Machine-learning prediction models for any blood component transfusion in hospitalized dengue patients.

BACKGROUND: Blood component transfusions are a common and often necessary medical practice during the epidemics of dengue. Transfusions are required for patients when they developed severe dengue fever or thrombocytopenia of 10×109/L or less. This study therefore investigated the risk factors, performance and effectiveness of eight different machine-learning algorithms to predict blood component transfusion requirements in confirmed dengue cases admitted to hospital. The objective was to study the risk factors that can help to predict blood component transfusion needs. METHODS: Eight predictive models were developed based on retrospective data from a private group of hospitals in India. A python package SHAP (SHapley Additive exPlanations) was used to explain the output of the "XGBoost" model. RESULTS: Sixteen vital variables were finally selected as having the most significant effects on blood component transfusion prediction. The XGBoost model presented significantly better predictive performance (area under the curve: 0.793; 95 % confidence interval: 0.699-0.795) than the other models. CONCLUSION: Predictive modelling techniques can be utilized to streamline blood component preparation procedures and can help in the triage of high-risk patients and readiness of caregivers to provide blood component transfusions when required. This study demonstrates the potential of multilayer algorithms to reasonably predict any blood component transfusion needs which may help healthcare providers make more informed decisions regarding patient care.

Diagnostic accuracy of saliva as a specimen for detection of SARS-CoV-2 by RT-PCR.

Context: COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an emerging pandemic that is rapidly spreading with more than 114 million confirmed cases and 2.5 million deaths by far. Nasopharyngeal swab (NPS) in VTM has been used as the gold standard respiratory specimen for SARS-CoV-2 reverse-transcriptase real-time PCR (rRT-PCR) tests. But now the virus can also be detected in other clinical specimens like bronchoalveolar lavage, sputum, saliva, throat swab, blood, and stool specimens. Aims: The aim of this study was to determine the diagnostic potential of saliva as a sample in comparison to NPS for detection of SARS-CoV-2 by rRT-PCR. Settings and Design: A cross-sectional study was conducted among 256 paired samples (NPS and Saliva) received in the Department of Microbiology, SMS Medical College, Jaipur over a period of 2 months. Methods and Material: NPS from individuals were collected in a sterile tube containing Viral Transport Medium™. Before swab collection, whole saliva was collected by spitting from the suspected patient into a sterile container. Both were stored at room temperature and transferred to the diagnostic laboratory within four hours of collection where extraction was done using Perkin Elmer chemagic extractor and rRT- PCR was performed using NIV, Pune mastermix. Results: Sensitivity, specificity, PPV, and NPV of RT-PCR for the diagnosis of COVID-19 in saliva were 84.26%, 100%, 100%, and 54.05%, respectively. The accuracy of detection of COVID-19 by saliva samples compared to the routinely used NPS samples (considered as the standard reference) for RT PCR was 86.72%. Conclusions: Our results show that saliva as a reliable sample type for SARS-CoV-2 detection.

Secondary infections modify the overall course of hospitalized patients with COVID-19: a retrospective study from a network of hospitals across North India.

