Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2).

BACKGROUND: These studies assessed the efficacy and safety of fevipiprant, an oral antagonist of the prostaglandin D2 (PGD2) receptor (DP2), compared with placebo when added to standard-of-care (SoC) asthma therapy in patients with uncontrolled asthma. METHODS: ZEAL-1 (NCT03215758) and ZEAL-2 (NCT03226392) are two replicate, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies in which fevipiprant 150 mg once daily (o.d.) or placebo was added to SoC asthma therapy in patients aged ≥12 years with uncontrolled asthma. Primary endpoint: change from baseline in pre-dose forced expiratory volume in 1 s (FEV1) after 12 weeks' treatment. Key secondary endpoints: daytime asthma symptom score, short-acting ß-agonist (SABA) use and Asthma Quality-of-Life Questionnaire (AQLQ+12) score after 12-weeks treatment. FINDINGS: 662 patients in ZEAL-1 and 685 patients in ZEAL-2 completed the treatment period. In ZEAL-1, the least squares (LS) mean change from baseline in pre-dose FEV1 was 112 mL in fevipiprant vs 71 mL in placebo group (difference [∆]:41 mL; 95% CI: -6, 88; adjusted p-value 0·088). In ZEAL-2, the LS mean change in pre-dose FEV1 was 126 mL and 157 mL in the fevipiprant and placebo groups, respectively (∆:-31 mL; 95% CI: -80, 18; adjusted p-value 0·214). For both studies, there were no statistically significant differences in the key secondary objectives between the treatment groups. INTERPRETATION: The ZEAL studies did not demonstrate significant improvement in lung function or other clinical outcomes. These results suggest that DP2 receptor inhibition with fevipiprant is not effective in the studied patient population.

Prevalencia de complicaciones mayores en nefrolitotomía percutánea en una clínica de tercer nivel en Medellín entre 2015­2017 / Prevalencia de complicaciones mayores en nefrolitotomía percutánea en una clínica de tercer nivel en Medellín entre 2015­2017

Objetivo La Urolitiasis constituye un motivo de consulta común, con una alta incidencia y prevalencia. Cuando los cálculos renales son mayores a 20 mm, la primera línea de tratamiento es la nefrolitotomía percutánea. En Colombia existe poca información sobre la evaluación de las características de los pacientes y las complicaciones asociadas a ese procedimiento quirúrgico. Este estudio, busca determinar la prevalencia de las complicaciones en nefrolitotomía percutánea en una clínica de Medellín entre los años 2015 y 2017. Métodos Estudio observacional retrospectivo en el que se analiza la prevalencia de complicaciones mayores que presentaron los pacientes sometidos a nefrolitotomía percutánea en una clínica de tercer nivel en la ciudad de Medellín entre los años 2015 y 2017. Resultados a 176 pacientes se les realizó Nefrolitotomía percutánea entre el 2015 y el 2017. Se encontró una prevalencia de complicaciones mayores de 11,4%. El 60,2% de los pacientes que presentaron complicaciones fueron mujeres y la edad media fue de 45,1 años (DE ± 12,5 años). El 60% de los cálculos eran coraliformes. El 45% ubicados en el caliz inferior; siendo bilaterales en el 40% de ellos. La complicación más frecuente, fueron los cálculos residuales en el 6,8% seguido de complicaciones pulmonares en el 6,3% e infecciosas en el 6,3%. Conclusiones La nefrolitotomía percutánea representa un procedimiento quirúrgico relativamente seguro para el abordaje de pacientes con alta carga litiásica con un porcentaje de complicaciones relativamente bajo.

