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BACKGROUND: Despite using identical evidence to support practice guidelines for lipid-lowering treatment in primary prevention of cardiovascular disease (CVD), it is unclear to what extent the 2018 American Heart Association/American College of Cardiology/Multisociety, 2016 US Preventive Services Task Force (USPSTF), 2020 Department of Veterans Affairs/Department of Defense, 2021 Canadian Cardiovascular Society, and 2019 European Society of Cardiology/European Atherosclerosis Society guidelines differ in grading and assigning levels of evidence and classes of recommendations (LOE/class) at a population level. METHODS: We included 7262 participants, aged 45 to 75 years, without history of CVD from the prospective population-based Rotterdam Study. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity for CVD events, and numbers needed to treat at 10 years were calculated. RESULTS: Mean age was 61.1 (SD 6.9) years; 58.2% were women. American Heart Association/American College of Cardiology/Multisociety, USPSTF, Department of Veterans Affairs/Department of Defense, Canadian Cardiovascular Society, and European Society of Cardiology/European Atherosclerosis Society strongly recommended statin initiation in respective 59.4%, 40.2%, 45.2%, 73.7%, and 42.1% of the eligible population based on high-quality evidence. Sensitivity for CVD events for treatment recommendations supported with strong LOE/class was 86.3% for American Heart Association/American College of Cardiology/Multisociety (IA or IB), 69.4% for USPSTF (USPSTF-B), 74.5% for Department of Veterans Affairs/Department of Defense (strong for), 93.3% for Canadian Cardiovascular Society (strong), and 66.6% for European Society of Cardiology/European Atherosclerosis Society (IA). Specificity was highest for the USPSTF at 45.3% and lowest for European Society of Cardiology/European Atherosclerosis Society at 10.0%. Estimated numbers needed to treat at 10 years for those with the strongest LOE/class were ranging from 20 to 26 for moderate-intensity and 12 to 16 for high-intensity statins. CONCLUSIONS: Sensitivity, specificity, and numbers needed to treat at 10 years for assigned LOE/class varied greatly among 5 CVD prevention guidelines. The level of variability seems to be driven by differences in how the evidence is graded and translated into LOE/class underlying the treatment recommendations by different professional societies. Efforts towards harmonizing evidence grading systems for clinical guidelines in primary prevention of CVD may reduce ambiguity and reinforce updated evidence-based recommendations.
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Aterosclerosis , Cardiología , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Veteranos , American Heart Association , Aterosclerosis/diagnóstico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/epidemiología , Canadá , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Persona de Mediana Edad , Prevención Primaria , Estudios Prospectivos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective. METHODS: Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment. RESULTS: Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,773,865 BRL. Using N + I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P + A versus sunitinib, with an estimated COPE of 3,773,865 BRL. Estimated NNT was 20 comparing N + I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. CONCLUSION: At the 12-month landmark, P + A suggests better economic scenario versus N + I as first-line mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator.
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Antineoplásicos Inmunológicos/economía , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Axitinib/economía , Axitinib/uso terapéutico , Brasil , Carcinoma de Células Renales/patología , Análisis Costo-Beneficio , Femenino , Gastos en Salud/estadística & datos numéricos , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Humanos , Ipilimumab/economía , Ipilimumab/uso terapéutico , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Modelos Económicos , Nivolumab/economía , Nivolumab/uso terapéutico , Supervivencia sin Progresión , Índice de Severidad de la Enfermedad , Sunitinib/economía , Sunitinib/uso terapéutico , Adulto JovenRESUMEN
Regression models for continuous, binary, nominal, and ordinal outcomes almost completely rely on parametric models, whereas time-to-event outcomes are mainly analyzed by Cox's Proportional Hazards model, an essentially non-parametric method. This is done despite a long list of disadvantages that have been reported for the hazard ratio, and also for the odds ratio, another effect measure sometimes used for time-to-event modelling. In this paper, we propose a parametric proportional risk model for time-to-event outcomes in a two-group situation. Modelling explicitly a risk instead of a hazard or an odds solves the current interpretational and technical problems of the latter two effect measures. The model further allows for computing absolute effect measures like risk differences or numbers needed to treat. As an additional benefit, results from the model can also be communicated on the original time scale, as an accelerated or a prolongated failure time thus facilitating interpretation for a non-technical audience. Parameter estimation by maximum likelihood, while properly accounting for censoring, is straightforward and can be implemented in each statistical package that allows coding and maximizing a univariate likelihood function. We illustrate the model with an example from a randomized controlled trial on efficacy of a new glucose-lowering drug for the treatment of type 2 diabetes mellitus and give the results of a small simulation study.