Objective: To gain better insight into the extent of secondary bacterial and fungal infections in hospitalized patients in India, and to assess how these alter the course of coronavirus disease 2019 (COVID-19) so that control measures can be suggested. Methods: In this retrospective, multicentre study, the data of all patients who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on reverse transcriptase polymerase chain reaction (RT-PCR), admitted to hospital between March 2020 and July 2021, were accessed from the electronic health records of a network of 10 hospitals across five states in North India. Results: Of 19,852 patients testing positive for SARS-CoV-2 on RT-PCR and admitted to the study hospitals during the study period, 1940 (9.8%) patients developed secondary infections (SIs). Patients with SIs were, on average, 8 years older than patients without SIs (median age 62.6 vs 54.3 years; P<0.001). The risk of SIs was significantly (P<0.001) associated with age, severity of disease at admission, diabetes, admission to the intensive care unit (ICU), and ventilator use. The most common site of infection was urine (41.7%), followed by blood (30.8%) and sputum/bronchoalveolar lavage/endotracheal fluid (24.8%); the least common was pus/wound discharge (2.6%). Gram-negative bacilli (GNB) were the most common organisms (63.2%), followed by Gram-positive cocci (GPC) (19.6%) and fungi (17.3%). Most patients with SIs were on multiple antimicrobials. The most commonly used antibiotics against GNB were beta-lactam/beta-lactamase inhibitors (76.9%), carbapenems (57.7%), cephalosporins (53.9%), and antibiotics against carbapenem-resistant Enterobacteriaceae (47.1%). Empirical use of antibiotics against GPC was seen in 58.9% of patients with SIs, and empirical use of antifungals was observed in 56.9% of patients with SIs. The average length of hospital stay for patients with SIs was almost twice as long as that of patients without SIs (median 13 vs 7 days). Overall mortality among patients with SIs (40.3%) was more than eight times higher than that among patients without SIs (4.6%). Only 1.2% of patients with SIs with mild COVID-19 at admission died, compared with 17.5% of those with moderate COVID-19 at admission and 58.5% of those with severe COVID-19 at admission (P<0.001). The mortality rate was highest in patients with bloodstream infections (49.8%), followed by those with hospital-acquired pneumonia (47.9%), urinary tract infections (29.4%), and skin and soft tissue infections (29.4%). The mortality rate in patients with diabetes with SIs was 45.2%, compared with 34.3% in those without diabetes (P<0.001). Conclusions: SIs complicate the course of patients hospitalized with COVID-19. These patients tend to have a much longer hospital stay, a higher requirement for oxygen and ICU care, and a significantly higher mortality rate compared with those without SIs. The groups most vulnerable to SIs are patients with more severe COVID-19, elderly patients and patients with diabetes. Judicious empirical use of combination antimicrobials in these groups of vulnerable patients can save lives. It is desirable to have region- or country-specific guidelines for appropriate use of antibiotics and antifungals to prevent their overuse.

Comparison of Tocilizumab and High-dose Methylprednisolone Pulse on Outcomes in Severe Corona Virus Disease-2019: TAME-COVID, a Retrospective Multicentric Study.

BACKGROUND: India recently encountered fierce second wave of coronavirus disease (COVID-19), and scarcity of novel medications added to the management challenges. Various studies have highlighted the effectiveness of tocilizumab and high-dose steroids in severe COVIDs, but none has compared their efficacy. MATERIALS AND METHODS: This retrospective multi-centric analysis compares intravenous tocilizumab (8 mg/kg/day, maximum dose-800 mg), and intravenous Methylprednisolone Pulse (MPS-1 g/day for 3 days) in severe COVID-19. Both the groups had additionally received the standard of care COVID treatment as per protocol. Outcomes were assessed at 30 days. RESULTS: A total of 336 patients, with 249 receiving MPS and 87 receiving tocilizumab were compared. Majority of these were males (72.9%) with a mean age of 57.4 ± 13.6 years. Diabetes was the most common comorbidity. Patients in both groups had comparable age distribution, comorbidities, presenting mean-arterial pressures, d-Dimer levels, serum ferritin, serum leukocyte-dehydrogenase, and procalcitonin. However, the tocilizumab group had more number of males, higher incidence of coronary artery disease, more tachypnea and leukocytosis, more number of patients with severe acute respiratory disease syndrome (PaO2/FiO2 ratio <100), and higher C-reactive protein levels at presentation. Both groups had comparable adverse events' profile. Tocilizumab group had lesser requirement of invasive ventilation than MPS group (17% vs. 29%, P = 0.038), however mortality at the end of 30 days follow-up was similar (36% vs. 34% respectively; P = 0.678). CONCLUSIONS: Tocilizumab decreased the need for invasive ventilation in severe COVID-19; however, it did not translate to improved survival. A planned prospective randomized study is recommended in this respect to compare their efficacy.

Identification of predictors and model for predicting prolonged length of stay in dengue patients.

