Carlo A. Marra

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

BACKGROUND Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. METHODS WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. FINDINGS Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. FUNDING US Presidents Emergency Plan for AIDS Relief.

Economic burden of asthma: a systematic review

BackgroundAsthma is associated with enormous healthcare expenditures that include both direct and indirect costs. It is also associated with the loss of future potential earnings related to both morbidity and mortality. The objective of the study is to determine the burden of disease costs associated with asthma.MethodsWe performed a systematic search of MEDLINE, EMBASE, CINAHL, CDSR, OHE-HEED, and Web of Science Databases between 1966 and 2008.ResultsSixty-eight studies met the inclusion criteria. Hospitalization and medications were found to be the most important cost driver of direct costs. Work and school loss accounted for the greatest percentage of indirect costs. The cost of asthma was correlated with comorbidities, age, and disease severity.ConclusionDespite the availability of effective preventive therapy, costs associated with asthma are increasing. Strategies including education of patients and physicians, and regular follow-up are required to reduce the economic burden of asthma.

Evaluating health-related quality-of-life studies in paediatric populations: some conceptual, methodological and developmental considerations and recent applications.

Although numerous paediatric-based health-related quality-of-life (HR-QOL) instruments are currently in use, there still remain conceptual, methodological and developmental issues to address. This paper provides an up-to-date critical review of the HR-QOL literature in paediatric medicine.Our analysis indicates that there is no consensus on how HR-QOL and overall QOL should be defined and measured in children. It is recommended that future studies focus on operationalising and distinguishing these constructs from each other and from traditional health-status measures. A clear empirical basis for generating instrument items and for prioritising specific domains must be described. Researchers should consider using the data gathered during their first interviews as a springboard from which to test their ideas of HR-QOL and QOL, reformulate concepts and subsequently retest their notions before developing instruments.Related to methodological challenges, consistency and agreement are still used interchangeably when comparing child and parent reports of children’s HR-QOL. The Pearson correlation is a measure of co-variation in scores, and not a measure of agreement. We recommend that researchers focus on determining agreement as opposed to consistency. Few, if any, attempts have been made to account for the possibility that a response shift may have occurred in the evaluation of HR-QOL. Most studies have compared HR-QOL scores of children with illness with their healthy peers. As such, there is a dearth of knowledge regarding the normative process of adaptation within the context of illness. It is recommended that researchers focus on gathering data using a relative standard of comparison. We further recommend that researchers interpret HR-QOL data in line with their intended purpose. Regarding developmental consideration, particular attention ought to be paid to developing instruments that consider children’s emerging sense of self, cognitive capacity and emotional awareness. Instruments that include items that are age appropriate are more likely to maximise reliability and validity of reports.The results of many HR-QOL instruments are applied in pharmacotherapeutic and pharmacoeconomic assessments. However, there has been relative infrequent application of economically valid HR-QOL tools (utility scales) and the use of HR-QOL scales as outcome measures in paediatric drug trials. As such, few cost-utility analyses have been performed to inform paediatric decision making. In addition, many of the concerns in the development of HR-QOL instruments should also be applied to the utility scales such that they reflect adequately children’s preferences for health states.

Antibiotic Use in Children Is Associated With Increased Risk of Asthma

BACKGROUND. Antibiotic exposure in early childhood is a possible contributor to the increasing asthma prevalence in industrialized countries. Although a number of published studies have tested this hypothesis, the results have been conflicting. OBJECTIVE. To explore the association between antibiotic exposure before 1 year of age and development of childhood asthma. METHODS. Using administrative data, birth cohorts from 1997 to 2003 were evaluated (N = 251817). Antibiotic exposure was determined for the first year of life. After the first 24 months of life, the incidence of asthma was determined in both those exposed and not exposed to antibiotics in the first 12 months of life. Cox proportional hazards models were used to adjust for potential confounders and determine the hazard ratios associated with antibiotic exposure for the development of asthma. RESULTS. Antibiotic exposure in the first year of life was associated with a small risk of developing asthma in early childhood after adjusting for gender, socioeconomic status at birth, urban or rural address at birth, birth weight, gestational age, delivery method, frequency of physician visits, hospital visit involving surgery, visits to an allergist, respirologist, or immunologist, congenital anomalies, and presence of otitis media, acute, or chronic bronchitis, and upper and lower respiratory tract infections during the first year of life. As the number of courses of antibiotics increased, this was associated with increased asthma risk, with the highest risk being in children who received >4 courses. All antibiotics were associated with an increased risk of developing asthma, with the exception of sulfonamides. CONCLUSIONS. This study provides evidence that the use of antibiotics in the first year of life is associated with a small risk of developing asthma, and this risk increases with the number of courses of antibiotics prescribed.

