Development of sustained release formulation of glipizide using natural polymer from Tamrindus indica for better patient compliance

The study was to design a drug product to reduce the frequency of dosing, increase therapeutic effectiveness and improvement in patient compliance, by developing sustained release matrix tablet of Glimepiride using tamrind gum as a release modifier. In current study tamrind gum is used as a polymer which is investigated for sustained release carrier. The pre-formulation studies of drug excipient mixtures were performed. The tablets formulated were evaluated by physicochemical studies, in- vitro drug release, kinetic studies and stability studies. Drug and polymers has no interaction as observed by FTIR and UV studies. All the physicochemical parameters of tablets were found in the limits. Glimepiride is used in the treatment type II diabetes mellitus and is a first third generation sulphonyl urea agent. The drug release pattern was studied for extended period of 12 hrs for the optimized formulations. The release of drug under kinetic studies showed that it follows first order models. The different tablet formulations were put to stability studies and it was observed that there were no significant changes in release pattern, physicochemical parameters and drug content. The present study result indicates the suitability of the tamrind gum polymer in the preparation of sustained release formulations of glimepiride. Keywords: Sustained Release, Glipizide , Natural Polymer, Tamrindus Indic

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

CASE SERIES OF Burkholderia Pseudomallei CAUSING MELIOIDOSIS (PULMONARY, CEREBRAL AND SPLENIC ABSCESS): Case Series of Burkholderia pseudomallei

ABSTRACT: Burkholderia pseudomallei is gram-negative bacilli present as soil saprophytes that causes a fatal disease called Melioidosis. Melioidosis is capable of causing cutaneous infection and systemic infections in the respiratory tract, cardiovascular, gastrointestinal, urinary, skin and soft tissue, musculoskeletal and central nervous systems. Here we report rare forms of pulmonary, cerebral, and splenic abscess case series of Melioidosis caused by B. pseudomallei. Imported cases have been reported among tourists, immigrants and soldiers who returned from endemic areas. The acquisition of infection is through percutaneous, inhalation, and ingestion of contaminated water, and person-to-person transmission is very rare. Melioidosis cases are mostly found in the rainfall season and are usually associated with risk factors like diabetes, alcoholism, and chronic renal diseases. However, 20 to 26% of cases were not associated with any predisposing conditions. The identification is based on colony morphology, Gram stain and antibiotic susceptibility testing, and other supportive automated and molecular assays when we suspect Burkholderia pseudomallei. There are two phases, the intensive and eradication phases in the management of melioidosis. In the intensive phase ceftazidime for 2 weeks showed efficacy in almost 50% of cases and the eradication phase treatment with co-trimoxazole along with doxycycline or amoxicillin/clavulanic acid for 3 to 6 months shown excellent response. The improper clinical diagnosis and management of Burkholderia pseudomallei can lead to complications. Hence early diagnosis with microbiological approaches like culture, biochemical reactions, or automated systems available and antimicrobial sensitivity testing will cure the patient easily without mortality

CASE SERIES OF EMERGING NOSOCOMIAL MULTIPLE DRUG RESISTANT PATHOGEN PROVIDENCIA RETTGERI CAUSING URINARY TRACT INFECTION

We report Case Series of Emerging Nosocomial Multiple Drug Resistant Pathogen Providencia rettgeri causing Urinary Tract Infections. The most common cause of catheter associated urinary tract infections (CAUTI), especially with long-term indwelling urinary catheters in elders, are P.rettgeri and P.stuartii. We are reporting 4 cases of UTI, which are hospital-acquired and CAUTI.  These cases are admitted to MICU for treatment purposes and later develop fever spikes after a few days and are evaluated and urine culture showed multi-drug-resistant Providencia rettgeri by VITEK. The empirical therapy was discontinued, managed with fosfomycin, and discharged later with follow-up. The various reports showed P.rettgeriis susceptible for amikacin, gentamicin, tobramycin and ciprofloxacin. In our case series, we isolated multi-drug-resistant strains of P.rettgeri showed resistance to piperacillin-tazobactam, cefuroxime, ceftriaxone, cefepime, ertapenem, imipenem, meropenem, gentamicin, tobramycin, ciprofloxacin, tigecycline, amikacin, colistin and sensitive only to fosfomycin. The significance of P.rettgeri in association with catheter-related bloodstream infections (CRBSI) and catheter-associated urinary tract infections (CAUTI) was unclear. Hence isolation of Providencia species twice from the clinical samples was considered for association with catheter infections. The proper selection of empirical antimicrobials, antibiotic sensitivity testing, avoiding misuse of antibiotics and implementing proper drug holiday and local antibiotic policy are considered appropriate combination protocol for managing emerging multi-drug-resistant nosocomial Providencia rettgeri strains