PURPOSE: Our objective is to identify the predictive factors and predict hospital length of stay (LOS) in dengue patients, for efficient utilization of hospital resources. METHODS: We collected 1360 medical patient records of confirmed dengue infection from 2012 to 2017 at Max group of hospitals in India. We applied two different data mining algorithms, logistic regression (LR) with elastic-net, and random forest to extract predictive factors and predict the LOS. We used an area under the curve (AUC), sensitivity, and specificity to evaluate the performance of the classifiers. RESULTS: The classifiers performed well, with logistic regression (LR) with elastic-net providing an AUC score of 0.75 and random forest providing a score of 0.72. Out of 1148 patients, 364 (32%) patients had prolonged length of stay (LOS) (> 5 days) and overall hospitalization mean was 4.03 ± 2.44 days (median ± IQR). The highest number of dengue cases belonged to the age group of 10-20 years (21.1%) with a male predominance. Moreover, the study showed that blood transfusion, emergency admission, assisted ventilation, low haemoglobin, high total leucocyte count (TLC), low or high haematocrit, and low lymphocytes have a significant correlation with prolonged LOS. CONCLUSION: Our findings demonstrated that the logistic regression with elastic-net was the best fit with an AUC of 0.75 and there is a significant association between LOS greater than five days and identified patient-specific variables. This method can identify the patients at highest risks and help focus time and resources.

Predictive Model Based on Health Data Analysis for Risk of Readmission in Disease-Specific Cohorts.

Background: Intervention planning to reduce 30-day readmission post-acute myocardial infarction (AMI) in an environment of resource scarcity can be improved by readmission prediction score. The aim of study is to derive and validate a prediction model based on routinely collected hospital data for identification of risk factors for all-cause readmission within zero to 30 days post discharge from AMI. Methods: Our study includes 2,849 AMI patient records (January 2005 to December 2014) from a tertiary care facility in India. EMR with ICD-10 diagnosis, admission, pathological, procedural and medication data is used for model building. Model performance is analyzed for different combination of feature groups and diabetes sub-cohort. The derived models are evaluated to identify risk factors for readmissions. Results: The derived model using all features has the highest discrimination in predicting readmission, with AUC as 0.62; (95 percent confidence interval) in internal validation with 70/30 split for derivation and validation. For the sub-cohort of diabetes patients (1359) the discrimination is slightly better with AUC 0.66; (95 percent CI;). Some of the positively associated predictive variables, include age group 80-90, medicine class administered during index admission (Anti-ischemic drugs, Alpha 1 blocker, Xanthine oxidase inhibitors), additional procedure in index admission (Dialysis). While some of the negatively associated predictive variables, include patient demography (Male gender), medicine class administered during index admission (Betablocker, Anticoagulant, Platelet inhibitors, Anti-arrhythmic). Conclusions: Routinely collected data in the hospital's clinical and administrative data repository can identify patients at high risk of readmission following AMI, potentially improving AMI readmission rate.

Resuscitative Effect of Centhaquine (Lyfaquin®) in Hypovolemic Shock Patients: A Randomized, Multicentric, Controlled Trial.

INTRODUCTION: Centhaquine (Lyfaquin®) showed significant efficacy as a resuscitative agent in animal models of haemorrhagic shock. Its safety and tolerability were confirmed in healthy human volunteers. In this study, our primary objective was to determine the safety, and the secondary objective was to assess the efficacy of centhaquine in patients with hypovolemic shock. METHODS: A prospective, multicentre, randomized phase II study was conducted in male and female patients aged 18-70 years with hypovolemic shock having systolic BP ≤ 90 mmHg. Patients were randomized in a 1:1 ratio to either the control or centhaquine group. The control group received 100 ml of normal saline infusion over 1 h, while the centhaquine group received 0.01 mg/kg of centhaquine in 100 ml normal saline infusion over 1 h. Every patient received standard of care (SOC) and was followed for 28 days. RESULTS: Fifty patients were included, and 45 completed the trial: 22 in the control group and 23 in the centhaquine group. The demographics of patients in both groups were comparable. No adverse event related to centhaquine was recorded in the 28-day observation period. The baseline, Injury Scoring System score, haemoglobin, and haematocrit were similar in both groups. However, 91% of the patients in the centhaquine group needed major surgery, whereas only 68% in the control group (p = 0.0526). Twenty-eight-day all-cause mortality was 0/23 in the centhaquine group and 2/22 in the control group. The percent time in ICU and ventilator support was less in the centhaquine group than in the control group. The total amount of vasopressors needed in the first 48 h of resuscitation was lower in the centhaquine group than in the control group (3.12 ± 2.18 vs. 9.39 ± 4.28 mg). An increase in systolic and diastolic BP from baseline through 48 h was more marked in the centhaquine group than in the control group. Compared with the control group, blood lactate level was lower by 1.75 ± 1.07 mmol/l in the centhaquine group on day 3 of resuscitation. Improvements in base deficit, multiple organ dysfunction syndrome (MODS) score and adult respiratory distress syndrome (ARDS) were greater in the centhaquine group than in the control group. CONCLUSION: When added to SOC, centhaquine is a well-tolerated and effective resuscitative agent. It improves the clinical outcome of patients with hypovolemic shock. TRIAL REGISTRATION: ClinicalTrials.gov identifier number: NCT04056065.

