Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data.

BACKGROUND: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. METHODS: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype. RESULTS: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes. CONCLUSIONS: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

Bioprosthetic tricuspid valve dysfunction in patients with transvalvular or epicardial pacing leads.

BACKGROUND: Dysfunction of native tricuspid valves due to transvenous pacing leads is well described. Patients with bioprosthetic tricuspid valve (BTV) who need ventricular pacing are often advised epicardial lead placement to avoid potential damage to the BTV although there are no data to support this. OBJECTIVE: The aim of the study was to assess the frequency of BTV dysfunction in patients with permanent transvenous right ventricular pacemaker lead and compare it to patients with epicardial leads. METHODS: A retrospective review of patients with BTV with ventricular pacing lead was conducted. Demographics, lead, BTV, and echocardiographic data were collected. Frequency of BTV dysfunction (moderate or severe) regurgitation or stenosis was compared between epicardial and transvalvular lead groups. RESULTS: Forty-six patients with BTV and ventricular pacing lead (20 transvalvular and 26 epicardial leads) were identified. Mean age was 46 years with the majority being female (85%) and with rheumatic heart disease (87%). Both groups were similar in age, sex, and indications for BTV. Mean echocardiographic follow-up was for 5.5 years (±4.1 years). BTV dysfunction was similar between the transvalvular group with six (30%) patients and the epicardial group with five (19.2%) patients. The incidence of BTV dysfunction was greater in patients in sinus rhythm compared to patients in atrial fibrillation (50% vs 10%, P  =  0.004). CONCLUSION: Development of BTV dysfunction is similar in patients with transvalvular ventricular leads and epicardial leads. The incidence of BTV dysfunction was higher in patients with sinus rhythm compared to atrial fibrillation.

Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study.

BACKGROUND: Acute Kidney injury (AKI) is common and increases mortality in the intensive care unit (ICU). We carried out this study to explore whether fluid overload is an independent risk factor for AKI. METHODS: Single-center prospective, observational study. Consecutively admitted, ICU patients were followed for development of AKI. Intravenous fluid volumes, daily fluid balances were measured, hourly urine volumes, daily creatinine levels were recorded. RESULTS: Three hundred thirty nine patients were included; AKI developed in 141 (41.6%) patients; RISK in 27 (8%) patients; INJURY in 25 (7%); FAILURE in 89 (26%) by the RIFLE criteria. Fluid balance was significantly higher in patients with AKI; 1755 ± 2189 v/s 924 ± 1846 ml, p < 0.001 on ICU day 1. On multivariate regression analysis, a net fluid balance in first 24 h of ICU admission, OR 1.02 (95% CI 1.01,1.03 p = 0.003), percentage of fluid accumulation adjusted for body weight OR1.009 (95% CI 1.001,1.017, p = 0.02), fluid balance in first 24 h of ICU admission with serum creatinine adjusted for fluid balance, OR 1.024 (95% CI 1.012,1,035, p = 0.005), Age, OR 1.02 95% CI 1.01,1.03, p < 0.001, CHF, OR 3.1 (95% CI 1.16,8.32, p = 0.023), vasopressor requirement on ICU day one, OR 1.9 (95% CI 1.13,3.19, p = 0.014) and Colistin OR 2.3 (95% CI 1.3, 4.02, p < 0.001) were significant predictors of AKI. There was no significant association between fluid type; Chloride-liberal, Chloride-restrictive, and AKI. CONCLUSIONS: Fluid overload is an independent risk factor for AKI.

The incidence of increased ICP in ICU patients with non-traumatic coma as diagnosed by ONSD and CT: a prospective cohort study.

BACKGROUND: Unexplained coma after critical illness can be multifactorial. We evaluated the diagnostic ability of bedside Optic Nerve Sheath Diameter [ONSD] as a screening test for non-traumatic radiographic cerebral edema. METHODS: In a prospective study, mixed medical-surgical intensive care units [ICU] patients with non-traumatic coma [GCS < 9] underwent bedside ultrasonographic ONSD measurements. Non-traumatic radiographic cerebral edema [NTRCE] was defined as > 5 mm midline shift, cisternal, sulcal effacement, or hydrocephalus on CT. RESULTS: NTRCE was identified in 31 of 102 patients [30.4 %]. The area under the ROC curve for detecting radiographic edema by ONSD was 0.785 [95 % CI 0.695-0.874, p <0.001]. ONSD diameter of 0.57 cm was found to be the best cutoff threshold with a sensitivity 84 % and specificity 71 %, AUC 0.785 [95 % CI 0.695-0.874, p <0.001]. Using ONSD as a bedside test increased the post-test odds ratio [OR] for NTRCE by 2.89 times [positive likelihood ratio], whereas post-test OR for NTRCE decreased markedly given a negative ONSD test [ONSD measurement less than 0.57 cm]; negative likelihood ratio 0.22. CONCLUSIONS: The use of ONSD as a bedside test in patients with non-traumatic coma has diagnostic value in identifying patients with non-traumatic radiographic cerebral edema.

