Improving the Cost-efficiency of Preventive Chemotherapy: Impact of New Diagnostics on Stopping Decisions for Control of Schistosomiasis.

BACKGROUND: Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. METHODS: Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. RESULTS: We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). CONCLUSIONS: We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis.

OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. METHODS: For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine-pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. FINDINGS: 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0-78·8), and 54·5% children (95% CI 50·4-58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2-77·3] treated per month and 53·0% [48·5-57·4] treated four times). In 779 individual case safety reports over 2015-16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7-93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015-16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10-30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4-1·2) in 2016 and 0·4% (0·1-0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2-1·2]), and the quintuple mutation associated with resistance to sulfadoxine-pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1-0·5) in 2016 and 1·0% (0·6-1·6) in 2018 (prevalence ratio 4·8 [1·7-13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child. INTERPRETATION: SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine-pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine-pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa. FUNDING: Unitaid.

Variability of treatment modalities and intensity in patients with severe haemophilia A on prophylaxis: Results from the Italian national registry.

BACKGROUND: A shift from a standard to a personalized prophylaxis has been increasingly adopted in patients with severe haemophilia A (SHA). This approach has raised the likelihood of a significant variability in the prophylactic approaches and the relative Factor VIII (FVIII) consumptions. The aim of our study was to assess the treatment variability of SHA patients without inhibitors and on prophylaxis regimen in Italy. MATERIAL AND METHODS: Data reported in the National Registry of Congenital Coagulopathies (NRCC) were analysed to assess treatment distribution within SHA patients without inhibitors, focussing on FVIII consumption in 2017, associated with prophylaxis regimen. The analysis was stratified based on age groups and Italian regions to describe the variability of FVIII consumption in Italy. RESULTS: In 2017, the Registry reported the therapeutic plans of 1068 SHA patients without inhibitors on prophylaxis. The mean (95% CI) individual consumption ranges from 123 127 IU (99 736-146 518) in the age group 0-6 years to 345 000 IU (336 000-354 000) in the age group >20 years. A significant FVIII consumption variability was identified within the adult population. Regions with less than 50 patients reported the higher variability in mean FVIII consumption per patient-year within the different age groups. Similar difference in FVIII consumption variability was reported also in the age groups comparing "low," "middle" and "high" patient volume regions. DISCUSSION: A reliable estimation of FVIII consumption for patients' treatment is necessary to manage and plan the appropriate budget and keep treatment's costs affordable. However, without the implementation of a methodology aiming to assess the overall value produced by these FVIII consumptions, the scenario will keep driven by FVIII consumptions, its costs and the budget available. An effort by haemophilic community, haemophilia treatment centres and institutions is required to develop and share this cultural shift in improving haemophilia management and assessment.

Cost-effectiveness of district-wide seasonal malaria chemoprevention when implemented through routine malaria control programme in Kita, Mali using fixed point distribution.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a strategy for malaria control recommended by the World Health Organization (WHO) since 2012 for Sahelian countries. The Mali National Malaria Control Programme adopted a plan for pilot implementation and nationwide scale-up by 2016. Given that SMC is a relatively new approach, there is an urgent need to assess the costs and cost effectiveness of SMC when implemented through the routine health system to inform decisions on resource allocation. METHODS: Cost data were collected from pilot implementation of SMC in Kita district, which targeted 77,497 children aged 3-59 months. Starting in August 2014, SMC was delivered by fixed point distribution in villages with the first dose observed each month. Treatment consisted of sulfadoxine-pyrimethamine and amodiaquine once a month for four consecutive months, or rounds. Economic and financial costs were collected from the provider perspective using an ingredients approach. Effectiveness estimates were based upon a published mathematical transmission model calibrated to local epidemiology, rainfall patterns and scale-up of interventions. Incremental cost effectiveness ratios were calculated for the cost per malaria episode averted, cost per disability adjusted life years (DALYs) averted, and cost per death averted. RESULTS: The total economic cost of the intervention in the district of Kita was US $357,494. Drug costs and personnel costs accounted for 34% and 31%, respectively. Incentives (payment other than salary for efforts beyond routine activities) accounted for 25% of total implementation costs. Average financial and economic unit costs per child per round were US $0.73 and US $0.86, respectively; total annual financial and economic costs per child receiving SMC were US $2.92 and US $3.43, respectively. Accounting for coverage, the economic cost per child fully adherent (receiving all four rounds) was US $6.38 and US $4.69, if weighted highly adherent, (receiving 3 or 4 rounds of SMC). When costs were combined with modelled effects, the economic cost per malaria episode averted in children was US $4.26 (uncertainty bound 2.83-7.17), US $144 (135-153) per DALY averted and US $ 14,503 (13,604-15,402) per death averted. CONCLUSIONS: When implemented at fixed point distribution through the routine health system in Mali, SMC was highly cost-effective. As in previous SMC implementation studies, financial incentives were a large cost component.