The Economic Impact of Obstructive Sleep Apnea

Untreated obstructive sleep apnea (OSA) increases healthcare utilization and is associated with reduced work performance and occupational injuries. The economic burden related to untreated OSA is substantial, accounting for billions of dollars per year. Furthermore, therapy of OSA is an extremely cost-efficient use of healthcare resources, comparing highly favorably with other commonly funded medical therapies. Governments, transportation agencies, industry, and insurance companies need to be better informed concerning the economic impact of untreated OSA and the benefits of therapy.

A comparison of four indirect methods of assessing utility values in rheumatoid arthritis.

Objectives:Utility scores can be assessed indirectly using preference-based instruments and used as weightings for quality-adjusted life years in economic analyses. It is not clear whether available instruments yield similar results or what domains of health are contributing to the overall score in a sample of patients with rheumatoid arthritis (RA). Subjects:Our study included 313 individuals with rheumatologist-confirmed RA. Measures:A self-completed survey that permitted scoring of 4 indirect utility instruments (the Health Utilities Index Mark 2 and 3 (HUI-2 and HUI-3), the EuroQoL (EQ-5D), and the Short Form 6D (SF-6D) was the basis of our study. Results:Mean (standard deviation) global utility scores were 0.63 (0.24) for the SF-6D, 0.66 (0.13) for the EQ-5D, 0.71 (0.19) for the HUI-2, and 0.53 (0.29) for the HUI-3 (P = 0.02 by repeated-measures analysis of variance). The intraclass correlation across all the indices was 0.67 (95% confidence interval 0.62–0.71). Bland-Altman plots revealed that agreement among instruments was poor at lower utility values. In this elderly RA sample, all of the global utilities mostly measured functional ability and pain. Conclusions:There are significant differences in utilities obtained from different indirect methods. Agreement among the instruments was moderate but poorer at lower utilities. It is unlikely that these utility values, if used as the weightings for quality-adjusted life years, would result in comparable estimates.

Does a home-based strength and balance programme in people aged ≥80 years provide the best value for money to prevent falls? A systematic review of economic evaluations of falls prevention interventions

Objectives To investigate the value for money of strategies to prevent falls in older adults living in the community. Design Systematic review of peer reviewed journal articles reporting an economic evaluation of a falls prevention intervention as part of a randomised controlled trial or a controlled trial, or using an analytical model. MEDLINE, PUBMED, EMBASE and NHS EED databases were searched to identify cost-effectiveness, cost–utility and cost–benefit studies from 1945 through July 2008. Main outcome measures The primary outcome measure was incremental cost-effectiveness, cost–utility and cost–benefit ratios in the reported currency and in pounds sterling at 2008 prices. The quality of the studies was assessed using two instruments: (1) an economic evaluation checklist developed by Drummond and colleagues and (2) the Quality of Health Economic Studies instrument. Results Nine studies meeting our inclusion criteria included eight cost-effectiveness analyses, one cost–utility and one cost–benefit analysis. Three effective falls prevention strategies were cost saving in a subgroup of participants: (1) an individually customised multifactorial programme in those with four or more of the eight targeted fall risk factors, (2) the home-based Otago Exercise Programme in people ≥80 years and (3) a home safety programme in the subgroup with a previous fall. These three findings were from six studies that scored ≥75% on the Quality of Health Economic Studies instrument. Conclusions Best value for money came from effective single factor interventions such as the Otago Exercise Programme which was cost saving in adults 80 years and older. This programme has broad applicability thus warranting warrants health policy decision-makers’ close scrutiny.

Physical activity as a mediator of the impact of chronic conditions on quality of life in older adults