Chloride-liberal fluids are associated with acute kidney injury after liver transplantation.

INTRODUCTION: Acute kidney injury (AKI) occurs frequently after liver transplantation and is associated with significant morbidity and mortality. Recent evidence has linked the predominant usage of 'chloride-liberal' intravenous fluids, such as 0.9% saline to the development of renal dysfunction in general critically ill patients. We compared the effects of perioperative fluid types on AKI in liver transplant recipients. METHODS: An observational analysis of liver transplant recipients over a 33-month period, between January 2010 and September 2013, was performed. Intensive care unit database and patient records were analyzed for determinants of early postoperative AKI. Univariate and multivariate regression analysis was carried out using a two-tailed P value less than 0.05 to establish significance. The institutional Research Ethics Committee approved the study methodology (RAC no. 2131 073). RESULTS: One hundred and fifty-eight liver transplants were performed, AKI developed in 57 (36.1%) patients: 39 (68.4%) fully recovered, 13 (22.8%) developed chronic renal failure and 10 (17.5%) required long-term hemodialysis. On univariate regression analysis, AKI was significantly associated with greater than 3,200 ml of chloride-liberal fluids infused within the first postoperative day (HR 5.9, 95% CI 2.64, 13.2, P < 0.001), greater than 1,500 ml colloids received in the operating room (hazard ratio (HR) 1.97, 95% CI 1.01, 3.8, P = 0.046), vasopressor requirement for 48 hours posttransplant (HR 3.34, 95% CI 1.55, 7.21, P = 0.002), hyperchloremia at day 2 (HR 1.09, 95% CI 1.01, 1.18, P = 0.015) and preoperative model for end-stage liver disease (MELD) score (HR 1.08, 95% CI 1.03, 1.13, P < 0.001). After stepwise multivariate regression, infusion of greater than 3,200 ml of chloride-liberal fluids (HR 6.25, 95% CI 2.69, 14.5, P < 0.000) and preoperative MELD score (HR 1.08, 95% CI 1.02, 1.15, P = 0.004) remained significant predictors for AKI. CONCLUSIONS: In a sample of liver transplant recipients, infusion of higher volumes of chloride-liberal fluids and preoperative status was associated with an increased risk for postoperative AKI.

Outcomes and Long-Term Survival of Adolescent and Young Adult Patients Admitted to the Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 152 Patients.

BACKGROUND AND OBJECTIVES: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. PATIENTS AND METHODS: AYA patients who underwent allo-HSCT and required ICU admission at a Tertiary care Centre, during the period of 2003-2013, were included in this retrospective review. This was a non-interventional study. Only outcomes after the first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. RESULTS: Overall, 152 patients were included (males, 60.5%); median age at transplantation was 24 years (interquartile range [IQR] 18-32.5); median age at admission to the ICU was 25.8 years (IQR 19-34). Eighty-four percent underwent transplantation for a hematological malignancy; 129 (85%) received myeloablative conditioning. Seventy-one percent of ICU admissions occurred within the first year after allo-HSCT. ICU admission was primarily due to respiratory failure (47.3%) and sepsis (43.4%). One hundred and three patients (68%) died within 28 days of ICU admission. The 1- and 5-year overall survival rates were 19% and 17%, respectively. Main causes for ICU-related death were refractory septic shock with multiorgan failure (n = 49, 32%) and acute respiratory distress syndrome (ARDS) (n = 39, 26%). Univariate analysis showed that ICU mortality was associated with an Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, a sequential organ failure assessment (SOFA score) > 12, a high lactate level, anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, a high international normalized ratio (INR) and acute graft-versus-host disease (GVHD). Multivariate analysis identified thrombocytopenia, high INR, and acute GVHD as independent predictors of mortality. CONCLUSIONS: In AYA allo-HSCT patients admitted to the ICU, mortality remains high. Higher SOFA and APACHE scores, the need for organ support, thrombocytopenia, coagulopathy, and acute GVHD predict poor outcomes.

Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'.

BACKGROUND: Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery. METHODS: Two hundred and fifty nine patients with pulmonary TB were randomized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses. Assessments were performed at 4, 8 and 12 weeks. Early secreted and T cell activated 6 kDa (ESAT6) and Mycobacterium tuberculosis sonicate (MTBs) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks. Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student's t-test and Chi2 tests. RESULTS: After 12 weeks, the vitamin D supplemented arm demonstrated significantly greater mean weight gain (kg)+3.75, (3.16-4.34) versus+2.61 (95% CI 1.99-3.23) p 0.009 and lesser residual disease by chest radiograph; number of zones involved 1.35 v/s 1.82 p 0.004 (95% CI 0.15, 0.79) and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline 'Deficient' 25-hydroxyvitamin D serum levels (p 0.021). CONCLUSIONS: Supplementation with high doses of vitamin D accelerated clinical, radiographic improvement in all TB patients and increased host immune activation in patients with baseline 'Deficient' serum vitamin D levels. These results suggest a therapeutic role for vitamin D in the treatment of TB. TRIAL REGISTRATION: ClinicalTrials.gov; No. NCT01130311; URL: clinicaltrials.gov.

A randomized, double-blind, placebo-controlled trial of oral montelukast in acute asthma exacerbation.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) are well established in the management of outpatient asthma. However, there is very little information as to their role in acute asthma exacerbations. We hypothesized that LTRAs may accelerate lung function recovery when given in an acute exacerbation. METHODS: A randomized, double blind, placebo-controlled trial was conducted at the Aga Khan University Hospital to assess the efficacy of oral montelukast on patients of 16 years of age and above who were hospitalized with acute asthma exacerbation. The patients were given either montelukast or placebo along with standard therapy throughout the hospital stay for acute asthma. Improvements in lung function and duration of hospital stay were monitored. RESULTS: 100 patients were randomized; their mean age was 52 years (SD +/- 18.50). The majority were females (79%) and non-smokers (89%). The mean hospital stay was 3.70 ± 1.93 days with 80% of patients discharged in 3 days. There was no significant difference in clinical symptoms, PEF over the course of hospital stay (p = 0.20 at day 2 and p = 0.47 at day 3) and discharge (p = 0.15), FEV1 at discharge (p = 0.29) or length of hospital stay (p = 0.90) between the two groups. No serious adverse effects were noted during the course of the study. CONCLUSION: Our study suggests that there is no benefit of addition of oral montelukast over conventional treatment in the management of acute asthma attack. TRIAL REGISTRATION NUMBER: 375-Med/ERC-04.

Atypical pathogens causing community-acquired pneumonia in adults.

OBJECTIVE: To determine the frequency of community-acquired respiratory pathogens with special focus on atypical organisms in patients presenting to a tertiary care facility with community-acquired pneumonia (CAP). METHODS: The descriptive study on adult patients was conducted from February 2007 to March 2008 at the Aga Khan University Hospital, Karachi. It comprised 124 consenting patients of age 16 and above who presentd with a diagnosis of community-acquired pneumonia. The diagnostic modalities used were based on significant changes in antibody titer or persisting high antibody titers in the case of Mycoplasma pneumoniae and Chalmydia pneumoniae infections, or bacterial antigen in urine, in the case of Legionella pneumophila serogroup 1 infection. Pyogenic bacteria were identified on the results of respiratory secretions or blood cultures. Continuous data and categorical variables were worked out using SPSS version 15. RESULTS: Among the 124 patients enrolled, an etiologic agent was identified in 44 (35.4%) patients. The most common organism was Mycoplasma pneumoniae (n = 21, 17%), followed by Chlamydia pneumoniae (n = 15, 12%), Streptococcus pneumoniae (n = 9, 7%), Haemophilus influenzae (n = 2, 1.6%), Klebsiella pneumoniae (n = 2, 1.6%) and Staphylococcus aureus (n = 1, 0.8%). Streptococcus pneumoniae was the most common organism isolated from blood cultures. No cases of Legionella pneumophila serogroup 1 were identified. CONCLUSIONS: Mycoplasma pneumoniae and Chalmydia pneumoniae are significant etiologic agents for community-acquired pneumonia occurring in Karachi. Local treatment guidelines for community-acquired pneumonia should include therapy directed specifically at these agents.