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Diabetes Mellitus Tipo 2 , Simulación por Computador , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Funciones de Verosimilitud , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de SupervivenciaRESUMEN
BACKGROUND: The well-established benefit of Low-Dense-Lipoprotein-cholesterol (LDL-c) lowering treatments (LLTs) has led clinical guidelines to lower the cardiovascular prevention targets. Despite this, there is a surprising scarcity of real-world studies (RWS) evaluating whether recommendations are applied in the routine clinical management of patients with type 2 diabetes (T2D). We therefore evaluated, in a large RWS, the pattern of LLTs use and the achievement of LDL-c targets in patients with T2D in Italian diabetes specialist clinics. METHODS: We collected data from 46 diabetes outpatient clinics (following 281,381 subjects), including 104,726 T2D patients, for whom use of LLTs between 2015 and 2016 was ascertained. We used the 2016 and 2019 European Atherosclerosis Society and European Society of Cardiology (EAS-ESC) guidelines to define cardiovascular risk categories, LDL-c targets, and the expected LDL-c reduction and cardiovascular benefit achievable with LLT intensification. RESULTS: 63,861 patients (61.0%) were on statin therapy, 9.2% of whom were also on ezetimibe. Almost all subjects were at high (29.3%) or very high (70.4%) cardiovascular risk, including 17% being in secondary prevention. Among very high-risk patients, 35% were not on statin despite half of them had LDL-c > 2.6 mmol/l, and only 15% of those on statins had LDL-c < 1.4 mmol/l. 83% of subjects in secondary prevention were on a statin, but half of them had LDL-c > 1.8 mmol/l. Overall, 35% and 14% of subjects achieved the LDL-c targets as suggested by 2016 and 2019 EAS-ESC Guidelines, respectively. Based on anticipated response to treatment, we estimated that 38% of the entire population would require high-intensity-statin (HI-statin), 27% a combination of HI-statin plus ezetimibe, and 27% the addition of proprotein-convertase-subtilisin/kexin-9 (PCSK9) inhibitors. These LLT intensifications would reduce the incidence of cardiovascular events by 32%, from 23.511 to 16.022 events per 100.000 patients/10-years (incidence-rate-ratio 0.68; 95% C.I 0.67-0.70, p < 0.001). CONCLUSIONS: Despite the increase in use of LLT in T2D over the last decades, a large proportion of subjects with T2D did not achieve their LDL-c targets. Given the very high cardiovascular risk of these patients, improving LLT is expected to have a dramatic impact on cardiovascular event prevention.