Anxiety in Parkinson's Disease: Correlation with Depression and Quality of Life.

Introduction Anxiety is common in patients with Parkinson's disease (PD). Its prevalence ranges from 20 to 40% but despite that, the high prevalence anxiety in PD is often undiagnosed and untreated. This research was aimed to study the pattern of anxiety with regard to its prevalence and risk factors and to establish the association of anxiety with depression and quality of life (QOL) in patients with PD. Methods A total of 105 patients with PD were prospectively observed. Demographic and clinical variables were recorded and patients were assessed for anxiety (the Parkinson anxiety scale [PAS]), depression (geriatric depression scale [GDS]), and QOL (Parkinson's Disease Questionnaire-39 [PDQ-39]). Multiple forward logistic regression analysis was done for parameters showing association with anxiety. Pearson's correlation was used to calculate the strength of association of depression and QOL with anxiety. Results Anxiety was present in 56 PD patients (53.3%). Episodic anxiety was noted in 50%, avoidance behavior in 35%, and persistent anxiety in 15% of these patients. There was significant association of anxiety with duration of disease ( p = 0.001), severity ( p < 0.005), levodopa equivalent dose (LED; p = 0.001), and tremor phenotype of PD ( p = 0.004). Anxiety coexisted with depression in 50 patients (79.4%), which was statistically significant in our cohort ( p = 0.001). There was significant linear relationship between the PAS and PDQ-39. Conclusion Anxiety exerts a negative impact on the QOL as revealed by proportionately worsening PDQ-39 and PAS scores. Screening for anxiety will allow efficient delivery of support and treatment to patients with PD and their families.

Safety and Efficacy of Sovateltide (IRL-1620) in a Multicenter Randomized Controlled Clinical Trial in Patients with Acute Cerebral Ischemic Stroke.

BACKGROUND: Sovateltide (IRL-1620, PMZ-1620), an endothelin-B receptor agonist, has been previously shown to increase cerebral blood flow, have anti-apoptotic activity and produce neurovascular remodeling when administered intravenously following acute cerebral ischemic stroke in rats. Its safety and tolerability were confirmed in healthy human volunteers (CTRI/2016/11/007509). OBJECTIVE: Our objective was to determine the safety, tolerability and efficacy of sovateltide as an addition to standard of care (SOC) in patients with acute cerebral ischemic stroke. METHODS: A prospective, multicentric, randomized, double-blind, placebo-controlled study was conducted to compare the safety (primary objective) and efficacy (secondary objective) of sovateltide in patients with acute cerebral ischemic stroke. Adult males or females aged 18-70 years who had experienced a radiologically confirmed ischemic stroke within the last 24 h were included in the study. Patients with intracranial hemorrhage and those receiving endovascular therapy were excluded. Patients randomized to the sovateltide group received three doses of sovateltide (each dose 0.3 µg/kg) administered as an intravenous bolus over 1 min at an interval of 3 ± 1 h on day 1, day 3 and day 6 (total dose of 0.9 µg/kg/day). Patients randomized to the placebo group received an equal volume of saline. Every patient in both groups received SOC for stroke. Efficacy was evaluated using neurological outcomes based on National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) scores from day 1 through day 90. Quality of life was measured using the EuroQoL-5 Dimensions (EQ-5D) and Stroke-Specific Quality of Life (SSQoL) at 60 and 90 days of follow-up. RESULTS: A total of 40 patients with acute cerebral ischemic stroke were enrolled in this study, of whom 36 completed the 90-day follow-up. Patients received saline (n = 18; 11 male and 7 female) or sovateltide (n = 18; 15 male and 3 female) within 24 h of onset of stroke. The number of patients receiving investigational drug within 20 h of onset of stroke was 14/18 in the saline group and 10/18 in the sovateltide group. The baseline characteristics and SOC in both cohorts was similar. Sovateltide was well-tolerated, and all patients received complete treatment with no incidence of drug-related adverse events. Hemodynamic, biochemical or hematological parameters were not affected by sovateltide. Sovateltide treatment resulted in improved mRS and BI scores on day 6 compared with day 1 (p < 0.0001), an effect not seen in the saline group. Sovateltide increased the frequency of favorable outcomes at 3 months. An improvement of ≥ 2 points on the mRS was observed in 60 and 40% of patients in the sovateltide and saline groups, respectively (p = 0.0519; odds ratio [OR] 5.25). An improvement on the BI of ≥ 40 points was seen in 64 and 36% of the sovateltide and saline groups, respectively (p = 0.0112; OR 12.44). An improvement of ≥6 points on the NIHSS was seen in 56% of patients in the sovateltide group versus 43% in the saline group (p = 0.2714; OR 2.275). The number of patients with complete recovery (defined as an NIHSS score of 0 and a BI of 100) was significantly greater (p < 0.05) in the sovateltide group than in the saline group. An assessment of complete recovery using an mRS score of 0 did not show a statistically significant difference between the treatment groups. Sovateltide treatment resulted in improved quality of life as measured by the EQ-5D and SSQoL on day 90. CONCLUSION: Sovateltide was safe and well-tolerated and resulted in improved neurological outcomes in patients with acute cerebral ischemic stroke 90 days post-treatment. TRIAL REGISTRATION: The study is registered at CTRI/2017/11/010654 and NCT04046484.

