Using Implementation Research to Inform Scaling of Parenting Programs: Independently Conducted Case Studies from Zambia and Bhutan.

Two case studies of parenting programs for parents of children 0 to 36 months of age, developed and implemented by Save the Children/Ministry of Health/Khesar Gyalpo University in Bhutan and UNICEF Zambia, were conducted by an independent research group. The focus was on how program delivery and scale-up were revised on the basis of feedback from implementation research. Feedback on workforce delivery quality was based on observations of deliveries using a monitoring form, as well as survey and interview data collected from the workforce. In-depth interviews with the resource team during the fourth year of implementation revealed how the feedback was used to address horizontal and vertical scaling. Delivery quality was improved in some cases by revising the delivery manual, offering refresher courses, and instituting regular monitoring. Scaling challenges in Zambia included slow progress with regard to reaching families in the two districts, which they addressed by trialing group sessions, and stemming workforce attrition. The challenges in Bhutan were low attendance and reducing the workload of providers. Vertical scaling challenges for both countries concerned maintaining demand through continuous advocacy at community and government levels to sustain financing and to show effectiveness in outcomes.

A Tale of Two Programs for Parents of Young Children: Independently-Conducted Case Studies of Workforce Contributions to Scale in Bhutan and Rwanda.

Two case studies of parenting programs, aiming to improve parenting practices and child development outcomes, and implemented by Save the Children/Ministry of Health/Khesar Gyalpo University in Bhutan and Boston College/University of Rwanda/FXB in Rwanda, respectively called Prescription to Play and Sugira Muryango, were conducted by an independent research and learning group. Implementation research focused on the workforce, a crucial but little-studied element determining the success of programs going to scale. Mixed methods were used to examine their training, workload, challenges, and quality of delivery. Health assistants in Bhutan and volunteers in Rwanda were trained for 10-11 days using demonstrations, role plays, and manuals outlining activities to deliver to groups of parents (Bhutan) or during home visits (Rwanda). Workers' own assessments of their delivery quality, their confidence, and their motivations revealed that duty, confidence, and community respect were strong motivators. According to independent observations, the quality of their delivery was generally good, with an overall mean rating on 10 items of 2.36 (Bhutan) and 2.44 (Rwanda) out of 3. The facilitators of scaling for Bhutan included institutionalizing training and a knowledgeable workforce; the barrier was an overworked workforce. The facilitators of scaling for Rwanda included strong follow-up supervision; the barriers included high attrition among a volunteer workforce.

Nurturing care during COVID-19: a rapid review of early evidence.

OBJECTIVES: The COVID-19 pandemic has brought significant changes to family life, society and essential health and other services. A rapid review of evidence was conducted to examine emerging evidence on the effects of the pandemic on three components of nurturing care, including responsive caregiving, early learning, and safety and security. DESIGN: Two academic databases, organisational websites and reference lists were searched for original studies published between 1 January and 25 October 2020. A single reviewer completed the study selection and data extraction with verification by a second reviewer. INTERVENTIONS: We included studies with a complete methodology and reporting on quantitative or qualitative evidence related to nurturing care during the pandemic. PRIMARY AND SECONDARY OUTCOME MEASURES: Studies reporting on outcomes related to responsive caregiving, early learning, and safety and security were included. RESULTS: The search yielded 4410 citations in total, and 112 studies from over 30 countries met our eligibility criteria. The early evidence base is weighted towards studies in high-income countries, studies related to caregiver mental health and those using quantitative survey designs. Studies reveal issues of concern related to increases in parent and caregiver stress and mental health difficulties during the pandemic, which was linked to harsher and less warm or responsive parenting in some studies. A relatively large number of studies examined child safety and security and indicate a reduction in maltreatment referrals. Lastly, studies suggest that fathers' engagement in caregiving increased during the early phase of the pandemic, children's outdoor play and physical activity decreased (while screen time increased), and emergency room visits for child injuries decreased. CONCLUSION: The results highlight key evidence gaps (ie, breastfeeding support and opportunities for early learning) and suggest the need for increased support and evidence-based interventions to ensure young children and other caregivers are supported and protected during the pandemic.

