Association and Mechanisms of Proton Pump Inhibitors Use with Type-2 Diabetes Mellitus Incidence in Adults: A Systemic Review and Metaanalysis.

BACKGROUND: Proton pump inhibitors (PPIs) are an extensively prescribed class of anti-ulcer drugs. This systematic review aimed to investigate the association between PPI use and the risk of new-onset diabetes mellitus or type 2 diabetes (T2DM) incidence. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov using the search terms "proton pump inhibitor," "proton pump inhibitors," "PPIs," "diabetes mellitus," and "type 2 diabetes" from inception to February 2023. Statistical analyses were performed using the "Review Manager 5.4" version, and a statistically highly significant P value <0.05 was set. RESULTS: This systematic review identified 12 studies (8 cohort, 1 RCT, and 3 case-control) with a total of 12, 64, 816 population, and the median age ranged from ≥18 yrs to ≤ 75 yrs. The pooled relative risk (RR) observations of a random-effects meta-analysis model showed that chronic exposure to PPI use has a significant association with T2DM risk incidence (RR, 2.44; 95% confidence interval, 1.31-4.54; I 2 = 99%, P < 0.00001). The systematic review findings of the three case-control studies also supported an association of dose-dependent and chronic use of PPIs with an incidence of T2DM among chronic users. CONCLUSION: The systematic review concludes that chronic PPI exposure increases the risk of T2DM incidence. The authors recommend the shortest possible duration of PPI use and not prescribing PPIs to high-risk prediabetics and those without a compelling indication for PPI use. Regular education to patients regarding adverse reactions with prolonged use may decrease the risk of adverse effects associated with PPIs. The authors suggest that gut dysbiosis, hypergastrinemia, hypomagnesemia, decreased pancreatic secretions and IGF-1 levels, and PXR activation associated with chronic acid suppression among chronic PPI users and the potency of PPIs might explain the association between abnormal glucose metabolism and T2DM incidence. Finally, the authors recommend further randomized controlled trials to investigate the association between PPIs and the risk of new-onset T2DM incidence.

A systematic review to identify novel clinical characteristics of monkeypox virus infection and therapeutic and preventive strategies to combat the virus.

Since May 2022, there has been a global increase in the number of Mpox virus (MPXV) cases in countries that were previously considered non-endemic. In July 2022, the World Health Organization (WHO) declared this outbreak a public health emergency of international concern. The objective of this systematic review is to examine the novel clinical features of Mpox and to assess the available treatment options for managing the disease in patients who are afflicted with it. We conducted a systematic search in several databases, including PubMed, Google Scholar, Cochrane Library, and the grey literature, from May 2022 to February 2023. We identified 21 eligible studies, which included 18,275 Mpox cases, for final qualitative analysis. The majority of cases were reported in men who have sex with men (MSM) and immunocompromised individuals with HIV (36.1%). The median incubation period was 7 days (IQR: 3-21). The novel clinical manifestations include severe skin lesions on the palms, oral and anogenital regions, as well as proctitis, penile edema, tonsillitis, ocular disease, myalgia, lethargy, and sore throat, without any preceding prodromal symptoms or systemic illness. In addition, fully asymptomatic cases were documented, and various complications, including encephalomyelitis and angina, were noted. Clinicians must be familiar with these novel clinical characteristics, as they can aid in testing and tracing such patients, as well as asymptomatic high-risk populations such as heterosexuals and MSM. In addition to supportive care, currently, there are several effective prophylactic and treatment strategies available to combat Mpox, including the vaccines ACAM2000 and MVA-BN7, as well as the immunoglobulin VIGIV and the antivirals tecovirimat, brincidofovir, and cidofovir against severe Mpox infection.

Clinical virology and effect of Covid-19 vaccination and monoclonal antibodies against highly infectious SARS- CoV-2 omicron sub variant BF.7 (BA.5.2.1.7): A systematic review.

Over time, the SARS-CoV-2 virus has acquired several genetic mutations, particularly on the receptor-binding domain (RBD) spike glycoprotein. The Omicron variant is highly infectious, with enhanced immune escape activity, and has given rise to various sub-lineages due to mutations. However, there has been a sudden increase in COVID-19 reports of the Omicron subvariant BF.7 (BA.2.75.2), which has the highest number of reported cases, accounting for 76.2% of all cases worldwide. Hence, the present systematic review aimed to understand the viral mutations and factors associated with the increase in the reports of COVID-19 cases and to assess the effectiveness of vaccines and mAbs against the novel Omicron variant BF.7. The R346T mutation on the spike glycoprotein RBD might be associated with increased infection rates, severity, and resistance to vaccines and mAbs. Booster doses of COVID-19 vaccination with bivalent mRNA booster vaccine shots are effective in curtailing infections and decreasing the severity and mortality by enhancing the neutralizing antibodies (Abs) against the emerging Omicron subvariants of SARS-CoV-2, including BF.7 and future VOCs.

