A comparative study of medical device regulation between countries based on their economies.

INTRODUCTION: Medical devices play a crucial role in healthcare, addressing the diagnosis, treatment, and monitoring of various medical conditions. This study conducts a comprehensive analysis of medical device regulations across nations, considering the economic contexts of diverse countries. AREAS COVERED: The research involves a comparative examination of medical device regulations, dissecting unique frameworks in countries like the United States (US), European Union (EU), India, and Africa. These nations were chosen based on economic significance, market influence, and regulatory structures. The study aims to achieve a nuanced understanding of global medical device regulation, develop strategies to enhance guidelines, especially in developing nations, and provide recommendations for improvements in relevant regions. EXPERT OPINION: Through this study, valuable insights are gained into the diverse regulatory frameworks governing medical devices globally. The analysis identifies areas within these frameworks that require improvement, as well as strategies to enhance regulatory guidelines, particularly addressing the specific needs of developing economies. Ultimately, the research provides significant recommendations for policymakers and industry stakeholders. By offering a deeper understanding of regulatory intricacies, this study establishes pragmatic approaches to address challenges within the medical device industry and improve the regulatory landscape on a global scale.

Preferences, Acceptability and Usage of Mobile Health Applications Among Undergraduate Nursing Students: A Multisite, Cross-Sectional Survey.

Introduction and objective: Mobile health applications (mHealth) can bring revolutionary changes to health care by making it more accessible, cost-effective, and efficient. The successful adoption of mHealth is largely determined by its acceptance by providers and end users. The acceptance of mHealth among nursing students, who are the future nurses, needs to be understood. This study aimed to determine the preferences, acceptability, and usage of mHealth applications among undergraduate nursing students. Methods: A descriptive cross-sectional study was conducted in two selected universities in southern and northern India. A convenience sample of 567 undergraduate nursing students was recruited for the study. The data were collected using a structured questionnaire via Google Forms. Results: mHealth applications were presently used by 32.9% of the students. The most common types of mHealth applications used were diet related (27.6%) and lifestyle related (23.4%). The majority of nursing students were willing to use mobile phones for consulting health professionals (78.8%) for prevention and management of health and disease. (83.1%), and for emergencies (73.3%). While more than half of the students were willing to recommend mHealth applications for patients, those students who were using two or more mHealth apps were more likely to recommend the same for the patients. Conclusion: The results of the study highlight about the usage of mobile health applications among the nursing students. The students consider mHealth applications to be useful for delivering health-related services to end users. The study underscores the need to sensitize students about the possible usage of mHealth in healthcare delivery.

Unveiling the therapeutic potential of a mutated paraoxonase 2 in diabetic retinopathy: Defying glycation, mitigating oxidative stress, ER stress and inflammation.

Paraoxonase 2 (PON2) is an intracellular anti-oxidant protein ubiquitously expressed in all cells and reduces reactive oxygen species, endoplasmic reticulum (ER) stress, further improves mitochondrial function and thereby shows anti-apoptotic function. In diabetes and its complications this PON gets glycated and becomes in effective. The PON activity is reported to be reduced in diabetic retinopathy and we have earlier showed Carboxy methyl lysine (AGE) decreased PON2 expression and activity in Human retinal endothelial cells (HREC) . In this study, we have designed and developed a mutated PON2 by in silico and in vitro approach which can resist glycation. Where in glycation-prone residues in PON2 was predicted using in silico analyses and a mutated PON2 was developed using in vitro site directed mutagenesis (SDM) assay mPON2 (mutant PON2-PON2-K70A) and its efficacy was compared with wPON2 (wild type PON2). CML glycated wPON2 and reduced its activity when compared with mPON2 in HREC confirmed by immunoprecipitation and in vitro experiments. Additionally, mPON2 interaction efficiency with its substrates was higher than wPON2 by insilico assay and demonstrated enhanced inhibition against CML-induced oxidative stress, ER stress, pro-inflammation, and mitochondrial fission than wPON2 by invitro assay. Further mPON2 showed increased inhibition of phosphorylation of NFĸB induced by CML. Our investigation establishes that the over expression of mPON2 in HREC can defy glycation and therefore mitigate ER stress and inflammation against CML than endogenous wPON2. These findings imply that mPON2 can be a beneficial therapeutic target against diabetic retinopathy.

Prolactin Inhibition in Peripartum Cardiomyopathy: Systematic Review and Meta-analysis.

Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all HF in pregnancy. Cardiac angiogenic imbalance caused by cleaved 16kDa prolactin has been hypothesized to contribute to the development of PPCM, fueling investigation of prolactin inhibitors for the management of PPCM. We conducted a systematic review and meta-analysis to assess the impact of prolactin inhibition on left ventricular (LV) function and mortality in patients with PPCM. We included English language articles from PubMed and EMBASE published upto March 2022. We pooled the mean difference (MD) for left ventricular ejection fraction (LVEF) at follow-up, odds ratio (OR) for LV recovery and risk ratio (RR) for all-cause mortality using random-effects meta-analysis. Among 548 studies screened, 10 studies (3 randomized control trials (RCTs), 2 retrospective and 5 prospective cohorts) were included in the systematic review. Patients in the Bromocriptine + standard guideline directed medical therapy (GDMT) group had higher LVEF% (pMD 12.56 (95% CI 5.84-19.28, I2=0%) from two cohorts and pMD 14.25 (95% CI 0.61-27.89, I2=88%) from two RCTs) at follow-up compared to standard GDMT alone group. Bromocriptine group also had higher odds of LV recovery (pOR 3.55 (95% CI 1.39-9.1, I2=62)). We did not find any difference in all-cause mortality between the groups. Our analysis demonstrates that the addition of Bromocriptine to standard GDMT was associated with a significant improvement in LVEF% and greater odds of LV recovery, without significant reduction in all-cause mortality.

Manual vs. mechanical ventilation in patients with advanced airway during CPR.

Early chest compressions and rapid defibrillation are important components of cardiopulmonary resuscitation (CPR). American heart association (AHA) recommends two breaths to be delivered for every 30 compressions for an adult cardiac arrest victim. Patient with an advanced airway like endotracheal tube (ETT) should be given one breath every 6 s without interruptions in chest compression (10 breaths per minute). All of the modern mechanical ventilators have option to generate spontaneous breaths by the patient if the patient has spontaneous respiratory efforts. During CPR, the mechanical ventilator is fallaciously sensing the chest compressions as patient's spontaneous trigger and thereby it delivers higher respiratory rates. Avoiding excessive ventilation is one of the components of high quality CPR as excessive ventilation decreases venous return thereby decreasing the cardiac output and also it affects intra-thoracic pressure thereby adversely affects intra-arterial pressure. As modern ventilators have trigger for spontaneous breaths and they will be erroneously triggered by chest compressions, it would be prudent to use volume marked resuscitation bags or manual breathing devices (manual self-inflating resuscitation bag, Bain's circuit) for delivering breaths which can be synchronised with compression phase of CPR at RR of 10 breaths per min with advanced airway in place. If any patient who is on mechanical ventilation develops cardiac arrest, patient should be disconnected from the mechanical ventilator and should be ventilated manually. Manual ventilation with aforementioned breathing devices should be used in a patient without and with advanced airway devices during CPR.

Paraoxonase 2 protects against the CML mediated mitochondrial dysfunction through modulating JNK pathway in human retinal cells.

BACKGROUND: Paraoxonase 2 (PON2) a known anti-apoptotic protein, has not been explored against Nε-(carboxymethyl)lysine (CML), induced mitochondrial dysfunction and apoptosis in human retinal cells. Hence this present study aims to investigate the potential role of PON2 in mitigating CML-induced mitochondrial dysfunction in these cells. METHODS: PON2 protein was quantified in HRECs (Human retinal endothelial cells), ARPE-19 (Retinal pigment epithelial cells) cells upon CML treatment and also in cadaveric diabetic retina vs respective controls. ROS production, mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP) opening, the release of Cyt-c, Bax, Caspase-3, Fis1, Mfn1, Mfn2, mitochondrial morphology, and the signaling pathway was assessed using DCFDA, JC-1, CoCl2, immunofluorescence or western blotting analysis in both loss-of-function or gain-of-function experiments. RESULTS: PON2 protein was downregulated in HREC and ARPE-19 cells upon CML treatment as well as in the diabetic retina (p = 0.035). Decrease in PON2 augments Fis1 expression resulting in fragmentation of mitochondria and enhances the ROS production, decreases MMP, facilitates mPTP opening, and induces the release of Cyt-c, which activates the pro-apoptotic pathway. Whereas PON2 overexpression similar to SP600125 (a specific JNK inhibitor) was able to decrease Fis1 (p = 0.036) and reverse the Bcl-2 and Bax ratio, and inhibit the JNK1/2 signaling pathway. CONCLUSION: Our results confirm that PON2 has an anti-apoptotic role against the CML mediated mitochondrial dysfunction and inhibits apoptosis through the JNK-Fis1 axis. GENERAL SIGNIFICANCE: We hypothesis that enhancing PON2 may provide a better therapeutic potential against diabetic vascular disease.

Exogenous administration of hydrogen sulfide alleviates homocysteine induced inflammation in ARPE-19 cells.