BackgroundChronic conditions could negatively affect the quality of life of older adults. This may be partially due to a relative lack of physical activity. We examined whether physical activity mediates the relationship between different chronic conditions and several health outcomes that are important to the quality of life of older adults.MethodsThe data were taken from the Canadian Community Health Survey (cycle 1.1), a cross-section survey completed in 2001. Only respondents who were 65 years or older were included in our study (N = 22,432). The Health Utilities Index Mark 3 (HUI3) was used to measure overall quality of life, and to measure selected health outcomes (dexterity, mobility, pain, cognition, and emotional wellbeing) that are considered to be of importance to the quality of life of older adults. Leisure-time physical activity was assessed by determining weekly energy expenditure (Kcal per week) based on the metabolic equivalents of self-reported leisure activities. Linear and logistic regression models were used to determine the mediating effect of leisure-time physical activity while controlling for demographic variables (age and sex), substance use (tobacco use and alcohol consumption), and obesity.ResultsHaving a chronic condition was associated with a relative decrease in health utility scores and a relative increase in mobility limitations, dexterity problems, pain, emotional problems (i.e., decreased happiness), and cognitive limitations. These negative consequences could be partially attributed to a relative lack of physical activity in older adults with a chronic condition (14% mediation for the HUI3 score). The corresponding degree of mediation was 18% for mobility limitations, 5% for pain, and 13% for emotional wellbeing (statistically significant mediation was not observed for the other health attributes). These values varied with respect to the different chronic conditions examined in our study.ConclusionOlder adults with chronic conditions are less likely to engage in leisure-time physical activities of at least 1,000 Kcal per week, and this association partially accounts for some negative consequences of chronic conditions, including mobility limitations, pain, and emotional problems. These findings provide support for health promotion programs that facilitate or encourage increased leisure-time physical activity in older people with chronic conditions.

Effectiveness and cost effectiveness of human papillomavirus vaccine: a systematic review.

AbstractThe recent approval of human papillomavirus (HPV) vaccine means that decision makers need information beyond that available from randomized clinical trials to recommend funding for this vaccination programme. Modelling and economic studies have addressed some of those information needs. We conducted a qualitative systematic review to summarize the existing data. Review articles were obtained from an extensive literature search on studies using mathematical modelling (either a Markov or transmission dynamic model) to determine the effectiveness or cost effectiveness of an HPV vaccine compared with the current cytology-based Pap smear screening programme.A total of 21 studies (but 22 models) were included in the review after being assessed for methodological quality. All of the included studies had used a mathematical model to determine the effectiveness of an HPV vaccine, whilst 13 had also conducted a cost-effectiveness analysis. Although the studies used different model structures, baseline parameters and assumptions, all studies showed that vaccination would decrease rates of HPV infection, precancerous lesions and cervical cancer. Studies had a consistent message with respect to cost effectiveness: a female-only vaccination programme is cost effective compared with the current cytology-based Pap smear screening programme, while the cost effectiveness of a male and female vaccination programme is generally not cost effective compared with female-only vaccination.

Infliximab Treatment of Rheumatoid Arthritis and Crohn's Disease

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and pharmacoeconomic impact of infliximab in the treatment of Crohns disease (CD) and rheumatoid arthritis (RA). DATA SOURCES: MEDLINE and Pre-MEDLINE (1966–June 2002) and manufacturer prescribing literature were employed to find English-language articles on infliximab. Additional studies and abstracts were identified from the bibliographies of reviewed literature and conference proceedings. STUDY SELECTION/DATA EXTRACTION: All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Safety data were extracted from clinical trials and postmarketing surveillance. Priority was given to randomized, double-blind, placebo-controlled studies for the assessment of efficacy. All available economic evaluations were included. DATA SYNTHESIS: Infliximab is a new monoclonal antibody that appears to work by a unique mechanism: inhibiting the action of tumor necrosis factor-α (TNF-α). Infliximab is administered by intravenous infusion. In clinical trials in CD, infliximab significantly decreased the CD activity index compared with placebo in treatment-resistant disease and significantly reduced the number of draining fistulas in fistulizing disease. In RA, when infliximab was added to methotrexate (MTX), it resulted in a significant improvement in most disease outcome measures when compared with MTX plus placebo. Few major adverse effects were reported in the clinical trials; however, serious adverse events, including malignancy and demyelination, have been reported in postmarketing surveillance. Also, increased susceptibility to infections (including tuberculosis) has been reported. CONCLUSIONS: Infliximab is an effective new agent for the treatment of CD and RA. Its apparent unique mechanism of action makes infliximab an important addition to therapy. Caution should be exercised when considering infliximab for individuals who have chronic or recurrent infections, mild congestive heart failure (New York Heart Association [NYHA] class I/II), nervous system disorders, or live or have lived in an area endemic for histoplasmosis. Infliximab is contraindicated for patients with a clinically important, active infection, moderate to severe congestive heart failure (NYHA class III/IV), or an allergy to mouse proteins or any of the ingredients in infliximab. Further long-term efficacy, safety, and economic data on infliximab are required. Also, for the treatment of RA, the burden of administering infliximab (as a 2-hour supervised infusion) has to be considered when choosing among anti-TNF-α medication (as the other 2 approved agents, etanercept and adalimumab, can be self-administered by subcutaneous injection).