Costs and Cost-Effectiveness of Malaria Control Interventions: A Systematic Literature Review.

OBJECTIVES: To systematically review the literature on the unit cost and cost-effectiveness of malaria control. METHODS: Ten databases and gray literature sources were searched to identify evidence relevant to the period 2005 to 2018. Studies with primary financial or economic cost data from malaria endemic countries that took a provider, provider and household, or societal perspective were included. RESULTS: We identified 103 costing studies. The majority of studies focused on individual rather than combined interventions, notably insecticide-treated bed nets and treatment, and commonly took a provider perspective. A third of all studies took place in 3 countries. The median provider economic cost of protecting 1 person per year ranged from $1.18 to $5.70 with vector control and from $0.53 to $5.97 with chemoprevention. The median provider economic cost per case diagnosed with rapid diagnostic tests was $6.06 and per case treated $9.31 or $89.93 depending on clinical severity. Other interventions did not share enough similarities to be summarized. Cost drivers were rarely reported. Cost-effectiveness of malaria control was reiterated, but care in methodological and reporting standards is required to enhance data transferability. CONCLUSIONS: Important information that can support resource allocation was reviewed. Given the variability in methods and reporting, global efforts to follow existing standards are required for the evidence to be most useful outside their study context, supplemented by guidance on options for transferring existing data across settings.

Assessing the cost and quality-of-life impact of on-demand-only medications for adults with hereditary angioedema.

Background: Novel subcutaneous (SC) prophylactic therapies are transforming the treatment landscape of hereditary angioedema (HAE). Although questions are being raised about their cost, little attention has been paid to the cost and quality of life (QoL) impact of using on-demand-only medications. Objective: We assessed the overall economic burden of on-demand-only treatment for HAE and compared patient QoL with patients who received novel SC prophylactic therapies. Methods: US Hereditary Angioedema Association members were invited to complete an anonymous online survey to profile attack frequency, treatment use, and the presence of comorbidities as well as economic and socioeconomic variables. We modeled on-demand treatment costs by using net pricing of medications in 2018, indirect patient and caregiver costs, and attack-related direct billed costs for emergency department admissions, physician office visits, and/or hospitalizations. QoL was assessed by using the Angioedema Quality of Life questionnaire. Results: A total of 1225 patients (31.4%) responded. Of these, 737 adults with HAE (type I or II) met the inclusion criteria and completed the survey. Per patient/year direct costs associated with modeled on-demand-only treatment totaled $363,795, with additional indirect socioeconomic costs of $52,576 per patient/year. The greatest improvement in QoL was seen in patients who used novel SC prophylactic therapies, with a 59.5% (p < 0.01) improvement in median impairment scores versus on-demand-only treatment. In addition, patients who used novel SC prophylactic therapies reported a 77% reduction in the number of attacks each year when compared with those who used on-demand-only treatment. Conclusion: Our real-world patient data showed the cost and QoL burden of HAE treatment with on-demand-only therapy. Use of novel SC prophylaxis can lead to sizeable reductions in attack frequency and statistically significant and clinically relevant improvements in QoL. These data could be useful to clinicians and patients as they consider therapy options for patients with HAE.

Clinical and economic burden of pre-emptive therapy of cytomegalovirus infection in hospitalized allogeneic hematopoietic cell transplant recipients.

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a retrospective study to determine the clinical and economic burden of pre-emptive therapy (PET) for CMV infection in 100 consecutive hospitalized adult CMV positive serostatus allo-HCT recipients and compared their hospitalization cost with allo-HCT recipients hospitalized with graft vs host disease without CMV infection (control group) and across 19 US cancer centers for hospitalized patients with CMV infection between 2012 and 2015 (Vizient database). A total of 192 CMV episodes of PET for CMV infection occurred within 1 year post-HCT. PET consisted of ganciclovir (41% of episodes), foscarnet (40%), and valganciclovir (38%) with the longest average length of stay in foscarnet-treated patients (41 days). The average direct cost per patient admitted for PET was $116 976 (range: $7866-$641 841) compared with $12 496 (range: $2004-$43 069) in the control group (P < .0001). The total direct cost per encounter was significantly higher in patients treated with foscarnet and had nephrotoxicity ($284 006) compared with those who did not ($112 195). The average cost amongst the 19 US cancer centers, including our institution, was $42 327 with major disparities in cost and clinical outcomes. PET for CMV infection is associated with high economic burden in allo-HCT recipients.

