A Systematic Review on Safety and Efficacy of Migalastat for the treatment of Fabry's Disease.

INTRODUCTION: Fabry's disease (FD) is a genetic lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) lost/reduced activity. We aim to systematically assess the safety and efficacy of Migalastat, an oral pharmacological chaperone, that has been approved for the treatment of FD in patients with amenable mutations. METHODS: We conducted literature search following the PRISMA guidelines in major databases up to 4 February 2024, for studies that assessed the clinical outcomes of migalastat in patients with FD. The New Castle Ottawa Scale was used to evaluate the quality of the included studies. RESULTS: A total of 2141 records were identified through database searches and register searches, amongst which 26 records were screened, and 12 of these were excluded. The remaining 14 reports were sought for retrieval. The 12 retrieved articles were assessed for eligibility and their quality was assessed after their inclusion. Amongst the included studies, 5 were of high quality, 6 were of medium quality, and 1 was of low quality. CONCLUSION: Migalastat showed varied effects on enzyme activity and substrate levels, with gender-specific differences noted in GL-3 substrate activity and eGFR. Overall, it improved cardiac and renal outcomes similarly to enzyme replacement therapy, with a comparable safety profile.

A systematic review and meta-analysis on efficacy and safety of Ganaxolone in epilepsy.

INTRODUCTION: Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy. METHODS: A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone. RESULTS: The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), p = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), p = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), p = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), p = 0.99] compared to placebo. CONCLUSION: Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile. PROSPERO REGISTRATION NUMBER: CRD42023434883.

A Rare Presentation of Extramedullary Hematopoiesis as an Adrenal Mass: A Case Report.

Hematopoiesis is an enormous and complex process. When the primary site of hematopoiesis fails to meet the requirements of the body in conditions like hemoglobinopathies or myelofibrosis, various extramedullary sites take on the role of blood formation. Extramedullary hematopoiesis most commonly occurs in the liver, spleen, and lymph nodes and is rarely found in the thymus, heart, breast, adrenal glands, paravertebral regions, intraspinal tissue, and brain. Extramedullary hematopoiesis can mimic neoplasms in which symptoms are caused by the mass effect of the lesion. We report a rare case of a 41-year-old female patient with a fibrohematopoietic adrenal mass mimicking a neoplasm for which she underwent an adrenalectomy.

Racial and Socioeconomic Differences in Heart Failure Hospitalizations and Telemedicine Follow-up During the COVID-19 Pandemic: Retrospective Cohort Study.

BACKGROUND: Low rates of heart failure (HF) hospitalizations were observed during the 2020 peak of the COVID-19 pandemic. Additionally, posthospitalization follow-up transitioned to a predominantly telemedicine model. It is unknown whether the shift to telemedicine impacted disparities in posthospitalization follow-up or HF readmissions. OBJECTIVE: The aim of this paper is to determine whether the shift to telemedicine impacted racial and ethnic as well as socioeconomic disparities in acute decompensated heart failure (ADHF) follow-up and HF readmissions. We additionally sought to investigate the impact of the COVID-19 pandemic on the severity of ADHF hospitalizations. METHODS: This was a retrospective cohort study of HF admissions across 8 participating hospitals during the initial peak of the COVID-19 pandemic (March 15 to June 1, 2020), compared to the same time frame in 2019. Patients were stratified by race, ethnicity, and median neighborhood income. Hospital and intensive care unit (ICU) admission rates, inpatient mortality, 7-day follow-up, and 30-day readmissions were assessed. RESULTS: From March 15, 2019, to June 1, 2020, there were 1162 hospitalizations for ADHF included in the study. There were significantly fewer admissions for ADHF in 2020, compared with 2019 (442 vs 720; P<.001). Patients in 2020 had higher rates of ICU admission, compared with 2019 (15.8% vs 11.1%; P=.02). This trend was seen across all subgroups and was significant for patients from the highest income quartile (17.89% vs 10.99%; P=.02). While there was a trend toward higher inpatient mortality in 2020 versus 2019 (4.3% vs 2.8%; P=.17), no difference was seen among different racial and socioeconomic groups. Telemedicine comprised 81.6% of 7-day follow-up in 2020, with improvement in 7-day follow-up rates (40.5% vs 29.6%; P<.001). Inequities in 7-day follow-up for patients from non-Hispanic Black racial backgrounds compared to those from non-Hispanic White backgrounds decreased during the pandemic. Additionally, those with telemedicine follow-up were less likely to be readmitted in 30 days when compared to no follow-up (13.8% vs 22.4%; P=.03). CONCLUSIONS: There were no major differences in HF ICU admissions or inpatient mortality for different racial and socioeconomic groups during the COVID-19 pandemic. Inequalities in 7-day follow-up were reduced with the advent of telemedicine and decreased 30-day readmission rates for those who had telemedicine follow-up.

