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1.
Rev Saude Publica ; 56: 100, 2022.
Article in English | MEDLINE | ID: mdl-36515302

ABSTRACT

OBJETIVE: To evaluate the effect of ribociclib versus endocrine therapy on productivity losses due to advanced breast cancer. METHODS: Productivity data from the MONALEESA-7 trial, obtained from the results of the application of the Work Productivity and Activity Impairment (WPAI) questionnaire on progression-free survival state (43-month follow-up), were extrapolated to the 10,936 Brazilian prevalent cases of premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. Productivity loss was determined by quantifying the economic costs of workforce dropout over time in both treatment arms and by discounting the economic costs of absenteeism and presenteeism from workforce retention. A human capital approach was used. RESULTS: Net productivity gains in the ribociclib arm were estimated at USD 4,285,525.00, representing 316,609 added work hours over 43 months and a mean of 2,009 added work weeks per year. CONCLUSIONS: The phase III MONALEESA-7 trial productivity results applied to the Brazilian premenopausal prevalent cases of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer showed that treatment with ribociclib + endocrine therapy improves workforce participation compared with endocrine therapy alone in premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer, with potential economic gains for the Brazilian society.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/drug therapy , Receptors, Estrogen/metabolism , Receptors, Estrogen/therapeutic use , Brazil , Antineoplastic Combined Chemotherapy Protocols
2.
Ther Adv Med Oncol ; 14: 17588359221081203, 2022.
Article in English | MEDLINE | ID: mdl-35251320

ABSTRACT

BACKGROUND: The phase III MONALEESA-7 trial (NCT02278120) assessed ribociclib + endocrine therapy (ET) versus ET in premenopausal women with HR+/HER2- advanced breast cancer (ABC). The relationship between work productivity loss (WPL) and domains of European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and the breast cancer (BC)-specific module (QLQ-BR23) has not been explored in ABC. In this post hoc analysis (data cutoff, November 30, 2018), we assessed the correlation between the WPL component of the Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire and EORTC QLQ-C30/BR23 domains. METHODS: We analyzed EORTC and WPAI:GH data from 329 patients in both treatment arms of MONALEESA-7 who were employed during the trial. Separate univariable mixed-model repeated measures (MMRM) regression models were fitted for each domain, with WPL as dependent variable and each EORTC domain score as a single fixed-effect covariate. Linear and quadratic relationships were considered based on the Akaike information criterion. Next, two separate multivariable MMRM regression models were fitted with WPL a dependent variable and all QLQ-C30/BR23 domain scores as fixed-effect covariates. The strength of correlation between WPL and EORTC domains was assessed in terms of minimally important differences for the QLQ-C30/BR23 modules. RESULTS: Our univariable analysis showed that greater WPL was statistically significantly associated with lower levels of overall quality of life (QoL) and other functional domains and with higher levels of all symptomatic domains of the QLQ-C30/BR23 modules. Our multivariable analysis determined that this correlation was primarily driven by changes in QoL; physical, role, social, and future perspective domains; and BC-specific symptomatic domains. CONCLUSION: This analysis determined the QoL domains that correlate with WPL in premenopausal patients with HR+/HER2- ABC. These results may inform prognostic tools to identify and characterize patients with greater risk for WPL and help design interventional strategies to minimize WPL.

3.
Rev. saúde pública (Online) ; 56: 100, 2022. tab
Article in English | LILACS | ID: biblio-1410045

ABSTRACT

ABSTRACT OBJETIVE To evaluate the effect of ribociclib versus endocrine therapy on productivity losses due to advanced breast cancer. METHODS Productivity data from the MONALEESA-7 trial, obtained from the results of the application of the Work Productivity and Activity Impairment (WPAI) questionnaire on progression-free survival state (43-month follow-up), were extrapolated to the 10,936 Brazilian prevalent cases of premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. Productivity loss was determined by quantifying the economic costs of workforce dropout over time in both treatment arms and by discounting the economic costs of absenteeism and presenteeism from workforce retention. A human capital approach was used. RESULTS Net productivity gains in the ribociclib arm were estimated at USD 4,285,525.00, representing 316,609 added work hours over 43 months and a mean of 2,009 added work weeks per year. CONCLUSIONS The phase III MONALEESA-7 trial productivity results applied to the Brazilian premenopausal prevalent cases of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer showed that treatment with ribociclib + endocrine therapy improves workforce participation compared with endocrine therapy alone in premenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer, with potential economic gains for the Brazilian society.