Cost analysis of ganciclovir and foscarnet in recipients of allogeneic hematopoietic cell transplant with cytomegalovirus viremia.

BACKGROUND: Ganciclovir (GCV) and foscarnet (FOS) are the most commonly used antivirals for preemptive treatment of cytomegalovirus (CMV) viremia in recipients of allogeneic hematopoietic cell transplantation (alloHCT). The current literature indicates similar efficacy between these agents. Thus, the primary consideration for choice of initial anti-CMV treatment is the safety profile, time period after alloHCT, and concern of myelosuppression or renal dysfunction. METHODS: Herein, we retrospectively reviewed medical records of 124 alloHCT recipients who received GCV or FOS between April 27, 2014, and December 31, 2015, during the first year post-transplant. Healthcare resource use included drug, hospitalization, home health, dialysis, and growth factor costs. RESULTS: Total duration of therapy was longer in the GCV group (37 days vs 28 days, P = .21) but hospitalization days were similar (9 days) in both groups. The total treatment cost was significantly lower in the GCV group ($38 100 vs $59 400, P < .05). CONCLUSION: Preemptive anti-CMV therapy is associated with major healthcare resource costs, which were greater in patients who required FOS than those who were treated with GCV.

Cost-Benefit Limitations of Extended, Outpatient Venous Thromboembolism Prophylaxis Following Surgery for Crohn's Disease.