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Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dislipidemias/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Prevención Primaria , Prevención Secundaria , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Regulación hacia Abajo , Quimioterapia Combinada , Utilización de Medicamentos , Dislipidemias/sangre , Dislipidemias/diagnóstico , Dislipidemias/epidemiología , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in subgroups with clinically and genetically defined risk. METHODS: We performed a post hoc analysis of the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) testing whether evolocumab reduces the risk of VTE events (deep venous thrombosis or pulmonary embolism). Data from FOURIER and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) were then combined in a meta-analysis to assess the class effect of PCSK9 inhibition on the risk of VTE. We also analyzed baseline lipids in FOURIER to investigate potential mechanisms explaining the reduction in VTE with evolocumab. Last, an exploratory genetic analysis was performed in FOURIER to determine whether a VTE polygenic risk score could identify high-risk patients who would derive the greatest VTE reduction from evolocumab. RESULTS: In FOURIER, the hazard ratio (HR) for VTE with evolocumab was 0.71 (95% CI, 0.50-1.00; P=0.05), with no effect in the 1st year (HR, 0.96 [95% CI, 0.57-1.62]) but a 46% reduction (HR, 0.54 [95% CI, 0.33-0.88]; P=0.014) beyond 1 year. A meta-analysis of FOURIER and ODYSSEY OUTCOMES demonstrated a 31% relative risk reduction in VTE with PCSK9 inhibition (HR, 0.69 [95% CI, 0.53-0.90]; P=0.007). There was no relation between baseline low-density lipoprotein cholesterol levels and magnitude of VTE risk reduction. In contrast, in patients with higher baseline lipoprotein(a) (Lp[a]) levels, evolocumab reduced Lp(a) by 33 nmol/L and risk of VTE by 48% (HR, 0.52 [95% CI, 0.30-0.89]; P=0.017), whereas, in patients with lower baseline Lp(a) levels, evolocumab reduced Lp(a) by only 7 nmol/L and had no effect on VTE risk (Pinteraction 0.087 for HR; Pheterogeneity 0.037 for absolute risk reduction). Modeled as a continuous variable, there was a significant interaction between baseline Lp(a) concentration and magnitude of VTE risk reduction (Pinteraction=0.04). A polygenic risk score identified patients who were at >2-fold increased risk for VTE and who derived greater relative (Pinteraction=0.04) and absolute VTE reduction (Pheterogeneity=0.009) in comparison with those without high genetic risk. CONCLUSIONS: PCSK9 inhibition significantly reduces the risk of VTE. Lp(a) reduction may be an important mediator of this effect, a finding of particular interest given the ongoing development of potent Lp(a) inhibitors.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticolesterolemiantes/uso terapéutico , LDL-Colesterol/sangre , Dislipidemias/tratamiento farmacológico , Lipoproteína(a)/sangre , Inhibidores de PCSK9 , Inhibidores de Serina Proteinasa/uso terapéutico , Tromboembolia Venosa/prevención & control , Trombosis de la Vena/prevención & control , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticolesterolemiantes/efectos adversos , Biomarcadores/sangre , Ensayos Clínicos como Asunto , Dislipidemias/sangre , Dislipidemias/diagnóstico , Dislipidemias/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiología , Embolia Pulmonar/prevención & control , Medición de Riesgo , Factores de Riesgo , Inhibidores de Serina Proteinasa/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiologíaRESUMEN
BACKGROUND: Japanese encephalitis (JE) virus is the leading vaccine-preventable cause of encephalitis in Asia. For most travelers, JE risk is very low but varies based on several factors, including travel duration, location, and activities. To aid public health officials, health care providers, and travelers evaluate the worth of administering/ receiving pre-travel JE vaccinations, we estimated the numbers-needed-to-treat to prevent a case and the cost-effectiveness ratios of JE vaccination for U.S. travelers in different risk categories. METHODS: We used a decision tree model to estimate cost per case averted from a societal and traveler perspective for hypothetical cohorts of vaccinated and unvaccinated travelers. Risk Category I included travelers planning to spend ≥1 month in JE-endemic areas, Risk Category II were shorter-term (<1 month) travelers spending ≥20% of their time doing outdoor activities in rural areas, and Risk Category III were all remaining travelers. We performed sensitivity analyses including examining changes in cost-effectiveness with 10- and 100-fold increases in incidence and medical treatment costs. RESULTS: The numbers-needed-to-treat to prevent a case and cost per case averted were approximately 0.7 million and $0.6 billion for Risk Category I, 1.6 million and $1.2 billion for Risk Category II, and 9.8 million and $7.6 billion for Risk Category III. Increases of 10-fold and 100-fold in disease incidence proportionately decreased cost-effectiveness ratios. Similar levels of increases in medical treatment costs resulted in negligible changes in cost-effectiveness ratios. CONCLUSION: Numbers-needed-to-treat and cost-effectiveness ratios associated with preventing JE cases in U.S. travelers by vaccination varied greatly by risk category and disease incidence. While cost effectiveness ratios are not the sole rationale for decision-making regarding JE vaccination, the results presented here can aid in making such decisions under very different risk and cost scenarios.