Objective Urolithiasis is a common reason to consult in medical practice. When stones are greater than 20 mm, the first line of treatment is percutaneous nephrolithotomy. This study aims to determine the prevalence of complications in percutaneous nephrolithotomy in a clinic in Medellín ­ Colombia between 2015 and 2017. Methods We present a retrospective observational study in which the prevalence of major complications in patients undergoing percutaneous nephrolithotomy was analyzed in a third level clinic in the city of Medellin - Colombia between 2015 and 2017. Results 176 patients underwent percutaneous nephrolithotomy between 2015 and 2017. A prevalence of complications greater than 11.4% was found. 60.2% of the patients who presented complications were women and the average age was 45.1 years (SD ± 12.5 years). 60% of the stones were staghorn. 45% located in the lower calyx; being bilateral in 40% of cases. The most frequent complication was residual stones in 6.8% followed by pulmonary complications in 6.3% and infectious in 6.3%. Conclusions Percutaneous nephrolithotomy represents a relatively safe surgical procedure for the management of patients with a high lithiasic load with a relatively low percentage of complications.

Understanding the economic value of molecular diagnostic tests: case studies and lessons learned.

Ten years after completion of the Human Genome Project, progress towards making "personalized medicine" a reality has been slower than expected. The reason is twofold. Firstly, the science is more difficult than expected. Secondly, limited progress has been made in aligning economic incentives to invest in diagnostics. This paper develops nine case studies of "success" where diagnostic tests are bringing personalized medicine into clinical practice with health and economic impact for patients, healthcare systems, and manufacturers. We focus on the availability of evidence for clinical utility, which is important not only for clinicians but also for payers and budget holders. We find that demonstrating diagnostic clinical utility and the development of economic evidence is currently feasible (i) through drug-diagnostic co-development, and (ii) when the research is sponsored by payers and public bodies. It is less clear whether the diagnostic industry can routinely undertake the work necessary to provide evidence as to the clinical utility and economic value of its products. It would be good public policy to increase the economic incentives to produce evidence of clinical utility: otherwise, opportunities to generate value from personalized medicine-in terms of both cost savings and health gains-may be lost.

Can and should value-based pricing be applied to molecular diagnostics?

Current pricing and reimbursement systems for diagnostics are not efficient. Prices for diagnostics are often driven by administrative practices and expected production cost. The purpose of the paper is to discuss how a value-based pricing framework being used to ensure efficient use and price of medicines could also be applied to diagnostics. Diagnostics not only facilitates health gain and cost savings, but also information to guide patients' decisions on interventions and their future 'behaviors'. For value assessment processes we recommend a two-part approach. Companion diagnostics introduced at the launch of the drug should be assessed through new drug assessment processes considering a broad range of value elements and a balanced analysis of diagnostic impacts. A separate diagnostic-dedicated committee using value-based pricing principles should review other diagnostics lying outside the companion diagnostics-and-drug 'at-launch' situation.

Psicosis alcohólica en el Hospital Mental de Antioquia, 1900-1930 / Alcoholic psychosis at Mental Hospital, Antioquia, Colombia, 1900-1930

El alcoholismo era un problema real en la ciudad de Medellín y en el departamento de Antioquia (Colombia) durante las tres primeras décadas del siglo XX; se lo enfocaba desde la perspectiva de un hábito que termina por dominar a quien lo asume; además, de acuerdo con los conocimientos médicos de ese período, era considerado como una enfermedad social, con connotaciones morales, físicas y sobre todo mentales. Las posibilidades médicas del momento eran escasas, el manicomio de la ciudad no contaba con las instalaciones adecuadas y las terapias disponibles para el alcoholismo eran limitadas; por lo tanto, se trataba de una enfermedad de pésimo pronóstico con pocas posibilidades de curación. Se presentan en este artículo los resultados de una investigación histórica sobre los primeros diagnósticos de psicosis alcohólica en el departamento de Antioquia, entre 1900 y 1930, incluyendo los diferentes enfoques clínicos y los recursos disponibles para su tratamiento. Se pretendió en el estudio evaluar los conocimientos médicos de la época sobre este asunto así como los primeros pasos del centro psiquiátrico más importante de la región.

