d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial.

Importance: Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established. Objective: To determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI. Design, Setting, and Participants: This 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022. Intervention: Two grams daily of d-mannose powder or matched volume of placebo powder. Main Outcomes and Measures: The primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions. Results: Of 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures. Conclusions and Relevance: In this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group. Trial Registration: isrctn.org Identifier: ISRCTN13283516.

Ivermectin for COVID-19 in adults in the community (PRINCIPLE): An open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes.

BACKGROUND: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials. METHODS: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 µg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome. TRIAL REGISTRATION: ISRCTN86534580. FINDINGS: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n = 2157), usual care (n = 3256), and other treatments (n = 3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months. INTERPRETATION: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted. FUNDING: UKRI/National Institute of Health Research (MC_PC_19079).

Post COVID syndrome: A novel challenge and threat to international health.

The global pandemic caused by the SARS-CoV-2 virus has affected every continent worldwide. The novelty of this virus, its mutations and the rapid speed and unprecedented rate at which it has torn through the global community has in turn lead to an innate lack of knowledge and information about the actual disease caused and the severity of the complications associated with COVID-19. The SARS-CoV-2 virus has been infecting individuals since 2019 and now as of 2022 has been circulating for just over 2 years within the global populous. As the number of cases have risen globally over this period (some of which having contracted the virus twice) further endeavours have been undertaken to better understand the pathogenesis and natural progression of the disease. A condition reported in some cases with extended bouts of sickness or symptoms following the initial infection with COVID was labelled "long COVID" towards the earlier phases of the pandemic (in the spring of 2020), but has only recently gained the global media and medical attention due to its affliction of more individuals on a global basis and has thus warranted further investigation. Long COVID is described as a persistent, long-term state of poor health following an infection with COVID-19. The effect of Long COVID is multisystemic in nature with a wide array of signs and symptoms. The most commonly reported clinical features of long COVID are: headaches, myalgia, chest pain, rashes, abdominal pain, shortness of breath, palpitations, anosmia, persistent cough, brain fogs, forgetfulness, depression, insomnia, fatigue and anxiety. This research aims to explore the symptomatology, pathophysiology as well as the treatment and prevention of Long COVID.

COVID-19: Lockdown and its impact on medical students: A cross sectional study from a medical school in Mauritius.

BACKGROUND: The objectives of the study were to identify the psychological impacts of lockdown on medical students due to COVID-19 and to discover the educational perplexities being faced by these students during the lockdown. METHODS: A cross-sectional study was conducted at Sir Seewoosagur Ramgoolam Medical College (SSRMC), Mauritius. Questions were designed after an extensive review of the literature, so as to ensure relevance to meet the objectives of the study. RESULTS: Out of 700 undergraduate medical students, 663 participated, which equates to a response rate of 95%. 348 (52.5 %) of the students were stationed in their hometown and the remaining 315 (47.5 %) were stationed in Mauritius. 464(70%) of the students suffered from the psychological impacts of lockdown whereas 634(95.6%) of students suffered from the educational impact thereof. Mauritian students suffered a greater educational impact aOR4.236[1.606-11.173]. Psychological impacts aOR 1.280 [0.917-1.789] and educational impacts aOR 2.464 [1.076-5.647] were more prevalent in hometown-based students. Students pursuing their clinical studies had aOR1.219 [ 0.531-2.798] a greater educational impact as compared to preclinical studies. CONCLUSION: Lockdown triggered both educational and psychological impacts on medical students. On a psychological basis it was proven that the lockdown induced a feeling of guilt and had a greater psychological impact in pre-clinical students. The COVID-19 situation was simultaneously indicated to be a motivator in the majority of students; however, juxtaposed to this was the fact that various students felt as if they couldn't study at the same level that they were accustomed to due to the uncertainty of the situation.

Mucormycosis and COVID-19 an epidemic in a pandemic?

Mucormycosis and aspergillosis are rare, invasive and life-threatening infections primarily caused by Rhizopus arrhizus and Aspergillus fumigatus with higher case fatality rates (>50%), respectively. Invasive Aspergillosis and Mucormycosis have been established and recognized as complications of the SARS-CoV-2 infection. Such cases have been intimately linked and related to prior corticosteroid therapy. With the new highly infectious Delta strain (B.1.617.2 and B.1.617.2.1 or AY.1) of the coronavirus which is running rampant throughout India causing unprecedented death tolls, a new crisis is evolving. Invasive "black fungus" (Mucormycosis) is creating an epidemic within a global pandemic. The unique socio-economic, genetic and health status of Indian population culminates into a melting pot which sustains the viable triad for the "black fungus" infection to gain a stronghold. Diabetes mellitus, immunosuppression and the current COVID-19 global pandemic with its massive surges in the country have produced the "perfect storm." Ophthalmologist across India have reported a surge in invasive Mucormycosis cases with a rise in orbital compartment syndrome often calling for radical procedures such as enucleation surgeries. The "black fungus" pandemic and invasive Mucormycosis resulted in the sinister secondary infections and complications are closely linked with the COVID-19 infection in India. It is therefore of the upmost importance that neighbouring countries particularly Nepal and other Asiatic nations take great cognizance of this indolent "black fungus killer" and ensure new screening and testing protocols for early identification to ensure effective management.