Profile of cerebrovascular accidents in subjects with or without type 2 diabetes mellitus in intensive care units of tertiary care centre.

BACKGROUND AND AIMS: Diabetes Mellitus (DM) is a modifiable and independent risk factor for stroke. As the clinical features, radiological profile, outcome and prognosis of the stroke in type 2 diabetic and non diabetic patients are significantly variable, we proposed to evaluate these variations of stroke in patients with or without Type 2 DM. MATERIAL AND METHODS: A prospective study was conducted from January, 2011 to June, 2012 on in-hospital admitted diabetic and non diabetic patients presenting with stroke. Data was recorded on a predesigned Performa. RESULTS: A total of 150 cases were enrolled into the study. Out of these, 66% of patients had ischemic stroke and 34% of patients had hemorrhagic stroke. Type 2 diabetes mellitus was present in 52% patients. Ischemic stroke was significantly higher in diabetics than non diabetics (P = 0.007); however, hemorrhagic stroke was more in non diabetics. Mean age was significantly higher in diabetics (P = 0.04). CAD (P = 0.04), recurrent stroke (P = 0.006) had significant association with diabetes. Large vessel stroke was more common than small vessel stroke. Anterior circulation stroke was more common than posterior circulation stroke. There was significant improvement in morbidity and disability of the patients on follow up with treatment. CONCLUSIONS: A greater incidence of anterior circulation ischemic stroke, and recurrent strokes occur in patients with DM.

Efficacy and outcome of intermittent peritoneal dialysis in patients with acute kidney injury: A single-center experience.

There are only a few reports on the role of peritoneal dialysis (PD) in critically ill patients requiring continuous renal replacement therapies (RRT). This study aimed to determine the efficacy and outcome of intermittent PD in acute kidney injury (AKI) patients in intensive care unit setting and to assess the procedure-related complications. This was a prospective, observational study conducted from March 1, 2015, to February 29, 2016, which included patients of either sex, aged ≥18 years, diagnosed with AKI, and undergoing RRT with intermittent PD sessions with more than 48 h of hospital stay. Patients were later shifted to sustained low- efficiency dialysis or hemodialysis, when they became hemodynamically stable. Hence, the patients who received at least 48 h of PD were included in the study. A total of 75 patients were enrolled. Overall, the mean age was 55.75 years, and around 64% were men. The most common indication to start PD was metabolic acidosis, and the most common cause of AKI was sepsis. A total of 21 patients survived, and the mortality rate was 72%. The average peritoneal urea clearance and creatinine clearance were 14.81 mL/min and 12.59 mL/min, respectively. Of the 66 patients on inotropes, 28 patients were tapered from inotropic support. Thirty-nine patients had hyperkalemia, and 27 patients had correction within 1 day of the start of PD. Forty-seven patients had correction of acidosis, and 33 of these achieved pH ≥7.25 within one day of PD. The most common complication that occurred was peri-catheter leaks followed by peritonitis. Acute PD can be an effective, simple, and safe bridge RRT in hemodynamically unstable patients until the achievement of hemodynamic stability to shift them to other modalities of RRT.

