RESUMEN
PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial (ClinicalTrials.gov identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.
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Glaucoma de Ángulo Cerrado/cirugía , Iridectomía/métodos , Iris/cirugía , Láseres de Estado Sólido/uso terapéutico , Anciano , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/fisiopatología , Gonioscopía , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Singapur , Tonometría Ocular , Resultado del Tratamiento , Agudeza Visual/fisiologíaRESUMEN
In the last decade, drug development has tackled substantial challenges to improve efficiency and facilitate access to innovative medicines. Integrated clinical protocols and the investigation of targeted oncology drugs in healthy volunteers (HVs) have emerged as modalities with an increase in scope and complexity of early clinical studies and first-in-human (FIH) studies in particular. However, limited work has been done to explore the impact of these two modalities, alone or in combination, on the scientific value and on the implementation of such articulated studies. We conducted an FIH study in HVs with an oncology targeted drug, an Mnk 1/2 small molecule inhibitor. In this article, we describe results, advantages, and limitations of an integrated clinical protocol with an oncology drug. We further discuss and indicate points to consider when designing and conducting similar scientifically and operationally demanding FIH studies.
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Antineoplásicos/efectos adversos , Enfermedades Cardiovasculares/diagnóstico , Protocolos Clínicos , Inhibidores de Proteínas Quinasas/efectos adversos , Proyectos de Investigación , Administración Oral , Adulto , Antineoplásicos/administración & dosificación , Enfermedades Cardiovasculares/inducido químicamente , Electrocardiografía , Voluntarios Sanos , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Masculino , Oncología Médica/métodos , Persona de Mediana Edad , Monitoreo Ambulatorio/métodos , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Adulto JovenRESUMEN
In clinical trials, where the outcome of interest is the occurrence of an event over a fixed time period, estimation of the event proportion at interim analysis can form a basis for decision-making such as early trial termination, sample size re-estimation, and/or dropping inferior treatment arms. In addition to derivation of mean squared error under an exponential time-to-event distribution, we performed a simulation study to examine the performance of five estimators of the event proportion when time to the event is assessable. The simulation results showed advantages of the Kaplan-Meier estimator over others in terms of robustness, and the bias and variability of the event proportion estimate. An example was given to illustrate how the estimators affect dropping treatment arms in a multi-arm multi-stage adaptive trial. We recommended the use of the Kaplan-Meier estimator and discourage the use of other estimators that discard the inherent time-to-event information.
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Determinación de Punto Final/estadística & datos numéricos , Modelos Estadísticos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Proyectos de Investigación/estadística & datos numéricos , Resultado del Tratamiento , Simulación por Computador , Humanos , Estimación de Kaplan-Meier , Probabilidad , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Tamaño de la Muestra , Factores de TiempoRESUMEN
INTRODUCTION: Dental caries, which is prevalent in Singapore preschoolers, is a disease that has a major impact on children's health and places a high cost on the society and health services. Oral health programmes for young children implemented in some parts of the world have been shown to be effective in the prevention of dental caries. We aimed to examine the clinical efficacy of a two-year oral health programme for infants and toddlers in Singapore. METHODS: 90 children and their caregivers participated in the programme, and 64 children, who were 24 months older than the intervention group at the initial visit, were recruited as controls in a quasi-experimental study design. We evaluated the presence of severe early childhood caries (SECC) and d3mfs in the control group at the initial visit and in the intervention group after the completion of the two-year programme. RESULTS: Some children in the intervention (7.8%) and control (31.3%) groups (p < 0.001) had SECC (difference 23.5%, 95% confidence interval 11%-36%). A higher percentage of children in the intervention group had d3mfs = 0 and habits associated with low risk for caries. The odds of SECC in the control group were three times higher than that for the intervention group, and the effect was significant (p = 0.037) after adjustment for other significant risk factors. CONCLUSION: The preventive oral health programme in Singapore was successful in reducing SECC among infants and toddlers when targeted behaviour modifications were implemented.
