Seropersistence of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine): 6-month follow-up of a randomized, controlled, observer-blind, phase 2/3 immuno-bridging study in Indian adults.

AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.

Economic Burden of Gaucher Disease at a Tertiary Care Public Hospital in Mumbai.

OBJECTIVES: To estimate the economic burden of patients diagnosed with Gaucher disease at a public hospital from a societal perspective. METHODS: Data from 30 Gaucher patients visiting the Genetic Clinic of the Department of Pediatrics at the study site in Mumbai was analyzed between January 2019 and January 2021. A cost of illness analysis was undertaken to estimate direct, indirect and intangible costs. Costs in treated and treatment naive groups were compared. RESULTS: The total cost (direct and indirect) for 30 patients was ₹25,45,74,743/- (3440199.2 USD). Majority of this cost (99.8%) was due to direct costs of which medications [Enzyme replacement therapy (ERT) and Substrate reduction therapy (SRT)] constituted 98.8%. The notional cost was ₹1,43,94,695. Total costs of 14 treated patients were ₹25,29,67,279 and 16 treatment naive patients were ₹16,15,064 with a ratio of 157:1. Direct costs and cost of school absenteeism were significantly higher in the treated subgroup. Overall, direct, total costs and costs of school absenteeism were significantly associated with age and disease duration. CONCLUSIONS: The economic burden of Gaucher disease is a staggering amount. This is an underestimate, as the expenses are highly subsidized in a public health facility. The highest contributor to cost component was direct costs, especially medication costs. Against the backdrop of the National Policy for Rare Diseases, resource allocation towards Gaucher disease should consider short term measures for judicious funding or reimbursement of disease-specific therapy and long-term cost-effective measures for promoting preventive strategies as the most practically feasible solution to reduce this economic burden.

Low-dose emicizumab prophylaxis in patients with severe hemophilia A: a retrospective study bringing new hope for our patients.

BACKGROUND: Low-dose emicizumab can potentially offer a cost-effective treatment option in persons with hemophilia A, especially in developing countries. OBJECTIVES: To compare the efficacy and safety of low-dose emicizumab with those on low-dose factor (F)VIII prophylaxis via chart review. METHODS: After ethics approval, chart data of 2 groups of patients were reviewed: group 1 (low-dose emicizumab, n = 10; 3 mg/kg monthly without a loading dose) and group 2 (low-dose FVIII prophylaxis, n = 10; 10-20 IU/kg of FVIII concentrates twice a week). Outcomes were target joints, annual bleeding rate, annual joint bleeding rate, Hemophilia Joint Health Score, nonactivated thromboelastometry-rotational thromboelastometry clotting time, plasma emicizumab levels, and direct costs of treatment. RESULTS: All outcome measures were significantly better in the low-dose emicizumab group than in the low-dose FVIII prophylaxis group. For nonactivated thromboelastometry-rotational thromboelastometry, median values after 6 months in the low-dose emicizumab group were comparable with values seen in patients with mild hemophilia, while the values in the low-dose FVIII prophylaxis group were similar to those of patients with moderate hemophilia. The direct cost of low-dose emicizumab was found to be approximately US $6000 and that for low-dose recombinant FVIII prophylaxis used in our study was US $6282 (the cost may range from US $3432 to $7920 depending on the type of factor) when compared to approximately US $15 000 for standard-dose emicizumab. CONCLUSION: Low-dose emicizumab offers a cost-effective treatment option and can improve access in developing countries. These findings need to be confirmed in a larger and better-controlled study.

Clinical studies with Cannabis in India - A need for guidelines for the investigators and ethics committees.

Cannabis is one of the world's oldest cultivated plants and the most commonly used recreational drug worldwide. The plant relevant for medicinal use is Cannabis sativa that has two pharmacologically active ingredients - delta-9-tetrahydrocannabinol that is psychoactive and cannabidiol that does not have psychotropic activity. The policy tapestry of Cannabis has undergone a significant change in the past few decades worldwide. Different countries have diverse policies, ranging from classifying use of Cannabis as illicit, to legalization of its use, both for medicinal and recreational purposes. Cannabis products are approved for use, for instance, in multiple sclerosis and Dravet syndrome (US Food Drug and Administration). Against this backdrop, we find that the knowledge foundations for use of Cannabis in clinical trials in India are still evolving. Conducting ethical research within a clinical trials framework is essential to understand dosing, formulation, shelf life, drug-drug interaction, tolerability, and safety before establishing its utility for various indications. In the absence of guidelines or a regulatory framework for conduct of these studies, the various Institutional Ethics Committees (IECs), which are responsible for reviewing projects related to Cannabis, face unique challenges with respect to the basic requirements. The principal investigators (PIs) are equally strained to find local guidance, recommendations, and literature in support of their application to the respective IEC, thus leading to an impasse and delay in initiating the proposed clinical studies with Cannabis. The present article addresses considerations, questions, and issues that affect the conduct of these clinical studies and recommends mandatory documents and some suggested guidelines for use by both PIs and IECs to take studies with Cannabis forward until such time that an interdisciplinary regulatory framework is firmed up by regulatory authority.