Subject(s)
Humans , Female , Women , Breast Neoplasms/therapy , Premenopause , Absenteeism , Workforce/economics
4.
Ther Adv Med Oncol ; 13: 17588359211000593, 2021.
Article in English | MEDLINE | ID: mdl-33948121

ABSTRACT

BACKGROUND: The global burden of breast cancer (BC) is high, especially in advanced stages. CDK 4/6 inhibitors represent a paradigm shift in the treatment of advanced BC HR+/HER2-, given the clinically and statistically significant gain in overall survival associated with this new class of medications. Nevertheless, as an innovation, the incorporation of these drugs impacts healthcare budgets, requiring cost-effectiveness analyses for decision-making. The aim of this study was to evaluate the cost-effectiveness of ribociclib plus letrozole compared with palbociclib plus letrozole or letrozole as monotherapy for first-line treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic BC (aBC) from a Brazilian private healthcare system perspective. METHODS: A model including progression-free survival (PFS), progressed disease, and death health states was used to simulate lifetime costs and outcomes. PFS and overall survival were derived from the MONALEESA-2 trial (lifetime horizon). Healthcare costs included drug acquisition and monitoring, subsequent therapies, adverse events, and end-of-life costs. Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The total cost of treatment with ribociclib plus letrozole was USD 72,091.82 versus USD 92,749.64 for palbociclib plus letrozole. Total QALYs were 3.30 and 3.16, respectively. Base-case analysis showed ribociclib as dominant over palbociclib in first-line treatment of women with HR+/HER2- aBC, associated with cost savings and QALY gains. The total cost of treatment with ribociclib plus letrozole was USD 83,058.73 versus USD 29,215.10 for letrozole. Total QALYs were 3.84 and 2.61, respectively. Compared with letrozole, ribociclib plus letrozole was associated with an incremental cost of USD 53,843.64 and an incremental QALY gain of 1.23, with incremental cost-effectiveness ratio of USD 43,826.91 per QALY gained. CONCLUSIONS: As demonstrated by the cost-effectiveness dominance over palbociclib, ribociclib results in savings when used as first-line treatment in postmenopausal women with HR+/HER2- aBC, warranting incorporation in the private healthcare system.

5.
Ann Thorac Surg ; 112(1): e27-e31, 2021 07.
Article in English | MEDLINE | ID: mdl-32562624

ABSTRACT

Endovascular repair has been introduced to decrease the morbidity and mortality associated with open surgical repair of aortic arch pathology. This case illustrates a 71-year-old male patient with an asymptomatic saccular aortic arch aneurysm treated by total endovascular aortic repair using 3-vessel inner branch stent graft. Postoperative course was unremarkable, and the patient was discharge home on postoperative day 3. Total endovascular aortic arch repair is a suitable alternative in higher-risk patients with aortic arch aneurysms who are not ideally suited for open surgical repair.


Subject(s)
Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis , Endovascular Procedures/methods , Stents , Aged , Aortic Dissection/diagnosis , Aorta, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/diagnosis , Computed Tomography Angiography , Humans , Male , Prosthesis Design
7.
J Oral Maxillofac Surg ; 75(12): 2638-2649, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28732219