Role Of Lung Ultrasound During Weaning In Patient With Mitral Regurgitation Post Angioplasty.

BACKGROUND: We hypothesize that a change in lung ultrasound score (LUS) can assist in the early diagnosis of weaning-induced respiratory failure (RF). The objective of this study was to determine the utility of LUS in weaning patients with mitral regurgitation (MR) from mechanical ventilation (MV). METHODS: This prospective observational study included patients with acute coronary syndrome (ACS) who required invasive MV after angiography/angioplasty. Echocardiography was performed and MR was recorded. When the patient was considered ready for extubation, a spontaneous breathing trial (SBT) was performed and pre- and post-SBT LUS was calculated. Patients who successfully passed the SBT were extubated and followed up for 48 hours for the signs of RF and outcomes. RESULTS: We enrolled 215 patients, out of which MR occurred in 51(23.7%) patients. On post-SBT lung ultrasound, patients with MR were more likely to have B2 lines compared to those without MR; 15.7% vs. 3.7%; p=0.002 and mean LUS was significantly higher for patients with MR as compared to patients without MR; 2.75±3.21 vs. 1.37± 2.02; p<0.001. Post-extubation RF and mean CCU stay were significantly higher in MR patients, 49.0% (25) vs. 32.3% (53); p=0.030 and 3.53±1.54 days vs. 2.41±1.1 days; p<0.001 respectively. However, re-intubation and coronary care unit (CCU) mortality rate were not significantly different between patients with and without MR; 7.8% (4/51) vs. 3.7% (6/164); p=0.215, and 5.9% (3/51) vs. 3% (5/164); p=0.35 respectively. CONCLUSIONS: Bedside LU is a convenient tool to detect changes in cardiopulmonary interactions during weaning for patients with MR post-ACS.

Predicting Post-Extubation Respiratory Failure After Myocardial Infarction Using The Rapid Shallow Breathing Index And Lung Ultrasound Score.

BACKGROUND: The Rapid Shallow Breathing Index (RSBI) has been hypothesized to have discriminating power for categorizing patients at higher risk of post-extubation respiratory failure (RF). Hence aim of this study was to determine the predictive value of RSBI for post-extubation RF in patients after acute myocardial infarction (AMI). METHODS: Consecutive, intubated patients admitted post-revascularization were included. RSBI and lung ultrasound score (LUS) were measured and post-extubation RF within 48 hours was recorded. RESULTS: RF was observed in 36.3% (78/215) patients. For the prediction of RF, RSBI and LUS had area under the curve of 0.670 and 0.635, respectively. The sensitivity, specificity, negative predictive value, and positive predictive value of RSBI >50.5 were 75.6%, 54.7%, 79.8%, and 48.8% respectively, while, the accuracy measures for the combination of RSBI with LUS >1.5 were 44.9%, 84.7%, 73.0%, and 62.5% respectively. CONCLUSIONS: Combined RSBI and LUS measured during spontaneous breathing trial in patients after an AMI, have high predictive abilities for identifying post-extubation RF.

Home Management of COVID-19 Patients: A Successful Model in Non-severe COVID-19 Patients in the Developing World.

Background Around 80-85% of coronavirus disease 2019 (COVID-19) cases were reported to have mild disease and home treatment of such patients was proved to be effective without significant morbidity or mortality. Therefore, the aim of this study was to assess the outcome of home management of non-severe COVID-19 infection in healthcare providers in the developing world. Methods This observational cohort study was conducted at the National Institute of Cardiovascular Diseases from June 2020 till January 2021. It included health care workers who tested positive for COVID-19 with non-severe infection and received home treatment. The COVID-19 management team monitored their symptoms and oxygen saturation over the phone. Need-based lab tests, X-rays, home proning, steroids, and oxygen were administered along with the standard intuitional management strategies. Study outcomes included duration of recovery, need for hospitalization, and expiry. Results A total of 128 patients were included, out of which 98 (76.6%) were male, and the mean age was 32.9 ± 5.9 years. Fever was the most common symptom, seen in 89.8% of patients. Most of the patients (85.9%) had no pre-existing comorbidities. Five patients received home oxygen therapy, seven received steroid therapy, and one received home pruning. The average time of recovery was 13.8 ± 8.1 days with no mortality; however, 14 (10.9%) patients were hospitalized due to worsening of symptoms. Conclusion Home treatment for COVID-19 patients with mild to moderate disease after appropriate risk assessment can be a safe and effective option to preserve hospital capacities for more needy and severely ill patients.