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Encefalitis Japonesa , Vacunas contra la Encefalitis Japonesa/economía , Viaje , Vacunación/economía , Asia , Encefalitis Japonesa/epidemiología , Encefalitis Japonesa/prevención & control , HumanosRESUMEN
The epidemiological association of cholesterol associated with low density lipoproteins (LDL-c) levels and the development of atherosclerotic vascular disease has been ratified by mendelian randomization studies. Paradoxically, the success of statins led to the underestimation of other lipid-lowering therapies and even the measurement of LDL-c. Recent studies show that the reduction of LDL-c to extraordinarily low levels through absorption inhibition, and, in a particularly intensive manner, with monoclonal antibodies against pro-protein convertase subtilisine Kesine 9 (PCSK9) continues to offer cardiovascular protection. However, the high cost and limited experience with PCSK-9 inhibitors advised a prudent use of them. An appropriate selection of patients most likely to benefit from treatment with PCSK9 inhibitors emerges as the basis for a consensus of international guidelines: the combination of a high absolute vascular risk and a greater expected benefit by the starting LDL-c levels.
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OBJECTIVES: The primary objective was to assess the utility of the number needed to treat (NNT) to inform decision-making in the context of paediatric oncology and to calculate the NNT in all superiority, parallel, paediatric haematological cancer, randomised controlled trials (RCTs), with a comparison to the threshold NNT as a measure of clinical significance. DESIGN: Systematic review DATA SOURCES: MEDLINE, EMBASE and the Cochrane Childhood Cancer Group Specialized Register through CENTRAL from inception to August 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Superiority, parallel RCTs of haematological malignancy treatments in paediatric patients that assessed an outcome related to survival, relapse or remission; reported a sample size calculation with a delta value to allow for calculation of the threshold NNT, and that included parameters required to calculate the NNT and associated CI. RESULTS: A total of 43 RCTs were included, representing 45 randomised questions, of which none reported the NNT. Among acute lymphoblastic leukaemia (ALL) RCTs, 29.2% (7/24) of randomised questions were found to have a NNT corresponding to benefit, in comparison to acute myeloid leukaemia (ALM) RCTs with 50% (3/6), and none in lymphoma RCTs (0/13). Only 28.6% (2/7) and 33.3% (1/3) had a NNT that was less than the threshold NNT for ALL and AML, respectively. Of these, 100% (2/2 ALL and 1/1 AML) were determined to be possibly clinically significant. CONCLUSIONS: We recommend that decision-makers in paediatric oncology use the NNT and associated confidence limits as a supportive tool to evaluate evidence from RCTs while placing careful attention to the inherent limitations of this measure.
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Neoplasias Hematológicas/terapia , Números Necesarios a Tratar , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Niño , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/normasRESUMEN
BACKGROUND: This work aimed to evaluate the efficacy and safety of routine tranexamic acid (TXA) use in elective orthopaedic lower limb joint replacement surgery. METHODS: This retrospective cohort study included all primary hip or knee replacement procedures by a single surgeon over a 6-year period. TXA was introduced during the study period as part of an enhanced recovery after surgery strategy. RESULTS: Of the 673 procedures, 446 cases (66.3%) received TXA. The median length of stay was 5 days (2-69) and 6 days (3-28) for the TXA and control groups, respectively (P < .001). Blood transfusion was required for 28 (6.3%) of the TXA cases versus 40 (17.6%) controls (P < .001). Complication rates were similar irrespective of TXA status. At multivariate analysis, TXA was significantly and independently associated with fewer blood transfusions (hazard ratio 0.309, 95% confidence interval: 0.168-0.568, P < .001), with a number needed to treat of 9 cases. TXA use was estimated to save between £67.89 and £155.90 per case. CONCLUSIONS: Routine prophylactic TXA administration for elective primary hip and knee replacement reduces the likelihood of postoperative transfusion with a number needed to treat of 9. Cost savings may be as high as £155.90 per case, and no safety concerns were noted.