BACKGROUND: Patients with Crohn's disease are at increased risk of postoperative venous thromboembolism. Historically, extended outpatient prophylaxis has not met conventional measures of societal cost-benefit advantage. However, extended prophylaxis for patients with Crohn's disease may be more cost-effective because of the patients' high thrombotic risk and long life expectancy. OBJECTIVE: This study aimed to assess the cost-effectiveness of extended prophylaxis in patients with Crohn's disease after abdominal surgery. DESIGN: A decision tree model was used to assess the incremental cost-effectiveness and cost per case averted with extended-duration venous thromboembolism prophylaxis following abdominal surgery. SETTING: The risk of a postdischarge thrombotic event, age at surgery, type of thrombotic event, prophylaxis risk reduction, bleeding complications, and mortality were estimated by using existing published sources. PATIENTS: Studied were patients with Crohn's disease versus routine care. INTERVENTION: We constructed a decision analysis to compare costs and outcomes in patients with Crohn's disease postoperatively with and without extended prophylaxis over a lifetime horizon. MAIN OUTCOME MEASURES: Productivity costs ($) and benefits (quality-adjusted life-year) were used to reflect a societal perspective and were time discounted at 3%. Multivariable probabilistic sensitivity analysis accounted for uncertainty in probabilities, costs, and utility weights. RESULTS: With the use of reference parameters, the individual expected societal total cost of care was $399.83 without and $1387.95 with prophylaxis. Preventing a single mortality with prophylaxis would cost $43.00 million (number needed to treat: 39,839 individuals). The incremental cost was $1.90 million per quality-adjusted life-year. Adjusting across a range of scenarios upheld these conclusions 88% of the time. With further sensitivity testing, subpopulations with postdischarge thrombosis rates greater than 4.9% favors postoperative extended-duration venous thromboembolism prophylaxis. LIMITATIONS: Further investigation is needed to determine if specific high-risk individuals can be preemptively identified in the Crohn's surgical population for targeted prophylaxis. CONCLUSION: Extended prophylaxis in patients with Crohn's disease postoperatively is not cost-effective when the cumulative incidence of posthospital thrombosis remains less than 4.9%. These findings are driven by the low absolute risk of thrombosis in this population and the considerable cost of universal treatment. See Video Abstract at http://links.lww.com/DCR/A998. LIMITACIONES DE COSTO-BENEFICIO DE LA PROFILAXIS AMBULATORIA PROLONGADA DEL TROMBOEMBOLISMO VENOSO DESPUÉS DE CIRUGÍA EN CASOS DE ENFERMEDAD DE CROHN:: Los pacientes con enfermedad de Crohn tienen un mayor riesgo de tromboembolismo venoso postoperatorio. Históricamente, la profilaxis ambulatoria prolongada no ha cumplido con las medidas convencionales de ventajas en costo-beneficio para la sociedad. Sin embargo, la profilaxis prolongada en los pacientes con Crohn puede ser más rentable debido al alto riesgo trombótico y a una larga esperanza de vida en estos pacientes.Evaluar la rentabilidad de la profilaxis prolongada en pacientes postoperados de un Crohn.Se utilizó un modelo de árbol de decisión para evaluar el incremento de rentabilidad y el costo por cada caso evitado con la profilaxis prolongada de tromboembolismo venoso después de cirugía abdominal.Se calcularon utilizando fuentes publicadas el riesgo de evento trombótico posterior al alta, la edad del paciente al momento de la cirugía, el tipo de evento trombótico, la reducción del riesgo de profilaxis, las complicaciones hemorrágicas y la mortalidad.Se estudiaron los pacientes de atención rutinaria versus aquellos portadores de Crohn.Construimos un arbol de análisis decisional para comparar costos y resultados de pacientes portadores de Crohn, con y sin profilaxis prolongada en el postoperatorio en un horizonte de por vida.Los costos de productividad ($) y los beneficios (año de vida ajustado por calidad) se utilizaron para reflejar la perspectiva social y se descontaron en el tiempo de un 3%. El análisis de sensibilidad probabilística multivariable dió cuenta de la incertidumbre en las probabilidades, costos y peso de utilidades.Usando parámetros de referencia, el costo total social esperado de la atención individual fue de $ 399.83 sin y $ 1,387.95 con profilaxis. La prevención del deceso de un paciente con profilaxis costaría $ 43.00 millones (valor requerido para tratar: 39,839 individuos). El costo incrementado fue de $ 1.90 millones por año de vida ajustado por la calidad. El ajuste a través de una gama de escenarios confirmó estas conclusiones el 88% del tiempo. Con pruebas de sensibilidad adicionales, las subpoblaciones con tasas de trombosis posteriores al alta fueron superiores al 4,9% y favorecían la profilaxis prolongada del tromboembolismo venoso en el postoperatorio.Se necesita más investigación para determinar si se puede identificar de manera preventiva los individuos específicos de alto riesgo en la población quirúrgica de Crohn en casos de profilaxis dirigida.La profilaxis prolongada en pacientes postoperados de un Crohn no es rentable cuando la incidencia acumulada de trombosis posthospitalaria sigue siendo inferior al 4,9%. Estos hallazgos son impulsados por el bajo riesgo absoluto de trombosis en esta población y el costo considerable del tratamiento universal. Vea el resumen del video en http://links.lww.com/DCR/A998.

Cost-Effectiveness of Extended Thromboprophylaxis in Patients Undergoing Colorectal Surgery from a Canadian Health Care System Perspective.