ABSTRACT

PURPOSE: Perioperative systemic corticosteroids are broadly used in orthognathic surgery to prevent postoperative complications, but it is unclear whether this practice is beneficial and concerns about potential side effects have been raised. The purpose of this systematic review and meta-analysis was to assess the effects of perioperative systemic corticosteroids on clinically important outcomes in patients undergoing orthognathic surgery. MATERIALS AND METHODS: The authors conducted a systematic review of randomized controlled trials evaluating the effect of systemic corticosteroids in orthognathic surgery compared with placebo or any other intervention. The authors searched Medline, Embase, Cochrane Central, CINAHL, Lilacs, Scopus, and Web of Science and references of included trials. The primary outcome was the incidence of postoperative reintubation during the index hospitalization. The secondary outcomes were hospital length of stay, decreases in facial edema, and adverse events. Data were summarized using Mantel-Haenszel random-effects models. RESULTS: Of the 1,098 trials retrieved, 8 were included (n = 234). No trial evaluated the risk of postoperative reintubation. One trial evaluated the duration of hospital stay and showed no difference associated with the intervention. There was a decrease in facial edema with the use of systemic corticosteroids (n = 80; standardized mean difference, -1.07; 95% confidence interval, -1.99 to -0.16; I2 = 67%). Three trials reported side effects, such as postoperative surgical site bleeding, hypersensitivity, and stomach discomfort with intake of corticosteroids. The 8 trials had an unclear risk of bias. CONCLUSION: The authors observed no evidence of effect of systemic corticosteroids on the risk of reintubation and hospital length of stay in orthognathic surgery. Although facial edema decrease was observed to be improved with the intervention, adverse effects were inconsistently screened and reported. Thus, the use of systemic steroids in orthognathic surgery is not supported by strong evidence.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Orthognathic Surgical Procedures , Perioperative Care/methods , Postoperative Complications/prevention & control , Humans , Models, Statistical , Treatment Outcome
8.
Innovations (Phila) ; 12(4): 254-258, 2017.
Article in English | MEDLINE | ID: mdl-28598875

ABSTRACT

OBJECTIVE: Patients with a small aortic annulus (≤21 mm) have an increased risk of patient-prosthesis mismatch after valve replacement. The aim of this study was to compare the early hemodynamic performance of the balloon-expandable transaortic valve implantation Edwards system (SAPIEN) and the sutureless Perceval prostheses. METHODS: Fifty patients underwent transcatheter aortic valve implantation, and 113 patients underwent sutureless aortic valve replacement. Mean ± SD aortic annulus diameter was 19.7 ± 1 mm, with no significant difference between groups. SAPIEN valve size was 23 mm in 40 patients (80%) and 26 mm in 10 patients (20%). Perceval valve size was small in 45 patients (40%), medium in 62 patients (55%), and large in 6 patients (5%). Transthoracic Doppler echocardiographic images were collected at baseline and before discharge. RESULTS: There were no significant difference in predischarge effective orifice area (SAPIEN: 1.5 ± 0.5 cm and Perceval: 1.48 ± 0.34 cm, P = 0.58) and indexed effective orifice areas (SAPIEN: 0.93 ± 0.32 cm/m and Perceval: 0.88 ± 0.22 cm/m, P = 0.42). Predischarge mean ± SD transaortic gradient was lower with the SAPIEN than with Perceval valves (12 ± 6 and 17 ± 6 mm Hg, respectively, P < 0.001). Rates of moderate and severe prosthesis-patient mismatch were similar (SAPIEN: 44% and 10% and Perceval: 50% and 14%, P = 0.53 and 0.75, respectively). There were no moderate-severe paravalvular leaks. CONCLUSIONS: Although indexed effective orifice areas were similar, transcatheter aortic valve implantation with the balloon-expandable SAPIEN system yielded lower predischarge transaortic mean gradients than the surgically implanted Perceval, in patients with a small annulus.


Subject(s)
Aortic Valve , Transcatheter Aortic Valve Replacement , Aged , Aged, 80 and over , Aorta/diagnostic imaging , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve/surgery , Echocardiography, Doppler , Female , Heart Valve Prosthesis/adverse effects , Humans , Male , Postoperative Complications , Retrospective Studies , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/instrumentation , Transcatheter Aortic Valve Replacement/statistics & numerical data , Treatment Outcome
9.
Int J Public Health ; 62(1): 3-13, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27586037

ABSTRACT

OBJECTIVES: In Quebec, various actors fund activities aimed at increasing physical activity, improving eating habits and reducing smoking. The objective was to evaluate how effective does the healthy lifestyle habits promotion (HLHP) strategy need to be to make to offset its costs. METHODS: First, we built the logic model of the HLHP strategy. We then assessed the strategy's total cost as well as the direct health care expenditures associated with lifestyle-related risk factors (smoking, physical inactivity, insufficient intake of fruits and vegetables, obesity and overweight). Finally, we estimated the break-even point beyond which the economic benefits of the HLHP strategy would outweigh its costs. RESULTS: The HLHP strategy cost for 2010-2011 was estimated at $110 million. Direct healthcare expenditures associated with lifestyle-related risk factors were estimated at $4.161 billion. We estimated that 47 % of these expenditures were attributable to these risk factors. CONCLUSIONS: We concluded that the HLHP strategy cost corresponded to 5.6 % of the annual healthcare expenditures attributable to these risk factors. This study compared the economic value of HLHP activities against healthcare expenditures associated with targeted risk factors.


