Evaluation of quality of warfarin therapy by assessing patient\u27s time in therapeutic range at a tertiary care hospital in Pakistan

Objective: To assess the time in therapeutic range in patients on warfarin anti-coagulation therapy. Methods: The retrospective chart review was conducted at Aga Khan University Hospital, Karachi, and comprised data of patients having undergone anti-coagulation with warfarin from January 2013 to April 2015. To determine the mean time in therapeutic range, Rosendaal method was used. Association of time in therapeutic range with the composite outcome, bleeding and thromboembolic events was also assessed. Percentage of patients with time in therapeutic range \u3c60% was calculated. Results: There were 92 patients whose median time in therapeutic range was 34.9% (interquartile range: 20.0- 55.7). Overall, 71(77.2%) patients had time in therapeutic range below 60% which had statistically significant correlation with the composite outcome (p\u3c0.05). Number of comorbids was significant in predicting time in therapeutic range and patients with time in therapeutic range\u3c 60% (p\u3c0.05). Conclusion: Subjects had poor anti-coagulation quality. It might be prudent to move towards novel oral anticoagulant drugsas the first choice for therapeutic anti-coagulation

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Functional outcomes of poor ergonomic posture in university workers

Background and Objectives: Work-related musculoskeletal disorders are increasing due to poor posture adaptation. Increasing the use of technologies in the office settings is one of the main reasons behind muscle and soft tissue strains. The objective of the study was to determine the pattern of posture-related musculoskeletal pain in office workers.Methods: This observational study was conducted from 15th May, to 25th June, 2021. Data were collected by convenient sampling. The Nordic Musculoskeletal questionnaire on body postural habits was filled by 150 office workers from different universities of Lahore. Statistical Package for the Social Sciences software version 25 was used for statistical analysis.Results: There were 79 (52.7%) male and 71 (43.7%) female participants, with a mean age of 35.7 &plusmn; 5.14 years. Majority (51.3%) of the subjects reported sitting tilted forward, while a few used backrests and footrests for support. Prolonged crossed legs and twisted spine posture were also adopted by many subjects. Neck, lower back, and shoulder were the most affected regions, with increased musculoskeletal pain reported over the last 12 months. Due to recurrent pain in the neck, shoulder, and upper back, difficulty in carrying out routine jobs, housework, and hobbies was reported by 38.7%, 34.7%, and 30% of the subjects, respectively.Conclusion: Failure to adopt a good ergonomic approach leads to frequent musculoskeletal pain and difficulty in carrying out routine office and household work.</p

Menggagas Ilmu Ekonomi Islam

xxviii, 256 hal., bibl., index; 21c

Comparison of instrument-assisted soft tissue mobilization and proprioceptive neuromuscular stretching on hamstring flexibility in patients with knee osteoarthritis

Background The association between hamstring tightness and knee osteoarthritis (KOA) is significant because tight hamstrings can put more strain on the knee joint, reduce its range of motion, and cause compensatory movements that worsen the KOA. Objective To compare the effects of instrument-assisted soft tissue mobilization (IASTM) and proprioceptive neuromuscular (PNF) on hamstring flexibility in patients with KOA. Methods Data for the randomized controlled trial (NCT05110326) was collected from n = 60 participants randomly divided into group A received IASTM and group B received PNF stretching. In group A, the therapist made 30 strokes gentle strokes with the tool from the origin to the insertion while holding the plane at a 45-degree angle over the treatment area. In group B, PNF stretching was done with three repetitions and 10 seconds rest between each, after isometric contraction of the hamstring muscle using approximately 50% of their maximum strength, holding it for 8 seconds, and then releasing it. A 30-minute session was given to each patient three times per week and was given for 6 weeks. Outcome measures were the visual analog scale (VAS) for pain intensity, the active knee extension test (AKET) for hamstring flexibility, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for the health status of KOA patients. Results The study found a significant interaction (p < 0.001) between interventions and time across several measurements. After 6 weeks, both interventions resulted in significant improvements (p < 0.001) across all dependent variables, with group A (IASTM) showing more significant improvement in hamstring flexibility, pain reduction, and health status (p < 0.001) compared to group B (PNF). Conclusions Both the IASTM technique and PNF stretching resulted in increased hamstring flexibility, decreased pain, and enhanced general health. The IASTM technique, however, showed potential benefits over PNF stretching in terms of flexibility, pain relief, and public health enhancement. Physical therapists and manual therapists may prioritize the usage of the IASTM technique for patients who want to make significant changes in these areas

