Probiotic formulations and gastro-intestinal diseases in the paediatric population: a narrative review.

Background/Aim: Probiotics are live microbial supplements that improve the microbial balance in the host animal when administered in adequate amounts. They play an important role in relieving symptoms of many diseases associated with gastrointestinal tract, for example, in necrotizing enterocolitis (NEC), antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, Helicobacter pylori infections, and inflammatory bowel disease (IBD). In this narrative review, the authors aim to evaluate the role of different probiotic formulations in treating gastrointestinal diseases in pediatric population aged 18 years or younger and highlight the main considerations for selecting probiotic formulations for use in this population. Methodology: The authors searched PubMed and Clinicaltrials.gov from inception to 24th July 2022, without any restrictions. Using an iterative process, the authors subsequently added papers through hand-searching citations contained within retrieved articles and relevant systematic reviews and meta-analyses. Results: The effectiveness of single-organism and composite probiotics in treating gastrointestinal disorders in pediatric patients aged 18 or under were analyzed and compared in this study. A total of 39 studies were reviewed and categorized based on positive and negative outcomes, and compared with a placebo, resulting in 25 studies for single-organism and 14 studies for composite probiotics. Gastrointestinal disorders studied included NEC, acute gastroenteritis (AGE), Acute Diarrhea, Ulcerative Colitis (UC), and others. The results show that probiotics are effective in treating various gastrointestinal disorders in children under 18, with single-organism probiotics demonstrating significant positive outcomes in most studies, and composite probiotics showing positive outcomes in all studies analyzed, with a low incidence of negative outcomes for both types. Conclusion: This study concludes that single-organism and composite probiotics are effective complementary therapies for treating gastrointestinal disorders in the pediatric population. Hence, healthcare professionals should consider using probiotics in standard treatment regimens, and educating guardians can enhance the benefits of probiotic therapy. Further research is recommended to identify the optimal strains and dosages for specific conditions and demographics. The integration of probiotics in clinical practice and ongoing research can contribute to reducing the incidence and severity of gastrointestinal disorders in pediatric patients.

Postoperative delirium in 47 379 individuals undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis.

Objective: The study aims to discuss the assessment methods used for the incidence of in-hospital postoperative delirium (IHPOD) in transcatheter aortic valve replacement (TAVR) patients and explore possible strategies for preventing and reducing postoperative complications in the geriatric population. Methodology: An electronic search of PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials was conducted up to August 2021, to identify studies on the IHPOD following TAVR in patients above 70 years. The primary objective of the study was to determine the incidence of delirium following TAVR and procedures like transfemoral (TF) and non-TF approaches. The secondary objectives were to determine the incidence of stroke and incidence according to the confusion assessment method (CAM) diagnostic tool. The authors only included studies published in English and excluded patients with comorbidities and studies with inaccessible full-text. Results: Among the selected 42 studies with 47 379 patients, the incidence of IHPOD following TAVR was 10.5% (95% CI: 9.2-11.9%, I2=95.82%, P<0.001). Incidence based on CAM was 15.6% (95% CI: 10.5-20.7%, I2=95.36%, P<0.001). The incidence of IHPOD after TF-TAVR was 9.3% (95% CI: 7.6-11.0%, I2=94.52%, P<0.001), and after non-TF TAVI was 25.3% (95% CI: 15.4-35.1%, I2=92.45%, P<0.001). The incidence of stroke was 3.7% (95% CI: 2.9-4.5%, I2=89.76%, P<0.001). Meta-regression analyses between mean age (P=0.146), logistic EuroSCORE (P=0.099), or percentage of participants treated using the TF approach (P=0.276) were nonsignificant while stroke (P=0.010) was significant. When considering these variables, the residual heterogeneity remained high indicating that other variables influence the heterogeneity. Conclusion: IHPOD following TAVR was observed in 10.5% of individuals and in 15.6% using CAM. Its incidence was found to be three times higher after non-TF TAVR (25.3%) compared to TF TAVR (9.3%). Stroke showed an incidence of 3.7% after TAVR and was found to be significantly associated with the risk of developing delirium following TAVR. Further studies are needed to evaluate possible causes and risk factors responsible for delirium and to assess the role of anesthesia and cerebral embolic protection in preventing delirium after TAVR.