Perceptions Regarding COVID-19 Vaccination Among a Representative Pakistani Population Coming to Tertiary Care Cardiac Hospital.

BACKGROUND: The deleterious effects caused by coronavirus disease 2019 (COVID-19) infection have been compounded by COVID-19 vaccine hesitancy throughout the world, including Pakistan. We are lacking representative national data regarding the COVID-19 vaccine acceptance. This study aims to determine COVID-19 vaccination acceptance rates and predictors of its acceptance and hesitancy among a representative Pakistani population. METHODS: This cross-sectional study was conducted at the National Institute of Cardiovascular Disease, Karachi, from March 2021 to April 2021. Participants included patients, and their attendants visiting the outpatient clinics and healthcare workers of the institute. Participants were labeled as 'acceptant' or 'hesitant' based on their responses of 'yes' or 'no' and 'not sure' on the willingness to get vaccinated, respectively. The Chi-square test was used to calculate the significant association between different variables. A p-value ≤0.05 was set as a level of significance for all statistical analyses. RESULTS: Overall, 1500 participants were enrolled with a vaccine acceptance rate of only 49%. Factors like male gender, unmarried and employed status, higher education, high socioeconomic class, Punjabi and Sindhi ethnicity, medical professional, and self or family exposure of COVID-19 were positively related to COVID-19 vaccine acceptance. The commonest stated reason for the vaccine hesitancy was distrust in vaccine efficacy or fear of vaccine adverse effects. CONCLUSION: Vaccine hesitancy remains a serious challenge in our population, related to multiple demographic and thought factors. Focused actions and modification of these factors are the keys to conclude this COVID pandemic.

Assessing the Utility of End-Tidal Carbon Dioxide as a Marker for Fluid Responsiveness in Cardiogenic Shock.

Background Preventing end-organ failure in patients with shock requires rapid and easily accessible measurements of fluid responsiveness. Unlike septic shock, not all patients in cardiogenic shock are preload responsive. We conducted this study to determine the discriminant power of changes in end-tidal carbon dioxide (ETCO2), systolic blood pressure (SBP), inferior vena cava (IVC) collapsibility index (IVC-CI), and venous to arterial carbon dioxide (Pv-aCO2) gap after a fluid challenge and compared it to increases in cardiac output. Methodology In a prospective, quasi-experimental design, mechanically ventilated patients in cardiogenic shock were assessed for fluid responsiveness by comparing improvement in cardiac output (velocity time integral) with changes in ETCO2, heart rate, SBP, Pv-aCO2 gap, IVC-CI after a fluid challenge (a crystalloid bolus or passive leg raise). Results Out of 60 patients, with mean age 61.3 ± 14.8 years, mean acute physiology and chronic health evaluation (APACHE) score -14.82 ± 7.49, and median ejection fraction (EF) 25% (25-35), 36.7% (22) had non ST-segment elevation myocardial infarction (NSTEMI) and 60% (36) were ST-segment elevation myocardial infarction (STEMI). ETCO2 was the best predictor of fluid responsiveness; area under the curve (AUC) 0.705 (95% confidence interval (CI) 0.57-0.83), p=0.007, followed by reduction in Pv-aCO2 gap; AUC 0.598 (95% CI; 0.45-0.74), p= 0.202. Changes in SBP, mean arterial pressure (MAP), IVC-CI weren't significant; 0.431 (p=0.367), 0.437 (p=0.410), 0.569 (p=0.367) respectively. The discriminant value identified for ETCO2 was more than equal to 2 mmHg, with sensitivity 58.6%, specificity 80.7%, positive predictive value 73.9% [95% CI; 56.5% to 86.1%], negative predictive value 69.7% [95% CI; 56.7% to 76.9%]. Conclusions Change in ETCO2 is a useful bedside test to predict fluid responsiveness in cardiogenic shock.

Fluid Resuscitation In Cardiogenic Shock: An Assessment Of Responsiveness And Outcome.

