Patient-reported outcomes in randomised controlled trials on age-related macular degeneration

BACKGROUND/AIMS: The purpose of this systematic review was to identify the frequency and type of patient-reported outcome measures (PROMs) used in recent randomised controlled trials (RCTs) for age-related macular degeneration (AMD).

METHODS: The authors conducted a systematic search between January 2010 and November 2013 in MEDLINE, EMBASE, Scopus, Cochrane Library (Central) and the clinical trials registries (http://www.controlled-trials.com and http://www.ClinicalTrials.gov) according to defined inclusion criteria (RCTs on AMD in English). Two independent reviewers evaluated studies for inclusion. One reviewer extracted data of included studies, and a second masked reviewer assessed 10% to confirm accuracy in data collection. Reference lists of included papers and appendices of relevant Cochrane systematic reviews were scanned to identify other relevant RCTs. Information collected on extracted outcomes was analysed using descriptive statistics.

RESULTS: Literature and registry search yielded 3816 abstracts of journal articles and 493 records from trial registries. A total of 177 RCTs were deemed to have met inclusion criteria. Of the 858 outcomes reported, 38 outcomes were identified as PROMs (4.4%). Of the 177 RCTs examined, PROMs were used in 25 trials (14.1%). The National Eye Institute Visual Function Questionnaire-25 was the most frequently used PROM instrument (64% of RCTs with PROMs included).

CONCLUSIONS: This review highlights that a small proportion of AMD RCTs included PROMs as outcome measures and that there was a variety in the instruments used.

HIV-1 superinfection with a triple-class drug-resistant strain in a patient successfully controlled with antiretroviral treatment.

We report a case of HIV-1 superinfection (HSI) with a clade B, triple-class resistant virus in a patient successfully controlling viremia with continuous combination antiretroviral therapy started 8 years earlier during primary HIV infection. The course of HIV infection prior to HSI was monitored in both the source partner and recipient (8 and 11 years, respectively) and 4 years following HSI. This case report demonstrates re-infection with HIV-1 despite effective combination antiretroviral therapy.

Única dosis de gabapentin preoperatorio para analgesia postoperatoria: revisión de literatura

Introducción: el dolor postoperatorio supone un reto para todo anestesiólogo, en los últimos años se ha propuesto el Gabapentin preoperatorio como una buena opción paraanalgesia postoperatoria sin efectos secundarios. Metodología: se realizó una revisión sistemática incluyendo ensayos clínicos controlados realizados en pacientes adultos sometidos a diferentes tipos de cirugía. Se hizo una búsqueda en las bases de datos (PUBMED, EMBASE, LILACS, SCIELO), utilizando los términos “gabapentin”, “postoperative pain”, se extrajeron datos con los estudios incluidos. Resultados: se encontraron un total de 155 artículos, 16 de ellos cumplieron criterios de inclusión. Todos fueron evidencia tipo Ib. Las dosis utilizadas de gabapentin estuvieron entre 300 mg y 1200 mg y el intervalo de administración se encontró entre dos y una hora antes de cirugía, Hay una diferencia estadísticamente significativa en el manejo del dolor con el uso de Gabapentin preoperatorio (p<0,01) comparado contra placebo evaluado en el postoperatorio inmediato, a las 12 horas y 24 horas; así como tendencia a menor uso de opioides y menor náusea y vómito postoperatorio, Discusión: los resultados concuerdan con otros estudios similares realizados previamente y soportan el efecto del Gabapentin como analgésico directo y no solo como coadyuvante del manejo del dolor. Aún falta determinar cuál es la dosis más efectiva, aunque hasta la fecha el gabapentin supone menos efectos adversos, igualmente falta determinar si el efecto de menor nausea y vomito postoperatorio se relaciona con un efecto directo del gabapentin o por ahorro en consumo de opioides.Metodología Se realizó una revisión sistemática incluyendo ensayos clínicos controlados realizados en pacientes adultos sometidos a diferentes tipos de cirugía. Se hizo una búsqueda en las bases de datos (PUBMED, EMBASE, LILACS, SCIELO), utilizando los términos “gabapentin”, “postoperative pain”, se extrajeron datos con los estudios incluidos. ResultadosSe encontraron un total de 155 artículos, 16 de ellos cumplieron criterios de inclusión. Todos fueron evidencia tipo Ib. Las dosis utilizadas de gabapentin estuvieron entre 300 mg y 1200 mg y el intervalo de administración se encontró entre dos y una hora antes de cirugía, Hay una diferencia estadísticamente significativa en el manejo del dolor con el uso de Gabapentin preoperatorio (p<0,01) comparado contra placebo evaluado en el postoperatorio inmediato, a las 12 horas y 24 horas; así como tendencia a menor uso de opioides y menor náusea y vómito postoperatorio, DiscusiónLos resultados concuerdan con otros estudios similares realizados previamente y soportan el efecto del Gabapentin como analgésico directo y no solo como coadyuvante del manejo del dolor. Aún falta determinar cual es la dosis más efectiva, aunque hasta la fecha el gabapentin supone menos efectos adversos, igualmente falta determinar si el efecto de menor nausea y vomito postoperatorio se relaciona con un efecto directo del gabapentin o por ahorro en consumo de opioides.

Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta-analysis of individual patient data from randomised controlled trials

Background: The objective was to evaluate the efficacy and tolerability of donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations of mild to moderate Alzheimer's disease (AD). Method: A systematic review of individual patient data from Phase II and III double-blind, randomised, placebo-controlled studies of up to 24 weeks and completed by 20 December 1999. The main outcome measures were the ADAS-cog, the CIBIC-plus, and reports of adverse events. Results: A total of 2376 patients from ten trials were randomised to either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893). Cognitive performance was better in patients receiving donepezil than in patients receiving placebo. At 12 weeks the differences in ADAS-cog scores were 5 mg/day-placebo: - 2.1 [95% confidence interval (CI), - 2.6 to - 1.6; p < 0.001], 10 mg/day-placebo: - 2.5 ( - 3.1 to - 2.0; p < 0.001). The corresponding results at 24 weeks were - 2.0 ( - 2.7 to - 1.3; p < 0.001) and - 3.1 ( - 3.9 to - 2.4; p < 0.001). The difference between the 5 and 10 mg/day doses was significant at 24 weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC-plus at 12 weeks were: 5 mg/day-placebo 1.8 (1.5 to 2.1; p < 0.001), 10 mg/day-placebo 1.9 (1.5 to 2.4; p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to 2.4; p = 0.001) and 2.1 (1.6 to 2.8; p < 0.001). Donepezil was well tolerated; adverse events were cholinergic in nature and generally of mild severity and brief in duration. Conclusion: Donepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician-rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose. Copyright © 2004 John Wiley & Sons, Ltd.

Patient engagement and coaching for health: the PEACH study- a cluster randomised controlled trial using the telephone to coach people with type 2 diabetes to engage with their GPs to improve diabetes care: a study protocol.