A prospective study to assess the role of paraoxonase 1 genotype and phenotype on the lipid-lowering and antioxidant activity of statins.

Human paraoxonase 1 (PON1) enzyme protects against atherosclerosis by preventing low-density lipoprotein from oxidative modification. Upregulation of PON1 enzymatic activity is suggested to contribute to atheroprotective potential of statins. Glutamine (Q) to arginine (R) at site 192 and leucine (L) to methionine (M) substitution at site 55 polymorphisms influence the PON1 activity. The study assessed the role of PON1 polymorphisms on lipid-lowering and PON1-modulating activity of statins in a Western Indian cohort of patients with dyslipidemia. Lipid profile and PON1 activity were determined at baseline and 3 months after initiation of statin treatment. PON1 genotypes (QQ, QR, RR; LL, LM, and MM) were determined by PCR-RFLP. Paraoxon was used as a substrate for assessing PON1 activity by spectrophotometry. A total of 140 statin-naïve patients were enrolled; of them, 116 were available for final analysis. Fifty-seven (50%) had QQ, 39 (35%) had QR, and 17 (15%) had RR genotypes. Seventy-six (67%) patients had LL, 35 (31%) had LM, and 2 (2%) had MM genotypes. We observed no impact of PON1 polymorphisms on lipid parameters posttreatment. A significant increase was observed in the serum PON1 activity from a median (range) of 47.92 U/L (9.03-181.25) to 72.22 U/L (7.64-244.44) (P < 0.05) following statin treatment, which was independent from high-density lipoprotein (HDL) concentration. This increase was significantly greater in QQ compared to QR and RR genotypes (P = 0.01). To conclude, the important antioxidant properties of statins are exerted via the rise in serum PON1 activity, independent of HDL cholesterol concentrations. The increase was greater in individuals with QQ genotype. Future large-scale studies will validate the premise that QQ homozygotes see added benefits from statin treatment compared to R carriers. In the meantime, PON1 enzymatic activity remains an important marker to be measured while assessing pleotropic effects of statins in CAD.

Economic burden of beta-thalassaemia major receiving hypertransfusion therapy at a public hospital in Mumbai.

Background Treating beta-thalassaemia major may entail high costs with considerable out-of-pocket expenditure. Therefore, determination and valuation of the economic costs of a common haemoglobinopathy such as beta-thalassaemia major in India may provide insights to evolve policies for reduction or elimination of the disease. We estimated economic burden of beta-thalassaemia major in Mumbai in terms of cost to the family and the healthcare system. Methods This single-centre, prospective, cross-sectional, non-interventional study included children <12 years of age treated at the thalassaemia day care centre of a public hospital in Mumbai. The demographic data and treatment-related information was recorded. Cost of illness was studied from a societal perspective by the prevalence-based approach. Direct (medical and non-medical), indirect (loss of wages and loss of school days) and intangible costs (closed-ended iterative bidding) were calculated for each patient by interview. Results The total annual cost of treating 130 children with beta-thalassaemia major in Mumbai was ₹86 72 412 (US$ 127 535) or ₹66 710 (US$ 981) per patient per year and ₹12 82 30 412 (US$ 1 885 741) including intangible costs. Direct costs contributed to 94% of the cost of illness with chelation therapy (23%) and blood investigations (21%) being major contributors. Direct and indirect costs correlated significantly with duration of blood transfusion (p<0.05 and p=0.006, respectively), whereas indirect costs correlated with socioeconomic status (rho=0.25). Conclusion The majority (94%) of costs incurred by families for treatment of beta-thalassaemia major are direct costs, especially expenses for chelation and blood investigations. Even at subsidized rates, financial burden to the families from lower socioeconomic strata is likely to be considerable as these are out-of-pocket expenses. In consideration of the economic impact of treating beta-thalassaemia major in individual families, the healthcare system and society, it is prudent to promote and pursue long-term and short-term measures with urgent emphasis on prevention as a public health activity at the national level in India.