BACKGROUND: Fluid replacement for resuscitation in cardiogenic shock (CS) patients remains a point of debate in clinical practice. The purpose of the study was to assess the frequency of fluid responsiveness and outcomes of patients with cardiogenic shock receiving fluid resuscitation at the critical care unit (ICU) of a tertiary care cardiac center. METHODS: In this descriptive case series, in which all mechanically ventilated CS patients were evaluated who were assessed for fluid responsiveness by a fluid challenge. It was conducted at the critical care unit of a tertiary care cardiac center in Karachi, Pakistan, from January 2020 to June 2020, by including 41 consecutive patients. Fluid challenge was given as either a 250 ml crystallized bolus or a passive leg raise (PLR) manoeuvre. An increase in the velocity time integral (ΔVTI) of ≥ 10% was considered fluid responsiveness. RESULTS: A total of 41 patients were evaluated: 25 (61%) were males, and the mean age was 61.9±17.0 years, and 36.6% (15) of the patients presented with non-ST elevation myocardial infarction (NSTEMI), followed by anterior wall ST elevation myocardial infarction (31.7% (13)). Fluid responsiveness was observed in 48.8% (20/41). Mean VTI change after the fluid challenge was 1.07±0.86. Survival rate was 33.3% (7/21) in fluid responders vs. 50.0% (10/20) in non-fluid responders; p=0.279. CONCLUSIONS: Almost half of patients presenting with CS from acute coronary syndrome are responsive to fluids. These findings support the routine evaluation by fluid challenge in these patients. Fluid challenge can be by either PLR or fluid bolus.

Operationalisation of the Randomized Embedded Multifactorial Adaptive Platform for COVID-19 trials in a low and lower-middle income critical care learning health system.

The Randomized Embedded Multifactorial Adaptive Platform (REMAP-CAP) adapted for COVID-19) trial is a global adaptive platform trial of hospitalised patients with COVID-19. We describe implementation in three countries under the umbrella of the Wellcome supported Low and Middle Income Country (LMIC) critical  care network: Collaboration for Research, Implementation and Training in Asia (CCA). The collaboration sought to overcome known barriers to multi centre-clinical trials in resource-limited settings. Methods described focused on six aspects of implementation: i, Strengthening an existing community of practice; ii, Remote study site recruitment, training and support; iii, Harmonising the REMAP CAP- COVID trial with existing care processes; iv, Embedding REMAP CAP- COVID case report form into the existing CCA registry platform, v, Context specific adaptation and data management; vi, Alignment with existing pandemic and critical care research in the CCA. Methods described here may enable other LMIC sites to participate as equal partners in international critical care trials of urgent public health importance, both during this pandemic and beyond.

Variables predictive of outcome in patients with acute hypercapneic respiratory failure treated with noninvasive ventilation.

OBJECTIVE: To assess results with NIV in acute hypercapneic respiratory failure and to identify outcome predictors. METHODS: This was a retrospective observational study on consecutive patients presenting with acute type II respiratory failure and meeting criteria for NIV use over a 5 year period. Patients presenting with haemodynamic instability, inability to protect their airway, malignant arrhythmias and recent oesophageal surgery were excluded. Univariate and Multivariate regression analysis was used to determine the impact on survival. A p value of < 0.05 was considered statistically significant. Software used was SPSS 14. RESULTS: Total numbers of patients included were 119; 52.9% were males. Mean age was 63.4 +/- 11.9 years. Overall Survival to discharge rate was 76.5%, intubation rate was 12.6% and mean length of stay was 11.4 +/- 10.9 days. Statistically significant improvements were observed in the pH and PaCO2 at 24 hours and 48 hours compared to baseline (7.28 v/s 7.37, p < 0.001; 74.2 v/s 65, p < 0.001). On multivariate regression analysis, sepsis at admission predicted mortality (adjusted Odds ratio 26.4; 95% CI 2.3, 304, p < 0.009). A serum HCO3 > 35 Meq/L (adjusted Odds ratio 0.9; 95% CI 0.83, 0.98, p < 0.015) identified those less at risk for intubation. CONCLUSION: NIV was found to be both safe and effective in the management of acute hypercapneic respiratory failure. Sepsis and serum HCO3 at admission identified patients having poor outcomes.

How early do antibiotics have to be to impact mortality in severe sepsis? A prospective, observational study from an emergency department.

