Lasix for the prevention of de novo postpartum hypertension: A randomized placebo-controlled trial (LAPP Trial).

BACKGROUND: Birthing people with de novo postpartum hypertensive disorders remain among the highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit to oral loop-diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension OBJECTIVE: To evaluate whether oral furosemide can reduce risk for de novo postpartum hypertension (dnPPHTN) among high-risk birthing people by reducing post-delivery blood pressure. STUDY DESIGN: From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for dnPPHTN at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high-risk for the development of dnPPHTN based on a pre-specified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a five-day course of oral furosemide 20 mg daily or identical-appearing placebo starting within eight hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was the difference in mean arterial pressure (MAP) averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation. The study was powered to detect a 5 mmHg difference in mean MAP (standard deviation 6.4 mmHg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of dnPPHTN, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. RESULTS: The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between groups. There was no significant difference in mean MAP 24 hours prior to discharge (or antihypertensive initiation) in the furosemide group (88.9 ± 7.4 mmHg) compared to the placebo group (86.8 ± 7.1 mmHg; absolute difference 2.1 mmHg, 95% CI -1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed dnPPHTN and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between groups. CONCLUSIONS: De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces mean MAP in the 24 hours prior to discharge from the delivery hospitalization (or antihypertensive medication initiation) compared to placebo.

Multiple Clinical Indications of Mifepristone: A Systematic Review.

Mifepristone and misoprostol are globally used medications that have become disparaged through the stigmatization of reproductive healthcare. Patients are hindered from receiving prompt treatment in clinical scenarios where misoprostol and mifepristone are the drugs of choice. It is no exaggeration to emphasize that in cases where reproductive healthcare is concerned. The aim of this paper is to discuss the different indications of mifepristone and to delineate where the discrepancy in accessibility arises. For this systematic review, we included publications citing clinical trials involving the use and efficacy of mifepristone published in English within the date range of 2000 to 2023. Five databases were searched to identify relevant sources. These databases are Google Scholar, MEDLINE with full text through EBSCO, and three National Center for Biotechnology Information (NCBI) databases (NCBI Bookshelf, PubMed, and PubMed Central). Twenty-three records were ultimately included in this review. Mifepristone has been shown to have therapeutic effects in the treatment of psychiatric disorders, such as major depressive disorder and psychotic depression. There was a significant decrease in depression and psychiatric rating symptoms for patients taking mifepristone versus placebo with no adverse events. Mifepristone has also been shown to improve treatment course in patients with Cushing's disease (CD) who failed or are unable to undergo surgical treatment. In addition, mifepristone has been shown to be a successful treatment option for adenomyosis and leiomyomas. Patients had a statistically significant decrease in uterine volumes following mifepristone treatment, which aided in the alleviation of other symptoms, such as blood loss and pelvic discomfort. Mifepristone is a synthetic steroid that has immense potential to provide symptomatic relief in patients suffering from a wide array of complicated diseases. Historically, mifepristone has been proven to have an incredible safety profile. While further research is certainly needed, the politicization of its medical use for only one of its many indications has unfortunately led to the willful ignorance of its potential despite its evidence-based safety profile and efficacy.

The role of evaluation in iterative learning and implementation of quality of care interventions.

Background: The Lancet Global Health Commission (LGHC) has argued that quality of care (QoC) is an emergent property that requires an iterative process to learn and implement. Such iterations are required given that health systems are complex adaptive systems.Objective: This paper explores the multiple roles that evaluations need to play in order to help with iterative learning and implementation. We argue evaluation needs to shift from a summative focus toward an approach that promotes learning in complex systems. A framework is presented to help guide the iterative learning, and includes the dimensions of clinical care, person-centered care, continuum of care, and 'more than medicine. Multiple roles of evaluation corresponding to each of the dimensions are discussed.Methods: This paper is informed by reviews of the literature on QoC and the roles of evaluation in complex systems. The proposed framework synthesizes the multiple views of QoC. The recommendations of the roles of evaluation are informed both by review and experience in evaluating multiple QoC initiatives.Results: The specific roles of different evaluation approaches, including summative, realist, developmental, and participatory, are identified in relationship to the dimensions in our proposed framework. In order to achieve the potential of LGHC, there is a need to discuss how different evaluation approaches can be combined in a coherent way to promote iterative learning and implementation of QoC initiatives.Conclusion: One of the implications of the QoC framework discussed in the paper is that time needs to be spent upfront in recognizing areas in which knowledge of a specific intervention is not complete at the outset. This, of course, implies taking stock of areas of incompleteness in knowledge of context, theory of change, support structures needed in order for the program to succeed in specific settings. The role of evaluation should not be limited to only providing an external assessment, but an important goal in building evaluation capacity should be to promote adaptive management among planners and practitioners. Such iterative learning and adaptive management are needed to achieve the goals of sustainable development goals.