Background
The PEACH study is based on an innovative 'telephone coaching' program that has been used effectively in a post cardiac event trial. This intervention will be tested in a General Practice setting in a pragmatic trial using existing Practice Nurses (PN) as coaches for people with type 2 diabetes (T2D). Actual clinical care often fails to achieve standards, that are based on evidence that self-management interventions (educational and psychological) and intensive pharmacotherapy improve diabetes control. Telephone coaching in our study focuses on both. This paper describes our study protocol, which aims to test whether goal focused telephone coaching in T2D can improve diabetes control and reduce the treatment gap between guideline based standards and actual clinical practice.
Methods/design
In a cluster randomised controlled trial, general practices employing Practice Nurses (PNs) are randomly allocated to an intervention or control group. We aim to recruit 546 patients with poorly controlled T2D (HbA1c >7.5%) from 42 General Practices that employ PNs in Melbourne, Australia. PNs from General Practices allocated to the intervention group will be trained in diabetes telephone coaching focusing on biochemical targets addressing both patient self-management and engaging patients to work with their General Practitioners (GPs) to intensify pharmacological treatment according to the study clinical protocol. Patients of intervention group practices will receive 8 telephone coaching sessions and one face-to-face coaching session from existing PNs over 18 months plus usual care and outcomes will be compared to the control group, who will only receive only usual care from their GPs. The primary outcome is HbA1c levels and secondary outcomes include cardiovascular disease risk factors, behavioral risk factors and process of care measures.
Discussion
Understanding how to achieve comprehensive treatment of T2D in a General Practice setting is the focus of the PEACH study. This study explores the potential role for PNs to help reduce the treatment and outcomes gap in people with T2D by using telephone coaching. The intervention, if found to be effective, has potential to be sustained and embedded within real world General Practice.

The impact of patient sex on paramedic pain management in the prehospital setting

Objective: The aim of this study was to establish the impact of patient sex on the provision of analgesia by paramedics for patients reporting pain in the prehospital setting.
Methods: This retrospective cohort study of paramedic patient care records included all adult patients with a Glasgow Coma Score higher than 12 transported to hospital by ambulance in a major metropolitan area over a 7-day period in 2005. Data collected included demographics, patient report of pain and its type and severity, provision of analgesia by paramedics, and type of analgesia provided. The outcomes of interest were sex differences in the provision of analgesia. Data analysis was by descriptive statistics, χ2 test, and logistic regression.
Results: Of the 3357 patients transported in the study period, 1766 (53%) reported pain; this forms the study sample. Fifty-two percent were female, median age was 61 years, and median initial pain score (on a 0-10 verbal numeric rating scale) was 6. Forty-five percent of patients reporting pain did not receive analgesia (791/1766) (95% confidence interval [CI], 43%-47%), with no significant difference between sexes (P = .93). There were, however, significant sex differences in the type of analgesia administered, with males more likely to receive morphine (17%; 95% CI, 15%-20%) than females (13%; 95% CI, 11%-15%) (P = .01). The difference remains significant when controlled for type of pain, age, and pain severity (odds ratio, 0.61, 95% CI, 0.44-0.84).
Conclusion: Sex is not associated with the rate of paramedic-initiated analgesia, but is associated with differences in the type of analgesia administered.

Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

Background
The majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).

Methods/Design
The HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense®). The pharmacies have been randomised to either 'Pharmacist Care Group' (PCG) or 'Usual Care Group' (UCG). To check for 'Hawthorne effect' in the UCG, a third group of patients 'Hidden Control Group' (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.

Discussion
To our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the 'Hawthorne effect' in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.

Trial Registration
Australian New Zealand Clinical Trial Registry ACTRN12609000705280

Effectiveness of vertebroplasty using individual patient data from two randomised placebo controlled trials : meta-analysis

Objective To determine whether vertebroplasty is more effective than placebo for patients with pain of recent onset (≤6 weeks) or severe pain (score ≥8 on 0-10 numerical rating scale).

Design Meta-analysis of combined individual patient level data.

Setting Two multicentred randomised controlled trials of vertebroplasty; one based in Australia, the other in the United States.

Participants 209 participants (Australian trial n=78, US trial n=131) with at least one radiographically confirmed vertebral compression fracture. 57 (27%) participants had pain of recent onset (vertebroplasty n=25, placebo n=32) and 99 (47%) had severe pain at baseline (vertebroplasty n=50, placebo n=49).

Intervention Percutaneous vertebroplasty versus a placebo procedure.

Main outcome measure Scores for pain (0-10 scale) and function (modified, 23 item Roland-Morris disability questionnaire) at one month.