Better understanding extrapulmonary tuberculosis: A scoping review of public health impact in Pakistan, Afghanistan, India, and Bangladesh.

Background and Aims: South Asian countries, including Pakistan, Afghanistan, India, and Bangladesh, have a high prevalence of pulmonary and extra-pulmonary tuberculosis (EPTB). This prevalence is influenced by various risk factors such as ethnicity, nutrition, socioeconomic disparities, high out-of-pocket healthcare expenses, and specific Mycobacterium Tuberculosis (TB) lineages. The COVID-19 pandemic has likely hindered access to healthcare and led to under-reporting of EPTB cases nationally and internationally. This rapid review aimed to summarize the literature on the prevalence and disease outcomes of EPTB in the mentioned countries, compare the situations across countries, and provide recommendations for future action. Methods: The review utilized PubMed and Google Scholar databases to search for literature on EPTB in South Asian countries. The search string included keywords related to different forms of EPTB and the countries of interest while excluding pulmonary tuberculosis. Results: The results showed that both TB, including drug-resistant TB, and EPTB are prevalent and burdensome in South Asia. In Pakistan, pleural TB was the most commonly reported form of EPTB, followed by lymph node TB, abdominal TB, osteoarticular TB, Central Nervous System TB, and miliary TB. In India, lymph node TB(LNTB) was more common among EPTB cases. Bangladesh reported a high prevalence of EPTB involving lymph node, pleura, and abdomen, while Afghanistan had a higher prevalence of forms such as LNTB and tuberculous meningitis. Conclusion: In conclusion, the prevalence of EPTB in Pakistan, Afghanistan, India, and Bangladesh is alarmingly high and negatively impacts population health. Effective measures are needed for treatment and management of this condition, along with addressing current and future challenges. Strengthening the evidence base through surveillance and research is crucial to understand the patterns and significant factors related to EPTB, requiring investment in these areas.

Effects of myo-inositol vs. metformin on hormonal and metabolic parameters in women with PCOS: a meta-analysis.

OBJECTIVE: Polycystic Ovary Syndrome is the most prevalent hormonal disorder in females. Over the years, metformin (MET) has become the first-line choice of treatment; however, due to its gastrointestinal side effects, a more recent drug, myo-inositol (MI), has been introduced. We aim to conduct a systematic review and meta-analysis to compare the effects of MET and MI on hormonal and metabolic parameters. MATERIALS AND METHODS: Authors extensively searched PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science for randomized clinical trials (RCTs) until August 2021. Eight (n = 8) articles were included, with a total sample size of 1088, of which 460 patients received MET, 436 received MI, and 192 received a combination of both. Standard mean differences (SMDs) and Confidence Intervals (CIs) were used for data synthesis, and forest plots were made using Review Manager 5.4 for Statistical Analysis using the random-effect model. RESULTS: The meta-analysis indicates that there is no significant difference between MET and MI in terms of their effects on BMI (SMD = 0.16, 95% CI: - 0.11 to 0.43, p = 0.24), fasting insulin (SMD = 0.00, 95% CI: - 0.26 to 0.27, p = 0.97), fasting blood sugar (SMD = 0.11, 95% CI: - 0.31to 0.53, p = 0.60), HOMA index (SMD = 0.09, 95% CI: - 0.20 to 0.39, p = 0.50), and LH/FSH (SMD = 0.20, 95% CI: - 0.24 to 0.64, p = 0.37). BMI, fasting blood sugar, and LH/FSH ratio reported moderate heterogeneity because of the varying number of study participants. CONCLUSION: Our meta-analysis comparing hormonal and metabolic parameters between MET and MI did not show much significant difference, indicating both drugs are equally beneficial in improving metabolic and hormonal parameters in patients with PCOS.