Plasma homocysteine (Hcy) is an independent risk factor for Age related macular degeneration (AMD) and an inducer of inflammation. Homocysteine catabolism releases hydrogen sulfide (H2S). H2S has controversial effects on inflammation. In this study we have analysed the endogenous and exogenous H2S in modulating inflammation using adult retinal pigment epithelial (ARPE-19) cells as an in vitro model for AMD. ARPE-19 cells were treated with various concentrations of Hcy (15, 30 and 50 µM) for 3 h. Expression of Hcy transulfuration genes (CBS, CSE) by qPCR and western blot. H2S levels were measured using Free Radical Analyzer System (WPI, USA). The inflammatory markers (IL-6 and IL-8) were evaluated using real-time PCR and ELISA. Hcy exposure increased CBS protein expression, hydrogen sulfide levels and pro-inflammatory cytokines, modulating CBS by silencing did not alter H2S levels, but inhibition of CSE with PAG inhibited H2S production and decreased cytokine (IL-6 and IL-8) levels. On the contrary exogenous supply of hydrogen sulfide with NaHS and by compound 1c showed anti-inflammatory effects even in the presence of Hcy. This study shows that exogenous delivery of H2S decreases inflammation in retinal pigment epithelial cells on exposure to Hcy in ARPE-19 cells.

A Randomized Clinical Trial of Levonorgestrel Intrauterine System with or without Metformin for Treatment of Endometrial Hyperplasia without Atypia in Indian Women.

BACKGROUND: Endometrial cancer is the second most frequent genital malignancy in women, which is showing a constant rise all over world. Endometrial hyperplasia is the precursor of endometrial cancer. Levonorgestrel intrauterine system is the first line management in patients with endometrial hyperplasia without atypia. Metformin has shown to reverse endometrial hyperplasia, but its effectiveness and safety in endometrial hyperplasia is uncertain. OBJECTIVE: To compare the efficacy in terms of histopathological response, clinical response and safety at the end of 6 months in patients with endometrial hyperplasia without atypia managed with Levonorgestrel intrauterine system alone versus patients managed with Levonorgestrel intrauterine system plus metformin. METHODS: The randomized control trial was conducted on 51 cases of endometrial hyperplasia without atypia. Twenty-five subjects were prescribed metformin 500mg twice daily with Levonorgestrel intrauterine system and 26 subjects, with Levonorgestrel intrauterine system only for 6 months. At the end of 6 months, endometrial sampling was performed for histopathological response. RESULTS: Clinical response was observed in 23 of 25 subjects in metformin group and 22 of 24 in Levonorgestrel only group. The metformin group responded significantly with amenorrhea (p= 0.0053), while Levonorgestrel only group responded with regular cycles (p=0.027). At the end of study, of 46 subjects available for histopathological evaluation, 100% subjects in metformin group and 95.45% in Levonorgestrel only group (p=0.47826) showed complete response. The metformin group had a significant reduction in body mass index at end of study [P = 0∙023, 95% confidence interval (-1.7802, -0.1418)]. CONCLUSION: No significant difference in regression of endometrial hyperplasia was observed on adjunctive use of metformin but a significant reduction in BMI was observed. Use of metformin in obese patients may improve the treatment response.

Current concepts and clinical importance of glycemic variability.

BACKGROUND AND AIMS: Evolving evidence indicate that variations in blood glucose levels are likely to be an important factor in developing diabetic complications. Monitoring glucose fluctuations in patients remains as a therapeutic challenge and more evidence needs to be created in order to bring GV into limelight. This review encapsulates the most important findings conducted and discusses on them to provide readers a better understanding on this emerging subject. METHODS: Keyword-based comprehensive desktop search was conducted to gather the relevant literature. Triple-stage cascade type content analysis of the literature was conducted to draw relevant themes of discussions. RESULTS: High glycemic variability is associated with an increased risk of development of diabetic complications especially in cardiac conditions. The widely used and accepted metrics to determine the variations in blood glucose are Standard deviation (SD), MAGE (Mean amplitude of glycemic excursions) and MODD (Mean of daily differences). Occurrence of blood glucose variations affects at a molecular level thereby causing more harm than the occurrence of hyperglycemia alone. CONCLUSION: Available data suggest that Glycemic Variability should be used as an additional marker of glycemia. Additional research globally, and in India are required.

ERAS protocol with respiratory prehabilitation versus conventional perioperative protocol in elective gastrectomy- a randomized controlled trial.

