction Acute pancreatitis is defined as inflammation of the pancreas. The body responds to inflammation by producing excessive neutrophils and causing programmed cell death of lymphocytes. This leads to immunological instability, which increases the severity of the disease and mortality rate. Recent data suggest that markers of systemic inflammation are able to predict the prognosis of various diseases. Our study aims to assess the severity of acute pancreatitis in conjunction with these hematological markers of systemic inflammation. Materials and methods Our study was carried out in the emergency medicine department of a tertiary care hospital among patients diagnosed with acute pancreatitis. It was a retrospective study done by reviewing the hospital's medical records. Hematological indices such as hemoglobin levels, packed cell volume (PCV), red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), total leukocyte count (TLC), neutrophil count, lymphocyte count, monocyte count, platelet count, neutrophil to lymphocyte count ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) were observed to be associated with severity of pancreatitis. Those with computed tomography (CT) severity score >=7 were termed as severe pancreatitis, while those below 7 were considered mild to moderate. Results A total of 154 patients were included in the final analysis. The mean age of those patients was 48.47 ± 16.71 years. There were 94 male and 60 female patients. There was no difference found among the study groups with respect to mean hemoglobin levels, RBC count, PCV, MCV, MCH, MCHC, lymphocytes, and platelet counts. TLC (p<0.001), neutrophils (p<0.001), monocytes (p=0.008), NLR (p<0.001), and PLR (p=0.006) were found higher in severe pancreatitis, while LMR was found lower in severe pancreatitis (p=0.003). A linear relationship between the hematological indices and CT severity score has shown that TLC (p=0.015), neutrophils (p=0.005), NLR (p=0.001), and PLR (p<0.001) were positively correlated with severity while lymphocyte count (p=0.004) and LMR (p=0.005) were negatively correlated with severe pancreatitis. TLC and LMR were independent predictors of severe pancreatitis with an adjusted odds ratio of 12.80 and 5.47, respectively, on multivariable regression analysis. Conclusion Many markers correlated with the CT severity score, but few of them were able to demonstrate statistical significance on receiver operating characteristic (ROC) analysis.

Clinical, epidemiological, and diagnostic characteristics of esophageal carcinoma in a Pakistani population.

BACKGROUND: Esophageal cancer ranks eighth among the most prevalent cancers globally and is the sixth leading cause of mortality from malignancy worldwide; it is the 7th most prevalent malignancy in males and the 6th most prevalent malignancy in females. In Pakistan, the incidence is 4.1 per 100 000 with the province of Baluchistan having the greatest incidence. OBJECTIVE: Report trends and characteristics of esophageal cancer in Pakistan over the past 10 years. DESIGN: Cross-sectional, retrospective review of medical records. SETTING: Tertiary care hospital. PATIENTS AND METHODS: The study included all patients admitted with a diagnosis of esophageal carcinoma with a mass lesion or luminal narrowing. The records were for the period from January 2011 to September 2020. MAIN OUTCOME MEASURES: Gender, histopathological types/differentiation along with clinical/laboratory findings. SAMPLE SIZE: 1009 with a mean (standard deviation) age of 49.3 (14.2) and a median (interquartile range of 50 (22) years (443 males and 566 females with age of 51.0 [20] years and 47.9 [23.8] years, respectively). The male-to-female ratio was 1:1.2. RESULTS: Most patients (82.7%) had squamous cell carcinomas with a male-to-female ratio of 1:2; the remainder had adenocarcinomas with a male-to-female ratio of 4:1 (P<.001). Dysphagia, weight loss, and vomiting were the most prevalent symptoms. More adenocarcinoma masses were located distally compared with squamous cell carcinomas (P=.030), lesions were most likely to be ulcerated (P=.910). Luminal narrowing was slightly more frequent in squamous cell carcinoma (P=.215), thickening was more prominently circumferential in the adenocarcinomas. In squamous cell carcinoma, the most common variant was moderately differentiated while moderate to poorly differentiated variants were more common in adenocarcinoma. In the survival analysis, squamous cell carcinoma (P=.014 vs adenocarcinoma), particularly the well-differentiated type (P=.018 vs other variants), projected a better prognosis. CONCLUSION: Our study reports the most recent trends of esophageal carcinoma in this region. LIMITATIONS: Lack of metastatic workup, TNM staging, and mode of treatment, along with the overlapping pattern of histological variants. CONFLICT OF INTEREST: None.

Prognostic Value of Preoperative Pro-B-Type Natriuretic Peptide: Early Predictor of Cardiovascular Complications and Mortality After Major Abdominal Surgery.

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.

Hematological parameters predicting severity and mortality in COVID-19 patients of Pakistan: a retrospective comparative analysis.

