Safety of Intravenous Bisphosphonates for the Treatment of Hypercalcemia in Patients With Preexisting Renal Dysfunction.

BACKGROUND: Although intravenous (IV) bisphosphonates are first-line medications for the management of hypercalcemia, studies examining their use in patients with preexisting renal dysfunction are limited. OBJECTIVE: The objective of this study is to describe the safety and efficacy of pamidronate and zoledronic acid in the treatment of hypercalcemia in patients with baseline renal dysfunction. METHODS: A retrospective analysis was conducted of IV pamidronate and zoledronic acid in adult patients with hypercalcemia and creatinine clearance (CrCl) <60 mL/min. The primary endpoint was incidence of all-grade serum creatinine (SCr) elevations. Secondary endpoints included refractory hypercalcemia, hypocalcemia, osteonecrosis of the jaw (ONJ), corrected serum calcium (CSC) decrease ≥1.0 mg/dL by day 7 of bisphosphonate administration, and normalization of CSC ≤10.5 mg/dL by days 10 and 30. RESULTS: A total of 113 patients were included (n = 55 pamidronate, n = 58 zoledronic acid). The primary endpoint of all-grade SCr elevation occurred in 28 (24.8%) patients. Grades 3/4 SCr elevations occurred in 10.9% of patients treated with pamidronate and 1.7% of patients receiving zoledronic acid. Approximately 16% and 14% of patients developed grades 1 and 2 hypocalcemia, respectively, and there were no cases of ONJ. Overall, 64.6% of patients achieved normalization of CSC by day 10, and there were no statistical differences between bisphosphonate type and renal function. CONCLUSIONS AND RELEVANCE: The analysis suggests an association between IV bisphosphonates and increased rates of SCr elevations among patients with preexisting renal dysfunction. Future prospective studies are necessary to elucidate these findings.

Cerebral microbleeds: Causes, clinical relevance, and imaging approach - A narrative review.

With advances in magnetic resonance imaging (MRI) sequences, there has been increased identification of microbleed/microhemorrhage across different population ages, but more commonly in the older age group. These are defined as focal areas of signal loss on gradient echo MRI sequences (T2* and susceptibility-weighted images), which are usually <5 mm in size representing hemosiderin deposition with wide ranges of etiologies. Susceptibility-weighted imaging (SWI) has become a routine MRI sequence for practices across the globe resulting in better identification of these entities. Over the past decade, there has been a better understanding of the clinical significance of microbleeds including their prognostic value in ischemic and hemorrhagic stroke. Cerebral amyloid angiopathy and hypertension are the two most common causes of microbleeds following peripheral and central pattern, respectively. In the younger age group, microbleeds are more common due to familial conditions or a wide range of hypercoagulable states. This review outlines the pathophysiology, prevalence, and clinical implications of cerebral microhemorrhage along with a brief discussion about the technical considerations of SWI.

User Acceptability and Perceived Impact of a Mobile Interactive Education and Support Group Intervention to Improve Postnatal Health Care in Northern India: A Qualitative Study.

Background: Postnatal care, crucial for preventing and assessing complications after birth, remains low in India. An interactive mHealth community-based postnatal intervention was implemented to promote healthy maternal behaviors through knowledge and social support in rural Northern India. However, there is limited information on how virtual health interventions in resource-constrained settings are perceived by the users and which elements influence their engagement and sustained participation. Objective: We explored the user perceptions of acceptability and impact of a virtual interactive maternal and child health intervention pilot tested in Punjab State, India, including their perspectives on barriers and facilitators to engage with this intervention. Methods: This qualitative study was embedded within extensive mixed-method research, and oriented by the Realist Evaluation approach. Sixteen participants were recruited from the parent study. They were identified by purposive sampling to cover diverse levels of attendance and engagement with the intervention. In-depth interviews were conducted by phone. Following translation, a framework analysis was completed to search for the main themes. Feedback was requested from intervention moderators during the process to prioritize local interpretation. Results: Study participants reported overall satisfaction with the intervention. The mothers appreciated the educational material provided and the communication with other participants and health professionals. Across context, intervention, and actor domains, the barriers most commented on were network and connectivity challenges, lack of time due to household responsibilities, and feeling uncomfortable sharing personal experiences. Family buy-in and support were fundamental for overcoming the high domestic workload and baby care. Another facilitator mentioned was moderators' guidance on using the different intervention modalities. Regarding perceived impact, participants shared that MeSSSSage increased their capability and motivation to breastfeed, seek care as needed, and use contraception according to their preferences. Finally, participants suggested adding more topics to the educational content and adjusting the dynamics within the group calls to improve the intervention. Conclusions: This study identifies the high acceptability and perceived impact of a novel postnatal care program in a rural setting, including the users' perceived barriers to engaging with the intervention and possible solutions to overcome them. These findings enable refinement of the ongoing intervention, providing a more robust framing for its scalability and long-term sustainability. On a larger scale, conclusions from this research provide new insights and encouragement to global stakeholders who aspire to improve maternal and neonatal outcomes in low-income and middle-income countries through mHealth.