Subject(s)
Cost-Benefit Analysis , Health Expenditures , Health Promotion/economics , Healthy Lifestyle , Diet, Healthy , Humans , Models, Statistical , Obesity/prevention & control , Quebec , Risk Factors , Smoking Prevention
10.
Malar J ; 15(1): 347, 2016 07 07.
Article in English | MEDLINE | ID: mdl-27387549

ABSTRACT

BACKGROUND: To determine the impact of the introduction of artemisinin-based combination therapy (ACT) on parasite susceptibility, a molecular surveillance for antimalarial drug resistance was conducted on local isolates from the Hôpital Principal de Dakar between November 2013 and January 2014 and between August 2014 and December 2014. METHODS: The prevalence of genetic polymorphisms in antimalarial resistance genes (pfcrt, pfmdr1, pfdhfr and pfdhps) was evaluated in 103 isolates. RESULTS: The chloroquine-resistant haplotypes CVIET and CVMET were identified in 31.4 and 3.9 % of the isolates, respectively. The frequency of the pfcrt K76T mutation was increased from 29.3 % in 2013-2014 to 43.2 % in 2014. The pfmdr1 N86Y and Y184F mutations were identified in 6.1 and 53.5 % of the isolates, respectively. The pfdhfr triple mutant (S108N, N51I and C59R) was detected in the majority of the isolates (82.3 %). The prevalence of quadruple mutants (pfdhfr S108N, N51I, C59R and pfdhps A437G) was 40.4 %. One isolate (1.1 %) harboured the pfdhps mutations A437G and K540E and the pfdhfr mutations S108N, N51I and C59R. CONCLUSIONS: Despite a decline in the prevalence of chloroquine resistance due to the official withdrawal of the drug and to the introduction of ACT, the spread of resistance to chloroquine has continued. Furthermore, susceptibility to amodiaquine may be decreased as a result of cross-resistance. The frequency of the pfmdr1 mutation N86Y declined while the Y184F mutation increased in prevalence, suggesting that selective pressure is acting on pfmdr1, leading to a high prevalence of mutations in these isolates and the lack of specific mutations. The 50.5 % prevalence of the pfmdr1 polymorphisms N86Y and Y184F suggests a decrease in lumefantrine susceptibility. Based on these results, intensive surveillance of ACT partner drugs must be conducted regularly in Senegal.


Subject(s)
Antimalarials/pharmacology , Drug Resistance , Genes, Protozoan , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Amino Acid Substitution , Amodiaquine/pharmacology , Chloroquine/pharmacology , Humans , Membrane Transport Proteins/genetics , Multidrug Resistance-Associated Proteins/genetics , Peptide Synthases/genetics , Plasmodium falciparum/isolation & purification , Polymorphism, Genetic , Prevalence , Protozoan Proteins/genetics , Senegal , Tetrahydrofolate Dehydrogenase/genetics
11.
Interact Cardiovasc Thorac Surg ; 23(3): 371-6, 2016 09.
Article in English | MEDLINE | ID: mdl-27241051

ABSTRACT

OBJECTIVES: The aim of this study is to determine whether patients undergoing the Ross procedure with bicuspid aortic valves have pulmonary artery biomechanical properties different from those with tricuspid valves. METHODS: Thirty-two pulmonary arteries and 20 aortas were obtained from patients undergoing the Ross procedure at the time of surgery, from a cohort of 32 patients. The aortic valve was tricuspid in 5 patients (16%), bicuspid in 18 patients (56%) and unicuspid in 9 patients (28%). Histological analysis and ex vivo equi-biaxial tensile testing completed within 8 hours of surgery were used to evaluate differences in patient groups and between the pulmonary artery and the ascending aorta. RESULTS: There was no difference in thickness among pulmonary arteries when compared according to aortic valve phenotype (P = 0.94). There was no difference in the tensile tissue properties among aortas and pulmonary arteries when compared according to aortic valve phenotype, in either the circumferential or longitudinal axis. When compared according to the main surgical indication, pulmonary artery walls from patients with pure aortic regurgitation were less stiff than their counterparts (aortic regurgitation: 0.055 ± 0.037 MPa, aortic stenosis: 0.103 ± 0.051 MPa, mixed disease: 0.110 ± 0.044 MPa and aortic valve endocarditis: 0.216 ± 0.033 MPa, P = 0.002). There was no difference in the number of elastic lamellae in pulmonary artery specimens from the three different aortic valve phenotypes, as well as in the aortic specimens. CONCLUSIONS: No significant differences were observed in the biomechanical properties of pulmonary arteries when compared according to aortic valve phenotype.