Evaluation of clinical trials done for orphan drugs versus nonorphan drugs in infectious diseasesan eleven year analysis [2010-2020].

Background: The 1983 US Orphan Drug Act provided impetus for the development of new therapies for rare diseases. Several studies focused on the number of orphan designations over time. However, very few focused on clinical trials that lead to their approval, particularly for infectious diseases. Materials and Methods: All new drug approvals (orphan and non-orphan) by the US Food and Drug Administration (FDA) from January 2010 to December 31, 2020, were identified and details of approvals were taken from the US-FDA labels and summary reports for each drug. The pivotal trials for each were characterized based on their design. We tested the association of the type of drug approval with respect to the characteristics of trial using Chi-square test and generated crude odds ratios with 95% confidence intervals. Results: From the total 1122 drugs approved, 84 were for infectious diseases, of which 18 were orphan drugs and 66 were nonorphan. A total of 35 pivotal trials supported 18 orphan drug approvals, while 115 pivotal trials supported 66 nonorphan drugs. The median number of participants enrolled/trial for orphan drugs was 89, while for nonorphan drugs, it was 452 (P < 0.0001). Blinding was done for 13/35 (37%) orphan drugs versus 69/115 (60%) nonorphan drugs (P = 0.029); randomization was done for 15/35 (42%) orphan drugs versus 100/115 (87%) nonorphan drugs (P < 0.0001) and 20/35 (57%) of the orphan drugs got approval in phase II versus 8/115 (6%) of nonorphan drugs (P < 0.00001). Conclusion: A significant number of orphan drugs get approval based on early phase, nonrandomized, and unblinded with a smaller sample size as compared to nonorphan drugs.

An audit of institutional ethics committee queries raised after initial project submission by a single research department at a tertiary referral center in India.

Introduction: The institutional ethics committees (IECs) raise queries following protocol reviews. The quality of these queries would be a useful metric to assess how well the IEC executes its fundamental role of protecting participants. Methods: Queries received after the initial review and replies sent by a single research department were evaluated. A content analysis was done to identify the domains and categories of queries. We categorized these queries as administrative, ethics related, and scientific. The impact of each query in improving the science or safeguarding the rights and safety of research participants (ethics) was evaluated by two authors of this manuscript: one affiliated and the other nonaffiliated to the institute. Kappa statistics were used to evaluate for agreement between the two. Results: A total of 13 studies (investigator-initiated studies [IISs]: 7 and pharmaceutical industry-sponsored studies [PSSs]: 6) formed the final sample size for analysis. The total number of queries was 364 (IIS: 106 and PSS: 258; P < 0.001). With regard to the categories, we found n = 42 (11.54%) to be irrelevant at that stage of the review process; n = 51 (14.01%) were about information already available which the IEC had missed; n = 67 (18.41%) queries where the IEC needed paraphrasing; n = 50 (13.74%) were entirely relevant with the need for further clarification; and n = 154 (42.31%) had been missed by the investigator during the initial submission. The overall agreement between the affiliated and unaffiliated investigators was just 12.9% (P < 0.001). Conclusions: We found that approximately 25% of the queries raised by the IEC were redundant. It is our opinion that this redundancy could have been channeled into greater focus on scientific and ethical aspects of the protocol. Ongoing dialog between investigators and ethics committees may help address this. Perspectives between the affiliated and the unaffiliated investigators with regard to the relevance of queries were grossly different.

Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial.

INTRODUCTION: Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS: Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS: A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS: Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled study.

Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13-22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

Population Pharmacokinetics of Hydroxychloroquine Sulfate in Healthcare Workers, Given for Prophylaxis Against Coronavirus Disease 2019 (COVID-19) in India.