BACKGROUND: The objective of this study was to assess the promptness of antibiotic administration to patients presenting with sepsis and the effects on survival and length of hospitalization. METHODS: Consecutive, adult patients presenting with Systemic Inflammatory Response Syndrome (SIRS) to the emergency department of the Aga Khan University hospital were enrolled in a prospective, observational study over a period of 4 months. Univariate, multivariate regression modeling and one-way ANOVA were used to examine the effects of various variables on survival and for significant differences between timing of antibiotic administration and survival, two-sided p values < 0.05 were considered significant. RESULTS: One hundred and eleven patients were enrolled. Severe sepsis was present in 52% patients; the most frequent organism isolated was Salmonella typhi (18%). Overall mortality was 35.1%. One hundred (90.1%) patients received intravenous antibiotics in the Emergency room; average time from triage to actual administration was 2.48 +/- 1.86 hours. The timing of antibiotic administration was significantly associated with survival (F statistic 2.17, p = 0.003). Using a Cox Regression model, we were able to demonstrate that survival dropped acutely with every hourly delay in antibiotic administration. On multivariate analysis, use of vasopressors (adjusted OR 23.89, 95% CI 2.16,263, p = 0.01) and Escherichia coli sepsis (adjusted OR 6.22, 95% CI 1.21,32, p = 0.03) were adversely related with mortality. CONCLUSIONS: We demonstrated that in the population presenting to our emergency room, each hourly delay in antibiotic administration was associated with an increase in mortality.

Pacemaker patients' perception of unsafe activities: a survey.

BACKGROUND: Cardiac pacing is a recognized and widely used treatment for patients presenting with bradycardia. Physicians expect patients to return to normal activities almost immediately post implantation. However, patients themselves may perceive interference to pacemaker function by various routine activities and devices, and hence continue to lead restricted, disabled lives. The aim of this study is to determine if routine activities are perceived by pacemaker patients to interfere with their device function. METHODS: A descriptive cross sectional survey was carried out on consecutive patients at the pacemaker clinic at a public hospital in Karachi, Pakistan. A 47-question tool was developed and tested. Patients' perceptions of safety of performing various routine activities, along with socio-demographic data were recorded. RESULTS: The final sample included 93 adult patients (45% males). 41% were illiterate. 77.4% recalled receiving counselling at implantation, predominantly from the implanting physician and house staff. A considerable proportion of patients considered many routine activities unsafe including driving automobiles (28%), passing through metal detectors (31%), bending over (37%), and sleeping on the side of the pacemaker (30%). Also considered unsafe were operation of household appliances--TV/VCR (television/video cassette recorders) (53%), irons (55%)) and electrical wall switches (56%). For nearly all variables neither literacy nor history of counselling improved incorrect perceptions. CONCLUSION: This study shows that our pacemaker patients perceive many routine activities as unsafe, potentially leading to disabling life style modifications. The tremendous investment in pacemaker technology to improve patient performance is not going to pay dividends if patients continue to remain disabled due to incorrect perceptions. Further studies are required to determine the reasons for these misperceptions, and to determine if these problems also exist in, and hinder, other patient populations.

Impact of tigecycline versus imipenem-cilastatin on fibrinogen levels following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized-controlled study.

The aim of this prospective, randomized study was to compare the effects of tigecycline and imipenem-cilastatin on fibrinogen levels in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients were empirically randomized to receive tigecycline or imipenem-cilastatin. Fibrinogen levels were measured in both patient groups on days 1, 3, 5 and 8 of antibiotic therapy and 3 days after antibiotic therapy completion. Twenty patients received tigecycline and 22 patients received imipenem-cilastatin . Patients in the tigecycline group had lower mean fibrinogen levels compared to those in the imipenem-cilastatin group on day 3 (4.1 ± 1.2 vs. 5.9 ± 1.3 g/L; p < 0.001), day 5 (3.7 ± 1.2 vs. 6.5 ± 1.1 g/L; p < 0.001), day 8 (3.5 ± 1.3 vs. 5.8 ± 1.6 g/L; p < 0.001), and day 3 after antibiotic completion (4.1 ± 1.4 vs. 6.1 ± 1.6 g/L; p < 0.001). In conclusion, compared to imipenem-cilastatin, tigecycline was associated with a significant decrease in fibrinogen levels, following CRS and HIPEC.