Global prevalence and effect of comorbidities and smoking status on severity and mortality of COVID-19 in association with age and gender: a systematic review, meta-analysis and meta-regression.

A COVID-19 patient often presents with multiple comorbidities and is associated with adverse outcomes. A comprehensive assessment of the prevalence of comorbidities in patients with COVID-19 is essential. This study aimed to assess the prevalence of comorbidities, severity and mortality with regard to geographic region, age, gender and smoking status in patients with COVID-19. A systematic review and multistage meta-analyses were reported using PRISMA guidelines. PubMed/MEDLINE, SCOPUS, Google Scholar and EMBASE were searched from January 2020 to October 2022. Cross-sectional studies, cohort studies, case series studies, and case-control studies on comorbidities reporting among the COVID-19 populations that were published in English were included. The pooled prevalence of various medical conditions in COVID-19 patients was calculated based on regional population size weights. Stratified analyses were performed to understand the variations in the medical conditions based on age, gender, and geographic region. A total of 190 studies comprising 105 million COVID-19 patients were included. Statistical analyses were performed using STATA software, version 16 MP (StataCorp, College Station, TX). Meta-analysis of proportion was performed to obtain pooled values of the prevalence of medical comorbidities: hypertension (39%, 95% CI 36-42, n = 170 studies), obesity (27%, 95% CI 25-30%, n = 169 studies), diabetes (27%, 95% CI 25-30%, n = 175), and asthma (8%, 95% CI 7-9%, n = 112). Moreover, the prevalence of hospitalization was 35% (95% CI 29-41%, n = 61), intensive care admissions 17% (95% CI 14-21, n = 106), and mortality 18% (95% CI 16-21%, n = 145). The prevalence of hypertension was highest in Europe at 44% (95% CI 39-47%, n = 68), obesity and diabetes at 30% (95% CI, 26-34, n = 79) and 27% (95%CI, 24-30, n = 80) in North America, and asthma in Europe at 9% (95% CI 8-11, n = 41). Obesity was high among the ≥ 50 years (30%, n = 112) age group, diabetes among Men (26%, n = 124) and observational studies reported higher mortality than case-control studies (19% vs. 14%). Random effects meta-regression found a significant association between age and diabetes (p < 0.001), hypertension (p < 0.001), asthma (p < 0.05), ICU admission (p < 0.05) and mortality (p < 0.001). Overall, a higher global prevalence of hypertension (39%) and a lower prevalence of asthma (8%), and 18% of mortality were found in patients with COVID-19. Hence, geographical regions with respective chronic medical comorbidities should accelerate regular booster dose vaccination, preferably to those patients with chronic comorbidities, to prevent and lower the severity and mortality of COVID-19 disease with novel SARS-CoV-2 variants of concern (VOC).

Assessment of WHO core drug use indicators at a tertiary care Institute of National importance in India.

Rational prescribing of medicines is an important aspect of drug prescribing which helps in safe and efficacious and cost-effective drug treatment for patients. WHO Prescription indicators are intended to evaluate the services provided to the population concerning the rational use of medicines. The study aims to study prescription practices and rational use of medicines in the department of Internal medicine, using WHO prescribing indicators in a tertiary care teaching institute of national importance. A total of 50 prescriptions were digitally photographed and analysed for prescription practices and rational drug use, using standard WHO core prescribing indicators. A total of 301 drugs with multiple and diverse diagnoses were used. Statistical analysis was done using SPSS 22 version. The average number of drugs per prescription was 3.48%. It was found that only 13.79% of prescriptions have generic names, whereas 27.58% of patient encounters had at least one drug from the National List of Essential Medicine, 6.8% of prescriptions have antibiotics and 0.7% of prescriptions were injections. The number of prescriptions with fixed drug combinations was 27.55%. Indicators such as percentage of the National List of Essential Medicine, fixed drug combinations and prescribing with a generic name are used. Hence, we will suggest regular prescription audit practices and conducting CMEs and training workshops for clinicians for the rational use of medicines in all healthcare settings to succeed in the rational use of medicine.

A novel triple oral regime provides effective analgesia during extracorporeal shockwave lithotripsy for renal stones.

