An analysis of Nepal's Draft Mental Health Acts 2006-2017: competing values and power.

This qualitative study maps the process of drafting and consulting on Nepal's mental health legislation from 2006 to 2017. A total of 14 people were interviewed and interviews were analysed thematically. These themes were subsequently interpreted in light of Shiffman and Smith's policy analysis framework, as the process was found to be at the agenda-setting stage. Two groups of actors were identified with different views on appropriate policy content and how the policy process should be conducted. The first group included psychiatrists who initiated and controlled the drafting process and who did not consider people with psychosocial disabilities to be equal partners. The psychiatrists viewed forced detention and treatment as upholding people's right to health and lobbied the Ministry of Health and Population (MoHP) to pass the draft acts to parliament. The second included the rights-based civil society actors and lawyers who saw the right to equality before the law as of utmost priority, opposed forced detention and treatment, and actively blocked the draft acts at the MoHP. There is no clear legal definition of mental health and illness in Nepal, legal and mental capacity are not differentiated, and people with mental and behavioural conditions are assumed to lack capacity. The analysis indicates that there were few favourable conditions to support the progression of this policy into law. It is unclear whether the drafters or blockers will prevail in the future, but we predict that professionals will continue to have more input into content than service users due to national policy dynamics.

Implementing global positioning system trackers for people with dementia who are at risk of wandering.

OBJECTIVE: The main aim of this study was to evaluate the feasibility and acceptability of using a GPS tracker to mitigate the risks associated with wandering for people with dementia and those caring for them and further evaluate the impact of trackers in delaying 24-hour care and the potential for reducing the involvement of support services, such as the police, in locating patients. METHODS: We recruited forty-five wearers-carers dyads, and a GPS tracker was issued to each participant. Dyads completed pre-and post-outcome questionnaires after six months, and a use-log of experiences was maintained through monthly monitoring calls. At six months, focus groups were conducted with 14 dyads where they shared ideas and learning. Data analyses were performed on outcome questionnaires, use-log analysis, and focus groups discussion. RESULTS: A 24% (N = 14) attrition rate was recorded, with 76% (N = 34) of the participants completing pre- and post-outcome questionnaires, of which 41% (N = 14) attended four focus group meetings. Participants reported enhanced independence for wearers as fewer restrictions were placed on their movements, peace of mind and reduced burden for the carers with less need to involve police or social services, and delays in 24-hour care. CONCLUSION: The results supported the feasibility of routine implementation of GPS trackers in dementia care with clear guidance, monitoring and support to family carers on safe use. This could delay admission into 24-hour care as wearers and carers have a greater sense of safety and are better connected should help be required. Studies with larger sample sizes, diverse participants and health economic analysis are needed to develop the evidence base further ahead of the routine implementation of GPS trackers in health and social care services.

Psychotropic Medication Administration in Pediatric Emergency Departments.

BACKGROUND AND OBJECTIVES: Visits by youth to the emergency department (ED) with mental and behavioral health (MBH) conditions are increasing, yet use of psychotropic medications during visits has not been well described. We aimed to assess changes in psychotropic medication use over time, overall and by medication category, and variation in medication administration across hospitals. METHODS: We conducted a retrospective cross-sectional study of ED encounters by youth aged 3-21 with MBH diagnoses using the Pediatric Health Information System, 2013-2022. Medication categories included psychotherapeutics, stimulants, anticonvulsants, antihistamines, antihypertensives, and other. We constructed regression models to examine trends in use over time, overall and by medication category, and variation by hospital. RESULTS: Of 670 911 ED encounters by youth with a MBH diagnosis, 12.3% had psychotropic medication administered. The percentage of MBH encounters with psychotropic medication administered increased from 7.9% to16.3% from 2013-2022 with the odds of administration increasing each year (odds ratio, 1.09; 95% confidence interval, 1.05-1.13). Use of all medication categories except for antianxiety medications increased significantly over time. The proportion of encounters with psychotropic medication administered ranged from 4.2%-23.1% across hospitals (P < .001). The number of psychotropic medications administered significantly varied from 81 to 792 medications per 1000 MBH encounters across hospitals (P < .001). CONCLUSIONS: Administration of psychotropic medications during MBH ED encounters is increasing over time and varies across hospitals. Inconsistent practice patterns indicate that opportunities are available to standardize ED management of pediatric MBH conditions to enhance quality of care.

Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency.

ABSTRACT: Pyruvate kinase (PK) deficiency is a rare, hereditary disease characterized by chronic hemolytic anemia. Iron overload is a common complication regardless of age, genotype, or transfusion history. Mitapivat, an oral, allosteric PK activator, improves anemia and hemolysis in adult patients with PK deficiency. Mitapivat's impact on iron overload and ineffective erythropoiesis was evaluated in adults with PK deficiency who were not regularly transfused in the phase 3 ACTIVATE trial and long-term extension (LTE) (#NCT03548220/#NCT03853798). Patients in the LTE received mitapivat throughout ACTIVATE/LTE (baseline to week 96; mitapivat-to-mitapivat [M/M] arm) or switched from placebo (baseline to week 24) to mitapivat (week 24 to week 96; placebo-to-mitapivat [P/M] arm). Changes from baseline in markers of iron overload and erythropoiesis were assessed to week 96. Improvements in hepcidin (mean, 4770.0 ng/L; 95% confidence interval [CI], -1532.3 to 11 072.3), erythroferrone (mean, -9834.9 ng/L; 95% CI, -14 328.4 to -5341.3), soluble transferrin receptor (mean, -56.0 nmol/L; 95% CI, -84.8 to -27.2), and erythropoietin (mean, -32.85 IU/L; 95% CI, -54.65 to -11.06) were observed in the M/M arm (n = 40) from baseline to week 24, sustained to week 96. No improvements were observed in the P/M arm (n = 40) to week 24; however, upon transitioning to mitapivat, improvements similar to those observed in the M/M arm were seen. Mean changes from baseline in liver iron concentration by magnetic resonance imaging at week 96 in the M/M arm and the P/M arm were -2.0 mg Fe/g dry weight (dw; 95% CI, -4.8 to -0.8) and -1.8 mg Fe/g dw (95% CI, -4.4 to 0.80), respectively. Mitapivat is the first disease-modifying pharmacotherapy shown to have beneficial effects on iron overload and ineffective erythropoiesis in patients with PK deficiency. This trial was registered at www.ClinicalTrials.gov as #NCT03548220 (ACTIVATE) and #NCT03853798 (LTE).

Luspatercept stimulates erythropoiesis, increases iron utilization, and redistributes body iron in transfusion-dependent thalassemia.

Luspatercept, a ligand-trapping fusion protein, binds select TGF-ß superfamily ligands implicated in thalassemic erythropoiesis, promoting late-stage erythroid maturation. Luspatercept reduced transfusion burden in the BELIEVE trial (NCT02604433) of 336 adults with transfusion-dependent thalassemia (TDT). Analysis of biomarkers in BELIEVE offers novel physiological and clinical insights into benefits offered by luspatercept. Transfusion iron loading rates decreased 20% by 1.4 g (~7 blood units; median iron loading rate difference: -0.05 ± 0.07 mg Fe/kg/day, p< .0001) and serum ferritin (s-ferritin) decreased 19.2% by 269.3 ± 963.7 µg/L (p < .0001), indicating reduced macrophage iron. However, liver iron content (LIC) did not decrease but showed statistically nonsignificant increases from 5.3 to 6.7 mg/g dw. Erythropoietin, growth differentiation factor 15, soluble transferrin receptor 1 (sTfR1), and reticulocytes rose by 93%, 59%, 66%, and 112%, respectively; accordingly, erythroferrone increased by 51% and hepcidin decreased by 53% (all p < .0001). Decreased transfusion with luspatercept in patients with TDT was associated with increased erythropoietic markers and decreasing hepcidin. Furthermore, s-ferritin reduction associated with increased erythroid iron incorporation (marked by sTfR1) allowed increased erythrocyte marrow output, consequently reducing transfusion needs and enhancing rerouting of hemolysis (heme) iron and non-transferrin-bound iron to the liver. LIC increased in patients with intact spleens, consistent with iron redistribution given the hepcidin reduction. Thus, erythropoietic and hepcidin changes with luspatercept in TDT lower transfusion dependency and may redistribute iron from macrophages to hepatocytes, necessitating the use of concomitant chelator cover for effective iron management.

