MDS Associates (United States)

Objective This is the first multicenter, double blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of adjunctive zonisamide for the treatment of bipolar depression. Experimental design One hundred two patients with bipolar disorder, type I or II in the depressed phase of illness were randomized to either adjunctive zonisamide or placebo. The study consisted of three phases, a 7 to 30 day screening and stabilization phase, 6 weeks of blinded treatment and a 1 to 3 week discontinuation phase. MADRS score was the primary outcome variable. Secondary outcome measures included the YMRS, CGI-S, CGI-I, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and an a priori analysis of response and remission. Metabolic parameters including weight, waist-hip ratio, body mass index, fasting glucose, cholesterol and triglyceride levels were also evaluated. Side effects were measured using the SAFTEE. Principal observations There were no statistically significant differences in response between subjects treated with adjunctive zonisamide vs. placebo controls for the primary or secondary outcome measures. There were also no differences between the groups with regard to response rate or remission rate. Conclusions In contrast to preliminary open label studies that suggested a role for zonisamide in bipolar depression, we could not confirm these results in a large double blind controlled study.

The therapeutic potential of RNA and DNA is evident from numerous formulations approved by the FDA in recent years, with formulations based on RNAi standing out as a successful example. The new class of medicines based on RNAi combines the process of diagnosis and treatment via sequence-specific recognition of biomarker mRNAs and downregulation of their translation. While this approach proved clinically successful, safer, and more personalized options that mitigate adverse effects can be revealed by separating diagnostic and treatment steps. A concept is introduced that allows RNAi therapies to selectively exert their function within diseased cells. The reconfigurable nucleic acid nanoparticles, or recNANPs, recognize overexpressed cancer biomarkers and conditionally release RNAi inducers targeting apoptosis inhibitors in pancreatic cancer cells. RecNANPs are non-immunostimulatory, achieve prolonged gene silencing compared to conventional RNAi inducers, and can be combined with chemotherapy. It is anticipated that this modular platform will enable further advancements in the development of biocompatible nanodevices activated by intracellular variables of choice, facilitating treatment with a repertoire of nucleic acid therapies.

Aims Therapeutic advancements have significantly improved patient outcomes in blood cancers. However, racial and ethnic disparities persist in treatment and access to care. Telehealth offers a promising solution to these disparities by using electronic and telecommunication technologies to deliver healthcare remotely. Ensuring access to telehealth depends not just on the technologies, but on the broader enabling environment, especially policy harmonization, communications infrastructure, and skills. This paper aims to advocate for the expanded use of telehealth in blood cancer management, highlighting its potential to improve equity and outcomes. Materials and methods An expert forum discussion results informed this systematic literature review which was performed to better understand the applied Telehealth solutions and the expected benefits. The forum discussion and the literature review findings were aggregated and reviewed by experts and patient advocates with personal experience in blood cancer. Results Our review of the literature yielded 18 relevant papers. Studies included patients from various disease areas; some studies used broader definitions of cancer to include more patients (i.e. acute leukemias and malignant lymphomas), while others were more specific to a particular condition. The identified Telehealth solutions were classified into two groups: solutions focusing on electronic consultation (n = 10) and solutions focusing on a specific intervention to improve patients’ health status (n = 8). A larger variety of outcomes were found in these studies, including quality of life, patient and clinicians’ acceptance, adherence, costs, and resource use. Conclusions Initial findings demonstrate that telehealth can potentially improve patient outcomes for people living with blood cancer, including improved patient quality of life, increased clinician acceptance, better adherence, and reduced costs and resource use to the health system. While evidence for virtual consultations show promising results, further research is needed due to the variety of study settings evaluated in this review. Providers and health systems need additional data on the positive economic impact of Telehealth related to the diagnostic journey and access to treatment.

A key challenge in obtaining efficient and competitive retail rates in restructured electricity markets is constructing an appropriate default generation price. Default prices in restructured states are often set by competitive procurement auctions in which firms bid to supply a fixed percentage (i.e., tranches) of a utility's full-requirements load obligation (supply, capacity, ancillary services, and sometimes transmission). Auction clearing prices serve as a price heuristic for other competitive retail supply offers on the open market. Default service also substitutes for competitive retail supply for customers that cannot or will not shop. The efficiency and competitiveness of these auctions, therefore, is of societal importance. In this paper, regression analysis is performed on a unique ten-year dataset of wholesale, retail, and input market parameters for Ohio's four investor-owned utilities to evaluate factors that influence its auction results. The models indicate that auction clearing prices are determined in more complex ways than a simple pass through of wholesale market costs. They indicate that auction competitiveness is a key driver of efficient retail price. They also indicate that wholesale market volatility, which is more challenging for suppliers to hedge, leads to significantly inflated default service auction prices. The paper provides policy implications for the market design of competitive retail electricity markets. • Unique dataset developed to quantify determinants of default retail electricity prices. • Econometric analysis reveals competitiveness and implied volatility are key determinants. • Competitiveness of procurement auctions is a key driver of retail price. • Implied volatility is also a key driver of retail price markups. • Retail electricity price formation is not simply based upon wholesale market conditions.