Awake Prone Positioning for Non-Intubated COVID-19 Patients with Acute Respiratory Failure: A Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Awake prone positioning (APP) has been widely applied in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure. However, the results from randomised controlled trials (RCTs) are inconsistent. We performed a meta-analysis to assess the efficacy and safety of APP and to identify the subpopulations that may benefit the most from it. METHODS: We searched five electronic databases from inception to August 2022 (PROSPERO registration: CRD42022342426). We included only RCTs comparing APP with supine positioning or standard of care with no prone positioning. Our primary outcomes were the risk of intubation and all-cause mortality. Secondary outcomes included the need for escalating respiratory support, length of ICU and hospital stay, ventilation-free days, and adverse events. RESULTS: We included 11 RCTs and showed that APP reduced the risk of requiring intubation in the overall population (RR 0.84, 95% CI: 0.74-0.95; moderate certainty). Following the subgroup analyses, a greater benefit was observed in two patient cohorts: those receiving a higher level of respiratory support (compared with those receiving conventional oxygen therapy) and those in intensive care unit (ICU) settings (compared to patients in non-ICU settings). APP did not decrease the risk of mortality (RR 0.93, 95% CI: 0.77-1.11; moderate certainty) and did not increase the risk of adverse events. CONCLUSIONS: In patients with COVID-19-related acute hypoxemic respiratory failure, APP likely reduced the risk of requiring intubation, but failed to demonstrate a reduction in overall mortality risk. The benefits of APP are most noticeable in those requiring a higher level of respiratory support in an ICU environment.

COVID-19 vaccine hesitancy in conflict zones: A review of current literature.

Background: Vaccine hesitancy (VH) is prevalent in conflict zones due to a lack of essential resources and knowledge, thereby escalating the coronavirus disease of 2019 (COVID-19) cases in these territories. This has resulted in a higher incidence of cases from exposure to a single COVID-19 positive case and further burdens the health care system of conflict zones which are already on the brink of collapsing. Aim: This narrative review aims to determine VH to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in five conflict zones that include Somalia, Yemen, Palestine, Syria, and Afghanistan. Methodology: A Boolean search was carried out in MEDLINE-PubMed from inception till 6 June 2022. The search was performed by using the following keywords: "(SARS-CoV-2 OR covid OR covid 19) AND (vaccine hesitancy OR covid vaccine acceptance OR intention to vaccinate) AND (Syria OR Yemen OR Palestine OR Afghanistan OR Somalia"). The full text of all relevant articles in English along with their supplementary material was extracted. Results: All the included studies reported at least 30% or more increase in vaccine hesitancy among conflict settings. VH was mostly due to a lack of available resources, lack of appropriate knowledge, and believing misleading rumors about the vaccine. Discussion: Considering the massive amount of reluctance among people residing in conflict zones, the need to take effective measures against VH is undoubtedly apparent. This can be accomplished by carrying out mass vaccinations by the governments and proper health education through raising the public awareness regarding vaccines, thereby eliminating rumors that exacerbate the fear of adverse effects. Conclusion: The approach described in this article to combat VH can be implemented to increase vaccination rates and significantly alleviate R0 across the globe.

What has been learned about COVID-19 vaccine hesitancy in Pakistan: Insights from a narrative review.

Background: Vaccine hesitancy is not a new phenomenon to Pakistan. This is evidenced through the slow progress of previous vaccination campaigns and programs against MMR, BCG, and especially polio. This issue continues to persist and is therefore becoming the cause of low COVID-19 vaccination rates in Pakistan. Aim: To provide insights about COVID-19 vaccine hesitancy among Pakistanis, and its potential harm on public health. Moreover, we aim provide recommendations to counter the factors limiting the COVID-19 vaccination in Pakistan. Methodology: A Boolean search was conducted to find the literature in MEDLINE-PubMed, Google Scholar, and Clinicaltrials.gov databases up till March 16, 2022. Specific keywords were used which comprised of "SARS-CoV-2," "COVID-19," "vaccine hesitancy," "vaccine acceptance," "intention to vaccinate," and "Pakistan," with use of "OR" and "AND." Only free full-text original studies in English language were used to compare and contrast. Results: As proven by various studies, COVID-19 vaccination rates are influenced by multiple factors, including inaccurate beliefs about COVID-19, hesitancy amongst healthcare workers, uncertainty regarding vaccine's efficacy and fear of side effects. Various conspiracy theories and lower testing rates among others also add up to impose a negative impact on the vaccination rates and public health of Pakistan. This may lead to newer strains of potentially harmful COVID-19, mental health deterioration, and prolonged lockdowns. Conclusion: Vaccine hesitancy is a global public health threat, and its impacts are pronounced in Pakistan. This is reflected in the COVID-19 pandemic; low vaccination rates in Pakistan may lead to future outbreaks of new, potentially harmful, strains of COVID-19 which can prolong lockdowns in the country and affect mental health of the population. To improve the current situations, it is imperative for the government, educational institutes, and healthcare systems to develop trust and continually use dialogue, communication, and education to address misconceptions to improve COVID-19 vaccination in Pakistan.