Disadvantaged Neighborhoods Continue to Bear the Burden of Gun Violence.

INTRODUCTION: Gun violence is a pervasive and dynamic public health crisis causing substantial burden on communities and healthcare systems in the United States. Risk factor and outcome analyses are crucial to develop effective interventions. The aim of this study was to assess firearm injury in a diverse community setting as it relates to neighborhood socioeconomic disadvantage and changes over time following large-scale local interventions. METHODS: All county residents with firearm injury presenting to a Level 1 Trauma Center from January 2012 to December 2021 were retrospectively reviewed. Area Deprivation Index (ADI) was used to measure neighborhood socioeconomic disadvantage based on a nine-digit zip code at patients' home address. Injuries were also stratified by 5-year time periods, 2012-2016 and 2017-2021. Demographics and clinical data were analyzed including injury severity, hospital course, and discharge location. Data were compared by ADI quintile and between time periods using chi-squared, one-way analysis of variance, and Cochran-Armitage test. RESULTS: A total of 1044 injuries were evaluated. Patients were 93% male with mean age of 29 y (standard deviation 10.2) and were concentrated in the most disadvantaged neighborhoods (74% ADI Q5). Black or African American race was greater in the most disadvantaged ADI groups (76% versus 47%-66%; P <0.001). Percentage of total injuries in the most disadvantaged ADI group rose from 71% to 78% over time (P = 0.006). Mortality occurred in 154 (15%) patients overall, while most (71%) were discharged to home. Mortality declined from 18% to 11% over time (P <0.001). Medicaid utilization rose from 42% to 77% alongside a decrease in self-pay status from 44% to 4% (P <0.001). There were no clinically significant group differences in injury severity or clinical characteristics. CONCLUSIONS: Firearm injury remains concentrated in the most socioeconomically disadvantaged neighborhoods, and this disparity is increasing over time. Medicaid utilization rose and mortality decreased in this population over time. This research presents a method to inform and monitor local gun violence interventions using ADI to address public health equity.

Optical and x-ray characterization of the Daedalus ultrafast x-ray imager.

The Daedalus ultrafast x-ray imager is the latest generation in Sandia's hybrid CMOS detector family. With three frames along an identical line of sight, 1 ns minimum integration time, a higher full well than Icarus, and added features, Daedalus brings exciting new capabilities to diagnostic applications in inertial confinement fusion and high energy density science. In this work, we present measurements of time response, dynamic range, spatial uniformity, pixel cross-talk, and absolute x-ray sensitivity using pulsed optical and x-ray sources. We report a measured 1.5 Me- full well, pixel sensitivity at 9.58 × 10-7 V/e-, and an estimate of spatial uniformity at ∼5% across the sensor array.

Early Mobilization, Early Ambulation, and Burn Therapy in the Acute Hospital Setting.

Rehabilitation therapies in the burn acute care environment continue to evolve. Immediate access to therapy is considered standard, and therapy is a key component of the transprofessional care team. Early positioning, edema management, and therapy care in the intensive care unit (ICU) environment can limit later complications; mobility in the ICU can be engaged safely using a systems-based approach in the absence of nondirectable agitation. Later in the course of acute care, early ambulation is an appropriate intervention that can improve outcomes.

What is the Role of Whole Blood Transfusions on Trauma Patients?

Whole blood use in trauma has historically been limited to military use, but in recent years, there has been increasing data for use in civilian trauma. Emerging clinical data demonstrate an associated survival benefit, while some authors have also identified decreased use of an overall number of blood products and decreased complications. Use of whole blood is gradually moving toward becoming the standard of care in the hemorrhaging trauma patient.

SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers.

SLN124, an N-acetylgalactosamine conjugated 19-mer short interfering RNA, is being developed to treat iron-loading anemias (including beta-thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first-in-human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1.0, 3.0, and 4.5 mg/kg) in healthy volunteers. Twenty-four participants were randomized in three sequential cohorts of eight subjects, each to receive a single dose of either SLN124 or placebo (6:2 randomization), administered subcutaneously. There were no serious or severe adverse events, or discontinuations due to adverse events, and most treatment-emergent adverse events were mild, including transient mild injection site reactions, resolving without intervention. SLN124 was rapidly absorbed, with a median tmax of 4-5 h across all treatment groups, and largely eliminated from plasma by 48 h. Plasma concentrations increased in a greater than dose proportional fashion between treatment groups. In all SLN124 groups, a dose-related effect was observed across iron metabolism markers, and across erythroid markers, SLN124 resulted in increased plasma hepcidin levels, peaking around Day 29, and consequent dose-related sustained reductions in plasma iron and transferrin saturation with decreased reticulocyte production, MCHC, and MCV. Results suggest duration of action lasting up to 56 days after a single SLN124 dose, on hepcidin and hematological parameters of iron metabolism (serum iron and TSAT).

Diagnosis and Management of Pneumonia in Infants Less Than 90 Days of Age.

BACKGROUND: Current guidelines and recent studies on pediatric pneumonia pertain to children older than 3 months of age. Little information exists regarding the diagnostic evaluation, management, and outcomes of infants less than 90 days with pneumonia. METHODS: We compared infants <90 days of age diagnosed with pneumonia across 38 US children's hospitals from 2016 to 2021 to children 90 days to 5 years of age. We evaluated whether differences exist in patient characteristics, diagnostic testing, antibiotic treatment, and outcomes between young infants and older children. Additionally, we assessed seasonal variability and trends over time in pneumonia diagnoses by age group. RESULTS: Among 109 796 children diagnosed with pneumonia, 3128 (2.8%) were <90 days of age. Compared with older children, infants <90 days had more laboratory testing performed (88.6% vs 48.8%, P < .001; median number of laboratory tests 4 [interquartile range: 2-5] vs 0 [interquartile range: 0-3] respectively), with wide variation in testing across hospitals. Chest radiograph utilization did not differ by age group. Infants <90 days were more likely to be hospitalized and require respiratory support than older children. Seasonal variation was observed for pneumonia encounters in both age groups. CONCLUSIONS: Infants <90 days with pneumonia were more likely to undergo laboratory testing, be hospitalized, and require respiratory support than children 90 days to 5 years of age. This may reflect inherent differences in the pathophysiology of pneumonia by age, the manner in which pneumonia is diagnosed, or possible overuse of testing in infants.

Emergency Care Utilization for Mental and Sexual Health Concerns Among Adolescents Following Sexual Assault: A Retrospective Cohort Study.

PURPOSE: This study aimed to explore the health outcomes of adolescent survivors of sexual assault, as measured by subsequent emergency department (ED) utilization for mental and sexual health concerns. METHODS: This retrospective cohort study used the Pediatric Health Information System (PHIS) database. We included patients aged 11-18 years seen at a PHIS hospital with a primary diagnosis of sexual assault. The control group included age- and sex-matched patients seen for an injury. Participants were followed in PHIS for 3-10 years; subsequent ED visits for suicidality, sexually transmitted infection, pelvic inflammatory disease (PID), or pregnancy were identified, and likelihoods of each were compared using Cox proportional hazards models. RESULTS: The study population included 19,706 patients. ED return visit rates in the sexual assault and control groups were 7.9% versus 4.1% for suicidality, 1.8% versus 1.4% for sexually transmitted infection, 2.2% versus 0.8% for PID, and 1.7% versus 1.0% for pregnancy, respectively. Compared to controls, sexual assault patients were significantly more likely to return to the ED for suicidality throughout the follow-up period, with the highest hazard ratio of 6.31 (95% confidence interval 4.46-8.94) during the first 4 months. Sexual assault patients also had higher likelihood of returning for PID (hazard ratio 3.80, 95% confidence interval 3.07-4.71) throughout the follow-up period. DISCUSSION: Adolescents seen in the ED for sexual assault were significantly more likely to return to the ED for suicidality and sexual health concerns, highlighting the need for increased allocation of research and clinical resources to improve their care.

OUTCOMES OF MISSED DIAGNOSIS OF PEDIATRIC APPENDICITIS, NEW-ONSET DIABETIC KETOACIDOSIS, AND SEPSIS IN FIVE PEDIATRIC HOSPITALS.

BACKGROUND: Missed diagnosis can predispose to worse condition-specific outcomes. OBJECTIVE: To determine 90-day complication rates and hospital utilization after a missed diagnosis of pediatric appendicitis, new-onset diabetic ketoacidosis (DKA), and sepsis. METHODS: We evaluated patients under 21 years of age visiting five pediatric emergency departments (EDs) with a study condition. Case patients had a preceding ED visit within 7 days of diagnosis and underwent case review to confirm a missed diagnosis. Control patients had no preceding ED visit. We compared complication rates and utilization between case and control patients after adjusting for age, sex, and insurance. RESULTS: We analyzed 29,398 children with appendicitis, 5366 with DKA, and 3622 with sepsis, of whom 429, 33, and 46, respectively, had a missed diagnosis. Patients with missed diagnosis of appendicitis or DKA had more hospital days and readmissions; there were no significant differences for those with sepsis. Those with missed appendicitis were more likely to have abdominal abscess drainage (adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 2.4-3.6) or perforated appendicitis (aOR 3.1, 95% CI 2.5-3.8). Those with missed DKA were more likely to have cerebral edema (aOR 4.6, 95% CI 1.5-11.3), mechanical ventilation (aOR 13.4, 95% CI 3.8-37.1), or death (aOR 28.4, 95% CI 1.4-207.5). Those with missed sepsis were less likely to have mechanical ventilation (aOR 0.5, 95% CI 0.2-0.9). Other illness complications were not significantly different by missed diagnosis. CONCLUSIONS: Children with delayed diagnosis of appendicitis or new-onset DKA had a higher risk of 90-day complications and hospital utilization than those with a timely diagnosis.

Health-related quality of life in patients with ß-thalassemia: Data from the phase 3 BELIEVE trial of luspatercept.

BACKGROUND: Patients with transfusion-dependent (TD) ß-thalassemia require long-term red blood cell transfusions (RBCTs) that lead to iron overload, impacting health-related quality of life (HRQoL). METHODS: The impact of luspatercept, a first-in-class erythroid maturation agent, versus placebo on HRQoL of patients with TD ß-thalassemia was evaluated in the phase 3 BELIEVE trial. HRQoL was assessed at baseline and every 12 weeks using the 36-item Short Form Health Survey (SF-36) and Transfusion-dependent Quality of Life questionnaire (TranQol). Mean change in HRQoL was evaluated from baseline to week 48 for patients receiving luspatercept + best supportive care (BSC) and placebo + BSC and between luspatercept responders and non-responders. RESULTS: Through week 48, for both groups, mean scores on SF-36 and TranQol domains were stable over time and did not have a clinically meaningful change. At week 48, more patients who achieved clinical response (≥50% reduction in RBCT burden over 24 weeks) in the luspatercept + BSC group had improvement in SF-36 Physical Function compared with placebo + BSC (27.1% vs. 11.5%; p = .019). CONCLUSIONS: Luspatercept + BSC reduced transfusion burden while maintaining patients' HRQoL. HRQoL domain improvements from baseline through 48 weeks were also enhanced for luspatercept responders.

India and its pluralistic health system - a new philosophy for Universal Health Coverage.

In this article we attempt to put forth insights into using traditional medicine (TM) systems to achieve Universal Health Coverage (UHC). We discuss the need for reimagining India's health system and the importance of an inclusive approach for UHC. We comprehend the challenges with appropriate use of TM systems and the lessons from international experience of integrating TM systems. We highlight the pathways for better utilization of TM systems for UHC in India.

The Bottom Line: Trauma Center Viability During COVID-19.