BACKGROUND AND OBJECTIVES: COVID-19 is a global pandemic. In our study, we aimed to utilize the hematological parameters in predicting the prognosis and mortality in COVID-19 patients. MATERIALS AND METHODS: A retrospective, observational study was conducted to include all the admitted patients (n = 191) having COVID-19 Polymerase chain reaction (PCR) positive, and evaluated those for prognosis and disease outcome by utilizing several biochemical and hematological markers. RESULTS: Amongst the patients admitted in the ward versus in the intensive care unit (ICU), there were significant differences in mean hemoglobin (P = 0.003), total leukocyte count (P = 0.001), absolute neutrophil and lymphocyte counts (P < 0.001), absolute monocyte count (P = 0.019), Neutrophil-to-Lymphocyte ratio (NLR) and Lymphocyte-to-Monocyte ratio (LMR) (P < 0.001), Platelet-to-Lymphocyte ratio (PLR) and Lymphocyte-to C-reactive protein ratio (LCR) (P = 0.002), and C-reactive protein (CRP) levels (P < 0.001). Amongst the deceased patients, there was significant leukocytosis (P = 0.008), neutrophilia and lymphopenia (P < 0.001), increased NLR (P = 0.001), decreased LMR (P < 0.001), increased PLR (p = 0.017), decreased LCR (p = 0.003), and elevated CRP level (P < 0.001). A receiver operating characteristic curve obtained for the above parameters showed NLR (AUC: 0.841, PPV: 83.6%) and PLR (AUC: 0.703, PPV: 81.8%) for ICU patients, while NLR (AUC: 0.860, PPV: 91.1%) and PLR (AUC: 0.677, PPV: 87.5%) for the deceased patients had significant accuracy for predicting the disease severity of COVID-19 in comparison to survivors. CONCLUSION: The inflammatory markers and hematological indices are a good guide for predicting the severity and disease outcome of coronavirus disease. NLR and PLR are elevated in severe disease while LMR and LCR are inversely correlating with disease severity.

Role of Biochemical Markers in Invasive Ventilation of Coronavirus Disease 2019 Patients: Multinomial Regression and Survival Analysis.

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.

Sigmoid volvulus: a rare but unique complication of enteric fever.

We present a case of sigmoid volvulus in a young male patient with culture-proven Salmonella Typhi in the blood which was sensitive to Meropenem and Azithromycin only, presented with fever, vomiting, loose stools, hematochezia, abdominal distention and tenderness with no signs of perforation on erect chest x-ray. Further, radiological imaging showed signs of sigmoid volvulus. An urgent colonic decompression with untwisting of the mesentery was performed. In our case, it can be said that sigmoid volvulus was developed as a complication of multiple drug-resistant strains of Salmonella Typhi. The resistance is acquired by alteration in the genome sequence. Currently, it is important to control such an unknown outbreak of multiple drug-resistant strains of Salmonella Typhi as it is a serious health care issue of disease control and prevention in Pakistan.

Diagnostic Accuracy of Endoscopic Ultrasonography Versus the Gold Standard Endoscopic Retrograde Cholangiopancreatography in Detecting Common Bile Duct Stones.

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.

Severity of Non-B and Non-C Hepatitis Versus Hepatitis B and C Associated Chronic Liver Disease: A Retrospective, Observational, Comparative Study.

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 <0.05 was considered statistically significant (two-tailed). Results The mean age of the study population was 51.83 ± 13.67, with no difference in gender and type of CLD. The frequent co-morbidities (other than CLD) found in the study population were diabetes, hypertension, ischemic heart disease, and chronic kidney disease, with most of them having significant association with non-hepatitis B, C-CLD. Both types of CLD had equal gender proportion (p=0.708). Among the study groups, 56.28% (n=94) had hepatitis B, C-CLD, out of which 18 (19%) belonged to Child-Pugh class A, 36 (38%) to Child-Pugh class B, and 40 (43%) to Child-Pugh class C, whereas 43.72% (n=71) had non-hepatitis B, C-CLD, comprising of 13% (n=10) of Child-Pugh class A patients, 42% (n=31) of Child-Pugh class B patients, and 44% (n=32) of Child-Pugh class C patients (p=0.631). Bilirubin levels (p=0.055), serum creatinine (p=0.201), and International normalized ratio (INR) are found higher in non-hepatitis B, C-CLD (p=0.312), whereas thrombocytopenia was more likely to be associated with hepatitis B, C-CLD (p=0.205). Hyponatremia was slightly associated with non-hepatitis B, C-CLD (p=0.281). The mean MELD score was comparable among the two study groups in both Child-Pugh classes A and B, but in Child-Pugh class C it was significantly higher in non-hepatitis B, C-CLD patients as compared to hepatitis B, C--CLD (p=0.006). Conclusion Non-hepatitis B, C-CLD was proved to be milder in Child-Pugh class A as compared to hepatitis B, C-CLD, but its mortality risk increases with severity, as mean MELD score was found significantly higher in Child-Pugh class C. Our research was able to identify severe biochemical markers in both types of CLD.

A Comparative Study on the Use of Alprazolam and Melatonin for Sleep Disturbances in Hemodialysis Patients.

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.