Subject(s)
Aortic Valve Insufficiency/physiopathology , Aortic Valve Stenosis/physiopathology , Aortic Valve/abnormalities , Endocarditis/physiopathology , Heart Valve Diseases/physiopathology , Pulmonary Artery/physiopathology , Tricuspid Valve/physiopathology , Adult , Aortic Valve/physiopathology , Aortic Valve/surgery , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/surgery , Bicuspid Aortic Valve Disease , Elasticity , Endocarditis/surgery , Female , Heart Valve Diseases/surgery , Humans , Male , Middle Aged , Phenotype , Pulmonary Artery/pathology
12.
Antimicrob Agents Chemother ; 60(1): 624-7, 2016 01.
Article in English | MEDLINE | ID: mdl-26503652

ABSTRACT

The kelch 13 (K13) propeller gene is associated with artemisinin resistance. In a previous work, there were no mutations found in 138 Plasmodium falciparum isolates collected in 2012 and 2013 from patients residing in Dakar, Senegal (M. Torrentino-Madamet et al., Malar J 13:472, 2014, http://dx.doi.org/10.1186/1475-2875-13-472). However, the N554H, Q613H, and V637I mutations were identified in the propeller region of K13 in 92 (5.5%) isolates in 2013 and 2014. There were five polymorphisms identified in the Plasmodium/Apicomplexa-specific domain (K123R, N137S, N142NN/NNN, T149S, and K189T/N).


Subject(s)
Microfilament Proteins/genetics , Mutation , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Antimalarials/pharmacology , Artemisinins/pharmacology , Drug Resistance/genetics , Gene Expression , Humans , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Microfilament Proteins/chemistry , Microfilament Proteins/metabolism , Models, Molecular , Plasmodium falciparum/drug effects , Plasmodium falciparum/growth & development , Plasmodium falciparum/metabolism , Polymorphism, Genetic , Protein Structure, Secondary , Protein Structure, Tertiary , Protozoan Proteins/chemistry , Protozoan Proteins/metabolism , Senegal/epidemiology
13.
J Heart Valve Dis ; 25(6): 657-662, 2016 11.
Article in English | MEDLINE | ID: mdl-28290163

ABSTRACT

BACKGROUND: Freedom from structural valve deterioration (SVD) at 15 years with the Carpentier-Edwards (CE) Perimount pericardial valve in the aortic position was 60% in patients aged <60 years compared to 90% and 99% in patients aged 60-70 years and >70 years, respectively. The study aim was to focus on the causes of SVD requiring valve explant according to three different age groups: <60 years, 60-70 years, and >70 years. The short- and longterm clinical results of the patient cohort, followed for 25 years, are presented. METHODS: A retrospective review was made of 89 patients among 2,405 who had undergone elective aortic valve replacement (AVR) with CE pericardial valves between November 1981 and March 2011, and in whom the prosthesis explant was secondary to degeneration of the valve. RESULTS: Patients aged >70 years experienced more late complications such as endocarditis (p = 0.02) and mortality (p = 0.02). Following surgery for prosthesis explant and replacement, 39 of the 89 patients (44%) died. The average time to postoperative mortality in that population was 2.8 ± 3.6 years. On combining all causes of SVD, earlier dysfunction was noted in patients aged >60 years, and late dysfunction in patients aged <60 years (p = 0.003). However, there was no significant difference between groups in the process of degeneration (either calcification, pannus, tear, thrombus, endocarditis) (p = NS). No predictors were found of early and late dysfunction. CONCLUSIONS: Patients aged >60 years in whom a CE Perimount valve was implanted in the aortic position were more prone to early degeneration of their valve and related mortality. However, no predictors were found of early degeneration of the valve in that patient population.