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Caries Dental/prevención & control , Salud Bucal , Evaluación de Programas y Proyectos de Salud , Cuidadores , Preescolar , Odontología/métodos , Femenino , Costos de la Atención en Salud , Promoción de la Salud , Humanos , Lactante , Masculino , Pediatría , Análisis de Regresión , Proyectos de Investigación , Factores de Riesgo , SingapurRESUMEN
BACKGROUND: There is paucity of data examining the incidence and outcomes of young OHCA adults. The aim of this study is to determine the outcomes and characteristics of young adults who suffered an OHCA and identify factors that are associated with favourable neurologic outcomes. METHODS: All EMS-attended OHCA adults between the ages of 16 and 35 years in the Pan-Asian Resuscitation Outcomes Study (PAROS) registry were analysed. The primary outcome was favourable neurologic outcome (Cerebral Performance Category 1 or 2) at hospital discharge or at 30th day post OHCA if not discharged. Regression analysis was performed to identify factors associated with favourable neurologic outcomes. RESULTS: 66,780 OHCAs were collected between January 2009 and December 2013; 3244 young OHCAs had resuscitation attempted by emergency medical services (EMS). 56.8% of patients had unwitnessed arrest; 47.9% were of traumatic etiology. 17.2% of patients (95% CI: 15.9-18.5%) had return of spontaneous circulation; 7.8% (95% CI: 6.9-8.8%) survived to one month; 4.6% (95% CI: 4.0-5.4%) survived with favourable neurologic outcomes. Factors associated with favourable neurologic outcomes include witnessed arrest (adjusted RR=2.42, p-value<0.0001), bystander CPR (adjusted RR=1.57, p-value=0.004), first arrest shockable rhythm (adjusted RR=27.24, p-value<0.0001), and cardiac etiology (adjusted RR=3.99, p-value<0.0001). CONCLUSIONS: OHCA among young adults are not uncommon. Traumatic OHCA, occurring most frequently in young adults had dismal prognosis. First arrest rhythms of VF/VT/unknown shockable rhythm, cardiac etiology, bystander-witnessed arrest, and bystander CPR were associated with favourable neurological outcomes. The results of the study would be useful for planning preventive and interventional strategies, improving EMS, and guiding future research.
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Paro Cardíaco Extrahospitalario/fisiopatología , Adolescente , Adulto , Efecto Espectador , Reanimación Cardiopulmonar , Femenino , Humanos , Masculino , Paro Cardíaco Extrahospitalario/etiología , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Pronóstico , Sistema de Registros , Resucitación , Resultado del TratamientoRESUMEN
PURPOSE: To compare the safety and efficacy of different concentrations of atropine eyedrops in controlling myopia progression over 5 years. DESIGN: Randomized, double-masked clinical trial. PARTICIPANTS: A total of 400 children originally randomized to receive atropine 0.5%, 0.1%, or 0.01% once daily in both eyes in a 2:2:1 ratio. METHODS: Children received atropine for 24 months (phase 1), after which medication was stopped for 12 months (phase 2). Children who had myopia progression (≥-0.50 diopters [D] in at least 1 eye) during phase 2 were restarted on atropine 0.01% for a further 24 months (phase 3). MAIN OUTCOME MEASURES: Change in spherical equivalent and axial length over 5 years. RESULTS: There was a dose-related response in phase 1 with a greater effect in higher doses, but an inverse dose-related increase in myopia during phase 2 (washout), resulting in atropine 0.01% being most effective in reducing myopia progression at 3 years. Some 24%, 59%, and 68% of children originally in the atropine 0.01%, 0.1%, and 0.5% groups, respectively, who progressed in phase 2 were restarted on atropine 0.01%. Younger children and those with greater myopic progression in year 1 were more likely to require re-treatment. The lower myopia progression in the 0.01% group persisted during phase 3, with overall myopia progression and change in axial elongation at the end of 5 years being lowest in this group (-1.38±0.98 D; 0.75±0.48 mm) compared with the 0.1% (-1.83±1.16 D, P = 0.003; 0.85±0.53 mm, P = 0.144) and 0.5% (-1.98±1.10 D, P < 0.001; 0.87±0.49 mm, P = 0.075) groups. Atropine 0.01% also caused minimal pupil dilation (0.8 mm), minimal loss of accommodation (2-3 D), and no near visual loss compared with higher doses. CONCLUSIONS: Over 5 years, atropine 0.01% eyedrops were more effective in slowing myopia progression with less visual side effects compared with higher doses of atropine.