BACKGROUND: There is increasing evidence to support extended thromboprophylaxis after colorectal surgery to minimize the incidence of postdischarge venous thromboembolic events. However, the absolute number of events is small, and extended thromboprophylaxis requires significant resources from the health care system. OBJECTIVE: This study aimed to determine the cost-effectiveness of extended thromboprophylaxis in patients undergoing colorectal surgery for malignancy or IBD. DESIGN: An individualized patient microsimulation model (1,000,000 patients; 1-month cycle length) comparing extended thromboprophylaxis (28-day course of enoxaparin) to standard management (inpatient administration only) after colorectal surgery was constructed. SETTINGS: The sources for this study were The American College of Surgeons National Surgical Quality Improvement Project Participant User File and literature searches. OUTCOMES: Costs (Canadian dollars), quality-adjusted life-years, and venous thromboembolism-related deaths prevented over a 1-year time horizon starting with hospital discharge were determined. The results were stratified by malignancy or IBD. RESULTS: In patients with malignancy, extended prophylaxis was associated with higher costs (+113$; 95% CI, 102-123), but increased quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), resulting in an incremental cost-effectiveness ratio of 2473$/quality-adjusted life-year. For IBD, extended prophylaxis also had higher costs (+116$; 95% CI, 109-123), more quality-adjusted life-years (+0.05; 95% CI, 0.04-0.06), and an incremental cost-effectiveness ratio of 2475$/quality-adjusted life-year. Extended prophylaxis prevented 16 (95% CI, 4-27) venous thromboembolism-related deaths per 100,000 patients and 22 (95% CI, 6-38) for malignancy and IBD. There was a 99.7% probability of cost-effectiveness at a willingness-to-pay threshold of 50,000$/quality-adjusted life-year. To account for statistical uncertainty around variables, sensitivity analysis was performed and found that extended prophylaxis is associated with lower overall costs when the incidence of postdischarge venous thromboembolic events reaches 1.8%. LIMITATIONS: Significant differences in health care systems may affect the generalizability of our results. CONCLUSIONS: Despite the rarity of venous thromboembolic events, extended thromboprophylaxis is a cost-effective strategy. See Video Abstract at http://links.lww.com/DCR/A976. COSTO-EFECTIVIDAD DE LA TROMBOPROFILAXIS EXTENDIDA EN PACIENTES SOMETIDOS A CIRUGÍA COLORRECTAL DESDE UNA PERSPECTIVA DEL SISTEMA DE SALUD CANADIENSE:: Cada vez hay más pruebas que apoyen la tromboprofilaxis extendida después de la cirugía colorrectal para minimizar la incidencia de eventos tromboembólicos venosos después del alta hospitalaria. Sin embargo, el número absoluto de eventos es pequeño y la tromboprofilaxis extendida requiere recursos significativos del sistema médico.Determinar la rentabilidad (relación costo-efectividad) de la tromboprofilaxis extendida en pacientes sometidos a cirugía colorrectal por neoplasia maligna o enfermedad inflamatoria intestinal.Un modelo de microsimulación de paciente individualizado (1,000,000 de pacientes; ciclo de 1 mes) que compara la tromboprofilaxis extendida (curso de enoxaparina de 28 días) con el tratamiento estándar (solo para pacientes hospitalizados) después de la cirugía colorrectal.Archivo de usuario participante del Proyecto de Mejoramiento de la Calidad Quirúrgica del Colegio Nacional de Cirujanos Americanos (ACS-NSQIP) y búsquedas bibliográficas.Costos (en dólares Canadienses), años de vida ajustados por la calidad y muertes relacionadas con el tromboembolismo venoso prevenidas en un horizonte temporal de 1 año a partir del alta hospitalaria. Los resultados fueron estratificados por malignidad o enfermedad inflamatoria intestinal.En pacientes con neoplasias malignas, la profilaxis extendida se asoció con costos más altos (+113 $; IC del 95%, 102-123), pero con un aumento de la calidad de vida ajustada por años de vida (+0.05; IC del 95%, 0.04-0.06), lo que resultó en un incremento de relación costo-efectividad de 2473 $/año de vida ajustado por calidad. Para la enfermedad inflamatoria intestinal, la profilaxis extendida también tuvo costos más altos (+116 $; 95% IC, 109-123), más años de vida ajustados por calidad (+0.05; 95% IC, 0.04-0.06) y una relación costo-efectividad incremental de 2475 $/año de vida ajustado por calidad. La profilaxis prolongada evitó 16 (95% IC, 4-27) muertes relacionadas con tromboembolismo venoso por cada 100,000 pacientes y 22 (95% IC, 6-38) por malignidad y enfermedad inflamatoria intestinal, respectivamente. Hubo un 99.7% de probabilidad de costo-efectividad en un límite de disposición a pagar de 50,000 $/año de vida ajustado por calidad. Para tener en cuenta la incertidumbre estadística en torno a los variables, se realizó un análisis de sensibilidad y se encontró que la profilaxis extendida se asocia con menores costos generales cuando la incidencia de eventos tromboembólicos venosos después del alta hospitalaria alcanza 1.8%.Las diferencias significativas en los sistemas de salud pueden afectar la generalización de nuestros resultados.A pesar de la escasez de eventos tromboembólicos venosos, la tromboprofilaxis extendida es una estrategia rentable. Vea el video del resumen en http://links.lww.com/DCR/A976.

Isavuconazole to prevent invasive fungal infection in immunocompromised adults: Initial experience at an academic medical centre.

OBJECTIVE: To evaluate clinical and economic outcomes associated with the use of isavuconazole as antifungal prophylaxis in high-risk immunocompromised patients. PATIENTS/METHODS: Retrospective, single-centre cohort study of patients who received isavuconazole prophylaxis. Outcomes assessed included breakthrough IFI, early discontinuation of isavuconazole for any reason and antifungal prophylaxis prescribed at discharge. The impact on inpatient drug expenditure was evaluated using current isavuconazole and posaconazole drug costs per observed isavuconazole days of therapy (DOT) during the study period. RESULTS: One hundred thirty-eight courses of isavuconazole prophylaxis were administered to 98 inpatients (2193 DOT). Relapsed/refractory acute myelogenous leukaemia was the indication for prophylaxis in over half (59.4%) of patients. Breakthrough IFI occurred in 8 (5.8%) courses. Suspected drug-related toxicities led to early discontinuation in 6 (4.3%) courses (five hepatotoxicity, one drug rash). At discharge, 24 (17.4%) courses lacked insurance coverage for isavuconazole. The formulary switch to isavuconazole prophylaxis resulted in an estimated mean drug cost savings of $128.25 per DOT relative to estimated posaconazole costs (P < 0.001). CONCLUSION: Isavuconazole may be an option for antifungal prophylaxis in high-risk immunocompromised adults and has the potential to produce significant inpatient drug cost savings. Further studies are needed to confirm the clinical efficacy and cost-effectiveness of isavuconazole in this role.

Cost-Benefit Analysis of Malaria Chemoprophylaxis and Early Diagnosis for Korean Soldiers in Malaria Risk Regions.

BACKGROUND: Chemoprophylaxis has been used to prevent malaria among soldiers and secondary transmission, as it effectively facilitates a decline in disease occurrence and secondary prevention. However, poor compliance and decreased risk of exposure to malaria necessitate that control strategies be reestablished. METHODS: To predict the incidence of malaria according to a control strategy, we proposed a mathematical model for its transmission using epidemiological data from 2010 to 2012. The benefit component included in the analyses was the averted cost with each control strategy, and the cost components were the cost of implementing chemoprophylaxis and early diagnosis. RESULTS: The chemoprophylaxis regimen with hydroxychloroquine sulfate and primaquine was Intervention 1, the regimen with primaquine only was Intervention 2, and diagnosis with a rapid diagnostic test (RDT) kit within 5 days of fever was Intervention 3. The simulation indicated that the combined control program with chemoprophylaxis and early diagnosis would be the most effective strategy, whereas sole early diagnosis would be the least effective strategy. However, the cost-benefit ratio of chemoprophylaxis was less than Intervention 1, irrespective of the varying range of chemoprophylaxis compliance, and that of early diagnosis was more than Intervention 1, regardless of the varying early diagnosis rate and demand for the RDT kit. Although chemoprophylaxis would be more effective at reducing the incidence of malaria than early diagnosis, it is less economical due to the higher cost. CONCLUSION: Our results support the introduction of early diagnosis with a RDT kit to control malaria in the Republic of Korea Army.

Investment Success in Public Health: An Analysis of the Cost-Effectiveness and Cost-Benefit of the Global Programme to Eliminate Lymphatic Filariasis.

Background: It has been estimated that $154 million per year will be required during 2015-2020 to continue the Global Programme to Eliminate Lymphatic Filariasis (GPELF). In light of this, it is important to understand the program's current value. Here, we evaluate the cost-effectiveness and cost-benefit of the preventive chemotherapy that was provided under the GPELF between 2000 and 2014. In addition, we also investigate the potential cost-effectiveness of hydrocele surgery. Methods: Our economic evaluation of preventive chemotherapy was based on previously published health and economic impact estimates (between 2000 and 2014). The delivery costs of treatment were estimated using a model developed by the World Health Organization. We also developed a model to investigate the number of disability-adjusted life years (DALYs) averted by a hydrocelectomy and identified the cost threshold under which it would be considered cost-effective. Results: The projected cost-effectiveness and cost-benefit of preventive chemotherapy were very promising, and this was robust over a wide range of costs and assumptions. When the economic value of the donated drugs was not included, the GPELF would be classed as highly cost-effective. We projected that a typical hydrocelectomy would be classed as highly cost-effective if the surgery cost less than $66 and cost-effective if less than $398 (based on the World Bank's cost-effectiveness thresholds for low income countries). Conclusions: Both the preventive chemotherapy and hydrocele surgeries provided under the GPELF are incredibly cost-effective and offer a very good investment in public health.

Potential clinical and economic outcomes of active beta-D-glucan surveillance with preemptive therapy for invasive candidiasis at intensive care units: a decision model analysis.

