Obstructive Sleep Apnea: A Contributing Factor in Gout.

INTRODUCTION: Obstructive sleep apnea (OSA) is a comorbidity, which has shared risk factors with gout as well as causes pathophysiological mechanisms causing hyperuricemia. The relationship remains contentious. METHODS: TrinetX, a global federated research network that provides a dataset of electronic medical records from different healthcare organizations (HCOs). We utilized this network to query patients who had a BMI greater than 30 and then two subgroups were made based on the presence or absence of OSA. Furthermore, propensity score matching (PSM) was carried out to match age, sex, race, chronic kidney disease (CKD), heart failure, and the use of diuretics. Compare outcome analytic function was utilized to map the co-relation with Gout. RESULTS: A total of 3541566 patients who had a BMI >30 were identified, out of which 817638 (23.09%) patients had OSA. 7.19% of patients with OSA had gout while 2.84% without OSA had gout (p<0.0001). The odds of having gout are 2.65 times higher in patients with OSA than patients without OSA (hazard ratio is 2.393, 95% confidence interval (CI) 2.367-2.419, p<0.0001). After PSM, both the groups of obese patients with and without International Classification of Diseases, 10th Revision (ICD-10) diagnosis of OSA included 801526 patients, within which 6.93% of patients with OSA had gout while 4.63% of patients without OSA had gout (p<0.0001). The odds ratio was 1.533 (95% CI 1.512-1.554, p<0.0001) and the hazard ratio was 1.404 (95% CI 1.386-1.423). CONCLUSION: Our study demonstrated that there is a strong correlation between gout and OSA. Chronic hypoxia-induced hyperuricemia is the most widespread explanation. OSA is a treatable condition with timely diagnosis and proper treatment. Prospective cohort studies are required to further test the strength of the relationship between OSA and gout.

Impact of an Antimicrobial Stewardship Program on Broad Spectrum Antibiotics Consumption in the Intensive Care Setting.

Background and objectives: Antibiotics are the most commonly exploited agents in intensive care units. An antimicrobial stewardship program (ASP) helps in the optimal utilization of antibiotics and prevents the development of antibiotic resistance. The aim of this study was to assess the impact of ASP on broad-spectrum antibiotic consumption in terms of defined daily dose (DDD) and days of therapy (DOT) before and after the implementation of an ASP. Materials and methods: It was a prospective, quasi-experimental, pre- and post-study. Group A consisted of 5 months of ASP data, ASP activities were implemented during the next 2 months and continued. Group B (post-ASP) data was collected for the next 5 months. Total and individual DDDs and DOTs of broad-spectrum antibiotics utilized were compared between group A and group B. Results: Total DDDs used per 100 patient bed days were reduced by 18.72% post-ASP implementation (103.46 to 84.09 grams). The total DOT per 100 patient bed days used was 90.91 vs 71.25 days (21.62% reduction). As per the WHO classification of antibiotics use, the watch category (43.4% vs 43.04%) as well as reserve category (56.6% vs 56.97%) used between the two groups were found similar. The average length of stay (8.9 ± 2 days) after ASP was found significantly lesser than baseline (10.8 ± 3.4 days) (p < 0.05), however, there was no significant change in mortality between the two groups. Conclusion: Antimicrobial stewardship program implementation may reduce overall antibiotic consumption both in terms of DDD and DOT. How to cite this article: Zirpe KG, Kapse US, Gurav SK, Tiwari AM, Deshmukh AM, Suryawanshi PB, et al. Impact of an Antimicrobial Stewardship Program on Broad Spectrum Antibiotics Consumption in the Intensive Care Setting. Indian J Crit Care Med 2023;27(10):737-742.

Racial and regional disparities in deaths in breast cancer.

Breast cancer is the second most diagnosed malignancy in American women with a lifetime occurrence of 1 in 8 women in the United States. There has been a dearth of research focusing on regional differences in breast cancer mortality with respect to race in the US. It is crucial to identify regions that are lagging to uplift the outreach of breast cancer care to certain races. Data for this study were obtained from the 2016-2018 Nationwide Inpatient Sample. In-hospital mortality, race and hospital regions for the patients with the primary diagnosis of Malignant Neoplasms of Breast were studied. Baseline characteristics of participants were summarized using descriptive statistics. The patient population was stratified as per race, hospital region, gender, therapy received and family history. Logistic regression was performed to derive the odds ratio while adjusting for different variables. 99, 543 patients with metastatic breast cancer were identified. African Americans (AAs) were found to have the highest reported deaths at 5.54%, followed by Asians and Pacific Islanders at 4.80% and Caucasians 4.09% (p < 0.0001). The odds of dying were significantly higher in the AA population when compared to Caucasian population (OR 1.391 (1.286-1.504)), and the odds were consistently higher across all regions of the US. In terms of regional disparities with respect to race, AA's had highest mortality in the south whereas all other races had the highest mortality in the west. It was seen that races identifying as "others" had significantly higher odds of dying in the Northeast. It is crucial to identify racial differences in the various regions across the US in order to implement appropriate outreach strategies to tackle these disparities.