Mapping the evidence on health equity considerations in economic evaluations of health interventions: a scoping review protocol.

BACKGROUND: Equity in health has become an important policy agenda around the world, prompting health economists to advance methods to enable the inclusion of equity in economic evaluations. Among the methods that have been proposed to explicitly include equity are the weighting analysis, equity impact analysis, and equity trade-off analysis. This is a new development and a comprehensive overview of trends and concepts of health equity in economic evaluations is lacking. Thus, our objective is to map the current state of the literature with respect to how health equity is considered in economic evaluations of health interventions reported in the academic and gray literature. METHODS: We will conduct a scoping review to identify and map evidence on how health equity is considered in economic evaluations of health interventions. We will search relevant electronic, gray literature and key journals. We developed a search strategy using text words and Medical Subject Headings terms related to health equity and economic evaluations of health interventions. Articles retrieved will be uploaded to reference manager software for screening and data extraction. Two reviewers will independently screen the articles based on their titles and abstracts for inclusion, and then will independently screen a full text to ascertain final inclusion. A simple numerical count will be used to quantify the data and a content analysis will be conducted to present the narrative; that is, a thematic summary of the data collected. DISCUSSION: The results of this scoping review will provide a comprehensive overview of the current evidence on how health equity is considered in economic evaluations of health interventions and its research gaps. It will also provide key information to decision-makers and policy-makers to understand ways to include health equity into the prioritization of health interventions when aiming for a more equitable distribution of health resources. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered with Open Science Framework (OSF) Registry on August 14, 2019 (https://osf.io/9my2z/registrations).

The enigma of primary and secondary encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating Peritoneal Sclerosis (EPS) describes a variety of diseases that are frequently confused with different names and different etiopathogeneses. The aim of this article is to report personal experience of focusing on correct classification and the status of current diagnosis and treatment. METHODS: A retrospective analysis was performed. Age, sex, ethnic origin, past medical history, symptoms and their duration, radiological tools and signs, laboratory tests, preoperative diagnosis, surgical approach, intraoperative findings, pathological findings, hospital stay, morbidity and mortality were studied. RESULTS: A total of seven patients, including six males and one female, aged from 24 to 72 years were observed. Four patients had recurrent abdominal colic pain for 3 months, 1, 2 and 9 years; two patients also reported recurrent attacks but without any specification of the duration. All seven patients presented at the emergency department with abdominal pain that was mainly diffused over the entire abdomen. Six patients were submitted to a CT scan. Only in two patients was the diagnosis of EPS made preoperatively. All seven patients were submitted to open surgery. The hospital stay was between 4 and 60 days. One patient had morbidity, and one patient died of MOF. CONCLUSIONS: Currently, the correct identification of EPS is more easily possible than in the past, but the diagnosis is still a challenge. Surgery must be performed as soon as possible to avoid a poorer quality of life.

Patterns and outcomes of traumatic neck injuries: A population-based observational study.

