Publication of studies registered in Clinical Trials Registry of India: An audit of mood disorder research protocols from 2009-2019.

Background: Selective publication of studies has important scientific, ethical, and public health implications. Aim: We studied selective publication among mood disorder research protocols registered in the Clinical Trials Registry of India (CTRI) database. We also examined the frequency and nature of protocol deviations among the published articles. Methods: Using a systematic search strategy, we examined the publication status of all mood disorder-related research protocols registered in the CTRI database from inception till December 31, 2019. Logistic regression analysis was used to identify variables associated with selective publication. Results: Of 129 eligible protocols identified, only a third (n = 43, 33.3%) were published in literature; among those published, only 28 (21.7%) were placed in MEDLINE indexed journals. Protocol deviations were observed in more than half of the published papers (n = 25, 58.1%); many of these (41.9%) were related to sample size deviations, though, importantly, deviations in primary and secondary outcomes were also noted (16.2%). Retrospective registration of trials (odds ratio, 2.98, 95% confidence interval, 1.32-6.71) was significantly associated with publication; other variables, such as funding status or multicentric sampling, were not associated with eventual publication. Conclusions: Two out of three mood disorder research protocols registered in India do not translate into published research. These findings from a low- and middle-income country with limited spending on health care research and development represent wastage of resources and raise scientific and ethical concerns about unpublished data and futile patient participation in research.

Incidence and prevalence of depressive, anxiety, and insomnia symptoms among adult liver transplant recipients: A systematic review and meta-analysis.

OBJECTIVE: Psychological morbidity among transplant recipients may negatively impact post-transplantation outcomes. Our objectives were to compute pooled incidence and prevalence estimates for depressive, anxiety, and insomnia symptoms among adults who underwent liver transplant. METHODS: Electronic searches of MEDLINE, PubMed Central, CINAHL, and Google Scholar were carried out from inception to October 2022 to identify observational studies conducted among adult liver transplant recipients which measured depression, anxiety, and/or insomnia. We used the Joanna-Briggs tool for study quality appraisal. RESULTS: Sixty-five studies (pooled N = 12,183) provided data for meta-analysis. The one-year pooled point prevalence rate for depressive symptoms was 25% (95% Confidence Intervals [CI]: 20% to 30%; I2 = 94%; 37 studies; N = 6088) while that of anxiety and insomnia symptoms were 29% (95% CI: 21% to 38%; I2 = 96%; 28 studies; N = 4016) and 28% (95% CI: 16% to 43%; I2 = 98%; 14 studies; N = 1834), respectively. The findings remained robust across subgroup and sensitivity analyses. Most included studies had low or moderate risk of bias. CONCLUSIONS: Depressive, anxiety, and insomnia symptoms are commonly prevalent following liver transplantation. Our findings, though limited by high heterogeneity across analyses, have important implications for screening, management, and prevention of psychological morbidity in this group. SYSTEMATIC REVIEW REGISTRATION: This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD 42021276008).

Predictive validity of ESSENCE Q screening tool for early detection of neurodevelopmental disorder in children.

INTRODUCTION: Neurodevelopmental disorders (NDD) are a group of conditions that typically manifest early during the child's development with lifelong consequences. Early identification using efficient screening tools can positively modify the natural history of the disorder. ESSENCE Q is a simple questionnaire to detect ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations to reflect the co-existence of NDDs in children less than five years). There are limited studies on the validity of ESSENCE Q in detecting NDDs in young children in India. METHODS: We did a cross-sectional study in a tertiary care hospital to evaluate the validity of ESSENCE Q in detecting neurodevelopmental disorders. We translated the ESSENCE Q and subsequently used it to screen for NDD in 100 children aged 12-60 months. Clinical consensus diagnosis by two experienced experts was taken as the gold standard. RESULTS: 23% were diagnosed as having NDD as per the clinical consensus diagnosis. Around half the children (46%) were "at-risk for NDD" based on the ESSENCE Q scale. We found an optimal cut-off for ESSENCE Q of more than or equal to 4 with a sensitivity of 96%, a specificity of 82%, and a Youden index of 0.77. CONCLUSION: ESSENCE Q has good predictive validity to be used as a quick and easy screening tool to detect NDDs in young children under the age of 5 years.

Do Tamil newspapers educate the public about suicide? Content analysis from a high suicide Union Territory in India.