CASE SERIES OF ISOLATED PULMONARY NOCARDIOSIS AMONG POST-COVID-19 INDIVIDUALS

Nocardia infections are rare in an immunocompetent and healthy individual. It is frequently diagnosed and reported very late during the disease. Here we present an interesting case series of isolated pulmonary nocardiosis among post COVID-19 patients. A 45-year-old male presented to general medicine OPD with breathlessness and cough with expectoration. The patient was a known case of diabetes. A Sputum sample was sent for culture, gram, and acid-fast stain, and the nasopharyngeal swab was sent for RT-PCR and turned out to be COVID-19 negative. Gram stain showed numerous pus cells with filamentous hyphae-like structures. Nocardiosis was strongly considered based on imaging morphology. A 65-year-old female presented to OPD with fever, respiratory distress, and expectorating cough for one month. The patient was a not known case of diabetes and hypertension. The patient was diagnosed with pneumonia and had a history of COVID-19. The microscopic examination of the sputum sample revealed no fungal elements. The Gram and Ziehl-Neelsen stain showed pus cells with filamentous bacilli and no acid-fast bacilli. A 50-year-old male presented to general medicine OPD with breathlessness and expectorating cough for four weeks. The patient was a not known case of diabetes and hypertension. The sputum sample was negative for ZN stain; the Gram stain showed numerous pus cells with filamentous hyphae-like structures. The modified acid-fast staining was done for sputum and BAL samples in all cases showed filamentous weak acid-fast bacilli resembling Nocardia species. The patient did well with cotrimoxazole and was discharged later. The differential diagnosis of nocardia should always be in mind in case of lung infections. All respiratory samples must also be screened for Nocardia. The early diagnosis and management of pulmonary nocardiosis decide the patient’s prognosis

Tacrolimus as the first-line agent in adult-onset minimal change disease: A randomized controlled study

Steroids have been the cornerstone of first-line therapy in adult-onset minimal change disease (MCD). The period of exposure to high dose steroids may be longer in adult MCD patients and would result in higher rates of steroid-related side effects. Although tacrolimus (TAC) is known to be effective in steroid-dependent/resistant MCD as well as in nephrotic syndrome due to other causes, there are minimal data available for assessing the effectiveness of TAC as the first-line agent in adult MCD. This is a prospective, open-label, randomized controlled study conducted from April 2014 to March 2016. Patients were randomized into two groups A and B which received TAC for 12 months and oral steroids for six months, respectively. Primary outcomes were remission rates, drug resistance was measured at 6, 12,and 18 months in each group and secondary outcomes were relapse rates, sustained remission rates, dependency, and adverse effects were measured at 18 months in both groups. At six months, total response (TR, i.e., complete and partial remission) was achieved in 80% in the TAC group and 78.26% in the steroid group (P = 1.000). At 12 months, TR was 60% in the TAC group and 43.48% in the steroid group (P = 0.386). At 18 months, TR rate was 44% in the TAC group and 43.48% in the steroid group (P = 1.000). About 32% in the TAC group and 39.13% in steroid group had relapsed by 18 months. Serious adverse effects were similar in the two groups, but overall adverse effects were more in the steroid group. TAC as a primary agent is not inferior to steroids in inducing remission. TAC may be considered as an alternative agent to steroid in high-risk groups such as elderly patients, uncontrolled diabetes and young females as a primary agent in the management of adult MCD

Global Retinoblastoma Presentation and Analysis by National Income Level

This cross-sectional analysis reports the retinoblastoma stage at diagnosis across the world during a single year, investigates associations between clinical variables and national income level, and investigates risk factors for advanced disease at diagnosis. Key PointsQuestionIs the income level of a country of residence associated with the clinical stage of presentation of patients with retinoblastoma? FindingsIn this cross-sectional analysis that included 4351 patients with newly diagnosed retinoblastoma, approximately half of all new retinoblastoma cases worldwide in 2017, 49.1\% of patients from low-income countries had extraocular tumor at time of diagnosis compared with 1.5\% of patients from high-income countries. MeaningThe clinical stage of presentation of retinoblastoma, which has a major influence on survival, significantly differs among patients from low-income and high-income countries, which may warrant intervention on national and international levels. ImportanceEarly diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. ObjectivesTo report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and ParticipantsA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and MeasuresAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. ResultsThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4\%) were female. Most patients (n=3685 {[}84.7\%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n=2638 {[}62.8\%]), followed by strabismus (n=429 {[}10.2\%]) and proptosis (n=309 {[}7.4\%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5\%) patients having intraocular retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 {[}95\% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 {[}95\% CI, 4.30-7.68]). Conclusions and RelevanceThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs