Outcomes of Invasive and Noninvasive Ventilation in a Haitian Emergency Department.

Background: Limited data exist on the outcomes of patients requiring invasive ventilation or noninvasive positive pressure ventilation (NIPPV) in low-income countries. To our knowledge, no study has investigated this topic in Haiti. Objectives: We describe the clinical epidemiology, treatment, and outcomes of patients requiring NIPPV or intubation in an emergency department (ED) in rural Haiti. Methods: This is an observational study utilizing a convenience sample of adult and pediatric patients requiring NIPPV or intubation in the ED at an academic hospital in central Haiti from January 2019-February 2021. Patients were prospectively identified at the time of clinical care. Data on demographics, clinical presentation, management, and ED disposition were extracted from patient charts using a standardized form and analyzed in SAS v9.4. The primary outcome was survival to discharge. Findings: Of 46 patients, 27 (58.7%) were female, mean age was 31 years, and 14 (30.4%) were pediatric (age <18 years). Common diagnoses were cardiogenic pulmonary edema, pneumonia/pulmonary sepsis, and severe asthma. Twenty-three (50.0%) patients were initially treated with NIPPV, with 4 requiring intubation; a total of 27 (58.7%) patients were intubated. Among those for whom intubation success was documented, first-pass success was 57.7% and overall success was 100% (one record missing data); intubation was associated with few immediate complications. Twenty-two (47.8%) patients died in the ED. Of the 24 patients who survived, 4 were discharged, 19 (intubation: 12; NIPPV: 9) were admitted to the intensive care unit or general ward, and 1 was transferred. Survival to discharge was 34.8% (intubation: 22.2%; NIPPV: 52.2%); 1 patient left against medical advice following admission. Conclusions: Patients with acute respiratory failure in this Haitian ED were successfully treated with both NIPPV and intubation. While overall survival to discharge remains relatively low, this study supports developing capacity for advanced respiratory interventions in low-resource settings.

A Successful Model of Expedited Antiretroviral Therapy for Clinically Stable Patients Living With HIV in Haiti.

BACKGROUND: Recommendations for universal antiretroviral therapy have greatly increased the number of HIV-infected patients who qualify for treatment, particularly with early clinical disease. Less intensive models of care are needed for clinically stable patients. SETTING: A rapid pathway (RP) model of expedited outpatient care for clinically stable patients was implemented at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) Center, Port-au-Prince, Haiti. Expedited visits included nurse-led assessments and point-of-service antiretroviral therapy dispensing. METHODS: We conducted a retrospective analysis including patients who initiated RP care between June 1, 2014, and September 30, 2015, comparing outcomes of patients with timely visit attendance (never >3 days late) with patients with ≥1 nontimely visit within 6 months before RP enrollment. We calculated retention in care and adherence at 12 months, and assessed predictors of both outcomes. RESULTS: Of the 2361 patients who initiated RP care during the study period, 1429 (61%) had timely visit attendance and 932 (39%) had ≥1 nontimely visit before RP enrollment. Among RP-enrolled patients, 94% were retained at 12 months and 75% had ≥90% adherence, with higher proportions in those with timely pre-RP visits (95% vs. 92%; 87% vs. 55%). In multivariable analysis, pre-RP visit timeliness was associated with both retention (adjusted odds ratio: 1.67; 95% confidence interval: 1.08 to 2.59) and adherence (adjusted odds ratio: 4.53; 95% confidence interval: 3.58 to 5.72). CONCLUSIONS: RP care was associated with high levels of retention and adherence for clinically stable patients. Timeliness of pre-RP visits was predictive of outcomes after RP initiation.

Activity-based costing of health-care delivery, Haiti.

OBJECTIVE: To evaluate the implementation of a time-driven activity-based costing analysis at five community health facilities in Haiti. METHODS: Together with stakeholders, the project team decided that health-care providers should enter start and end times of the patient encounter in every fifth patient's medical dossier. We trained one data collector per facility, who manually entered the time recordings and patient characteristics in a database and submitted the data to a cloud-based data warehouse each week. We calculated the capacity cost per minute for each resource used. An automated web-based platform multiplied reported time with capacity cost rate and provided the information to health-facilities administrators. FINDINGS: Between March 2014 and June 2015, the project tracked the clinical services for 7162 outpatients. The cost of care for specific conditions varied widely across the five facilities, due to heterogeneity in staffing and resources. For example, the average cost of a first antenatal-care visit ranged from 6.87 United States dollars (US$) at a low-level facility to US$ 25.06 at a high-level facility. Within facilities, we observed similarly variation in costs, due to factors such as patient comorbidities, patient arrival time, stocking of supplies at facilities and type of visit. CONCLUSION: Time-driven activity-based costing can be implemented in low-resource settings to guide resource allocation decisions. However, the extent to which this information will drive observable changes at patient, provider and institutional levels depends on several contextual factors, including budget constraints, management, policies and the political economy in which the health system is situated.