Results For participants with pain of recent onset, between group differences in mean change scores at one month for pain and disability were 0.1 (95% confidence interval −1.4 to 1.6) and 0.2 (−3.0 to 3.4), respectively. For participants with severe pain at baseline, between group differences for pain and disability scores at one month were 0.3 (−0.8 to 1.5) and 1.4 (−1.2 to 3.9), respectively. At one month those in the vertebroplasty group were more likely to be using opioids.

Conclusions Individual patient data meta-analysis from two blinded trials of vertebroplasty, powered for subgroup analyses, failed to show an advantage of vertebroplasty over placebo for participants with recent onset fracture or severe pain. These results do not support the hypothesis that selected subgroups would benefit from vertebroplasty.

Randomised controlled trials and 'unexpected' adverse events associated with newly released drugs : improvements in pharmacovigilance systems are necessary for real-time identification of patient safety risks

Adverse drug events are one of the major causes of morbidity in developed countries, yet the drugs involved in these events have been trialled and approved on the basis of randomised controlled trials (RCTs), regarded as the study design that will produce the best evidence.

Though the focus on adverse drug events has been primarily on processes and outcomes associated with the use of these approved drugs, attention needs to be directed to the way in which the RCT study design is structured. The implementation of controls to achieve internal validity in RCTs may be the very controls that reduce external validity, and contribute to the levels of adverse drug events associated with the release of a new drug to the wider patient population.

An examination of these controls, and the effects they can have on patient safety, underscore the importance of knowing about how the clinical trials of a drug are undertaken, rather than relying only on the recorded outcomes.

As the majority of new drugs are likely to be prescribed to older patients who have one or more comorbidities in addition to that targeted by a new drug, and as the RCTs of those drugs typically under-represent the elderly and exclude patients with multiple comorbidities, timely assessment of drug safety signals is essential.

It is unlikely that regulatory jurisdictions will undertake a reassessment of safety issues for drugs that are already approved. Instead, reliance has been placed on adverse drug event reporting systems. Such systems have a very low reporting rate, and most adverse drug events remain unreported, to the eventual cost to patients and healthcare systems.

This makes it essential for near real-time systems that can pick up safety signals as they occur, so that modifications to the product information (or removal of the drug) can be implemented.

Factors limiting participation in arthritis self-management programmes : an exploration of barriers and patient preferences within a randomized controlled trial

Objective. To improve understanding of barriers to participation in community-based arthritis self-management programmes and patient preferences for self-management education.

Methods. Individuals with hip or knee OA referred to orthopaedic surgeons or rheumatologists at six public and private hospitals in Victoria, Australia, were recruited for a randomized controlled trial (RCT) of the Stanford Arthritis Self-Management Programme (ASMP). As part of the study design, potential participants were asked during the screening and recruitment process about reasons for being unable to attend the course, reasons for not participating in the study and individual preferences for course scheduling.

Results. Of 1125 individuals assessed, 216 (19%) were unable to attend six ASMP sessions. This was commonly due to physical limitations, including illness, restricted mobility and pain (22%), difficulty getting to or from courses (22%), work commitments (22%), the time commitment required (17%) and family roles (12%). Among those who did not want to participate in the study (n = 258), the overwhelming reason was disinterest (74%). Specific preferences for course scheduling were frequent, confirming the practical challenges faced in organizing courses for the RCT.

Conclusion. Incorporating patients from public and private settings, this study has elicited new insights into barriers to ASMP participation. Many people with hip or knee OA have limited capacity and motivation to attend community-based group programmes. Future self-management programmes and research should include more accessible options for those who cannot attend group-based programmes.