BACKGROUND: Several studies have investigated the efficacy of enhanced recovery programs in patients undergoing gastrectomy. The role of prehabilitation in these programs has not been evaluated in this subset of patients. This study incorporated incentive spirometry as a type of respiratory prehabilitation in the Enhanced Recovery After Surgery (ERAS) protocol for gastrectomy. METHODS: In this single-center, prospective, open-labeled randomized controlled trial, 58 patients were randomized into two groups - a conventional perioperative care group and an ERAS group. The patients in the ERAS group received a supervised regimen of preoperative volume-oriented incentive spirometry as respiratory prehabilitation in addition to other ERAS care elements. The length of hospitalization (LOH) was assessed as the primary outcome, while the postoperative peak expiratory flow rate (PEFR) and the incidence of surgical and pulmonary complications were the secondary outcomes. RESULTS: The patients in the ERAS group had a shorter median LOH compared to the conventional group (11 days vs 13 days, p = 0.003). The patients in the ERAS group also had smaller fall in postoperative PEFR from baseline, which was significant on the second postoperative day (p = 0.011). None of the patients were found to have anastomotic leaks. The incidence of surgical complications was comparable between the groups (p = 0.137). CONCLUSION: ERAS protocol reduced the duration of hospitalization without increasing the complications compared to conventional perioperative protocol. Respiratory prehabilitation in the form of a supervised schedule of incentive spirometry helped in the preservation of lung functions in the postoperative period.

Positive end-expiratory pressure as a novel method to thwart CO2 leakage from capnothorax in robotic-assisted thoracoscopic surgery.

Capnography and end tidal CO2 (EtCO2) aids the anaesthesiologist in diagnosing problems during all phases of general anaesthesia. Negative arterial to end-tidal carbon-dioxide gradient during anaesthesia has been reported in various conditions including pregnancy, infants and inadvertent exogenous addition of carbon dioxide (CO2) to the expired gas in case of thoracoscopic procedures with iatrogenic injury to lung parenchyma/bronchial tree. Thus, airway injury or intentional opening of airway as a part of surgical step can be diagnosed using a negative arterial and end tidal CO2 gradient. Higher optimal PEEP can be used as a splint across the bronchial cuff in one-lung ventilation which prevents leak from capnothorax and decrease inadvertent entry of CO2 in to the expired gases which erroneously increase arteriolar to end tidal CO2 gradient.

Effect of advanced glycation end product on paraoxonase 2 expression: Its impact on endoplasmic reticulum stress and inflammation in HUVECs.

BACKGROUND: Paraoxonase (PON), an antioxidant enzyme, comprises of three members (PON1, 2 and 3). Hyperglycemia accelerates formation of AGE in diabetes which mediates endothelial dysfunction. PON1 is studied in diabetes due to its association with HDL, lipid peroxidation and vascular complications but PON2 is not explored much. Recently decreased PON2 activity is reported in monocytes of Type 2 diabetes mellitus (T2DM) patients but its regulation by factors like high glucose and AGE has not been studied. AIM: The aim of the current study is to identify the effect of AGEs on PON2 expression and activity and its implications on endothelial dysfunction in HUVECs. MAIN METHODS: HUVECs were exposed to Glycated albumin (GA)/Carboxymethyl lysine (CML) for 24 h to check for PON2 expression. The ER stress markers GRP78 and IRE1α, pro-inflammatory genes MCP-1, IL-6, IL-8, ICAM1, VCAM1 were assessed by qPCR, western blotting/ELISA. Endothelial-leukocyte adhesion and ROS were assessed using Calcein AM and DCFDA method. One-way ANOVA and student's t-test was done using Graphpad Prism. KEY FINDINGS: AGE exposure significantly decreased PON2 expression and activity with increased oxidative stress, ER stress and inflammation. PON2 overexpression significantly reduced ROS, ER stress and inflammation as well as inhibited NFκB, and ERK1/2, phosphorylation induced by GA/CML treatment. Concomitantly, silencing of PON2 accelerated AGEs induced effects. SIGNIFICANCE: This is the first study to show that both GA and CML down regulates the PON2 expression and activity in HUVECs and over expression of PON2 alleviates AGEs induced endothelial dysfunction.

Spontaneous ventilation as a key ventilation technique during open airway phase in tracheal resection and reconstruction: A case series.

Anaesthetic management of tracheal resection and reconstruction in patients with difficult tracheal pathologies, poses unique challenges-such as pre-operative assessment and preparation, the induction of general anaesthesia, airway sharing with surgeons during the intra-operative period while performing resection and reconstruction, emergence from general anaesthesia, and post-operative care. While there are no guidelines on choosing the ideal airway technique for the intra-operative period, we describe a simple-yet-effective airway modality, viz. spontaneous ventilation, as a key airway technique during the crucial open airway phase during tracheal reconstruction.