Few data are available about the epidemiology of cutaneous lupus erythematosus (CLE) in the Southern hemisphere and in multiethnic populations. We describe the prevalence, incidence, and clinical characteristics of isolated CLE in the multiethnic population of Reunion Island, France, including patients with dark skin. The study was performed in all public hospitals and private dermatology practices in Reunion Island. Cases were identified through informatics databases. Cases were defined as isolated CLE, meaning they did not fulfill the criteria for systemic lupus erythematosus (SLE). Incident cases were collected from 2008 to 2021. Prevalence was calculated on January 1, 2022. A capture-recapture analysis was performed to estimate both prevalence and incidence. A total of 268 cases of CLE were identified and 218 were incident cases. The standardized prevalence of CLE was 43 out of 100,000 persons and the average annual standardized incidence was 3.1 per 100,000 person-years (PY). With a capture-recapture analysis, prevalence and annual incidence were estimated to be 99 out of 100,000 persons (95% CI 77.10-136.45) and 5.7 per 100,000 PY (95% CI 4.40-7.95), respectively. The mean age at diagnosis was 41.7 years and the ratio of female to male individuals was 4:1. Patients with dark skin had a higher rate of discoid CLE and were more likely to receive immunosuppressants. Generalized discoid CLE, panniculitis, and overlapping subtypes of CLE appeared as predictive markers of progression toward SLE. The prevalence and incidence of CLE in the multiethnic population of Reunion Island seem higher than in light-skinned populations. We highlight new risk factors of evolution toward SLE that should be known by practitioners to adjust follow-up.

Medication nonadherence in systemic lupus erythematosus (SLE) leads to poor clinical outcomes. We developed a clinician-led adherence intervention that involves reviewing real-time pharmacy refill data and using effective communication to address nonadherence. Prior pilot testing showed promising effects on medication adherence. Here, we describe further evaluation of how clinicians implemented the intervention and identify areas for improvement. We audio recorded encounters of clinicians with patients who were nonadherent (90-day proportion of days covered [PDC] < 80% for SLE medications). We coded recordings for intervention components performed, communication quality, and time spent discussing adherence. We also conducted semistructured interviews with patients and clinicians on their experiences and suggestions for improving the intervention. We assessed change in 90-day PDC post intervention. We included 25 encounters with patients (median age 39, 100% female, 72% Black) delivered by 6 clinicians. Clinicians performed most intervention components consistently and exhibited excellent communication, as coded by objective coders. Adherence discussions took an average of 3.8 minutes, and 44% of patients had ≥ 20% increase in PDC post intervention. In structured interviews, many patients felt heard and valued and described being more honest about nonadherence and more motivated to take SLE medications. Patients emphasized patient-clinician communication and financial and logistical assistance as areas for improvement. Some clinicians wanted additional resources and training to improve adherence conversations. We provide further evidence to support the feasibility, acceptability, and fidelity of the adherence intervention. Future work will optimize clinician training and evaluate the intervention's effectiveness in a large, randomized trial.

Aim and Objectives: (The objectives of the study are as follows: 1) To compare the Blood loss in both early cord clamping (ECC) versus delayed cord clamping (DCC) (in the third stage of labor). (2) To compare the third-stage complications following ECC versus of DCC in anemic pregnant females. (3) To compare Maternal hemoglobin and hematocrit at 24 h of delivery in both ECC versus DCC. Methods: This prospective study was carried out in the Department of Obstetrics and Gynaecology in Lady Hardinge Medical College and Associated Hospitals, New Delhi pregnant women. A total of 120 anemic pregnant women between 32 and 40 weeks of gestation admitted in the labour room were enrolled in the study (hemoglobin between 7 and 10.9 g%). Twenty patients were lost to follow-up. Third-stage complications of 46 women who underwent ECC (&lt;60 s) were compared with 54 women who underwent DCC (more than 60 s to &lt;3 min). Maternal hemoglobin and hematocrit at 24 h of delivery were also compared between both groups. Results: The mean blood loss in both the groups was 325±89.287 and 326.85±66.384, comparable statistically with p=0.906. Out of 100 patients enrolled, only two patients had postpartum hemorrhage. Each one belonged to each group (p&lt;0.909). None of the groups had retained placenta showing no statistical significance between two groups (p&lt;1). DCC was not associated with increased risk of third-stage complications whether in cesarean section or vaginal delivery. There were no differences in operative time, post-delivery decrease in hematocrit, rates of postpartum hemorrhage, bleeding complications, maternal blood transfusions, and therapeutic hysterectomy between the two groups. Conclusions: DCC is safe for mother especially in anemic mothers also as it does not increase the mean blood loss and also it has beneficial effect on neonates. No difference in third-stage complications and maternal hemoglobin and hematocrit levels at 24 h in both groups. It should be recommended in routine practice where it is not contraindicated especially in resource-poor settings.