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The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8 mg/kg (n = 165) or placebo (n = 164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4.08 to 7.79 for the intent-to-treat population, 3.18-6.07 for patients with ≥2 risk factors, and 2.98-5.65 for patients with ≥3 risk factors. At various time points, and dependent on the risk group, 3-8 patients would need to be treated with brentuximab vedotin consolidation therapy to prevent a disease progression/death, compared with placebo. Patients with increased risk of relapse may benefit most from brentuximab vedotin.
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Antineoplásicos Inmunológicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Inmunoconjugados/uso terapéutico , Neoplasia Residual/patología , Adolescente , Adulto , Anciano , Brentuximab Vedotina , Terapia Combinada , Quimioterapia de Consolidación , Progresión de la Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/mortalidad , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To conduct a systematic review and meta-analysis investigating the efficacy and safety of medical expulsive therapy (MET) in low risk of bias (RoB) randomised controlled trials (RCTs). METHODS: A Cochrane style systematic review was conducted on published literature from 1990 to 2016, to include low RoB and a power calculation. A pooled meta-analysis was conducted. RESULTS: The MET group included 1387 vs 1381 patients in the control group. The analysis reveals α-blockers increased stone expulsion rates (78% vs 74%) (P < 0.001), whilst calcium channel blockers (CCBs) had no effect compared to controls (79% vs 75%) (P = 0.38). In the subgroup analysis, α-blockers had a shorter time to stone expulsion vs the control group (P < 0.001). There were no significant differences in expulsion rates between the treatment groups and control group for stones <5 mm in size (P = 0.48), proximal or mid-ureteric stones (P = 0.63 and P = 0.22, respectively). However, α-blockers increased stone expulsion in stones >5 mm (P = 0.02), as well as distal ureteric stones (P < 0.001). The α-blocker group developed more side-effects (6.6% of patients; P < 0.001). The numbers needed to treat for α-blockers was one in 14, for stones >5 mm one in eight, and for distal stones one in 10. CONCLUSION: The primary findings show a small overall benefit for α-blockers as MET for ureteric stones but no benefit with CCBs. α-blockers show a greater benefit for large (>5 mm) ureteric stones and those located in the distal ureter, but no benefit for smaller or more proximal stones. α-blockers are associated with a greater risk of side-effects compared to placebo or CCBs.
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BACKGROUND: The number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. Several methods can be used to calculate NNTs, and they should be applied depending on the different study characteristics, such as the design and type of variable used to measure outcomes. Whether or not the most recommended methods have been applied to calculate NNTs in studies published in the medical literature is yet to be determined. The aim of this study is to assess whether the methods used to calculate NNTs in studies published in medical journals are in line with basic methodological recommendations. METHODS: The top 25 high-impact factor journals in the "General and/or Internal Medicine" category were screened to identify studies assessing pharmacological interventions and reporting NNTs. Studies were categorized according to their design and the type of variables. NNTs were assessed for completeness (baseline risk, time horizon, and confidence intervals [CIs]). The methods used for calculating NNTs in selected studies were compared to basic methodological recommendations published in the literature. Data were analyzed using descriptive statistics. RESULTS: The search returned 138 citations, of which 51 were selected. Most were meta-analyses (n = 23, 45.1%), followed by clinical trials (n = 17, 33.3%), cohort (n = 9, 17.6%), and case-control studies (n = 2, 3.9%). Binary variables were more common (n = 41, 80.4%) than time-to-event (n = 10, 19.6%) outcomes. Twenty-six studies (51.0%) reported only NNT to benefit (NNTB), 14 (27.5%) reported both NNTB and NNT to harm (NNTH), and 11 (21.6%) reported only NNTH. Baseline risk (n = 37, 72.5%), time horizon (n = 38, 74.5%), and CI (n = 32, 62.7%) for NNTs were not always reported. Basic methodological recommendations to calculate NNTs were not followed in 15 studies (29.4%). The proportion of studies applying non-recommended methods was particularly high for meta-analyses (n = 13, 56.5%). CONCLUSIONS: A considerable proportion of studies, particularly meta-analyses, applied methods that are not in line with basic methodological recommendations. Despite their usefulness in assisting clinical decisions, NNTs are uninterpretable if incompletely reported, and they may be misleading if calculating methods are inadequate to study designs and variables under evaluation. Further research is needed to confirm the present findings.