INTRODUCTION: The COVID-19 pandemic was a potential threat to the viability of trauma centers and health systems in general. We sought to answer the question of how COVID-19 was associated with patient characteristics as well as trauma center volume, finances, and viability. METHODS: We reviewed 6375 patients admitted to our verified Level 1 trauma center during two time periods: pre-COVID (February 2019-February 2020) and COVID (March 2020-March 2021). Three thousand ninety-nine patients were admitted pre-COVID and 3276 were admitted during COVID. Data including case-mix index (CMI), total contribution margin, insurance status, age, race, gender, ethnicity, and injury mechanism were collected from the trauma registry and finance databases and analyzed. A P < 0.05 was considered significant. RESULTS: Trauma admissions decreased initially during COVID but returned to and ultimately surpassed admission trends pre-COVID. Trauma revenue and patient acuity increased significantly along with a decrease in the number of underinsured patients during COVID. When evaluating all service lines, the trauma center was the highest contributor to overall hospital revenue. CONCLUSIONS: Despite a decrease in admissions for other service lines and a pause in elective surgeries during the pandemic, the trauma center remained unaffected. In addition, trauma was the most significant contributor to the bottom line of the health system. These findings underscore the need to maintain and even increase trauma center resources and staffing to ensure that optimal care is provided to critically ill and injured patients.

Trends and Variation in Pediatric Anaphylaxis Care From 2016 to 2022.

BACKGROUND: Variation in the use of treatments and hospitalization for anaphylaxis would suggest a lack of consensus in therapeutic approach. OBJECTIVE: To evaluate trends and practice variation in the emergency department (ED) care of children with anaphylaxis in a large US cohort. METHODS: We conducted a 48-site retrospective cohort study using the Pediatric Health Information System from January 2016 through September 2022. Children younger than 18 years with a primary diagnosis of anaphylaxis were included. Care trends were assessed using negative binomial regression modeling. Rates of medication use, hospitalizations, and revisits were reported as medians with interquartile ranges (IQRs). RESULTS: There were 42,909 ED visits for anaphylaxis, with a 4.2% per-year increase in visit incidence (95% CI, 1.8-6.7) during the study period. The median hospitalization rate was 3.5% (IQR, 2.2-6.0), and the 3-day ED revisit rate was 0.6% (IQR, 0.4-0.9). The hospital-level median use of therapies included intramuscular epinephrine (55.3%; IQR, 50.1-59.9), systemic steroids (73.8%; IQR, 63.9-81.4), antihistamines (59.9%; IQR, 53.5-65.5), H2-receptor antagonists (56.8%; IQR, 42.3-66.2), bronchodilators (15.1%; IQR, 12.5-17.0), inhaled epinephrine (1.1%; IQR, 0.6-1.9), and fluid boluses (19.8%; IQR, 11.3-29.3). Severe reactions requiring intensive care unit admission (1.5%; IQR, 0.8-2.2), vasopressors (0.3%; IQR, 0.0-0.6), and intubation (0.2%; IQR, 0.0-0.3) were rare. CONCLUSIONS: ED visits for anaphylaxis increased during the study period, but hospitalization rates were low. Substantial variation exists between EDs regarding the use of anaphylaxis therapies, supporting the need for future research to evaluate the efficacy of these medications.

Whole Blood Resuscitation is Safe in Pediatric Trauma Patients: A Multicenter Study.

INTRODUCTION: Whole blood (WB) resuscitation has been associated with a mortality benefit in trauma patients. Several small series report the safe use of WB in the pediatric trauma population. We performed a subgroup analysis of the pediatric patients from a large prospective multicenter trial comparing patients receiving WB or blood component therapy (BCT) during trauma resuscitation. We hypothesized that WB resuscitation would be safe compared to BCT resuscitation in pediatric trauma patients. METHODS: This study included pediatric trauma patients (0-17 y), from ten level-I trauma centers, who received any blood transfusion during initial resuscitation. Patients were included in the WB group if they received at least one unit of WB during their resuscitation, and the BCT group was composed of patients receiving traditional blood product resuscitation. The primary outcome was in-hospital mortality with secondary outcomes being complications. Multivariate logistic regression was performed to assess for mortality and complications in those treated with WB vs BCT. RESULTS: Ninety patients, with both penetrating and blunt mechanisms of injury (MOI), were enrolled in the study (WB: 62 (69%), BCT: 28 (21%)). Whole blood patients were more likely to be male. There were no differences in age, MOI, shock index, or injury severity score between groups. On logistic regression, there was no difference in complications. Mortality was not different between the groups (P = .983). CONCLUSION: Our data suggest WB resuscitation is safe when compared to BCT resuscitation in the care of critically injured pediatric trauma patients.