Mortality among adult hospitalized patients during the first wave and second wave of COVID-19 pandemic at a tertiary care center in India.

The similarities and differences between the mortality patterns of the two waves in India remain largely unknown. This was a retrospective study of medical records conducted in the COVID data center of our hospital This study analyzed data of patients who died in the month of August, 2020 to October 2020 (one month before and after the peak of first wave i.e., 16th September, 2020) and April 2021 to June 2021 (one month before and after the peak of second wave i.e., 6th May, 2021), corresponding to an equal part of the pandemic during first (2020) and second (2021) wave. Out of 1893 patients in the study, 764 patients were admitted during the first wave and 1129 patients during the second wave of pandemic. In total, 420 patients died during the entire study period. Of those, 147 (35%) deaths occurred during the first wave and 273 (65%) during the second wave, reflecting a case fatality rate (CFR) of 19.2% during the first wave and a CFR of 24.18%. There were no significant differences in the age group, gender, presenting complaints, duration of stay and comorbidities. However, the deceased COVID-19 patients had an increase in case fatality rate, average duration of symptoms from onset to hospital admission (DOSHA) and a major shift from MODS to ARDS being the cause of death during the second wave of pandemic. This study demonstrates increased CFR, average DOSHA and a paradigm shift to ARDS as cause of mortality during the second peak of the pandemic. It is necessary to remain vigilant of newer COVID-19 variants of concern, follow COVID-19 appropriate behaviors and keep emphasizing on care of high-risk groups including patients with comorbidities and elderly population to prevent mortality.

Haloperidol-induced parkinsonism is attenuated by varenicline in mice.

Background Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). However, there is no known drug to stop/slow down this neurodegeneration. Varenicline is an anti-smoking drug and has the potential to prevent neurodegeneration. Thus, the present study was designed to evaluate the effect of varenicline in animal models of PD. Methods Levodopa and haloperidol were administered in doses of 30 and 1 mg/kg, intraperitoneally (i.p.), respectively. Group 1 was administered haloperidol; groups 2, 3 and 4 were administered haloperidol along with varenicline in doses of 0.5, 1.5 and 2.5 mg/kg, i.p., respectively and group 5 was administered levodopa along with haloperidol. Varenicline was administered daily, 30 min prior to the administration of haloperidol. Varenicline was administered for the first 8 days, and then from the 9th day until the 15th day. Behavioral assessment (rotarod and catalepsy tests) was performed on days 9 and 15. Assessment of striatal dopamine levels and histopathology were also performed. Results In the haloperidol-treated groups, significant decrease in latency to fall off (on rotarod) and increase in catalepsy duration (in catalepsy test) were observed as compared to the control group. In the levodopa-treated group, significant increase in latency to fall off the rotarod and significant decrease in catalepsy duration were observed as compared to the haloperidol-treated groups. Further, on day 9, varenicline (2.5 mg/kg) significantly increased the latency to fall off the rotarod, while varenicline (0.5 and 1.5 mg/kg) did not cause any significant change in latency to fall off the rotarod as compared to the haloperidol-treated group. On day 15, significant increase in latency to fall off the rotarod was observed in varenicline (at all doses) as compared to the haloperidol-treated group. In the catalepsy test, the varenicline-treated (at all doses) groups showed significant decrease in duration of catalepsy on day 9 and day 15 as compared to the haloperidol-treated group. Significant decrease in striatal dopamine levels was observed among the haloperidol-treated groups as compared to the control group. Further, varenicline-treated (at all doses) and levodopa-treated groups showed significant increase in striatal dopamine levels when compared with the haloperidol-treated group. In histology, varenicline (0.5 mg/kg) showed moderate decrease in neurons, while varenicline (1.5 and 2.5 mg/kg) showed mild decrease in neurons. However, the levodopa-treated group did not show any significant decrease in neurons. Thus, varenicline has shown promising results and has provided novel strategy for the treatment of PD.

An embedded barcode for "connected" malaria rapid diagnostic tests.