CONTEXT: Analgesia during extracorporeal shockwave lithotripsy for renal stone is an essential component. It not only makes the procedure comfortable but also increases the stone-free rate. AIMS: The aim of this study was to evaluate the efficacy of triple oral analgesic agents on stone fragmentation and pain relief in comparison to injectable analgesic agents. SETTINGS AND DESIGN: This prospective randomized study included 68 patients of renal calculi of size 5-15 mm. SUBJECTS AND METHODS: Group A had 32 patients, who received injection pentazocine and injection diclofenac, 45 min before the procedure. Group B consisted of 28 patients, who received a combination of oral acetaminophen, 325 mg, oral diclofenac 50 mg, and oral tramadol 37.5 mg, 45 min prior. Procedural findings, pain score visual analog scale (VAS), fragmentation rate, and outcome were recorded. STATISTICAL ANALYSIS USED: Independent t-test and Pearson's correlation test. RESULTS: A total of 60 patients were analyzed. The mean age was 40.2 ± 11.8 years. Both groups were comparable in body mass index, stone size, number, and density. Group A required more shocks than Group B (4274 vs. 3693, P = 0.043). A lower energy level of shocks (kV) was tolerated in Group A (2.5 vs. 3.2, P = 0.002). Group A required more sittings than Group B (2.3 vs. 1.9, P = 0.037). VAS score was significantly less in Group B (2.9 vs. 4.9, P = 0.0001). The overall fragmentation rate was similar among groups (81.2% vs. 89.3%); hence, the successful outcome was (59.4% vs. 75.0%, P = 0.274). The occurrence of adverse events was also equivalent in both groups (P = 0.199). CONCLUSIONS: Triple oral regime provides better analgesic effect and quicker stone-free rate than injectable agents but with similar final outcome.

Primary Adenocarcinoma of the Bulbomembranous Urethra in a 33-Year-Old Male Patient.

Primary Urethral Carcinoma (PUC) is considered as a rare tumour, accounts for less than 1% of all malignancies and an incidence rate of four cases per million patients. Incidence increases with the patient's age and most commonly present in seventh decades. Urothelial carcinoma is the most common type (76%) of the PUC, adenocarcinoma accounts for less than 5% of the PUC. No definitive protocol for tumour management for urethral adenocarcinoma has been described in the literature due to lack of prospective study and scarcity of the cases. Treatment usually depends on the site and stage of the tumour. We hereby report a case of 33-year-old male patient with urethral adenocarcinoma of bulbomembranous urethra spread to the prostatic urethra and left side inguinal lymph node. He was treated through multimodal therapy with surgery plus adjuvant chemotherapy.

Giant Pyonephrosis Due to Ureteropelvic Junction Obstruction: A Case Report.

Pyonephrosis is a suppurative infection of upper urinary tract due to obstruction of the ureter. It is usually associated with suppurative damage of renal parenchyma and renal function loss. Patients are mostly symptomatic but may remain asymptomatic in 15% of cases. Severe infection in pyonephrosis may lead to urosepsis and may endangered life, if timely not treated with surgical intervention. We hereby report a rare case of Giant Pyonephrosis (GP), contained 11 liters of pus, due to Ureteropelvic Junction (UPJ) obstruction presented with haematuria. The patient was treated with open nephrectomy. The aetiology, clinical features, diagnosis and management of pyonephrosis with the review of literature of GP in the background of a rare case report have been discussed here.

Bilateral Single System Orthotopic Ureterocele with Bilateral Multiple Calculi Presented with Retention of Urine - an Urological Emergency.

The ureterocele is an uncommon congenital anomaly of the lower ureter. Ureterocele with a single pelvicalyceal system, bilateral, and orthotopic variety is less common. Calculi within bilateral ureterocele are a rare occurrence. To the best of our knowledge, only a few similar cases have been reported in the literature. Among the all reported presentations of this type of ureterocele, presentation with Acute Urinary Retention (AUR) has not been described in the literature. We present a case of nine-year-old child having bilateral, single system orthotopic ureterocele with calculi in bilateral ureterocele and presented with AUR due to obstructive bulbar urethral calculus. The bilateral endoscopic incision was given and all four calculi were removed endoscopically through percutaneous route. Voiding cystourethrography after two years follow-up was non-refluxing. The purpose of reporting this case is the rarity of the disease and to emphasize that delay in diagnosis and treatment of these cases may lead to complications such as recurrent urinary tract infection and renal failure.

Bilateral Staghorn Calculus with Forgotten Double J Stent in Ileal Conduit Patient - A Rare Urological Challenge.