High frequency and molecular epidemiology of metallo-β-lactamase-producing gram-negative bacilli in a tertiary care hospital in Lahore, Pakistan

Abstract Background Metallo-β-lactamase (MBL)-producing isolates have a strong impact on diagnostic and therapeutic decisions. A high frequency of MBL-producing gram-negative bacilli has been reported worldwide. The current study was based on determining the incidence of MBL-producing imipenem-resistant clinical isolates and investigating the β-lactamase gene variants in strains conferring resistance to a carbapenem drug (imipenem). Methods A total of 924 gram negative isolates were recovered from a tertiary care hospital in Lahore, Pakistan, during a two-year period (July 2015 to February 2017). The initial selection of bacterial isolates was based on antibiotic susceptibility testing. Strains resistant to imipenem were processed for the molecular screening of β-lactamase genes. Statistical analysis for risk factor determination was based on age, gender, clinical specimen and type of infection. Results The rate of imipenem resistance was calculated to be 56.51%. Among the 142 strains processed, the phenotypic tests revealed that the incidence of MBLs was 63.38% and 86.61% based on the combination disc test and the modified Hodge test, respectively. The frequencies of bla TEM, bla SHV, bla OXA, bla IMP-1, and bla VIM genes were calculated to be 46%, 34%, 24%, 12.5% and 7%, respectively. The co-expression of bla MBL (bla IMP and bla VIM) and bla ESBL (bla TEM, bla SHV, bla OXA) was also detected through multiplex and singleplex PCR. bla OXA, bla TEM and bla SHV coexisted in 82% of the isolates. Co-expression of ESBL and MBL genes was found in 7% of the isolates. Conclusion To our knowledge, this is the first report from Pakistan presenting the concomitant expression of bla OXA, bla TEM and bla SHV with bla IMP-1 and bla VIM in MBL-producing gram-negative bacilli

Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2 Gene Underlying Nephrotic Syndrome

Background and Objectives: Nephrotic syndrome (NS) is a kidney disease where the patient has a classic triad of signs and symptoms including hypercholesterolemia, hypoalbuminemia, proteinuria (&gt;3.5 g/24 h), and peripheral edema. In case of NS, the damaged nephrons (structural and functional unit of the kidney) filter unwanted blood contents to make urine. Thus, the urine contains unwanted proteins (proteinuria) and blood cells (hematuria), while the bloodstream lacks enough protein albumin (hypoalbuminemia). Nephrotic syndrome is divided into two types, primary NS, and secondary NS. Primary NS, also known as primary glomerulonephrosis, is the result of a glomerular disease that is limited to the kidney, while secondary NS is a condition that affects the kidney and other parts of the body. The main causes of primary NS are minimal change disease, membranous glomerulonephritis, and focal segmental glomerulosclerosis. In the present study we recruited a family segregating primary NS with the aim to identify the underlying genetic etiology. Such type of study is important in children because it allows counseling of other family members who may be at risk of developing NS, predicts risk of recurrent disease phenotypes after kidney transplant, and predicts response to immunosuppressive therapy. Materials and Methods: All affected individuals were clinically evaluated. Clinical examination, results of laboratory tests, and biopsy investigations led us to the diagnosis. The next-generation sequencing technique (whole-exome sequencing) followed by Sanger sequencing identified a novel homozygous splice site variant (NM_173689.7: c.941-3C&gt;T) in the CRB2 gene. The variant was present in a homozygous state in the affected individuals, while in a heterozygous state in phenotypically normal parents. Results: The study expanded the spectrum of the mutations in the gene CRB2 responsible for causing NS. Conclusions: In addition, the study will also help in genetic counseling, carrier testing, and prenatal and/or postnatal early diagnosis of the disease in the affected family