Subject(s)
Aortic Valve/pathology , Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis , Pericardium/pathology , Pericardium/surgery , Age Factors , Aged , Female , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/mortality , Humans , Male , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/pathology , Prosthesis Failure , Reoperation , Retrospective Studies
14.
Malar J ; 14: 60, 2015 Feb 06.
Article in English | MEDLINE | ID: mdl-25849097

ABSTRACT

BACKGROUND: In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. Since the introduction of ACT, there have been very few reports on the level of Plasmodium falciparum resistance to anti-malarial drugs. An ex vivo susceptibility study was conducted on local isolates obtained from the Hôpital Principal de Dakar (Dakar, Senegal) from November 2013 to January 2014. METHODS: Eighteen P. falciparum isolates were sussessfully assessed for ex vivo susceptibility to chloroquine (CQ), quinine (QN), monodesethylamodiaquine (MDAQ), the active metabolite of amodiaquine, mefloquine (MQ), lumefantrine (LMF), artesunate (AS), dihydroartemisinin (DHA), the active metabolite of artemisinin derivatives, pyronaridine (PND), piperaquine (PPQ), and, Proveblue (PVB), a methylene blue preparation, using the HRP2-based ELISA test. RESULTS: The prevalence of isolates with reduced susceptibility was 55.6% for MQ, 50% for CQ, 5.6% for QN and MDAQ, and 0% for DHA, AS and LMF. The mean IC50 for PND, PPQ and PVB were 5.8 nM, 32.2 nM and 5.3 nM, respectively. CONCLUSIONS: The prevalence of isolates with a reduced susceptibility to MQ remains high and stable in Dakar. Since 2004, the prevalence of CQ resistance decreased, but rebounded in 2013 in Dakar. PND, PPQ and PVB showed high in vitro activity in P. falciparum parasites from Dakar.


Subject(s)
Antimalarials/pharmacology , Drug Resistance , Plasmodium falciparum/drug effects , Female , Humans , Inhibitory Concentration 50 , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Male , Prevalence , Senegal/epidemiology
15.
J Health Econ Outcomes Res ; 3(1): 13-23, 2015.
Article in English | MEDLINE | ID: mdl-34430665

ABSTRACT

New discoveries are a critical priority for the pharmaceutical industry. However, the use of fixed incremental cost-effectiveness (ICER) thresholds for health technology assessment (HTA) may compromise incentives to innovate and affect future treatment options. This paper highlights the impact of generic drug price policies on pharmaceutical innovation in the context of fixed ICER thresholds and proposes a new consideration for the cost-effectiveness analysis (CEA). There is a direct causal relationship between HTA and the market price of a drug; in jurisdictions where HTA agencies apply fixed ICER thresholds as an important reimbursement listing criterion, the incremental cost of a new drug is expected to be proportional to its incremental benefit over the comparator. However, the comparator price is subject to market forces or sudden policies and may change markedly affecting the cost-effectiveness assessment (e.g. where the comparator patent has expired). Since recent generic price regulations increased the price gap between drugs' generic and patented versions, it is harder to achieve a sufficient level of incremental benefits in order to offset incremental prices of new treatments. Consequently, even promising drugs may have challenges to show attractive ICERs and research and development (R&D) investments may become unattractive in certain disease area. In order to promote innovation in therapeutic fields with unmet medical needs, a compromise would be to include the comparator's patented price in the CEA instead of the generic drug. By identifying the relevant disease areas, decision makers and HTA authorities could therefore convey the importance of investing in these therapeutic areas to manufacturers.