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Números Necesarios a Tratar , Humanos , Factor de Impacto de la Revista , Publicaciones Periódicas como AsuntoRESUMEN
BACKGROUND: Recent studies suggest that androgen deprivation therapy (ADT) is associated with increased cardiovascular (CV) risk for patients with hormone-sensitive prostate cancer (PCa) and pre-existing CV disease. This risk seems to be different for the gonadotropin-releasing hormone (GnRH) agonists leuprolide and goserelin and GnRH antagonists, whereas the slightly more expensive GnRH antagonist shows a beneficial risk profile. The present study assesses the cost effectiveness of degarelix compared to leuprolide for PCa patients with increased CV risk. METHODS: This analysis is based on a pooled analysis of six phase III, randomized, controlled trials comparing the GnRH agonists leuprolide and goserelin with the GnRH antagonist degarelix. For the combined endpoint of CV events or death a superiority of degarelix was determined with a Number-Needed-to-Treat of 12. From the perspective of German statutory health insurance, this evaluation estimates and compares the additional drug costs of degarelix treatment to the cost of one (avoided) CV event. The CV event costs were estimated via emergency treatment and transportation, inpatient treatment, and rehabilitation. The difference of these two cost pools divided by 12 yields the average saving per patient and year. RESULTS: For every 12 PCa patients with CV history that are treated with GnRH antagonists to prevent one CV event, there will be additional drug costs in comparison with leuprolide treatment of 3111 per year. Costs of 8447 per year are prevented. Therefore, each patient with a history of CV who is treated with degarelix instead of a leuprolide generates savings of 445 per patient and year. CONCLUSIONS: Compared to leuprolide, degarelix is cost effective for patients with increased CV risk.
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Enfermedades Cardiovasculares/inducido químicamente , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Leuprolida/economía , Leuprolida/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/economía , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/economía , Antineoplásicos Hormonales/uso terapéutico , Análisis Costo-Beneficio , Humanos , Leuprolida/efectos adversos , Masculino , Metaanálisis como Asunto , Oligopéptidos/efectos adversos , Oligopéptidos/economía , Oligopéptidos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
PURPOSE: We systematically evaluated the Bosniak classification system with malignancy rates of each Bosniak category, and assessed the effectiveness related to surgical treatment and oncologic outcome based on recurrence and/or metastasis. MATERIALS AND METHODS: In a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria, we selected 39 publications for inclusion in this analysis and categorized them into 1) surgical cohorts-all cysts treated surgically and 2) radiological cohorts-cysts with surgical treatment or radiological followup. RESULTS: A total of 3,036 complex renal cysts were categorized into Bosniak II, IIF, III and IV. In surgical and radiological cohorts pooled estimates showed a malignancy prevalence of 0.51 (0.44, 0.58) in Bosniak III and 0.89 (0.83, 0.92) in Bosniak IV cysts, respectively. Stable Bosniak IIF cysts showed a malignancy rate of less than 1% during radiological followup (surveillance). Bosniak IIF cysts, which showed reclassification to the Bosniak III/IV category during radiological followup (12%), showed malignancy in 85%, comparable to Bosniak IV cysts. The estimated surgical number needed to treat to avoid metastatic disease of Bosniak III and IV cysts was 140 and 40, respectively. CONCLUSIONS: The effectiveness of the Bosniak classification system for complex renal cysts was high in categories II, IIF and IV, but low in category III, and 49% of Bosniak III cysts was overtreated because of a benign outcome. This surgical overtreatment combined with the excellent outcome for Bosniak III cysts may suggest that surveillance is a rational alternative to surgery. This will require further study to assess whether surveillance of Bosniak III cysts will prove safe.