Forgotten DJ stent associated stone formation is not an uncommon entity. Here we are reporting the uncommon case of bilateral staghorn calculus due to forgotten DJ stent who had undergone radical cystectomy with ileal conduit diversion six years back. Management of these cases is a challenging urological situation due to inaccessible ureteric orifices. Patient was successfully treated with minimally invasive therapy in the form of combined bilateral PCNL (Percutaneous Nephrolithotomy) and ESWL (Extracorporeal Shock Wave Lithotripsy) therapy. The purpose of reporting this case is to highlight the grave consequences of a forgotten DJ stent and to discuss the difficulties encountered during the surgical steps of stone removal.

Can a brief period of double J stenting improve the outcome of extracorporeal shock wave lithotripsy for renal calculi sized 1 to 2 cm?

PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) is an established modality for renal calculi. Its role for large stones is being questioned. A novel model of temporary double J (DJ) stenting followed by ESWL was devised and outcomes were assessed. MATERIALS AND METHODS: The study included 95 patients with renal calculi sized 1 to 2 cm. Patients were randomized into 3 groups. Group 1 received ESWL only, whereas group 2 underwent stenting followed by ESWL. In group 3, a distinct model was applied in which the stent was kept for 1 week and then removed, followed by ESWL. Procedural details, analgesic requirements, and outcome were analyzed. RESULTS: Eighty-eight patients (male, 47; female, 41) were available for analysis. The patients' mean age was 37.9±10.9 years. Stone profile was similar among groups. Group 3 received fewer shocks (mean, 3,155) than did group 1 (mean, 3,859; p=0.05) or group 2 (mean, 3,872; p=0.04). The fragmentation rate was similar in group 3 (96.7%) and groups 1 (81.5%, p=0.12) and 2 (87.1%, p=0.16). Overall clearance in group 3 was significantly improved (83.3%) compared with that in groups 1 (63.0%, p=0.02) and 2 (64.5%, p=0.02) and was maintained even in lower pole stones. The percentage successful outcome in groups 1, 2, and 3 was 66.7%, 64.5%, and 83.3%, respectively (p=0.21). The analgesic requirement in group 2 was higher than in the other groups (p=0.00). Group 2 patients also had more grade IIIa (2/3) and IIIB (1/2) complications. CONCLUSIONS: Stenting adversely affects stone clearance and also makes the later course uncomfortable. Our model of brief stenting followed by ESWL provided better clearance, comfort, and a modest improvement in outcome with fewer sittings and steinstrasse in selected patients with large renal calculi.

Comparative study of a new technique using nephroscope and resectoscope sheath and the percutaneous cystolithotripsy for the treatment of bladder calculus.

INTRODUCTION: Several minimally invasive approaches are available for the treatment of bladder stones, with each having its own advantages and disadvantages. We devised a new technique to overcome a few limitations of conventional techniques and compared its efficacy with conventional percutaneous cystolithotripsy (PCCL) technique. MATERIAL AND METHODS: This was a randomized, open-label, prospective, controlled study conducted from July 2015 to December 2016 that included 62 patients with bladder calculus of ≥2 cm in size. Patients were randomly assigned into two groups. Patients from Group 1 were treated with new a technique using a transurethral nephroscope via resectoscope outer sheath and patients from Group 2 were treated with conventional PCCL. RESULTS: Overall, the mean (SD) age was 53.3 (11.4) years and 49.9 (12.8) years for Group 1 and 2, respectively; and stone size was 3.2 (0.8) and 3.2 (0.7), respectively. Operative time was similar in both groups (32.7 [8.7] versus 34.3 [7.0]; P = 0.428). The length of hospital stay was higher in Group 2 (2.1 [0.4]) as compared to Group 1 (1.2 [0.5]) (P = 0.000). Stones were completely cleared in all patients.Group 2 patients required more analgesics and had more complications like hematuria and wound infection. CONCLUSIONS: Results showed that cystolithotripsy with nephroscope via resectoscope sheath is an alternative to the conventional PCCL techniques as the new technique was associated with lesser complications, better cosmetic outcome and minimal analgesic requirement.

Adult Idiopathic Renal Vein Thrombosis Mimicking Acute Pyelonephritis.

Renal Vein Thrombosis (RVT) is a rarely encountered condition. It occurs due to a hypercoagulable state in the body, caused by nephrotic syndrome and membranous nephropathy in the adults. Mode of presentation is variable. In chronic form, it may remain silent for a long time and presenting later with symptoms of pedal oedema, varicocele, proteinuria. In acute state, it manifests as flank pain, nausea or haematuria. We present a case of 25-year-old male, with left sided flank pain, haematuria and nausea for 4 days. Ultrasound showed enlarged kidney with altered echogenecity. No calculus was found on x-ray. Empirical antibiotics were started considering possibility of Acute Pyelonephritis (APN). With no improvement seen after 3 days along with no growth on urine culture, CT-urography was done. It revealed enlarged non-excreting left kidney with thrombus seen over left renal vein extending into Inferior Vena Cava (IVC). Immediate anticoagulant therapy was started. Patients recovered gradually and after 6 months, follow-up CT showed disappearance of thrombosis. Anticoagulants were withdrawn gradually. So we highlight the possibility of RVT as a differential diagnosis to APN or renal colic and its evaluation and management.

Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles.

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1-100 µg/ml) for 24-96 h to establish the temporal effects of DEHP on the follicle. Following 24-96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17ß-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis.

Unrecognized catatonia as a cause for delayed weaning in Intensive Care Unit.

The cause of altered sensorium in critical care settings includes metabolic derangements, drug and toxin overdose, central nervous system infections, neurodegenerative disorders, vascular events, hypo-perfusion states, and septic encephalopathy. Here, we present a case of an elderly woman who presented to us with altered sensorium with respiratory failure requiring mechanical ventilation. Her metabolic parameters, imaging, and cerebrospinal fluid study were all normal despite that she continued to remain in altered sensorium and had an unrecognized behavioral state that delayed her weaning.

Oral manifestations of hypothyroidism: a case report.

Hypothyroidism can be due to thyroid failure (primary hypothyroidism) or pituitary or hypothalamic disease (secondary hypothyroidism). A 20-year-old female patient reported with a complaint of the presence of milk teeth in mouth since 10-12 years. Intraorally, multiple retained decidious and missing permanent teeth were present. Macroglossia was evident. Skeletal and dental malocclusion (class II) secondary to hypothyroidism was the clinical diagnosis. A comprehensive treatment plan was formulated. We present this case so as to make the oral health professionals aware of this condition efficiently.

A comparative study between microwave irradiation and sodium hypochlorite chemical disinfection: a prosthodontic view.

BACKGROUND: Prosthodontic procedures involving dental impressions, stone casts, record bases and prostheses may cause transmission of microorganisms between the patient, the dentist, auxiliary staff and laboratory personnel. In recent times, microwave radiation has gained wider acceptance in the field of applied science and has been used to reduce concentrations of bacteria and fungi, to dry dental casts,and to sterilize preparation media. OBJECTIVE: This in-vitro study was conducted to compare microwave irradiation and 0.07% sodium hypochlorite chemical disinfection. The study also evaluated the effect of microwave irradiation and 0.07% sodium hypochlorite chemical disinfection on the dimensional stability of Kalstone casts. MATERIALS AND METHODS: Forty impressions were made and divided into two groups of 20 each. Each group was contaminated with Staphylococcus aureus and Pseudomonas aeruginosa respectively. Each impression was divided into three parts and marked A, B, C. Impressions were then poured in kalastone. Part A of 20 kalastone casts were microwave disinfected, and Part B were chemically disinfected (0.07% NaOCl) while Part C were not disinfected and used as control. RESULTS: On comparing the significant difference was seen in the microbial load between microwave and chemical disinfection (Z=56.480; p<0.001). CONCLUSION: On the basis of observations made for the antimicrobial assessment the microwave irradiated Kala stone casts proved to be a better disinfection method when compared with 0.07% sodium hypochlorite chemically disinfected incorporated cast. No significant difference was seen in the dimensional stability of Kala stone discs.

Co-treatment of mouse antral follicles with 17ß-estradiol interferes with mono-2-ethylhexyl phthalate (MEHP)-induced atresia and altered apoptosis gene expression.

Mono-2-ethyhexyl phthalate (MEHP) is a metabolite of a plasticizer found in many consumer products. MEHP inhibits mouse ovarian follicle growth by reducing 17ß-estradiol (E2) production. Yet, whether MEHP causes follicle death (atresia) is unclear. We hypothesized that MEHP causes atresia by altering apoptosis gene expression, and that E2 co-treatment blocks these effects. Follicles were exposed to MEHP (0.36-36µM)±E2 for 48-96h to determine the effect of MEHP±E2 on atresia and gene expression. MEHP increased atresia, but this effect was blocked by co-treatment with E2. MEHP increased the expression of the pro-apoptotic gene Aifm1, but decreased that of the pro-apoptotic gene Bok and the anti-apoptotic gene Bcl2l10. E2 interfered with MEHP-induced changes in Aifm1 and Bcl2l10. Our findings suggest that decreased E2 levels are required for MEHP-induced follicle atresia and that Aifm1, Bok, and Bcl2l10 are involved in this process.