16.
Malar J ; 13: 472, 2014 Dec 04.
Article in English | MEDLINE | ID: mdl-25471113

ABSTRACT

BACKGROUND: The emergence of Plasmodium falciparum resistance to artemisinin and its derivatives, manifested as delayed parasite clearance following the treatment, has developed in Southeast Asia. The spread of resistance to artemisinin from Asia to Africa may be catastrophic for malaria control and elimination worldwide. Recently, mutations in the propeller domain of the Kelch 13 (k13) gene (PF3D71343700) were associated with in vitro resistance to artemisinin and with delayed clearance after artemisinin treatment in southern Asia. The aim of the study was to characterize the genetic variability of k13 and to evaluate the molecular resistance to artemisinin for the first time in Senegal. METHODS: Plasmodium falciparum isolates were collected from 138 malaria patients in Dakar and its districts during the rainy season of October 2012 to January 2013 at the Hôpital Principal de Dakar. The k13 gene was amplified using nested PCR and sequenced. RESULTS: A very limited variability within the k13 gene in Senegalese P. falciparum isolates was identified. No polymorphism was detected in the six k13-propeller blades. Only two mutations, T149S (6.3%) and K189T (42.2%), and one (N) or two (NN) asparagine insertion at the codon 142 (4.7 and 6.3%, respectively) were detected in the Plasmodium/Apicomplexa-specific domain. None of the polymorphisms associated with artemisinin resistance in Southeast Asia was detected in the 138 P. falciparum from Dakar. DISCUSSION: The present data do not suggest widespread artemisinin resistance in Dakar in 2012-2013. Notably, the C580Y, R539T or Y493H substitutions that were associated with in vitro resistance or delayed parasite clearance in Southeast Asia were not observed in Dakar, nor were any of the polymorphisms observed in parasites from Southeast Asia, nor the M476I mutation that was selected in vitro with artemisinin pressure in a African parasite line.


Subject(s)
Antimalarials/pharmacology , Artemisinins/pharmacology , Drug Resistance , Lactones/pharmacology , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Polymorphism, Genetic , Protozoan Proteins/genetics , Amino Acid Substitution , DNA, Protozoan/chemistry , DNA, Protozoan/genetics , Genotype , Humans , Malaria, Falciparum/parasitology , Mutation, Missense , Plasmodium falciparum/classification , Plasmodium falciparum/isolation & purification , Polymerase Chain Reaction , Senegal , Sequence Analysis, DNA
17.
Can J Cardiol ; 30(10): 1250.e23-5, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25154802

ABSTRACT

A 73-year-old man presented with intermittent chest pain radiating to the back, which had started 12 hours earlier. On the day after emergency consultation, a thoracic scan showed an acute aortic intramural hematoma starting at the sinotubular junction with an ascending aorta diameter of 5.7 cm. One hour after the initial scan, the patient had acute chest pain followed by a loss of consciousness. A second scan was obtained 2 hours after the initial scan and showed a type A aortic dissection that extended from the sinotubular junction to the descending aorta.


Subject(s)
Aortic Aneurysm, Thoracic/etiology , Aortic Diseases/complications , Aortic Dissection/etiology , Hematoma/complications , Aged , Aortic Diseases/diagnostic imaging , Chest Pain/etiology , Disease Progression , Fatal Outcome , Hematoma/diagnostic imaging , Humans , Male , Tomography, X-Ray Computed
18.
Z Gesundh Wiss ; 21(6): 523-533, 2013.
Article in English | MEDLINE | ID: mdl-24293810

ABSTRACT

AIM: Dental caries is a major public health problem worldwide, with very significant deleterious consequences for many people. The available data are alarming in Canada and the province of Quebec. The water fluoridation program has been shown to be the most effective means of preventing caries and reducing oral health inequalities. This article analyzes the cost-effectiveness of Quebec's water fluoridation program to provide decision-makers with economic information for assessing its usefulness. METHODS: An approach adapted from economic evaluation was used to: (1) build a logic model for Quebec's water fluoridation program; (2) determine its implementation cost; and (3) analyze its cost-effectiveness. Documentary analysis was used to build the logic model. Program cost was calculated using data from 13 municipalities that adopted fluoridation between 2002 and 2010 and two that received only infrastructure grants. Other sources were used to collect demographic data and calculate costs for caries treatment including costs associated with travel and lost productivity. RESULTS: The analyses showed the water fluoridation program was cost-effective even with a conservatively estimated 1 % reduction in dental caries. The benefit-cost ratio indicated that, at an expected average effectiveness of 30 % caries reduction, one dollar invested in the program saved $71.05-$82.83 per Quebec's inhabitant in dental costs (in 2010) or more than $560 million for the State and taxpayers. CONCLUSION: The results showed that the drinking-water fluoridation program produced substantial savings. Public health decision-makers could develop economic arguments to support wide deployment of this population-based intervention whose efficacy and safety have been demonstrated and acknowledged.