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Enfermedades Renales Quísticas/epidemiología , Neoplasias Renales/clasificación , Recurrencia Local de Neoplasia/epidemiología , Nefrectomía/estadística & datos numéricos , Medios de Contraste/administración & dosificación , Progresión de la Enfermedad , Humanos , Riñón/diagnóstico por imagen , Riñón/patología , Riñón/cirugía , Enfermedades Renales Quísticas/diagnóstico por imagen , Enfermedades Renales Quísticas/patología , Enfermedades Renales Quísticas/prevención & control , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/epidemiología , Neoplasias Renales/patología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Prevalencia , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the short-term efficacy of venlafaxine extended release (ER) 75-225 mg/day compared with placebo for treating major depressive disorder (MDD) and to examine associations between baseline characteristics and efficacy outcomes in MDD patients treated with venlafaxine ER 75-225 mg/day. RESEARCH DESIGN AND METHODS: This meta-analysis included published and unpublished short-term, double-blind, placebo-controlled, Wyeth/Pfizer sponsored studies of venlafaxine ER at doses up to 225 mg/day in adults with MDD. CLINICAL TRIAL REGISTRATION: All trials were conducted before trial registration became mandatory. MAIN OUTCOME MEASURES: Change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score was analyzed over time using a mixed-effects model for repeated measures with terms for study, treatment group, visit, interaction between treatment group and visit, and baseline score as a covariate. Associations between baseline demographic and clinical characteristics and the probability of HAM-D17 response and remission at week 8 were evaluated using logistic regression models, with terms for study, treatment group, and baseline characteristics in the models. Safety and tolerability was assessed based on adverse events (AEs) and discontinuations due to AEs. RESULTS: The full analysis set included 1087 patients from five studies that fulfilled selection criteria. Statistically significant separation between venlafaxine ER and placebo groups for HAM-D17 total score was seen at week 2 and all subsequent assessments (p-values <.0001). There was no significant interaction between treatment and baseline HAM-D17 total score. Probability of HAM-D17 remission at week 8 decreased with increasing baseline HAM-D17 total score (p = .0012; OR: 0.94); however, baseline HAM-D17 total score did not predict response. Discontinuations due to AEs were reported for 9.4% of venlafaxine-ER-treated patients compared with 3.6% of placebo-treated patients. Key limitations: Five studies met the criteria for inclusion. Several differences in design between included studies limited the analysis: one study did not include a week 3 assessment (the week 3 time point was therefore dropped from the analysis), one study had two venlafaxine ER dose arms, which were combined into one group for the meta-analysis, and mixed- and flexible-dose studies were pooled. CONCLUSIONS: Venlafaxine ER 75-225 mg/day effectively reduced symptoms of depression in patients with MDD overall and in patients with either lower (≤23) or higher (>23) HAM-D17 total score at baseline.
Asunto(s)
Antidepresivos de Segunda Generación/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Clorhidrato de Venlafaxina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Preparaciones de Acción Retardada , Femenino , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Enfermedades Cardiovasculares/prevención & control , Toma de Decisiones , Dislipidemias/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Participación del Paciente , Medicina Preventiva/métodos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Toma de Decisiones Clínicas , Dislipidemias/diagnóstico , Dislipidemias/mortalidad , Medicina Basada en la Evidencia , Conocimientos, Actitudes y Práctica en Salud , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Números Necesarios a Tratar , Medición de Riesgo , Factores de RiesgoRESUMEN
In the previous article in this series on common pitfalls in statistical analysis, we looked at the difference between risk and odds. Risk, which refers to the probability of occurrence of an event or outcome, can be defined in absolute or relative terms. Understanding what these measures represent is essential for the accurate interpretation of study results.
RESUMEN
Apart from commercial reasons, two motivations have led to the introduction of SSRIs to replace the first and second generation antidepressants already available. One was the search for a more rational treatment, based on specific mechanisms, the other the development of effective treatments with fewer side effects, particularly for older patients, who have a greater sensitivity to cardio-vascular and central nervous system effects. The first has been frustrated up to a point, in that SSRIs and other single mechanism drugs do not appear to be more effective than the earliest relatively non-specific antidepressants. The second has been fulfilled, in that SSRIs generally are better tolerated in older patients and in overdose. However, there is a spectrum of other side effects that are particularly relevant in older age and that need attention when treating depression in this particular patient group.