Early initiation of antifungal treatment for invasive candidiasis is associated with change in mortality. Beta-D-glucan (BDG) is a fungal cell wall component and a serum diagnostic biomarker of fungal infection. Clinical findings suggested an association between reduced invasive candidiasis incidence in intensive care units (ICUs) and BDG-guided preemptive antifungal therapy. We evaluated the potential cost-effectiveness of active BDG surveillance with preemptive antifungal therapy in patients admitted to adult ICUs from the perspective of Hong Kong healthcare providers. A Markov model was designed to simulate the outcomes of active BDG surveillance with preemptive therapy (surveillance group) and no surveillance (standard care group). Candidiasis-associated outcome measures included mortality rate, quality-adjusted life year (QALY) loss, and direct medical cost. Model inputs were derived from the literature. Sensitivity analyses were conducted to evaluate the robustness of model results. In base-case analysis, the surveillance group was more costly (1387 USD versus 664 USD) (1 USD = 7.8 HKD), with lower candidiasis-associated mortality rate (0.653 versus 1.426 per 100 ICU admissions) and QALY loss (0.116 versus 0.254) than the standard care group. The incremental cost per QALY saved by the surveillance group was 5239 USD/QALY. One-way sensitivity analyses found base-case results to be robust to variations of all model inputs. In probabilistic sensitivity analysis, the surveillance group was cost-effective in 50 % and 100 % of 10,000 Monte Carlo simulations at willingness-to-pay (WTP) thresholds of 7200 USD/QALY and ≥27,800 USD/QALY, respectively. Active BDG surveillance with preemptive therapy appears to be highly cost-effective to reduce the candidiasis-associated mortality rate and save QALYs in the ICU setting.

Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit.

OBJECTIVES: The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD. METHODS: A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia. IFD was classified according to the revised European Organisation for Research and Treatment of Cancer criteria. Cost analysis was performed from an Australian public hospital perspective. RESULTS: Ninety-eight patients were included in the audit; 83 (85%) received PAP. Most patients (49/83, 59%) switched between two different antifungal agents, predominantly between liposomal amphotericin B and an azole. Five proven/probable and six possible IFD cases were identified. Proven/probable IFD was most common in patients receiving the BFM95 chemotherapy protocol. The incidence of proven/probable IFD was significantly lower in patients receiving PAP compared with those who did not (2/78, 2.6% versus 3/14, 21.4%; P = 0.024). For every five patients receiving PAP, one proven/probable IFD case would be prevented. Proven/probable IFD was associated with an additional median cost of 121,520 Australian dollars (95% CI: 90,781-180,141 Australian dollars; P < 0.001) compared with patients without IFD. CONCLUSIONS: This is the first multicentre study evaluating PAP use in patients with ALL. With the caveats of interpretation of retrospective, non-randomized data, PAP was associated with a reduced IFD risk.

Schistosomiasis in school-age children in Burkina Faso after a decade of preventive chemotherapy.

OBJECTIVE: To assess the impact of a decade of biennial mass administration of praziquantel on schistosomiasis in school-age children in Burkina Faso. METHODS: In 2013, in a national assessment based on 22 sentinel sites, 3514 school children aged 7-11 years were checked for Schistosoma haematobium and Schistosoma mansoni infection by the examination of urine and stool samples, respectively. We analysed the observed prevalence and intensity of infections and compared these with the relevant results of earlier surveys in Burkina Faso. FINDINGS: S. haematobium was detected in 287/3514 school children (adjusted prevalence: 8.76%, range across sentinel sites: 0.0-56.3%; median: 2.5%). The prevalence of S. haematobium infection was higher in the children from the Centre-Est, Est and Sahel regions than in those from Burkina Faso's other eight regions with sentinel sites (P < 0.001). The adjusted arithmetic mean intensity of S. haematobium infection, among all children, was 6.0 eggs per 10 ml urine. Less than 1% of the children in six regions had heavy S. haematobium infections - i.e. at least 50 eggs per 10 ml urine - but such infections were detected in 8.75% (28/320) and 11.56% (37/320) of the children from the Centre-Est and Sahel regions, respectively. Schistosoma mansoni was only detected in two regions and 43 children - i.e. 1 (0.31%) of the 320 from Centre-Sud and 42 (8.75%) of the 480 from Hauts Bassins. CONCLUSION: By mass use of preventive chemotherapy, Burkina Faso may have eliminated schistosomiasis as a public health problem in eight regions and controlled schistosome-related morbidity in another three regions.

"There is no free here, you have to pay": actual and perceived costs as barriers to intermittent preventive treatment of malaria in pregnancy in Mali.