Healthcare workers (HCWs) and frontline workers were recommended hydroxychloroquine (HCQ) 400 mg twice a day on day 1, followed by 400 mg once weekly for the next 7 weeks, as prophylaxis against COVID-19. There was limited information on the population pharmacokinetics (popPK) of HCQ in an Indian setting when administered for prophylaxis against COVID-19, and hence this study was proposed. It was a multicentric prospective study conducted at 3 sites in India wherein HCWs who were already on HCQ prophylaxis, who were about to start prophylaxis or who had stopped the prophylaxis for any reason were enrolled. Each participant gave 2 to 6 blood samples at different time points and whole-blood HCQ concentrations were assayed using liquid chromatography with tandem mass spectrometry (LC MS/MS). popPK analysis was performed using PUMAS 1.1.0. A total of N = 338 blood samples from N = 121 participants were included in the popPK analysis. A 2-compartment structural model with linear elimination was able to explain the observed data. Body weight was found to be a significant covariate influencing drug clearance. The final model was assessed using goodness-of-fit plots, a visual predictive check and a bootstrap, all of which confirmed that the model was appropriate. Simulations based on the current regimen showed that trough values were below the half-maximal effective concentration (EC50) of 0.7 µmol against COVID-19. A new weight-based dosage regimen was proposed to maintain the trough concentration above the EC50 threshold.

An audit of US FDA warning letters issued to sponsors, institutional review boards and investigators over a six-year period.

The present audit was carried out with the objective of evaluating warning letters (WLs) issued to trial sponsors, clinical investigators and institutional review boards (IRBs) by the United States Food and Drug Administration during a six-year period and compare it with two similar earlier audits. WLs were reviewed and classified as per stakeholders and further categorised as per predefined violation themes. The chi-square test was performed for trend analysis of WLs. A total of 62 WLs were issued to the three stakeholders. The maximum number of WLs were issued to the clinical investigators (36/62, 58.06%), followed by sponsors (19/62, 30.64%), and least to the IRBs (7/62, 11.29%). Among sponsors, lack of standard operating procedures for the monitoring, receipt, evaluation and reporting of post-marketing adverse drug events was the most common violation theme (8/19, 42.1%). Among clinical investigators, deviation from investigational plan was the most common violation theme (31/36, 86.11%.). For IRBs, inadequate documentation was the most common violation theme (6/7, 85.71%). We saw an overall reduction in the number of WLs issued to the stakeholders. Thus, we identified multiple areas on which each stakeholder should work for improvement.

An Audit of Black Box Warnings (BBWs) in the United States Food and Drug Administration (US-FDA) Database - A Five-Year Analysis.

BACKGROUND: The Black-Box Warning (BBW) is the most serious warning that US-FDA can ask for on a drug's labelling. BBWs represent key safety concerns uncovered either during dossier review or post-approval. We have conducted the present study with the primary objective of assessing BBWs issued by the US-FDA. METHODS: BBWs were identified on US-FDA's website from 1st January 2015 to 31st December, 2019. Prescribing information was used to identify and characterize BBWs into new and minor/major updates on a previous BBW. The therapeutic class of the drug, nature [Biological/New Molecular entity (NME)], formulation type, expected duration of use, along with the year of first approval of the molecule with BBWs were evaluated. RESULTS: A total of n = 167 BBWs were issued by the FDA of which 53 (31.7%) had major updates, 57(34.1%) had minor updates and 57(34.1%) were new BBWs. A total of 137(82%) of BBWs were with NME's whereas 30(18%) were with biologics. Drugs for neurology 40(25.5%)had the highest number of BBWs, followed by oncology 38(24.2%). Among the type of BBWs, cardiovascular risk 31 (15%) were the highest. CONCLUSION: Practicing physicians need to understand that benefit-risk of a drug is dynamic and keep abreast of new data related to it.

A Systematic Review and Meta-Analysis of the Safety of Hydroxychloroquine in a Randomized Controlled Trial and Observational Studies.

INTRODUCTION: Hydroxychloroquine (HCQ) has recently become the focus of attention in the current COVID-19 pandemic. With an increase in the off-label use of HCQ, concern for the safety of HCQ has been raised. We, therefore, performed this systematic review to analyze the safety data of HCQ against placebo and active treatment in various disease conditions. METHODS: We searched PubMed, Embase, and Cochrane for Randomized Controlled Trials (RCTs) and Observational Studies (OSs) that evaluated HCQ for the treatment of any disease other than COVID19 in adult patients up to May 2020. We assessed the quality of the included studies using Risk of Bias 2 (for RCTs) and Newcastle-Ottawa Scale (for OSs). Data were analyzed with randomeffect meta-analysis. Sensitivity and subgroup analyses were performed to identify heterogeneity. RESULTS: A total of 6641 studies were screened, and 49 studies (40 RCTs and 9 OSs) with a total sample size of 35044 patients were included. The use of HCQ was associated with higher risks of TDAEs as compared to placebo/no active treatment [RR 1.47, 95%CI 1.03-2.08]. When HCQ was compared with active treatments, the risks of AEs [RR 0.74, 95% CI 0.63-0.86] and TDAEs were less in the HCQ arm [RR 0.57, 95% CI 0.39-0.81]. The outcomes did not differ in the sensitivity analysis. CONCLUSION: The results suggest that the use of HCQ was associated with a lower risk of AEs and TDAEs as compared to active treatment, whereas posing higher risk of TDAEs as compared to placebo.