Prevalence of Malnutrition in Parkinson's Disease and Correlation with Gastrointestinal Symptoms.

BACKGROUND: Parkinson's disease (PD) patients are at a higher risk of malnutrition with the overall prevalence estimated to be 3%-60%, but there are limited data in India regarding nutritional assessment of PD. AIM: This study aims to assess nutritional status of PD patients and correlate the disease factors and gastrointestinal tract (GIT) symptoms with nutritional status. MATERIALS AND METHODS: The PD cohort was assessed for demographic factors, nutritional assessment was done by Mini-Nutritional Assessment (MNA) Scale, and GI symptoms were assessed by validated scales. Age- and gender-matched cohort controls were randomly selected to correlate the GIT symptoms influencing nutritional status. The study population was divided into two groups according to the MNA score; Group I malnourished/at risk of malnutrition (score <23.5) or Group II normal nutrition (>23.5). The two subgroups were then compared. RESULTS: We assessed 75 patients of PD and 35 age- and gender-matched controls. According to anthropometric criteria, 23% of the PD population was underweight, and according to biochemical assessment, 17.3% had hypoalbuminemia along with anemia. According to MNA scale, 12% were malnourished and 45.3% were at risk of malnutrition. Hence, a total of 57.3% patients in Group I (with abnormal nutrition) as compared to 14% of the controls were at risk of malnutrition while none was found to be malnourished. In our study, GIT symptoms, such as sialorrhea and dysphagia was reported by 29.3% each and constipation by 41.3% patients. While comparing GI symptoms within the two MNA groups, there was statistically significant relationship of all GI manifestations, sialorrhea (P = 0.041), dysphagia (P = 0.00081), and constipation (P = 0.0042) with malnutrition. There was no statistical significant difference between groups for age (P = 0.54), gender (P = 0.903), and duration of disease (P = 0.743). CONCLUSIONS: The data suggest that about 45% of PD patients are at risk of malnourishment. MNA Score is a validated nutritional assessment tool and anthropometric or biochemical measures alone cannot identify all the malnourished population. PD patients at risk of malnutrition or malnourished do have symptoms of dysphagia, sialorrhea, and constipation as compared to PD patients with normal nutrition.

Enhancement of oral bioavailability of poorly water soluble carvedilol by chitosan nanoparticles: Optimization and pharmacokinetic study.

A major challenge associated with the oral delivery of anti-hypertensive drugs is their poor water solubility and low oral bioavailability. Carvedilol (CAR), a potential beta-blocker is hydrophobic drug that exhibit limited therapeutic effect through oral conventional drug delivery systems. For this reason, it is prerequisite to further investigate and develop an alternative drug delivery system so as to improve therapeutic efficacy of carvedilol as well as to minimize side effects of conventional treatment therapy. In the present study, it was aimed to develop nanoparticles (NPs) of a hydrophobic antihypertensive agent, Carvedilol by using chitosan (CS) as biodegradable polymer. Carvedilol chitosan nanoparticles (CAR-CS-NPs) were prepared by ionic gelation technique using sodium tripolyphosphate (TPP) as a crosslinking agent. The NPs were optimized and validated by Box-Behnken design (BBD). The optimized formulation showed particle size 102.12 nm and drug entrapment efficiency 71.26 ±â€¯1.16%. The drug release profile of CAR-CS NPs showed biphasic release pattern with an initial burst release in the first 2 h followed by a controlled release over a period of 72 h. The pharmacokinetic results revealed that the optimized chitosan nanoparticles formulation have higher bioavailability than marketed tablet formulation which indicates CAR-CS NPs as an effective strategy to delivery poorly water soluble drugs.

Paired blood cultures increase the sensitivity for detecting pathogens in both inpatients and outpatients.