Alcoholism was a real problem in Medellín (Colombia) during the first three decades of the XX century. It was focused as a habit that finally dominated people who assumed it. According to the medical knowledge at that time, alcoholism was a social disease with moral, physical, and mental connotations. Therapeutic options for alcoholic patients were limited, and the only mental institution in the city lacked adequate facilities. Consequently, the probability of cure was low, and the prognosis, poor. This article presents the results of a historic investigation about the early diagnosis of alcoholic psychosis in the department of Antioquia (Colombia) between 1900 and 1930. The different clinical approaches to alcoholism and the resources available for treatment are included. We aimed at evaluating the medical knowledge on alcoholism at the beginning or the XX century, and to describe the early steps of the main regional psychiatric center.

Recombinant erythropoietin for chemotherapy-related anaemia: economic value and health-related quality-of-life assessment using direct utility elicitation and discrete choice experiment methods.

OBJECTIVE: To assess both the health-related quality of life (HR-QOL) and the economic value of erythropoietin treatment in chemotherapy-related anaemia using direct utility elicitation and discrete choice experiment (DCE) methods from a societal perspective in the UK. METHODS: The time trade-off (TTO) method was employed to obtain utility values suitable for the calculation of QALYs for no, mild, moderate and severe anaemia. Health-state descriptions were developed using the Functional Assessment of Cancer Therapy - Anaemia (FACT-AN) subscale and the EQ-5D questionnaires, and were validated by clinical experts and patients. In addition, a DCE was implemented to elicit preferences for various anaemia treatment scenarios. The DCE analysis comprised important aspects of treatment identified from a literature review and by consultation with expert clinicians and cancer patients. The DCE included cost as an attribute in order to elicit willingness-to-pay (WTP) values (pound, 2004 values). The two methods were applied in the same cross-sectional sample of 110 lay people. Face-to-face interviews were conducted between February and March 2004. RESULTS: The mean utility scores were 0.86 (standard error [SE] 0.014) for the no-anaemia state, and 0.78 (SE 0.016), 0.61 (SE 0.020) and 0.48 (SE 0.020) for the mild, moderate and severe anaemia states, respectively. The DCE results revealed the following preferences as significant predictors of choice: higher level of relief from fatigue, lower duration of administration, subcutaneous/intravenous administration versus cannula injection, GP versus hospital location, lower risk of infection or allergic reactions and lower cost per month to the patient. Attribute levels were valued higher for recombinant erythropoietin than for blood transfusion; this is reflected in an incremental welfare value of 368 pounds (95% CI 318, 419). CONCLUSIONS: The results highlight a societal view that the severity of chemotherapy-related anaemia will significantly affect cancer patients' HR-QOL. The DCE survey shows that the public value favourably the attributes of treatment with recombinant erythropoietin, and indicates a likely patient preference for treatment with recombinant erythropoietin over blood transfusion.

Genetic screening, health care and the insurance industry. Should genetic information be made available to insurers?

The potential use of genetic tests in insurance has raised concerns about discrimination and individuals losing access to health care either because of refusals to test for treatable diseases, or because test-positives cannot afford premiums. Governments have so far largely sought to restrict the use of genetic information by insurance companies. To date the number of tests available with significant actuarial value is limited. However, this is likely to change, raising more clearly the question as to whether the social costs of adverse selection outweigh the social costs of individuals not accessing health care for fear of the consequences of test information being used in insurance markets. In this contribution we set out the policy context and model the potential trade-offs between the losses faced by insurers from adverse selection by insurees (which will increase premiums reducing consumer welfare) and the detrimental health effects that may result from persons refusing to undergo tests that could identify treatable health conditions. It argues that the optimal public policy on genetic testing should reflect overall societal benefit, taking account of these trade-offs. Based on our model, the factors that influence the outcome include: the size of and value attached to the health gains from treatment; deterrent effects of a disclosure requirement on testing for health reasons; incidence of the disease; propensity of test-positives to adverse select; policy value adverse selectors buy in a non-disclosure environment; and price elasticity of demand for insurance. Our illustrative model can be used as a benchmark for developing other scenarios or incorporating real data in order to address the impact of different policies on disclosure and requirement to test.