COVID-19 and mutations a threat level assessment.

A mutation is defined as an alteration in the DNA or RNA sequences of a genome which may consequently confer a new phenotypic and or genotypic advantage both increasing the virulence as well as the survival of a virus or pathogen. At this current point in time there are 4 known major variants of the original SARS-CoV-2 virus, namely the English variant (B.1.1.7), the South African variant (B.1.351), Brazilian variants (VOC202101/02 (P.1) and VUI202101/01) and a variant similar to that of the South African variant found in North America (B.1.526), all of which have varying levels of resistance and infectivity. It is evident that the SARS-CoV-2 variants pose an international health risk, the mutations of E484K and N501Y are the two most implicated mutations. E484K being the most concerning as it aids in immune evasion and drastically causes the efficacy of the current vaccines to be reduced by large margins. The most worrisome variant is the South African or B.1.351 which harbors the above mutations. It is of the upmost importance that targeted vaccines are synthesized to ensure that immunized individuals have effective protection against these variants. Until these specific targeted vaccines are synthesized the current vaccines offer little long-term protection, however do confer a level of immunity to stop severe infections. It is thus advised that current vaccination programs should continue in earnest as a degree of protection is conferred.

D-MannosE to prevent Recurrent urinary tract InfecTions (MERIT): protocol for a randomised controlled trial.

INTRODUCTION: Recurrent urinary tract infections (RUTIs) have a significant negative impact on quality of life and healthcare costs. To date, daily prophylactic antibiotics are the only treatment which have been shown to help prevent RUTIs. D-mannose is a type of sugar which is believed to inhibit bacterial adherence to uroepithelial cells, and is already being used by some women in an attempt to prevent RUTIs. There is currently insufficient rigorous evidence on which to base decisions about its use. The D-mannose to prevent recurrent urinary tract infections (MERIT) study will evaluate whether D-mannose is clinically and cost-effective in reducing frequency of infection and symptom burden for women presenting to UK primary care with RUTI. METHODS AND ANALYSIS: MERIT will be a two-arm, individually randomised, double blind placebo controlled, pragmatic trial. Participants will be randomised to take D-mannose powder or placebo powder daily for 6 months. The primary outcome will be the number of medical attendances attributable to symptoms of RUTI. With 508 participants we will have 90% power to detect a 50% reduction in the chance of a further clinically suspected UTI, assuming 20% lost to follow-up. Secondary outcomes will include: number of days of moderately bad symptoms of UTI; time to next consultation; number of clinically suspected UTIs; number of microbiologically proven UTIs; number of antibiotic courses for UTI; quality of life and healthcare utilisation related to UTI. A within trial economic evaluation will be conducted to examine cost-effectiveness of D-mannose in comparison with placebo. A nested qualitative study will explore participants' experiences and perceptions of recruitment to, and participation in a study requiring a daily treatment. ETHICS AND DISSEMINATION: Ethical approval has been obtained from South West-Central Bristol Research Ethics Committee. Publication of the MERIT study is anticipated to occur in 2021. TRIAL REGISTRATION NUMBER: ISRCTN 13283516.

Omicron: The pandemic propagator and lockdown instigator - what can be learnt from South Africa and such discoveries in future.

The SARS-CoV-2 virus which causes the disease termed COVID-19 ripped through the globe in the latter part of 2019 and has left a state of fear, death and destruction in its wake. The Omicron variant was officially announced by the South African authorities on the 24th of November 2021, with the first confirmed sample of the infection being collected on the 9th of November 2021. The initial cases were flagged as a possible new variant due to the stark differences in the presentation and clinical features of the patients. At the time of Omicron's discovery, the predominant variant circulating within South Africa was the Delta variant B.1.617.2 which typically presented with more severe and distinct symptoms. Omicron spread rapidly within the Southern Africa and abroad, principally South Africa, Botswana, Hongkong and Israel were among the first countries to record cases of the new variant. The first European case of the Omicron variant was confirmed on the 26th of November 2021 in Belgium. Towards the end of November 2021 cases of the new variant had been confirmed and recorded in France, the United Kingdom, Germany, Portugal and Scotland. Additional cases of the Omicron variant have been confirmed in Canada, Australia, India and United States. At this current point in the development of the Omicron upsurge in cases the international community should aim for further vaccinations among their fellow countrymen, but more so vaccine equality should be ensured. Such equality should be ensured in the developing nations as the virus does not respect any boundaries or territories and thus a higher level of vaccination worldwide will confer greater protection to the global community as a whole.