A qualitative study to understand sociocultural beliefs around perinatal and neonatal health in rural areas of Mohali, Punjab, India.

Introduction: Globally, 600,000 mothers (15-49 years) die every year due to pregnancy and childbirth-related complications. Wide variations are seen in cultural practices and beliefs surrounding this period of a woman's life. The present study explores the cultural beliefs and practices of women and families during pregnancy and the postnatal period in order to understand what behavioral management strategies are required to improve maternal and infant outcomes during pregnancy and the postpartum period. Methods: The study was conducted in a rural area of Punjab, from December 2019 to March 2021. A total of 20 women (up to 3 months postpartum, age >18 years, were interviewed. Results: In general, women described eating varied and fairly healthy diets during pregnancy, especially nutritious warm food, following traditional practices. Other cultural practices included restrictions on movement and mobile phone use and the use of unsafe home remedies to promote infant safety and wellbeing, such as using gripe water, applying black pencil to the baby's eyes, and feeding the baby honey. A few were not inclined to engage with these and other cultural expectations, preferring instead to follow contemporary practices influenced by social media. These practices included being accompanied by a family member during delivery, celebrating the baby's birth regardless of sex, and early bathing post-delivery. Discussion: It can be concluded that while many traditional practices are still followed in India, there are new beliefs and behaviors arising from an intersection between culture and technology. Developing strategies that acknowledge older beliefs and modern approaches is essential to promoting better antenatal and postpartum care.

Preliminary impact of an mHealth education and social support intervention on maternal health knowledge and outcomes among postpartum mothers in Punjab, India.

Background: Significant disruptions in the perinatal continuum of care occur postpartum in India, despite it being a critical time to optimize maternal health and wellbeing. Group-oriented mHealth approaches may help mitigate the impact of limited access to care and the lack of social support that characterize this period. Our team developed and pilot tested a provider-moderated group intervention to increase education, communication with providers, to refer participants to in-person care, and to connect them with a virtual social support group of other mothers with similarly aged infants through weekly calls and text chat. Methods: We analyzed the preliminary effectiveness of the pilot intervention on maternal health knowledge through 6 months postpartum among 135 participants in Punjab, India who responded to baseline and endline surveys. We described change in knowledge of maternal danger signs, birth preparedness, postpartum care use, postpartum physical and mental health, and family planning use over time between individuals in group call (synchronous), other intervention (asynchronous), and control groups. Results: Participant knowledge regarding danger signs was low overall regarding pregnancy, childbirth and the postpartum period (mean range of 1.13 to 2.05 at baseline and 0.79 to 2.10 at endline). Group call participants had a significantly higher increase over time in knowledge of danger signs than other intervention and control group participants. Birth preparedness knowledge ranged from mean 0.89-1.20 at baseline to 1.31-2.07 at baseline, with group call participants having significantly greater increases in comparison to the control group. Group call participants had nearly three-fold increased odds of postpartum health check with a clinical provider than other intervention participants (OR 2.88, 95% CI 1.07-7.74). No differences were noted in postpartum depressive and anxiety symptoms. Conclusions: Preliminary effectiveness results are promising, yet further robust testing of the MeSSSSage intervention effectiveness is needed. Further development of strategies to support health knowledge and behaviors and overcoming barriers to postpartum care access can improve maternal health among this population.

The supply is there. So why can't pregnant and breastfeeding women in rural India get the COVID-19 vaccine?