19.
Ann Thorac Surg ; 96(6): 2116-22, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24035304

ABSTRACT

BACKGROUND: Several methods of aortic clamping have been described for minimally invasive mitral valve surgery (MIMVS). The aim of this study was to compare the endoaortic balloon occlusion technique with the transthoracic clamp approach in terms of perioperative outcomes. METHODS: Between May 2006 and October 2011, a total of 259 patients underwent MIMVS through a 4 to 5 cm right anterolateral minithoracotomy. In 243 (93.8%) of these, the aorta was clamped using either the endoaortic balloon occlusion technique (endoballoon, n = 140) or the transthoracic clamp technique (transthoracic, n = 103). RESULTS: Patients in the endoballoon group had significantly longer operating time (4.3 ± 1.0 hours vs 3.2 ± 0.8 hours, p < 0.001), cardiopulmonary bypass time (143 ± 44 minutes vs 111 ± 29 minutes , p < 0.001), and cross-clamp time (114 ± 38 minutes vs 86 ± 23 minutes , p < 0.001). Perioperative blood loss was higher in the endoballoon group (287 ± 239 mL vs 213 ± 189 mL, p = 0.008) as was the mean postoperative creatinine kinase-MB level (36 ± 44 µg/L vs 26 ± 12 µg/L, p = 0.011). The repair rate was 99% or greater in both groups (p = 0.99). All patients left the operating room with no or trivial residual mitral regurgitation on transesophageal echocardiographic evaluation. In the endoballoon group there was 1 stroke (1%) and 5 myocardial infarctions (4%), compared with 2 strokes (2%) in the transthoracic group (p = not significant). There were 4 cases of postoperative cardiogenic shock, all of which occurred in the endoballoon group (p = 0.14). In-hospital mortality occurred in 2 patients from each group (p = 0.99). CONCLUSIONS: Minimally invasive mitral valve surgery can be performed successfully using either the endoaortic balloon technique or the transthoracic clamp approach. However, the transthoracic technique results in shorter operation time, less perioperative bleeding and better myocardial protection.


Subject(s)
Balloon Occlusion/methods , Minimally Invasive Surgical Procedures/methods , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Echocardiography, Transesophageal , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Length of Stay/trends , Male , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/mortality , Quebec/epidemiology , Retrospective Studies , Survival Rate/trends , Time Factors
20.
Am J Geriatr Psychiatry ; 21(6): 536-48, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23567409

ABSTRACT

OBJECTIVE: To estimate the excess healthcare costs attributable to depression and anxiety in a public managed care system. METHODS: The data were retained from a population-based health survey on 2,494 community-dwelling older adults age 65 years or more participating in the ESA (Étude sur la Santé des Aînés) study. Depression and anxiety were assessed using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria and measured at two time points 1 year apart. Annual healthcare costs considered included hospitalizations, emergency and outpatient visits, physician fees, and outpatient medications. Health service use and costs were identified from provincial administrative databases. Costs were studied as a function of the presence (yes/no) of depression and anxiety, and as persistence, incidence/remission, and no illness. Generalized linear models with a gamma distribution (log link) were used to control for a number of factors. RESULTS: Participants with depression had higher outpatient mental health-related costs. Participants with anxiety had higher total healthcare costs and specifically outpatient costs and inpatient costs. As opposed to people without depression and anxiety, persistent cases had higher mean costs followed by people with the disorders for only part of the year. Most of these differences were explained by sociodemographic and clinical factors. The excess annual adjusted healthcare costs of depression, anxiety, and comorbid depression and anxiety reached $27.4, $80.0, and $119.8 million per 1,000,000 population of elderly, respectively. CONCLUSION: The excess costs of depression and anxiety in community-dwelling elderly are just as significant as those observed for adults even when productivity losses are not considered. Adequately managing depression and anxiety in the older adult population may lead to important healthcare cost savings for society.


Subject(s)
Anxiety/economics , Anxiety/therapy , Depression/economics , Depression/therapy , Health Care Costs/statistics & numerical data , Managed Care Programs/economics , Aged , Case-Control Studies , Female , Health Services/economics , Health Services/statistics & numerical data , Health Surveys , Humans , Linear Models , Male , Quebec
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