Healthcare Resource Use, Costs, and Disease Progression Associated with Diabetic Nephropathy in Adults with Type 2 Diabetes: A Retrospective Observational Study.

INTRODUCTION: Diabetic nephropathy (DN) is a progressive kidney disease resulting as a complication of diabetes mellitus. This study evaluated the disease progression and economic burden of DN among commercially insured patients with type 2 diabetes in the USA. METHODS: The research design was a retrospective observational study based on healthcare claims data. The Truven MarketScan Databases (2004-2014) were queried for adults with type 2 diabetes with at least one urine albumin test (index, randomly selected) after diagnosis and at least one test after the index. On the basis of the index test, patients were classified into normoalbuminuria, microalbuminuria, or macroalbuminuria groups. Nephropathy-related treatment use was measured in the 6 months after the index, disease progression was assessed from the index to the end of data availability, and annual all-cause and nephropathy-related costs and healthcare resource use (HRU) were assessed up to 2 years from the index. Outcomes were compared between any two groups, controlling for baseline demographics. RESULTS: A total of 23,235 patients were identified and classified into normoalbuminuria (N = 18,409), microalbuminuria (N = 3863), or macroalbuminuria (N = 963) groups. Patients with albuminuria were more likely to be older, male, and have a higher burden of baseline comorbidities and HRU. Within 6 months following the index, 12-20% of patients with albuminuria were not treated with any relevant recommended treatment. Compared to the normoalbuminuria group, patients with macroalbuminuria had a significantly greater risk of disease progression (hazard ratio [HR] = 1.44), and both albuminuria groups were more likely to require dialysis (HR = 4.23 and 40.14 for micro- and macroalbuminuria, respectively; all p < 0.05). Annual all-cause (2016 US dollars, $3580 and $12,830 higher for micro- and macroalbuminuria vs. normoalbuminuria, respectively) and nephropathy-related ($362 and $3716) costs increased significantly with increasing nephropathy severity, consistent with the trend in increased HRU. CONCLUSIONS: Diabetic nephropathy may be undertreated or inappropriately treated. It was also associated with significantly higher costs, HRU, and risk of disease progression among commercially insured patients with type 2 diabetes in the USA. FUNDING: Takeda Development Center Americas, Inc.

Clinical Outcomes Associated with Switching or Discontinuation from Anti-TNF Inhibitors for Nonmedical Reasons.

PURPOSE: This study evaluated clinical outcomes and health care resource utilization associated with nonmedical switching from or discontinuation of anti-tumor necrosis factor (TNF) therapies in US clinical practice. METHODS: Responding physicians extracted data from the medical charts of patients with Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, or psoriatic arthritis who achieved response on an anti-TNF therapy. Physicians selected 2 cohorts of patients that were matched on diagnosis: patients who were switched/discontinued, for nonmedical reasons, from the anti-TNF therapy on which they achieved response (switchers/discontinuers), and patients who continued on their anti-TNF (continuers). Switchers/discontinuers were followed up for 12 months from the date of discontinuation (index date); continuers were followed up for 12 months from the date of an office visit within 2 months of the matched switcher/discontinuer׳s index date. Multivariate regression was used to compare disease flares, disease control, and health care resource utilization between cohorts, with adjustment for baseline characteristics. Subgroup analyses compared data from the continuer cohort to those from (1) patients who were switched to another biologic therapy and (2) patients who were switched to conventional therapy or discontinued from all therapy. FINDINGS: A total of 377 matched pairs of continuers and switchers/discontinuers were analyzed (N = 754), with the latter cohort comprising 284 patients (73.3%) who were and 93 (24.7%) who did not switch to another treatment (biologic or conventional treatment) immediately after discontinuation. Switchers/discontinuers had more frequent flares than did continuers, across severity levels (adjusted incidence rate ratios = 1.67, 2.36, and 3.48 for mild, moderate, and severe flares, respectively; all, P < 0.05). Switchers/discontinuers had a lower rate of well-controlled disease symptoms (46.9% vs 88.1%; adjusted odds ratio = 0.11; P < 0.001). Switchers/discontinuers also had more frequent inpatient hospitalizations, emergency department visits, and outpatient visits (adjusted incidence rate ratios = 3.58, 5.73, and 1.12, respectively; all, P < 0.001). Findings from the subgroup analyses of data from the 183 patients who switched to a biologic therapy and 194 who switched to conventional therapy or discontinued from all therapy were largely consistent with the overall analysis. IMPLICATIONS: In this study, switching/discontinuation from an anti-TNF therapy for nonmedical reasons was associated with significantly worse clinical outcomes and increased health care resource utilization-factors that should be considered when developing treatment algorithms.