BACKGROUND: "There is no free here," the words of a Malian husband, illustrate how perceptions of cost can deter uptake of intermittent preventive treatment of malaria in pregnancy (IPTp). The Malian Ministry of Health (MOH) recommends a minimum of three doses of IPTp at monthly intervals. However, despite a national policy that IPTp be provided free of charge, only 35% of pregnant women receive at least one dose and less than 20% receive two or more doses. METHODS: This study explored perceptions and experiences of IPTp cost in Mali and their impact on uptake, using qualitative interviews and focus groups with pregnant women, husbands and mothers-in-law. Study team members also interviewed and observed health workers at four health centres, two in Sikasso Region and two in Koulikoro. RESULTS: Despite national-level policies, actual IPTp costs varied widely at study sites-between facilities, and visits. Pregnant women may pay for IPTp, receive it free, or both at different times. Health centres often charge a lump sum for antenatal care (ANC) visits that includes both free and fee-based drugs and services. This makes it difficult for women and families to distinguish between free services and those requiring payment. As a result, some forego free care that, because it is bundled with other fee-based services and medications, appears not to be free. Varying costs also complicate household budgeting for health care, particularly as women often rely on their husbands for money. Finally, while health facilities operating under the cost-recovery model strive to provide free IPTp, their own financial constraints often make this impossible. CONCLUSIONS: Both actual and perceived costs are currently barriers to IPTp uptake. Given the confusion around cost of services in the two study regions, more detailed national-level studies of both perceived and actual costs could help inform policy and programme decisions promoting IPTp. These studies should evaluate both quantitatively and qualitatively the cost information provided to and understood by pregnant women and their families. Meanwhile, unbundling free and fee-based services, making clear that IPTp is free, and ensuring that it is provided at no cost could help increase uptake. Free community-based distribution might be another route to increased uptake and adherence.

[How to assess curative and/or preventive effects of psychotropic drugs?] / Comment évaluer l'effet curatif et/ou préventif des psychotropes ?

Proving the efficacy of a psychotropic drug is a medical, scientific and ethical need. Psychotropic drug development is now a highly complex process, which takes several years and which is very expensive. It involves multiple steps of preclinical and clinical pharmacological refinement and testing. Methodology of studies to prove curative or preventive effect of psychotropic drugs is well codified. Preclinical studies include pharmacokinetic data, toxicology and performance in various animal models of pathology. Clinical phases are centered on randomized controlled double blind trials for demonstrating efficacy and safety/tolerability. This methodology follows strict criteria to avoid bias and to prove internal and external validity of the results. All the results from randomized controlled trials or RCTs lead to different levels of evidence of Evidence-Based Medicine (EBM): gold standard is RCTs while the lowest reference is clinical case or expert opinion. However, it is possible to level criticism at these data issued from RCTs. The main matter is that studies do not reflect the healthcare reality in daily life. For these reasons, a real debate between evaluation of efficacy and effectiveness is acute. Effectiveness refers to the overall effects of psychotropic drugs in naturalistic conditions. Furthermore, analysis of costs and financial benefits are more and more important from social and economic points of view. Official agencies and health insurances look after them very carefully. This article deals with these issues and provides examples using data from the international literature. These examples are drawn from RCTs, naturalistic studies, meta-analysis, pharmaco-economic studies and concern neuroleptics, antipsychotics, antidepressants, and mood-stabilizers.

[Latest international guidelines for screening, prevention and treatment of familial breast cancer - implications for the relevant practice in Hungary]. / Az örökletes emlorák szurésének, megelozésének és kezelésének új nemzetközi irányvonalai - hazai vonatkozásokkal.

INTRODUCTION: Screening, prevention and treatment of familial breast cancer require a multidisciplinary approach. New guidelines were published in the United Kingdom for the management of familial breast cancer. AIM: The authors summarise these new guidelines and analyse the relevant practice in Hungary. METHOD: Relevant guidelines of the National Institute for Health and Care Excellence and Familial Breast Cancer Report (NHS Scotland) are described. RESULTS: New guidelines will increase the number of genetic tests as well as genetic counselling. An increase in the number of breast magnetic resonance imaging is expected, too. Chemoprevention can be offered for individuals with medium risk and above. Promising trials are underway with platinum based chemotherapy and polyADP-ribose polimerase inhibitors for the systemic treatment of familial breast cancer. The increase in the number of genetic tests, counselling, and breast magnetic resonance imaging may have a significant impact on health care budget. CONCLUSIONS: These guidelines will change some aspects of the current management of familial breast cancer. Orv. Hetil., 2016, 157(28), 1117-1125.