Evaluation of efficacy and safety of fosfomycin versus nitrofurantoin for the treatment of uncomplicated lower urinary tract infection (UTI) in women - A systematic review and meta-analysis.

Urinary tract infections (UTI) are among the most frequent medical conditions requiring outpatient treatment. Single dose oral fosfomycin (300 mg) and the older nitrofurantoin (100 mg for 5 days) have been found to be more effective than other first-line drugs in multiple studies. This systematic review and meta-analysis were carried out with the objective of evaluating their comparative efficacy and safety in the management of uncomplicated UTI. Two authors independently searched PubMed, Cochrane Central, Embase, and Google Scholar till Nov 2020 using MeSH terms and free text. Randomized controlled trials (RCTs) comparing both drugs for efficacy and safety in uncomplicated UTI in adult women were included. The primary outcome measures were microbiological and clinical cure rates. The search resulted in n = 663 studies out of which only four studies (three for treatment of uncomplicated UTI in women and one for asymptomatic bacteriuria in pregnancy) satisfied the selection criteria. No significant differences in clinical, (RR 0.95, 95% CI - 0.81, 1.12) and microbiological cure, (RR 0.96, 95% CI - 0.84, 1.08) were found within 4 weeks of treatment. The incidence of adverse events was found to be more in fosfomycin relative to the nitrofurantoin group (RR 1.05, 95% CI - 0.59, 1.87). Hence, single-dose fosfomycin presents a potentially useful and safe treatment option for the treatment of uncomplicated UTI in women and asymptomatic bacteriuria in pregnancy.

An analysis of invitations for article submission received via emails.

Predatory journals charge publication fees from authors and publish without an adequate peer review, and often do not provide editorial and/or publishing services. Our objective was to evaluate e-mail solicitations received by authors in a defined time period to identify attributes of these solicitations as a metric to identify legitimacy of the journal. All e-mails seeking article submission received between January 1 and September 30, 2019, were evaluated. Each e-mail along with its respective webpage was evaluated for the journal's and publisher's names, mention of peer review, any assurance of publication, a mention of article processing charges (APC), composite invites [in the e-mail] and mention of peer review, the presence and functionality of archives, presence of manuscript management tab, mention of APC [on the webpage]. Descriptive statistics were used for the analysis. Of the 135 e-mails screened, 100 were finally included in the analysis. We found that 72% of the journals and/ or publishers were included in Beall's list. According to our criteria, a total of 85% of the solicitations were from journals that we identified as "presumed predatory". Our study has identified assurance of publication, rapid turnaround time, ambiguous information in the email and webpage, false claims of indexing as some descriptors which may help young authors and researchers assess a journal's legitimacy.

Evaluation of satisfaction and reasons for participation in a Covid-19 vaccine clinical trial: A single-centre, observational study.

Background In May 2020, WHO recognized the role of extensive immunization for interrupting the transmission of the SARS-CoV-2 virus. The development of such vaccines in clinical trials relies upon participants who are expected to be vested in the research process. Assessment of participant factors such as motivation and satisfaction are hence important to gauge perspective and ensure successful conduct and completion of these trials. Methods We administered a validated three-domain questionnaire to and documented the binary categorical responses (yes/no) of participants (after informed consent) who had taken both doses of COVOVAX™ in a phase 3 trial at our institute. Association of the dependent variables (participant responses) with the independent variables (participant demographics and socioeconomic strata) was computed using Chi-square test at 5% significance. In case of a significant association, Bonferroni post-hoc test was applied for multiple comparisons. Results Of the 78 participants who were administered the questionnaire, two-thirds were highly satisfied with their experience at our site. Gaining access to a new vaccine was a primary motivation overall (74%) and also in graduates (p=0.03) and middle-class population (p=0.002), whereas the lower-middle class population (p<0.0001) and those educated till secondary school (p=0.003) took part due to the long wait for government-approved vaccines. Conclusion Participants in a Covid-19 vaccine trial at Mumbai were largely satisfied with the care given to them though altruism did not feature as a primary reason for participation.