The objective of this study was to show the differences between paired blood cultures (PBC) versus single blood cultures (SBC) in the microbiologic yield, the sensitivity to detect pathogens and the time to positivity (TTP). We performed a retrospective study examining 112,570 blood culture samples over a 5-year period from July 2011 to May 2016 in the BacT/ALERT® 3D automated blood culture system (bioMérieux, Marcy l'Etoile, France). Bacteria and yeasts were identified using the VITEK® 2 Compact system (bioMérieux, Marcy l'Etoile, France). True-positives and contaminated bottles were defined and analysed separately. We analysed TTP and adherence to blood volume guidelines for a convenience sample of 510 and 999 sequential positive cultures, respectively. Out of 49,438 PBC samples, 5810 (11.7%) were positive. In 63,132 SBC samples, 4552 (7.2%) were positive (p < 0.0001). In PBC, 5371 (10.9%) were true-positives and 439 (0.9%) contaminants. In SBC, 4095 (6.5%) were true-positives and 457 (0.7%) contaminants. In the inpatient departments (IPD), the most common isolate was Escherichia coli (n = 1373), followed by Klebsiella pneumoniae (n = 1206), whereas in the outpatient departments (OPD), the most common isolates were Salmonella typhi (n = 612) and S. paratyphi A (n = 278). In the analysis of TTP, 98% grew within 72 h, 91% within 48 h and 89% within 36 h. In the blood volume analysis, 90% of the cultures had optimal blood volume. A significantly higher positivity rate was seen in PBC compared with SBC. Our study adds to the increasing evidence of improved microbial yield of clinically significant bacteria and fungi by performing PBC instead of SBC and adhering to blood volume collection guidelines.

Trend in prevalence of coronary artery disease and risk factors over two decades in rural Punjab.

OBJECTIVES: The burden of coronary artery disease (CAD) has increased in the last three decades in low-income and middle-income countries including India. CAD is responsible for 20% deaths in India. The burden of CAD has increased due to a higher prevalence of risk factors related to the changing lifestyle. We studied the change in prevalence of CAD and risk factors over 20 years in a rural area. METHODS: A rural population of adults over the age of 30 years from three villages of Punjab was surveyed for the prevalence of CAD and its risk factors in 1994 and 2014 using similar research methodology. CAD was diagnosed by Epstein and clinical criteria. Blood pressure, anthropometry, ECG and biochemical analysis were carried out. The findings of two surveys were compared with a look at the change in the prevalence of CAD and its risk factors over 20 years. RESULTS: The overall age standardised prevalence of CAD increased from 2.79% in 1994 to 4.06% (p<0.05) in 2014. There was a significant increase in the prevalence of several risk factors including sedentary lifestyle (8.2% vs 41.3%, p<0.001), hypertension (14.5% vs 26.5%, p<0.001), diabetes (4.7% vs 9.7%, p<0.001), obesity (16.6% vs 35.4, p<0.001) and hypercholesterolaemia (7% vs 9.6%, p 0.011). In contrast, cigarette smoking (8.9% vs 3%, p<0.001) and use of desi ghee (51.4% vs 28.5%, p<0.001) decreased. CONCLUSIONS: In a rural population of Punjab, the prevalence of several CAD risk factors like sedentary lifestyle, hypertension, diabetes, obesity and hypercholesterolaemia increased over 20 years. These changes in risk factors were associated with a modest increase in prevalence of CAD.

Assessment of fatigue in Parkinson's disease: Indian perspective.