Despite COVID-19 vaccines being available to pregnant women in India since summer 2021, little is known about vaccine uptake among this high need population. We conducted mixed methods research with pregnant and recently delivered rural women in northern India, consisting of 300 phone surveys and 15 in-depth interviews, in November 2021. Only about a third of respondents were vaccinated, however, about half of unvaccinated respondents reported that they would get vaccinated now if they could. Fears of harm to the unborn baby or young infant were common (22% of unvaccinated women). However, among unvaccinated women who wanted to get vaccinated, the most common barrier reported was that their health care provider refused to provide them the vaccine. Gender barriers and social norms also played a role, with family members restricting women's access. Trust in the health system was high, however, women were most often getting information about COVID-19 vaccines from sources that they did not trust, and they knew they were getting potentially poor-quality information. Qualitative data shed light on the barriers women faced from their family and health care providers but described how as more people got the vaccine that norms were changing. These findings highlight how pregnant women in India have lower vaccination rates than the general population, and while vaccine hesitancy does play a role, structural barriers from the health care system also limit access to vaccines. Interventions must be developed that target household decision-makers and health providers at the community level, and that take advantage of the trust that rural women already have in their health care providers and the government. It is essential to think beyond vaccine hesitancy and think at the system level when addressing this missed opportunity to vaccinate high risk pregnant women in this setting.

A Mobile Education and Social Support Group Intervention for Improving Postpartum Health in Northern India: Development and Usability Study.

BACKGROUND: Structural and cultural barriers limit Indian women's access to adequate postnatal care and support despite their importance for maternal and neonatal health. Targeted postnatal education and support through a mobile health intervention may improve postnatal recovery, neonatal care practices, nutritional status, knowledge and care seeking, and mental health. OBJECTIVE: We sought to understand the feasibility and acceptability of our first pilot phase, a flexible 6-week postnatal mobile health intervention delivered to 3 groups of women in Punjab, India, and adapt our intervention for our next pilot phase, which will formally assess intervention feasibility, acceptability, and preliminary efficacy. METHODS: Our intervention prototype was designed to deliver culturally tailored educational programming via a provider-moderated, voice- and text-based group approach to connect new mothers with a social support group of other new mothers, increase their health-related communication with providers, and refer them to care needed. We targeted deployment using feature phones to include participants from diverse socioeconomic groups. We held moderated group calls weekly, disseminated educational audios, and created SMS text messaging groups. We varied content delivery, group discussion participation, and chat moderation. Three groups of postpartum women from Punjab were recruited for the pilot through community health workers. Sociodemographic data were collected at baseline. Intervention feasibility and acceptability were assessed through weekly participant check-ins (N=29), weekly moderator reports, structured end-line in-depth interviews among a subgroup of participants (15/29, 52%), and back-end technology data. RESULTS: The participants were aged 24 to 28 years and 1 to 3 months postpartum. Of the 29 participants, 17 (59%) had their own phones. Half of the participants (14/29, 48%) attended ≥3 of the 6 calls; the main barriers were childcare and household responsibilities and network or phone issues. Most participants were very satisfied with the intervention (16/19, 84%) and found the educational content (20/20, 100%) and group discussions (17/20, 85%) very useful. The participants used the SMS text messaging chat, particularly when facilitator-moderated. Sustaining participation and fostering group interactions was limited by technological and sociocultural challenges. CONCLUSIONS: The intervention was considered generally feasible and acceptable, and protocol adjustments were identified to improve intervention delivery and engagement. To address technological issues, we engaged a cloud-based service provider for group calls and an interactive voice response service provider for educational recordings and developed a smartphone app for the participants. We seek to overcome sociocultural challenges through new strategies for increasing group engagement, including targeting midlevel female community health care providers as moderators. Our second pilot will assess intervention feasibility, acceptability, and preliminary effectiveness at 6 months. Ultimately, we seek to support the health and well-being of postpartum women and their infants in South Asia and beyond through the development of efficient, acceptable, and effective intervention strategies.

Access to and Use of Mobile Phone by Postpartum, Married Women in Punjab, India: Secondary Analysis of mHealth Intervention Pilot Data.