Adverse effects of long-term Levothyroxine therapy in Subclinical Hypothyroidism.

Levothyroxine, also known as L-thyroxine, is a manufactured form of the thyroid hormone thyroxine which is considered to be a gold-standard therapy for treating an underactive thyroid gland (hypothyroidism). Some experts highlight benefits of LT4 replacement therapy, others specify the harmful effects of it, in regards to treating subclinical hypothyroidism. With respect to current guidelines for the consistent dosing of levothyroxine for treating hypothyroidism, we aim to highlight limitations of long-term use of Levothyroxine therapy in SCH. Apropos of the studies published to date, we look into the appropriate dosing of Levothyroxine in SCH by physicians.

Revival of the heterologous prime-boost technique in COVID-19: An outlook from the history of outbreaks.

BACKGROUND: The heterologous prime-boost vaccination technique is not novel as it has a history of deployment in previous outbreaks. AIM: Hence, this narrative review aims to provide critical insight for reviving the heterologous prime-boost immunization strategy for SARS-CoV-2 vaccination relative to a brief positive outlook on the mix-dose approach deployed in previous and existing outbreaks (ie, Ebola virus disease (EVD), malaria, tuberculosis, hepatitis B, HIV and influenza virus). METHODOLOGY AND MATERIALS: A Boolean search was carried out to find the literature in MEDLINE-PubMed, Clinicaltrials, and Cochrane Central Register of Controlled Trials databases up till December 22, 2021, using the specific keywords that include "SARS-CoV2", "COVID-19", "Ebola," "Malaria," "Tuberculosis," "Human Immunodeficiency Virus," "Hepatitis B," "Influenza," "Mix and match," "Heterologous prime-boost," with interposition of "OR" and "AND." Full text of all the related articles in English language with supplementary appendix was retrieved. In addition, the full text of relevant cross-references was also retrieved. RESULTS: Therefore, as generally evident by the primary outcomes, that is, safety, reactogenicity, and immunogenicity reported and updated by preclinical and clinical studies for addressing previous and existing outbreaks so far, including COVID-19, it is understood that heterologous prime-boost immunization has been proven successful for eliciting a more efficacious immune response as of yet in comparison to the traditional homologous prime-boost immunization regimen. DISCUSSION: Accordingly, with increasing cases of COVID-19, many countries such as Germany, Pakistan, Canada, Thailand, and the United Kingdom have started administering the heterologous vaccination as the technique aids to rationalize the usage of the available vaccines to aid in the global race to vaccinate majority to curb the spread of COVID-19 efficiently. However, the article emphasizes the need for more large controlled trials considering demographic details of vaccine recipients, which would play an essential role in clearing the mistrust about safety concerns to pace up the acceptance of the technique across the globe. CONCLUSION: Consequently, by combatting the back-to-back waves of COVID-19 and other challenging variants of concerns, including Omicron, the discussed approach can also help in addressing the expected evolution of priority outbreaks as coined by WHO, that is, "Disease X" in 2018 with competency, which according to WHO can turn into the "next pandemic" or the "next public health emergency," thus would eventually lead to eradicating the risk of "population crisis."

COVID-19 and mucormycosis superinfection: Exploring the missing pathophysiological links.

The coronavirus disease 2019 continues to unearth new facets that portend grave clinical implications. In recent times, there has been mounting fervor regarding coronavirus disease 2019 and mucormycosis superinfection. While the correlation between the two is conspicuous, the underlying pathophysiological mechanisms that render a patient with coronavirus disease 2019 susceptible to mucormycosis, or vice versa, are still elusive.