A study protocol of a randomised controlled trial incorporating a health economic analysis to investigate if additional allied health services for rehabilitation reduce length of stay without compromising patient outcomes

Background
Reducing patient length of stay is a high priority for health service providers. Preliminary information suggests additional Saturday rehabilitation services could reduce the time a patient stays in hospital by three days. This large trial will examine if providing additional physiotherapy and occupational therapy services on a Saturday reduces health care costs, and improves the health of hospital inpatients receiving rehabilitation compared to the usual Monday to Friday service. We will also investigate the cost effectiveness and patient outcomes of such a service.
Methods/Design A randomised controlled trial will evaluate the effect of providing additional physiotherapy and occupational therapy for rehabilitation. Seven hundred and twelve patients receiving inpatient rehabilitation at two metropolitan sites will be randomly allocated to the intervention group or control group. The control group will receive usual care physiotherapy and occupational therapy from Monday to Friday while the intervention group will receive the same amount of rehabilitation as the control group Monday to Friday plus a full physiotherapy and occupational therapy service on Saturday. The primary outcomes will be patient length of stay, quality of life (EuroQol questionnaire), the Functional Independence Measure (FIM), and health utilization and cost data. Secondary outcomes will assess clinical outcomes relevant to the goals of therapy: the 10 metre walk test, the timed up and go test, the Personal Care Participation Assessment and Resource Tool (PC PART), and the modified motor assessment scale. Blinded assessors will assess outcomes at admission and discharge, and follow up data on quality of life, function and health care costs will be collected at 6 and 12 months after discharge. Between group differences will be analysed with analysis of covariance using baseline measures as the covariate. A health economic analysis will be carried out alongside the randomised controlled trial.
Discussion This paper outlines the study protocol for the first fully powered randomised controlled trial incorporating a health economic analysis to establish if additional Saturday allied health services for rehabilitation inpatients reduces length of stay without compromising discharge outcomes. If successful, this trial will have substantial health benefits for the patients and for organizations delivering rehabilitation services.

Patient comfort in the intensive care unit : a multicentre, binational point prevalence study of analgesia, sedation and delirium management

Objective: To measure the prevalence of assessment and management practices for analgesia, sedation and delirium in patients in Australian and New Zealand intensive care units.
Materials and Methods: We developed survey items from a modified Delphi panel and included them in a binational, point prevalence study. We used a standard case report form to capture retrospective patient data on management of analgesia, sedation and delirium at the end of a 4-hour period on the study day. Other data were collected during independent assessment of patient status and medication requirements.
Results: Data were collected on 569 patients in 41 ICUs. Pain assessment was documented in the 4 hours before study observation in 46% of patients. Of 319 assessable patients, 16% had moderate pain and 6% had severe pain. Routine sedation assessment using a scale was recorded in 63% of intubated and ventilated patients. When assessed, 38% were alert and calm, or drowsy and rousable, 22% were lightly to moderately sedated, 31% were deeply sedated (66% of these had a documented indication), and 9% were agitated or restless. Sedatives were titrated to a target level in 42% of patients. Routine assessment of delirium occurred in 3%, and at study assessment 9% had delirium. Wrist or arm restraints were used for 7% of patients.
Conclusions: Only two-thirds of sedated patients had their sedation levels formally assessed, half had pain assessed and very few had formal assessment of delirium. Our description of current practices, and other observational data, may help in planning further research in this area.

Improving the care of children with advanced cancer by using an electronic patient-reported feedback intervention : results from the PediQUEST randomized controlled trial.

This study aimed to determine whether feeding back patient-reported outcomes (PROs) to providers and families of children with advanced cancer improves symptom distress and health-related quality of life (HRQoL).

Effectiveness of patient feedback as an educational intervention to improve medical student consultation (PTA Feedback Study): study protocol for a randomized controlled trial.

Oral feedback from clinical educators is the traditional teaching method for improving clinical consultation skills in medical students. New approaches are needed to enhance this teaching model. Multisource feedback is a commonly used assessment method for learning among practising clinicians, but this assessment has not been explored rigorously in medical student education. This study seeks to evaluate if additional feedback on patient satisfaction improves medical student performance.