BACKGROUND: Responsible media reporting of suicide is a key population-level suicide prevention strategy. Thus far, there has been no systematic analysis of media reporting of suicide in Puducherry, a consistently high suicide burden state in India. AIM: To evaluate the adherence of media reports of suicide against the World Health Organization (WHO) guidelines in Puducherry. METHOD: We conducted a year-round content analysis of all suicide-related reports in the two most widely read vernacular dailies of Puducherry. We used a pre-defined data extraction form and coded each item based on the WHO reporting guidelines. RESULTS: A total of 318 suicide reports were retrieved. Harmful reporting practices such as mentioning the method of suicide (99.1%), description of the steps involved (68.2%) and location of suicide (86.5%), monocausal explanations (91.8%), and inciting life events (52.5%) were common. Helpful practices such as mentioning warning signs (1.3%), recognizing links with mental health disorders (3.8%) and effects on bereaved persons (2.2%) were rare. Only one article (0.31%) included any content related to educational/preventive aspects of suicide. CONCLUSION: Media reporting of suicide in Puducherry, India, does not adhere to reporting guidelines and there is very little focus on educating the public about preventive aspects of suicide. Urgent efforts are warranted to improve the quality of media reporting which should include the development of national guidelines on suicide reporting and collaborative efforts that take into account barriers and perspectives of media professionals.

Hollow Microcapsules as Periocular Drug Depot for Sustained Release of Anti-VEGF Protein.

Diseases affecting the posterior segment of the eye such as age-related macular degeneration and diabetic retinopathy are leading causes of blindness all over the world. The current treatment regimen for such diseases involves repeated intravitreal injections of anti- Vascular Endothelial Growth Factor (VEGF) proteins. This method is highly invasive and can lead to severe complications. In an attempt to develop less invasive alternatives, we propose the use of a controlled release system consisting of anti-VEGF loaded hollow microcapsules that can be administered periocularly to form drug eluting depots on the episcleral surface. The microcapsules with either positive or negative surface charge were prepared by a layer by layer approach and showed pH responsive permeability switching. An ex vivo experiment using porcine sclera indicated positively charged microcapsules remained on the episcleral surface over four days while the negatively charged microcapsules were washed away. These positively charged microcapsules were then loaded with anti-VEGF protein ranibizumab using pH dependent permeability switching and protein release from the microcapsules were studied using an in vitro setup. An ex vivo experiment utilizing porcine sclera demonstrated sustained release of ranibizumab over seven days with zero-order kinetics.

Characterization of liposomal carriers for the trans-scleral transport of Ranibizumab.

Age-related macular degeneration (AMD) is a leading cause of blindness in the modern world. The standard treatment regimen for neovascular AMD is the monthly/bimonthly intravitreal injection of anti-VEGF agents such as ranibizumab or aflibercept. However, these repeated invasive injections can lead to sight-threatening complications. Sustained delivery by encapsulation of the drug in carriers is a way to reduce the frequency of these injections. Liposomes are biocompatible, non-toxic vesicular nanocarriers, which can be used to encapsulate therapeutic agents to provide sustained release. The protein encapsulation was performed by a modified dehydration-rehydration (DRV) method. The liposomes formed were characterized for size, zeta potential, encapsulation efficiency, stability, in vitro release, and ex vivo release profiles. In addition, the localization of the liposomes themselves was studied ex vivo. Entrapment-efficiency of ranibizumab into 100-nm liposomes varied from 14.7 to 57.0%. Negatively-charged liposomes prepared from DPPC-DPPG were found to have the slowest release with a low initial burst release compared to the rest of liposomal formulations. The ex vivo protein release was found to slower than the in vitro protein release for all samples. In conclusion, the DPPC-DPPG liposomes significantly improved the encapsulation and release profile of ranibizumab.

Drug delivery to the eye: what benefits do nanocarriers offer?

Ocular drug delivery has seen several advances in the past few decades, with respect to new drugs, improved formulations, targeted delivery, as well as exploration of new routes of drug administration. New materials have been explored for encasing existing drugs, which can enhance treatment by increasing bioavailability, decreasing toxicity, providing better tissue adherence, targeted delivery as well as increased duration of action. The challenges and requirements are different for the anterior and posterior ocular segments. This review summarizes the recent advances in sustained ocular therapy, both to the anterior and posterior segments, which have been made possible, thanks to nanotechnology. We also discuss the distribution and fate of these nanocarriers themselves, postadministration, as well as clearance from ocular tissues.