Pentosan polysulfate for the treatment of hemorrhagic cystitis after allogeneic hematopoietic cell transplant.

INTRODUCTION: Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms. METHODS AND RESULTS: This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10). CONCLUSION: Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.

Day 4 vs. day 12 G-CSF administration following reduced intensity peripheral blood allogeneic stem cell transplant.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) hastens neutrophil engraftment and reduces infections after allogeneic hematopoietic cell transplant (alloHCT), yet the optimal start date is unknown. Additionally, concurrent G-CSF and methotrexate for graft-vs-host disease (GVHD) prophylaxis may potentiate myelosuppression, and prolonged G-CSF is costly. Our institution changed from day + 4 to day + 12 G-CSF initiation following reduced intensity (RIC) alloHCT with methotrexate GVHD prophylaxis. METHODS: We retrospectively compared day + 4 and day + 12 G-CSF initiation after RIC alloHCT from 2017-2021. The primary endpoint was the time to neutrophil engraftment. Secondary endpoints included length of stay (LOS) and the time to platelet engraftment as well as the incidence of infectious events, acute GVHD (aGVHD), and mucositis. RESULTS: Thirty-two patients were included in each group with similar baseline characteristics. We observed faster neutrophil engraftment (median 12 vs. 15 days, p = 0.01) and platelet engraftment (median 13 vs. 15 days, p = 0.026) with day + 4 vs. day + 12 G-CSF initiation. Median LOS was 23 days (range, 19-32) with day + 4 initiation vs. 24 days (21-30) with day + 12 (p = 0.046). The incidence of culture-negative febrile neutropenia (p = 0.12), any grade aGVHD (p = 0.58), and grade 2-4 mucositis (p = 0.8) were similar between groups. CONCLUSION: Compared to day + 4, day + 12 G-CSF initiation following RIC alloHCT had a longer time to neutrophil and platelet engraftment. Day + 12 initiation also resulted in longer LOS, which while statistically significant, was potentially of limited clinical significance. These findings are hypothesis generating.

Evaluation of the management of PARP inhibitor toxicities in ovarian and endometrial cancer within a multi-institution health-system.

INTRODUCTION: Poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) have become a cornerstone of therapy in the management ovarian cancer and other cancers. PARPi are associated with significant toxicities and management strategies are primarily founded on clinical trial experience. This study aimed to provide an evaluation of patients receiving PARPi therapy within an academic health-system. METHODS: A retrospective, observational study of adult patients with gynecologic malignancy was conducted at the University of Pennsylvania Health System. Data was collected on patients prescribed a PARPi between December 2014 and October 2019. The primary endpoint was the status of PARPi therapy at the end of the study period. Key secondary endpoints included toxicity management strategies, time to discontinuation due to toxicity, progression free survival (PFS), and overall survival (OS). RESULTS: Of the 85 patients included, 45 (53%) received olaparib, 24 (28%) niraparib, and 16 (19%) rucaparib. Twenty-nine patients (34%) continued on therapy, 15 (18%) discontinued due to toxicity, and 41 (48%) discontinued due to progression. Fifty-one percent of patients required a dose reduction due to toxicities. The median time to discontinuation due to toxicity was 69 days (9-353). Median PFS was 181 days (9-365) and median OS was 338 days (9-365). CONCLUSION: PARPi therapy is associated with numerous toxicities that are best managed through a multi-modal approach. Importantly, about half the patients in the current study required a dose reduction. Overall, this observational study outlines the incidence of PARPi toxicities and reviews potential management strategies, further guiding practitioners in an area with limited real-world experience.

AM Versus PM Postoperative Administration of Warfarin With a Mechanical Mitral Valve.