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial.

BACKGROUND: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. METHODS: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. RESULTS: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. CONCLUSIONS: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. TRIAL REGISTRATION: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

Wandering Cancer Cells: Metastatic Renal Cell Carcinoma Without Evidence of a Primary Tumor.

Renal cell carcinoma (RCC) usually presents clinically in the advanced stage including bone metastasis. However metastatic RCC without evidence of a primary tumor in the kidney is extremely rare. We herein report a case of a 70-year-old male initially evaluated for bone lesion and diagnosed with biopsy-proven metastatic clear cell RCC without a renal primary. Given the rare nature of the disease, there is no standardized course of treatment that has yet been established. We believe that our case will add to the body of knowledge about uncommon oncologic instances and consolidate the information that has already been published.

Hydroxychloroquine pre-exposure prophylaxis for COVID-19 among healthcare workers: Initial experience from India.

Background: Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities. Objectives: Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19. Methods: Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3-7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results. Results: Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3-9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13-0.83, P = 0.01) and the number needed to treat was 12. Conclusion: HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19.

Evaluating the Correlation of Bariatric Surgery and the Prevalence of Cancers in Obese Patients: A Study of the National Inpatient Sample (NIS) Database.

Purpose Obesity is a global pandemic that exerts a significant burden on healthcare worldwide. Multiple cancers, as well as deaths from the same, are more prevalent in obese patients. Bariatric surgery has been shown to be the most effective way of treating obesity once other measures have been exhausted. There is no concordant data available to support that bariatric surgery can reduce the prevalence of cancer. Using one of the largest data samples, we evaluate the correlation of bariatric surgery in morbidly obese patients with the prevalence of obesity-related cancers (breast, endometrial, esophageal, colorectal, prostate, and renal) in morbidly obese patients. Patients and methods A sample of 7,672,508 morbidly obese patients was identified from the 1994 to 2004 records of the National Inpatient Sample (NIS) database, divided into those who did and did not undergo bariatric surgery, and studied for the prevalence of obesity-associated cancers. Results Obesity was predominantly seen in the Caucasian population (68.22%). The mean age of cases who underwent bariatric surgery was younger when compared to those who did not undergo the procedure (43.89±25.16 vs. 54.90±36.40, p-value <0.0001). The highest bariatric surgery rate was seen in the Northeast (5.57%), followed by the West (4.15%), South (3.02%), and Midwest (2.96%) (p-value <0.0001). Overall, the odds of morbidly obese patients who underwent bariatric surgery and developed cancer are: esophageal cancer 0.19 (0.1218-0.3078, p <0.0001), colorectal cancer 0.0368 (0.0275- 0.0493, p <0.0001), endometrial cancer 0.0155 (0.0099-0.0244, p <0.0001), breast cancer 0.0712 (0.0582-0.0871, p <0.0001), prostate cancer 0.0285 (0.0199-0.0408, p <0.0001) and renal cancer 0.0182 (0.0106-0.0314, p <0.0001). The odds of cancer post-bariatric surgery remained significantly lower even after matching certain confounding factors. Conclusions The odds of developing breast, esophageal, prostate, renal, and colorectal cancers are significantly lower in morbidly obese patients who undergo bariatric surgery.

Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study.

BACKGROUND: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection. METHODS: We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%. FINDINGS: Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61). INTERPRETATION: This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Post COVID-19 sequelae: A prospective observational study from Northern India.

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.

Effectiveness of an institutional COVID-19 central sampling team during pandemic at a tertiary care centre.