BACKGROUND: As mobile phone uptake in India continues to grow, there is also continued interest in mobile platform-based interventions for health education. There is a significant gender gap in mobile phone access-women's access to mobile phones is constrained by economic and social barriers. Pregnancy and postpartum care is one of many targets for mobile health (mHealth) interventions that particularly rely upon women's access to and facility with mobile phone use. OBJECTIVE: We aimed to describe the dynamics and patterns of married pregnant and postpartum women's mobile phone access and use (among both phone owners and nonowners) who participated in an mHealth postpartum care intervention and to identify potential barriers to their participation in mobile platform-based interventions. METHODS: A secondary analysis was performed on mixed methods data obtained for a pilot mHealth intervention for postpartum care of mothers in rural Punjab from July 2020 to February 2021. Two formative sources included exploratory in-depth interviews among postpartum women (n=20; 1-3 months postpartum) and quantitative maternal health survey among women who were pregnant or who had recently given birth (n=102). We also utilized mixed methods intervention assessment data from early postpartum women who participated in the pilot intervention (n=29), including intervention moderator perspectives. Qualitative and quantitative analyses were performed, and pertinent findings were grouped thematically. RESULTS: The majority of women owned a phone (maternal health survey: 75/102, 74%; demographic survey: 17/29, 59%), though approximately half (53/102, 52%) still reported sharing phones with other family members. Sharing a phone with female family members typically allowed for better access than sharing with male family members. Some households had strict preferences against daughters-in-law having phones, or otherwise significantly restricted women's phone access. Others reported concerns about phone use-related health hazards for mother and infant during the pregnancy or postpartum period. CONCLUSIONS: These findings suggest nuance regarding what is meant by women's phone ownership and access-there were numerous additional constraints on women's use of phones, particularly during pregnancy and the postpartum period. Future research and mHealth interventions should probe these domains to better understand the dynamics governing women's access, use, and fluency with mobile phones to optimally design mHealth interventions.

Lack of an effect of high dose isoflavones in men with prostate cancer undergoing androgen deprivation therapy.

PURPOSE: The profound hypogonadism due to androgen deprivation therapy for prostate cancer results in complications such as sexual dysfunction, poor quality of life, vasomotor symptoms and altered cognition. Since estrogen is associated with cardiovascular risks, phytoestrogens are being increasingly evaluated as a potential treatment for these adverse effects. We evaluated the effects of high dose isoflavones, equivalent to that consumed by Asian populations, on the aforementioned consequences of androgen deprivation therapy. MATERIALS AND METHODS: A total of 33 men undergoing androgen deprivation therapy for prostate cancer were enrolled in this randomized, double-blind, placebo controlled, 12-week pilot trial. Participants were randomly assigned to receive 20 gm soy protein containing 160 mg total isoflavones (17) vs taste matched placebo, that is 20 gm whole milk protein (16). The study was performed at a tertiary care center in the United States. RESULTS: At baseline the groups were well matched in demographic parameters, sleep quality, cognition and overall quality of life. However, men in the isoflavone group had a higher baseline prevalence of hot flashes and poor intercourse satisfaction compared to those on placebo. At 12 weeks there were no significant differences between the 2 groups in any outcome measure. CONCLUSIONS: This pilot study of high dose isoflavones in androgen deprived men showed no significant improvement in cognition, vasomotor symptoms or any other aspect of quality of life measures compared to placebo. Future studies should use variable doses of isoflavones for a longer period before ruling out beneficial isoflavone effects in this population.

One-pot sequential multicomponent reaction between in situ generated aldimines and succinaldehyde: facile synthesis of substituted pyrrole-3-carbaldehydes and applications towards medicinally important fused heterocycles.

An efficient sequential multi-component method for the synthesis of N-arylpyrrole-3-carbaldehydes has been developed. This reaction involved a proline-catalyzed direct Mannich reaction-cyclization sequence between succinaldehyde and in situ generated Ar/HetAr/indolyl-imines, followed by IBX-mediated oxidative aromatization in one-pot operation. The practical utility of this procedure is shown at gram-scale and the synthesis of diverse bioactive fused heterocyclic scaffolds such as pyrroloquinoline, pyrrolo-oxadiazole, dihydro pyrroloquinoline, and pyrrolo-phenanthridine.

Crystal structure of 2-methyl-4-[(thio-phen-2-yl)methyl-idene]-1,3-oxazol-5(4H)-one.

The asymmetric unit of the title compound, C9H7NO2S, contains two crystallographically independent mol-ecules (A and B). Both mol-ecules are almost planar [maximum deviations = 0.047 (1) and 0.090 (1) Å, respectively, for the S atoms] with the oxazole and thio-phene rings being inclined to one another by 2.65 (16)° in mol-ecule A and by 4.55 (15)° in mol-ecule B. In the crystal, the individual mol-ecules are linked via C-H⋯O hydrogen bonds, forming -A-B-A-B- chains along the [10-1] direction. The chains are linked via C-H⋯π and π-π inter-actions [inter-centroid distances = 3.767 (2) and 3.867 (2) Å] involving inversion-related oxazole and thio-phene rings in both mol-ecules, forming a three-dimensional structure.