Background: Currently, there are no guidelines regarding the optimal daily timing of inpatient warfarin administration. Objective: The purpose of this study was to determine whether dosing warfarin in the morning will have a significant impact on therapeutic international normalized ratio (INR) achievement compared with evening administration in mechanical mitral valve patients initiated on warfarin following cardiac surgery. Methods: This was a single-center, pre- and post-retrospective cohort conducted between 2014 and 2018. One-hundred fifty-four adult patients who underwent a mechanical mitral valve replacement or alternative cardiac surgery with a history of a mechanical mitral valve were enrolled. The primary outcome was achievement of therapeutic INR at any time point after initiation of warfarin. Pre-intervention administration timing was 6 pm and post-intervention timing was 10 am. Results: Baseline characteristics including age, sex, and race were similar between the 2 groups (P = NS for each characteristic). Therapeutic INR achievement was significantly improved at all time points following 10 am warfarin administration compared with 6 pm (hazard ratio = 1.69; P = .005). Mean time-to-therapeutic INR was 7.37 days in the post-intervention group and 8.39 days in the pre-intervention group (P = .073). There were no significant differences in INR >4, bleeding, or thrombotic complications between groups. Conclusion and Relevance: This retrospective analysis suggests that there may be a postoperative benefit in therapeutic INR achievement in mechanical valve patients when dosing warfarin in the morning compared with evening administration. Large-scale studies should be conducted to further elucidate the potential benefit across more heterogeneous populations.

Effects of oil from the 2010 Macondo well blowout on marsh foraminifera of Mississippi and Louisiana, USA.

Foraminifera responded to both heavy and light oiling of marshes relative to unoiled control sites by changes to both standing stock and depth of habitation (DOH) in sediment following the 2010 Macondo well blowout. Push cores were taken from the middle marsh at sites classified as unoiled, lightly oiled, and heavily oiled based on concentrations of total polycyclic aromatic hydrocarbons ([TPAH]). Cores were sliced and stained with rose Bengal to detect live specimens of foraminifera. Short-term, sediment-mixing depths were determined using the penetration depths of excess (234)Th, and sedimentary organic carbon and carbonate were measured to distinguish depositional environments. Marsh foraminifera reacted to the highest oil concentration (5,000-18,000 ng/g of TPAH) by reducing standing stock and shortening the DOH compared with the control sites. At a second, less heavily oiled site, foraminifera responded with a shallower DOH, but with a boom in standing stock. Deformed, dead foraminifera occurred in all heavily oiled cores-but not elsewhere. Live foraminifera responded with a population boom at lightly oiled sites with [TPAH] near 1,100 ng/g. Changes in standing stock and DOH with [TPAH] suggest disturbance to the marsh food web, apparently due to oil pollution, and support the use of foraminifera as sentinel species.

Sodium channels and mammalian sensory mechanotransduction.

BACKGROUND: Members of the degenerin/epithelial (DEG/ENaC) sodium channel family are mechanosensors in C elegans, and Nav1.7 and Nav1.8 voltage-gated sodium channel knockout mice have major deficits in mechanosensation. ß and γENaC sodium channel subunits are present with acid sensing ion channels (ASICs) in mammalian sensory neurons of the dorsal root ganglia (DRG). The extent to which epithelial or voltage-gated sodium channels are involved in transduction of mechanical stimuli is unclear. RESULTS: Here we show that deleting ß and γENaC sodium channels in sensory neurons does not result in mechanosensory behavioural deficits. We had shown previously that Nav1.7/Nav1.8 double knockout mice have major deficits in behavioural responses to noxious mechanical pressure. However, all classes of mechanically activated currents in DRG neurons are unaffected by deletion of the two sodium channels. In contrast, the ability of Nav1.7/Nav1.8 knockout DRG neurons to generate action potentials is compromised with 50% of the small diameter sensory neurons unable to respond to electrical stimulation in vitro. CONCLUSION: Behavioural deficits in Nav1.7/Nav1.8 knockout mice reflects a failure of action potential propagation in a mechanosensitive set of sensory neurons rather than a loss of primary transduction currents. DEG/ENaC sodium channels are not mechanosensors in mouse sensory neurons.