BACKGROUND: An efficient sampling is one of the key methods to identify all those affected by coronavirus disease 2019 (COVID-19). OBJECTIVES: To analyze how efficient setting up of a central sampling team would be to prevent any outbreak within the institution by minimizing the movement of suspected COVID-19 patients admitted in the inpatient wards. The secondary objective was to train maximum resident doctors to collect samples of admitted patients. METHODOLOGY: A central sampling team comprising of resident doctors from various departments was made who did sampling of the suspected COVID-19 inpatients admitted under various specialties. RESULTS: There were a total of 341 patients [209 males (61.29%), 132 females (38.7%)] and 335 patients underwent sampling. There was a positive correlation between: (1) number of calls from a department vs percentage of positive samples in that department [Pearson correlation coefficient (R) = 0.47; P = 0.026], (2) number of samples taken by resident of a particular department from central sampling team vs number of positive samples taken by resident of that department [R = 0.8739, P = 0.01] and (3) number of visits to a department vs number of residents trained in that department [R = 0.93; P = 0.00001]. CONCLUSION: Formulation of a central sampling team led to changes like a separate donning and doffing area in each ward and training of many resident doctors posted in different wards. This made each ward self-sufficient in collection of samples. This venture also ensured minimal movement of suspected COVID-19 patients in the hospital and thus least exposure to the hospital staff.

Gargle lavage & saliva: Feasible & cheaper alternatives to nasal & throat swabs for diagnosis of COVID-19.

Background & objectives: In the present scenario, the most common sample for diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) is nasal and throat swab (NTS). Other sampling options such as gargle lavage have found limited application in clinical use mostly because of unavailability of an appropriate gargling liquid. This study was conducted to assess the stability of SARS-CoV-2 RNA in normal saline at 4°C that can serve as a gargling liquid as well as a transport medium. The study also looked at the agreement between NTS and gargle lavage/saliva for the detection of SARS-CoV-2. Methods: In 29 consecutive real-time RT-PCR (rRT-PCR) positive COVID-19 patients, paired NTS, gargle and saliva samples were taken. Samples were processed by rRT-PCR for the detection of SARS-CoV-2 RNA. To assess the SARS-CoV-2 RNA stability in normal saline, gargle lavage specimens were divided into two aliquots; one subset of the specimen was run within 4-6 h along with the routine samples (NTS and saliva) and the other subset was stored at 4°C and processed after 24-30 h. Agreement between cycle threshold (Ct) values from both the runs was compared using Bland-Altman (BA) analysis. Results: The positivity rates of rRT-PCR in NTS, saliva and gargle lavage samples were 82.7 (24/29), 79.3 (23/29) and 86.2 per cent (25/29), respectively. BA plot showed a good agreement between the Ct values of fresh and stored gargle samples, stipulating that there were no significant differences in the approximate viral load levels between the fresh and stored gargle lavage samples (bias: E gene -0.64, N gene -0.51, ORF gene -0.19). Interpretation & conclusions: Our study results show stability of SARS-CoV-2 RNA in the gargle samples collected using normal saline up to 24-30 h. Gargle lavage and saliva specimen collection are cost-effective and acceptable methods of sampling for the detection of SARS-CoV-2 RNA by rRT-PCR. These simplified, inexpensive and acceptable methods of specimen collection would reduce the cost and workload on healthcare workers for sample collection.

Clinical predictors of long COVID-19 and phenotypes of mild COVID-19 at a tertiary care centre in India.

A variable proportion of patients develop persistent/prolonged symptoms of Coronavirus Disease 2019 (COVID-19) infection (long COVID). We aimed to study the clinical predictors of persistent symptoms in patients with mild COVID-19 at 30 days post discharge (long COVID-19). We also tried to identify symptom clusters among mild COVID-19 patients. Fifty-seven patients admitted at a tertiary care centre after a positive RT-PCR report over a period of 2 months, were enrolled in the study. Details of presentation, history of illness, laboratory investigations and disease outcomes were recorded from documented medical records and discharge slip. The patients were contacted (telephonically) at 30 days after discharge and enquired regarding persistent symptoms, if any. Follow up data at 30 days post-discharge was available for 53 patients. Among them, the most common persistent symptom was fatigue (22.6%), followed by cough (9.4%) and myalgias (7.5%). There was a significant association of persistent symptoms with diarrhoea at presentation [OR 14.26 (95% CI 2.30-142.47; p = 0.009] and gap between symptom onset and admission [OR 1.40 (95% CI 1.08-1.93; p = 0.020] on multivariate logistic regression analysis. On cluster analysis, three phenotypes of mild COVID-19 were identified, which may have implications on monitoring and management. There appears to be a positive association of diarrhoea as a presenting manifestation and gap between symptom onset and admission with the persistence of symptoms classified as long COVID-19, even in mild illness. We also identified multiple phenotypes of mild COVID-19 illness, which warrant further exploration.