Many countries are shifting their efforts from malaria control to disease elimination. New technologies will be necessary to meet the more stringent demands of elimination campaigns, including improved quality control of malaria diagnostic tests, as well as an improved means for communicating test results among field healthcare workers, test manufacturers, and national ministries of health. In this report, we describe and evaluate an embedded barcode within standard rapid diagnostic tests as one potential solution. This information-augmented diagnostic test operates on the familiar principles of traditional lateral flow assays and simply replaces the control line with a control grid patterned in the shape of a QR (quick response) code. After the test is processed, the QR code appears on both positive or negative tests. In this report we demonstrate how this multipurpose code can be used not only to fulfill the control line role of test validation, but also to embed test manufacturing details, serve as a trigger for image capture, enable registration for image analysis, and correct for lighting effects. An accompanying mobile phone application automatically captures an image of the test when the QR code is recognized, decodes the QR code, performs image processing to determine the concentration of the malarial biomarker histidine-rich protein 2 at the test line, and transmits the test results and QR code payload to a secure web portal. This approach blends automated, sub-nanomolar biomarker detection, with near real-time reporting to provide quality assurance data that will help to achieve malaria elimination.

Mobile phone imaging and cloud-based analysis for standardized malaria detection and reporting.

Rapid diagnostic tests (RDTs) have been widely deployed in low-resource settings. These tests are typically read by visual inspection, and accurate record keeping and data aggregation remains a substantial challenge. A successful malaria elimination campaign will require new strategies that maximize the sensitivity of RDTs, reduce user error, and integrate results reporting tools. In this report, an unmodified mobile phone was used to photograph RDTs, which were subsequently uploaded into a globally accessible database, REDCap, and then analyzed three ways: with an automated image processing program, visual inspection, and a commercial lateral flow reader. The mobile phone image processing detected 20.6 malaria parasites/microliter of blood, compared to the commercial lateral flow reader which detected 64.4 parasites/microliter. Experienced observers visually identified positive malaria cases at 12.5 parasites/microliter, but encountered reporting errors and false negatives. Visual interpretation by inexperienced users resulted in only an 80.2% true negative rate, with substantial disagreement in the lower parasitemia range. We have demonstrated that combining a globally accessible database, such as REDCap, with mobile phone based imaging of RDTs provides objective, secure, automated, data collection and result reporting. This simple combination of existing technologies would appear to be an attractive tool for malaria elimination campaigns.

Reversal of propoxur-induced impairment of step-down passive avoidance, transfer latency and oxidative stress by piracetam and ascorbic acid in rats.

Propoxur, a carbamate pesticide has been shown to adversely affect memory and induce oxidative stress. The present study was designed to correlate the effect of propoxur, piracetam (a nootropic drug) and ascorbic acid (an antioxidant) on oxidative stress and cognitive function. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and non-protein thiol (NP-SH) levels. A significant reduction in SDL and prolongation of TL was found for the propoxur-treated group at weeks 6 and 7 as compared with control (p<0.001). One week treatment by piracetam (400mg/kg/d, i.p.) or ascorbic acid (120mg/kg/d, i.p.) antagonized the effect of propoxur on SDL as well as TL. Both piracetam and ascorbic acid attenuated the propoxur-induced increase in brain MDA levels and decrease in brain NP-SH levels. Results of the present study show that ascorbic acid and piracetam have the potential to reverse cognitive dysfunction and oxidative stress induced by propoxur in the brain.

Anxiogenic and proconvulsant effect of gatifloxacin in mice.

The present study was performed to assess the neurological and neurobehavioural effects of gatifloxacin after its oral administration in two doses: 25 and 50 mg/kg for 7 days and 14 days in mice. The neurobehavioural parameters used for the short-term study (x 7 days) were pentylenetetrazole-induced seizure, forced swim test, elevated plus-maze, spontaneous alternation behaviour and rota-rod tests. However, only pentylenetetrazole-induced seizure and rota-rod tests were performed in long term (x 14 days) study. The results showed proconvulsant effect of gatifloxacin (50 mg/kg) in pentylenetetrazole-induced seizure test after both short- and long-term administration studies. Gatifloxacin in both doses showed an anxiogenic effect. However, in both doses, it did not show any effect on memory and mood as the drug did not show any effect in alternation behaviour and forced swim tests. In the long term study, gatifloxacin in 50 mg/kg, p.o. produced grip impairing effect only after 14 days of administration. These results reveal that gatifloxacin possesses proconvulsant and anxiogenic effects but it does not have an effect on mood and memory. Besides, long term administration of gatifloxacin for 14 days was found to reduce grip strength indicating its movement impairing effect in mice.