OBJECTIVES: We aimed to analyze the pattern and outcome of traumatic neck injury (TNI) in a small population. MATERIALS AND METHODS: It is a retrospective analysis of all TNI patients who were admitted to the trauma center between 2008 and 2012. Patients' demographics, details of TNI, associated injuries, hospital course, and mortality were analyzed. RESULTS: A total of 51 TNI cases were included revealing an overall incidence of 0.61/100,000 population. The mean age was 31 ± 9 years. The most frequent mechanism of injury was motor vehicle crash (29.4%) followed by stab (17.6%), machinery injury (17.6%), fall (9.8%), and assault (7.8%). Larynx, thyroid gland, trachea, jugular veins, and carotid were the commonly injured structures. The majority of cases had Zone II TNI whereas isolated injury was observed in 11 cases. TNI were mainly presented with active bleeding (38%), hypovolemic shock (16%) and respiratory distress (16%). Surgical interventions mainly included simple repair and closure (53%), vein ligation (12%), repair of major arteries (4%), tracheal repair (6%), larynx and hypopharynx repair (4%), and repair of parotid gland (2%). Neck exploration was performed in 88%, and emergency tracheostomy was required in 18% of cases. Overall mortality rate was 11.8%, of which five patients had associated injuries, and one had isolated TNI. CONCLUSION: TNI are not frequent but represent an alarming serious entity in Qatar. Patients with persistent signs of major injuries should undergo early operative interventions. Moreover, the effective injury prevention program should be developed to minimize these preventable injuries in the majority of cases.

Body composition monitoring and nutrition in maintenance hemodialysis and CAPD patients--a multicenter longitudinal study.

Hydration and nutritional status of end stage renal disease (ESRD) patients are linked to increased morbidity and mortality. Body composition monitoring (BCM) by multi-frequency bioimpedance spectroscopy (MFBS) is considered to be a superior modality of fluid assessment in chronic kidney disease (CKD) dialysis. We did a longitudinal prospective study in South India on maintenance hemodialysis (MHD) and continuous ambulatory peritoneal dialysis (CAPD) patients over 24 months and looked at impact of baseline nutritional parameters and body composition parameters on 24-month mortality. Ninety-nine patients stable on dialysis for at least 3 months were recruited (MHD 85, CAPD 14) at baseline and at 24 months, 41 were alive and 33 had expired, 12 had undergone renal transplant and 13 were lost to follow-up. BCM and nutritional assessment were done at baseline and at follow-up. Baseline overhydration (OH) differed significantly between surviving and dead patients (p < 0.05). Receiver operating characteristic (ROC) curve between OH and mortality showed that the best cut-off point to differentiate between survived and expired patients was 3.15 L. ROC curve for BMI showed lower than cut-off of 22.65 kg/m(2) to predict mortality with sensitivity 41.30% and specificity 81.81%. At follow-up, triceps skin fold thickness (TSF), biceps skin fold thickness (BSF) and mid arm circumference (MAC) increased significantly from baseline (p < 0.001, p = 0.001 and p < 0.001, respectively). Overhydration and BMI are important predictors of mortality in dialysis patients. Improvement in anthropometric markers TSF, BSF and MAC in MHD patients was associated with survival.

Tumor associated mesenchymal stem cells protects ovarian cancer cells from hyperthermia through CXCL12.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise in treatment of ovarian carcinosis. Despite its efficiency for the treatment of peritoneal carcinosis from digestive tract neoplasia, it has failed to demonstrate significant benefit in ovarian cancers. It is therefore essential to understand the mechanism underlying resistance to HIPEC in ovarian cancers. Mesenchymal stem cells (MSC) play an important role in the development of ovarian cancer metastasis and resistance to treatments. A recent study suggests that MSCs may be cytotoxic for cancer cells upon heat shock. In contrast, we describe the protective role of MSC against hyperthermia. Using cytokine arrays we determined that the tumor associated MSC (TAMC) secrete pro-tumoral cytokines. We studied the effect of hyperthermia in co-culture setting of TAMC or BM-MCS associated with ovarian cancer cell lines (SKOV3 and CaOV3) with polyvariate flow cytometry. We demonstrate that hyperthermia does not challenge survival of TAMC or bone marrow derived MSC (BM-MSC). Both TAMC and BM-MSC displayed strong protective effect inducing thermotolerance in ovarian cancer cells (OCC). Transwell experiments demonstrated the role of secreted factors. We showed that CXCL12 was inducing thermotolerance and that inhibition of CXCL12/CXCR4 interaction restored cytotoxicity of hyperthermia in co-culture experiments. Contrary to the previous published study we demonstrated that TAMC and BM-MSC co-cultured with OCC induced thermotolerance in a CXCL12 dependant manner. Targeting the interaction between stromal and cancer cells through CXCL12 inhibition might restore hyperthermia sensitivity in ovarian cancers, and thus improve HIPEC efficiency.