HIV-Associated Anal Cancer.

Anal cancer, despite being a rare malignancy, is increasing in incidence, accounting for 0.5% of all new cancer cases in the United States, with rate of new cases being 1.9 per 100,000 men and women. It is common in immunocompromised individuals, especially those with malignancy, human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection. Despite similar treatment of anal cancer in both HIV-positive and negative patients, guidelines for prevention and treatment of therapy-related side effects are rarely studied. While these patients have a better prognosis on HAART, limited guidelines exist regarding appropriate therapy. There is a common link between HPV and HIV and the transmission of one is associated with increased risk of transmission of the other. HPV vaccine which is known to prevent high-grade cervical intraepithelial neoplasia is thought to also decrease the incidence of anal intraepithelial neoplasia. The association of HPV vaccine in the prevention of anal cancer in high-risk groups with HIV is a scarcely studied subject that requires further research.

PSMA: a game changer in the diagnosis and treatment of advanced prostate cancer.

Although management of advanced prostate cancer is evolving, a lot of work remains to be done for patients who have exhausted all options. Molecular targeting of prostate specific membrane antigen (PSMA) is valuable not only for diagnostic but also for therapeutic reasons. PSMA is thus considered to be useful in a theranostic approach. PSMA scans are upcoming diagnostic modalities which detect metastatic lesions that are missed by conventional imaging modalities. PSMA ligand therapy is also an upcoming treatment modality that has been proven to be beneficial with minimal toxicity in patients with advanced prostate cancer that have progressed on prior therapy. In this review article, we summarize the current knowledge regarding PSMA diagnostics and PSMA ligand therapies and discuss their implication in the treatment of advanced prostate cancer.

Risk factors of multidrug-resistant bacterial infections among patients admitted in a tertiary care hospital of north India.

INTRODUCTION: Infections with drug-resistant organisms (DRO) have been associated with poor patient outcomes. To tackle this global problem, it is necessary to understand the risk factors that predispose to infections with DRO. METHODOLOGY: This was a prospective observational study conducted over a three-year period at a tertiary-care hospital. Bacterial culture isolates from patients admitted in medicine wards with community or hospital-acquired infections were included. Logistic regression analysis was used to determine risk factors for drug-resistant infections. RESULTS: Of the 295 patients with 323 isolates included, 40 (12.3%) had non-MDR (N-MDR) infections, 86 (26.6 %) had MDR infections and 197 (61%) had possible extensively drug-resistant (P-XDR) infections. History of previous admission in the preceding three months (Odds Ratio, OR = 4.53, 95% Confidence interval, CI = 1.8 - 11.42, p = -0.01), high SOFA score at admission (OR = 1.14, 95% CI = 1.0 - 1.290, p = -0.039) and prolonged duration of ventilation (OR = 1.25, 95% CI = 1.05 - 1.41, p = -0.012) were independently associated P-XDR infections when compared to patients with N-MDR. CONCLUSIONS: High rate of multidrug-resistant infections in the studied area is alarming. In this single-centre study, we elicited various risk factors for drug-resistant bacterial infections ranging from patient characteristics to iatrogenic risk factors during the hospital stay. Infections with P-XDR and MDR isolates independently increased hospital and ICU stay duration and were associated with increased mortality.

High prevalence of plasma EBV DNA among the HIV positive individuals, with or without malignancies, attending the clinic at AIIMS, New Delhi.

Epstein-Barr Virus (EBV) is associated with the Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL respectively). HIV is a risk factor for EBV infections and previously published data indicate that HIV infected individuals have higher chances of getting EBV infections compared to HIV uninfected individuals. Very limited information is available from India about the the prevalence of EBV in HIV positivity, with or without malignancy. In a recent study (Sinha et al. Current HIV Res 16:1-6, 2018) from All India Institute of Medical Sciences (AIIMS), New Delhi, we have shown that 2% among the HIV-1 infected individuals have malignancies including HL and NHL. To determine the prevalence of EBV among these individuals, clinical specimen obtained from ART clinic of AIIMS were tested for the presence of EBV DNA in plasma samples by quantitative real-time PCR. We have observed high prevalence of EBV (30%) among the 92 specimen tested. Prevalence is higher in patients with malignancy (37%) compared to those without maliganancy (27%). No correlation was observed with the CD4 counts or HIV viral load with EBV positivity.