CONTEXT: Fatigue is one of the most frequent nonmotor manifestations in Parkinson's disease (PD), having a major effect on quality of life but is not reported in Indian patients. AIMS: To evaluate the frequency of fatigue in a cohort of PD population and its correlation with disease. SETTINGS AND DESIGN: Fatigue Severity Scale (FSS) was translated and validated in local vernacular language. All patients of PD visiting neurology outpatient department of a tertiary care hospital. SUBJECTS AND METHODS: A total of 150 patients were screened, and 104 were included in this study. They were divided into - Group I with fatigue (score of >4 in each item) and Group II without fatigue. STATISTICAL ANALYSIS: Data were analyzed by SPSS software version 20.0. Spearman correlation was used to evaluate the convergent validity of the FSS-Ind score with PD-related variables. The principal components analysis was applied to detect the domain structure of the FSS. RESULTS: Of the total 104 patients, 68 (65.3%) patients experienced fatigue. The duration of disease was significantly more (P = 0.021) in Group I (4.39 ± 3.8 years) than in the Group II (3.13 ± 1.6 years). The severity of disease also showed a positive correlation with fatigue with 50.9% patients in H and Y stage >3 experiencing fatigue. 69.1% patients of tremor phenotype experienced fatigue as compared to 32.3% of rigid phenotype. There was no relation of fatigue with age, gender, H and Y stage, levodopa equivalent dose and mean Unified PD Rating Scale motor III score. CONCLUSIONS: Translated version of the FSS, FSS-Ind has high internal consistency and validity which supports its application as an effective tool in detecting fatigue in patients with PD. Fatigue in PD was related to duration and phenotype of the disease.

Nanotechnology Based Approaches for Enhancing Oral Bioavailability of Poorly Water Soluble Antihypertensive Drugs.

Oral administration is the most convenient route among various routes of drug delivery as it offers high patient compliance. However, the poor aqueous solubility and poor enzymatic/metabolic stability of drugs are major limitations in successful oral drug delivery. There are several approaches to improve problems related to hydrophobic drugs. Among various approaches, nanotechnology based drug delivery system has potential to overcome the challenges associated with the oral route of administration. Novel drug delivery systems are available in many areas of medicine. The application of these systems in the treatment of hypertension continues to broaden. The present review focuses on various nanocarriers available in oral drug administration for improving solubility profile, dissolution, and consequently bioavailability of hydrophobic antihypertensive drugs.

A prospective, randomized, double-blind, multicentre, parallel-group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC-3197) and adalimumab (Humira) in patients with rheumatoid arthritis.

AIM: In this study, efficacy, tolerability and safety of biosimilar adalimumab (Exemptia; Zydus Cadila) was compared with reference adalimumab (Humira; AbbVie) in patients with moderate to severe rheumatoid arthritis (RA). METHOD: In this multicentre, prospective, randomized, double-blind, active controlled parallel arm study, 120 patients with moderate to severe RA were given 40 mg of either test adalimumab (Exemptia) or reference adalimumab (Humira) by subcutaneous route every other week for 12 weeks. The primary endpoint was proportion of responders in two tretament groups by American College of Rheumatology 20 (ACR20) at week 12. The secondary endpoints were change in Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and proportion of patients with an ACR50 and ACR70 response in two treatment groups at week 12. Safety outcomes were also assessed. RESULTS: After 12 weeks, patients treated every other week with test adalimumab (Zydus Cadila) had statistically similar response rates as compared to reference adalimumab (AbbVie): ACR20 (82% vs. 79.2%; P > 0.7); ACR50 (46%, vs. 43.4%; P > 0.7); ACR70 (14% vs. 15.1%; P > 0.8). The change in DAS28-CRP score was -2.1 ± 1.09 and -2.1 ± 1.21, in test and reference products, respectively. It was statistically significant compared to baseline, but not significantly different between the two products. Three serious adverse events and no death was reported during the study. Both adalimumab preparations were safe and well tolerated in this study. CONCLUSION: The results demonstrated biosimilarity with respect to efficacy, tolerability and safety of test adalimumab (Exemptia) and reference adalimumab (Humira) in patients with moderate to severe RA.

Amorphous solid dispersion technique for improved drug delivery: basics to clinical applications.

Solid dispersion has emerged as a method of choice and has been extensively investigated to ascertain the in vivo improved performance of many drug formulations. It generally involves dispersion of drug in amorphous particles (clusters) or in crystalline particles. Comparatively, in the last decade, amorphous drug-polymer solid dispersion has evolved into a platform technology for delivering poorly water-soluble small molecules. However, the success of this technique in the pharmaceutical industry mainly relies on different drug-polymer attributes like physico-chemical stability, bioavailability and manufacturability. The present review showcases the efficacy of amorphous solid dispersion technique in the research and evolution of different drug formulations particularly for those with poor water soluble properties. Apart from the numerous mechanisms of action involved, a comprehensive summary of different key parameters required for the solubility enhancement and their translational efficacy to clinics is also emphasized.