Real-World Analysis of Medical Costs and Healthcare Resource Utilization in Elderly Women with HR+/HER2- Metastatic Breast Cancer Receiving Everolimus-Based Therapy or Chemotherapy.

INTRODUCTION: The objective of this study was to analyze medical costs and healthcare resource utilization (HRU) associated with everolimus-based therapy or chemotherapy among elderly women with hormone-receptor-positive, human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC). METHODS: Elderly women (≥65 years) with HR+/HER2- mBC who failed a non-steroidal-aromatase-inhibitor and subsequently began a new line of treatment with everolimus-based therapy or chemotherapy for mBC (index therapy) during July 20, 2012 to March 31, 2014 were identified from two large commercial claims databases. All-cause, BC-, and adverse event (AE)-related medical costs (2014 USD), and all-cause and AE-related HRU per patient per month (PPPM) were compared between patients treated with everolimus-based therapy and chemotherapy across their first four lines of therapy for mBC. Adjusted costs and HRU differences were estimated by pooling all lines and using multivariable models adjusted for differences in patient characteristics. RESULTS: In total, 925 elderly patients (mean age approximately 73 years) with HR+/HER2- mBC met the inclusion criteria; 230 received everolimus-based therapy (240 lines) and 737 received chemotherapy (939 lines). Compared with chemotherapy, everolimus-based therapy was associated with significantly lower total all-cause PPPM medical services costs (adjusted mean difference: $4007), driven by lower inpatient ($1994) and outpatient ($1402) costs; lower BC-related medical services costs ($3129), driven by both BC-related inpatient ($1883) and outpatient costs ($913); and lower AE-related medical services costs ($1873; all P < 0.01). Additionally, compared to patients treated with chemotherapy, patients treated with everolimus-based therapy had fewer all-cause outpatient visits (adjusted incidence rate ratio = 0.69), BC-related outpatient visits (0.66), other-medical-service visits (0.65), and AE-related HRU (0.59), which was driven by significantly fewer AE-related outpatient visits (0.56; all P < 0.01). Subgroup analyses comparing medical costs of everolimus-based therapy with capecitabine monotherapy showed consistent results overall. CONCLUSION: This retrospective claims database analysis of elderly women with HR+/HER2- mBC in the United States showed that everolimus-based therapy was associated with significantly lower all-cause, BC-related, and AE-related medical services costs and less use of healthcare resources compared with chemotherapy. FUNDING: Novartis.

Rethinking the cost of healthcare in low-resource settings: the value of time-driven activity-based costing.

Low-income and middle-income countries account for over 80% of the world's infectious disease burden, but <20% of global expenditures on health. In this context, judicious resource allocation can mean the difference between life and death, not just for individual patients, but entire patient populations. Understanding the cost of healthcare delivery is a prerequisite for allocating health resources, such as staff and medicines, in a way that is effective, efficient, just and fair. Nevertheless, health costs are often poorly understood, undermining effectiveness and efficiency of service delivery. We outline shortcomings, and consequences, of common approaches to estimating the cost of healthcare in low-resource settings, as well as advantages of a newly introduced approach in healthcare known as time-driven activity-based costing (TDABC). TDABC is a patient-centred approach to cost analysis, meaning that it begins by studying the flow of individual patients through the health system, and measuring the human, equipment and facility resources used to treat the patients. The benefits of this approach are numerous: fewer assumptions need to be made, heterogeneity in expenditures can be studied, service delivery can be modelled and streamlined and stronger linkages can be established between resource allocation and health outcomes. TDABC has demonstrated significant benefits for improving health service delivery in high-income countries but has yet to be adopted in resource-limited settings. We provide an illustrative case study of its application throughout a network of hospitals in Haiti, as well as a simplified framework for policymakers to apply this approach in low-resource settings around the world.

Pharmacological validation of Trypanosoma brucei phosphodiesterases B1 and B2 as druggable targets for African sleeping sickness.

Neglected tropical disease drug discovery requires application of pragmatic and efficient methods for development of new therapeutic agents. In this report, we describe our target repurposing efforts for the essential phosphodiesterase (PDE) enzymes TbrPDEB1 and TbrPDEB2 of Trypanosoma brucei , the causative agent for human African trypanosomiasis (HAT). We describe protein expression and purification, assay development, and benchmark screening of a collection of 20 established human PDE inhibitors. We disclose that the human PDE4 inhibitor piclamilast, and some of its analogues, show modest inhibition of TbrPDEB1 and B2 and quickly kill the bloodstream form of the subspecies T. brucei brucei . We also report the development of a homology model of TbrPDEB1 that is useful for understanding the compound-enzyme interactions and for comparing the parasitic and human enzymes. Our profiling and early medicinal chemistry results strongly suggest that human PDE4 chemotypes represent a better starting point for optimization of TbrPDEB inhibitors than those that target any other human PDEs.