PARP inhibitors: shifting the paradigm in the treatment of pancreatic cancer.

Pancreatic cancer, being one of the most fatal cancers, is the 7th leading cause of death globally. Cancer that is resistant to current treatment proves that there is a need for personalized and targeted therapy, based on the tumor and genomic markers. Pembrolizumab and Larotrectinib are examples of current medications used as targeted therapy in pancreatic cancer. Pancreatic cancer has many different molecular subgroups, providing the opportunity for the development of new drugs that can target these groups. Poly (ADP-Ribose) polymerase inhibitors (PARPi) are a group of drugs inhibiting PARP to decrease the stability of the cancer cells. Currently, PARPi are mostly used in ovarian and breast cancer. There are multiple studies that have shown positive effects of PARPi in decreasing the tumor burden in advanced pancreatic cancer. PARPi are the future of pancreatic cancer management, and hence it is important to understand their mechanism, resistance pathways, and their application in the real world.

Rapid chromatographic immunoassay-based evaluation of COVID-19: A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India.

Background & objectives: Coronavirus disease 2019 (COVID-19) has so far affected over 41 million people globally. The limited supply of real-time reverse transcription-polymerase chain reaction (rRT-PCR) kits and reagents has made meeting the rising demand for increased testing incompetent, worldwide. A highly sensitive and specific antigen-based rapid diagnostic test (RDT) is the need of the hour. The objective of this study was to evaluate the performance of a rapid chromatographic immunoassay-based test (index test) compared with a clinical reference standard (rRT-PCR). Methods: A cross-sectional, single-blinded study was conducted at a tertiary care teaching hospital in north India. Paired samples were taken for RDT and rRT-PCR (reference standard) from consecutive participants screened for COVID-19 to calculate the sensitivity and specificity of the RDT. Further subgroup analysis was done based on the duration of illness and cycle threshold values. Cohen's kappa coefficient was used to measure the level of agreement between the two tests. Results: Of the 330 participants, 77 were rRT-PCR positive for SARS-CoV-2. Sixty four of these patients also tested positive for SARS-CoV-2 by RDT. The overall sensitivity and specificity were 81.8 and 99.6 per cent, respectively. The sensitivity of RDT was higher (85.9%) in participants with a duration of illness ≤5 days. Interpretation & conclusions: With an excellent specificity and moderate sensitivity, this RDT may be used to rule in COVID-19 in patients with a duration of illness ≤5 days. Large-scale testing based on this RDT across the country would result in quick detection, isolation and treatment of COVID-19 patients.

Trends in incidence and epidemiologic characteristics of cerebral venous thrombosis in the United States.

OBJECTIVE: To test the hypothesis that race-, age-, and sex-specific incidence of cerebral venous thrombosis (CVT) has increased in the United States over the last decade. METHODS: In this retrospective cohort study, validated ICD codes were used to identify all new cases of CVT (n = 5,567) in the State Inpatients Databases (SIDs) of New York and Florida (2006-2016). A new CVT case was defined as first hospitalization for CVT in the SID without prior CVT hospitalization. CVT counts were combined with annual Census data to compute incidence. Joinpoint regression was used to evaluate trends in incidence over time. RESULTS: From 2006 to 2016, annual age- and sex-standardized incidence of CVT in cases per 1 million population ranged from 13.9 to 20.2, but incidence varied significantly by sex (women 20.3-26.9, men 6.8-16.8) and by age/sex (women 18-44 years of age 24.0-32.6, men 18-44 years of age 5.3-12.8). Incidence also differed by race (Blacks: 18.6-27.2; Whites: 14.3-18.5; Asians: 5.1-13.8). On joinpoint regression, incidence increased across 2006 to 2016, but most of this increase was driven by an increase in all age groups of men (combined annualized percentage change [APC] 9.2%, p < 0.001), women 45 to 64 years of age (APC 7.8%, p < 0.001), and women ≥65 years of age (APC 7.4%, p < 0.001). Incidence in women 18 to 44 years of age remained unchanged over time. CONCLUSION: CVT incidence is disproportionately higher in Blacks compared to other races. New CVT hospitalizations increased significantly over the last decade mainly in men and older women. Further studies are needed to determine whether this increase represents a true increase from changing risk factors or an artifactual increase from improved detection.