Keith Tomlin

The benefits to communities and individuals of screening for active tuberculosis disease: a systematic review [State of the art series. Case finding/screening. Number 2 in the series].

BACKGROUND Screening for tuberculosis (TB) disease aims to improve early TB case detection. The ultimate goal is to improve outcomes for people with TB and to reduce Mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. Before screening programmes are recommended, evidence is needed of individual and/or community-level benefits. METHODS We conducted a systematic review of the literature to assess the evidence that screening for TB disease 1) initially increases the number of TB cases initiated on anti-tuberculosis treatment, 2) identifies cases earlier in the course of disease, 3) reduces mortality and morbidity, and 4) impacts on TB epidemiology. RESULTS A total of 28 798 publications were identified by the search strategy: 27 087 were excluded on initial screening and 1749 on full text review, leaving 62 publications that addressed at least one of the study questions. Screening increases the number of cases found in the short term. In many settings, more than half of the prevalent TB cases in the community remain undiagnosed. Screening tends to find cases earlier and with less severe disease, but this may be attributed to case-finding studies using more sensitive diagnostic methods than routine programmes. Treatment outcomes among people identified through screening are similar to outcomes among those identified through passive case finding. Current studies provide insufficient evidence to show that active screening for TB disease impacts on TB epidemiology. CONCLUSION Individual and community-level benefits from active screening for TB disease remain uncertain. So far, the benefits of earlier diagnosis on patient outcomes and transmission have not been established.

Reasons for Receiving or Not Receiving HPV Vaccination in Primary Schoolgirls in Tanzania: A Case Control Study

Background There are few data on factors influencing human papillomavirus (HPV) vaccination uptake in sub-Saharan Africa. We examined the characteristics of receivers and non-receivers of HPV vaccination in Tanzania and identified reasons for not receiving the vaccine. Methods We conducted a case control study of HPV vaccine receivers and non-receivers within a phase IV cluster-randomised trial of HPV vaccination in 134 primary schools in Tanzania. Girls who failed to receive vaccine (pupil cases) and their parents/guardians (adult cases) and girls who received dose 1 (pupil controls) of the quadrivalent vaccine (Gardasil™) and their parents/guardians (adult controls) were enrolled from 39 schools in a 1∶1 ratio and interviewed about cervical cancer, HPV vaccine knowledge and reasons why they might have received or not received the vaccine. Conditional logistic regression was used to determine factors independently associated with not receiving HPV vaccine. Results We interviewed 159 pupil/adult cases and 245 pupil/adult controls. Adult-factors independently associated with a daughter being a case were older age, owning fewer household items, not attending a school meeting about HPV vaccine, and not knowing anyone with cancer. Pupil-factors for being a case included having a non-positive opinion about the school de-worming programme, poor knowledge about the location of the cervix, and not knowing that a vaccine could prevent cervical cancer. Reasons for actively refusing vaccination included concerns about side effects and infertility. Most adult and pupil cases reported that they would accept the HPV vaccine if it were offered again (97% and 93% respectively). Conclusions Sensitisation messages, especially targeted at older and poorer parents, knowledge retention and parent meetings are critical for vaccine acceptance in Tanzania. Vaccine side effects and fertility concerns should be addressed prior to a national vaccination program. Parents and pupils who initially decline vaccination should be given an opportunity to reconsider their decision.

Internet-based cohort study of HIV testing over 1 year among men who have sex with men living in England and exposed to a social marketing intervention promoting testing

Objectives Increasing HIV testing among men who have sex with men (MSM) is a major policy goal in the UK. Social marketing is a common intervention to increase testing uptake. We used an online panel of MSM to examine rates of HIV testing behaviour and the impact of a social marketing intervention on them. Method MSM in England were recruited to a longitudinal internet panel through community websites and a previous survey. Following an enrolment survey, respondents were invited to self-complete 13 surveys at monthly intervals throughout 2011. A unique alphanumeric code linked surveys for individuals. Rates of HIV testing were compared relative to prompted recognition of a multi-part media campaign aiming to normalise HIV testing. Results Of 3386 unique enrolments, 2047 respondents were included in the analysis, between them submitting 15 353 monthly surveys (equivalent to 1279 years of follow-up), and recording 1517 HIV tests taken, giving an annual rate of tests per participant of 1.19 (95% CI 1.13 to 1.25). Tests were highly clustered in individuals (61% reported no test during the study). Testing rates were higher in London, single men and those aged 25–34 years. Only 7.6% recognised the intervention when prompted. After controlling for sociodemographic characteristics and exposure to other health promotion campaigns, intervention recognition was not associated with increased likelihood of testing. Higher rates of testing were strongly associated with higher number of casual sexual partners and how recently men had HIV tested before study enrolment. Conclusions This social marketing intervention was not associated with increased rates of HIV testing. More effective promotion of HIV testing is needed among MSM in England to reduce the average duration of undiagnosed infection.

Neonatal Ventilation with Inhaled Nitric Oxide vs. Ventilatory Support without Inhaled Nitric Oxide for Infants with Severe Respiratory Failure Born at or Near Term: The INNOVO Multicentre Randomised Controlled Trial

Background: Evidence from European centres to support the use of nitric oxide (NO) in mature newborns with evidence of severe respiratory failure is sparse. Methods: Infants of >33 weeks’ gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomised to receive or not to receive inhaled NO (iNO). The study was not blinded. Results: Sixty infants were recruited (29 allocated iNO, 31 no iNO) from 15 neonatal units in the UK, Finland, Belgium and the Republic of Ireland. 15/60 recruited babies died, and 8.1% of the survivors (4/45) were classified as severely disabled at 1 year. There was no statistically significant difference between the randomised groups in terms of the primary outcome of death or severe disability by the corrected age of 1 year (relative risk = 0.96 (95% confidence interval = 0.46–2.03); p = 0.86) (Fisher’s exact p = 1.00). The costs of NO were outweighed by reduced extra corporeal membrane oxygenation costs in the iNO group. The mean total hospitalisation costs were lower in the iNO group, although the mean difference (£1,697) was not statistically significant (95% confidence interval = –14,472 to 11,478). Conclusions: The results complement those of previous studies that suggest NO is cost-effective and reduces the need for extra corporeal membrane oxygenation in this group of babies. Overall survival rates compare unfavourably with results of US trials.

Verteporfin Photodynamic Therapy Cohort Study: Report 2: Clinical Measures of Vision and Health-Related Quality of Life

PURPOSE To quantify decreases in health-related quality of life (HRQoL) for given deterioration in clinical measures of vision; to describe the shape of these relationships; and to test whether the gradients of these relationships change with duration of visual loss. DESIGN A prospective, longitudinal study of patients treated with verteporfin photodynamic therapy in the United Kingdom National Health Service. PARTICIPANTS Patients with neovascular age-related macular degeneration (AMD) treated in 18 ophthalmology departments in the United Kingdom with expertise in management of neovascular AMD. METHODS Responses to HRQoL questionnaires (Short Form 36 [SF-36] and National Eye Institute Visual Functioning Questionnaire [NEIVFQ]) and clinical measures of vision were recorded at baseline and at follow-up visits. Mixed regression models were used to characterize the relationships of interest. MAIN OUTCOME MEASURES Measures of vision were best-corrected visual acuity (BCVA) and contrast sensitivity (CS). The SF-36 physical and mental component scores (PCS and MCS), SF-6D utility, and distance, near, and composite NEIVFQ scores were derived to characterize HRQoL. RESULTS The SF-6D, PCS, and MCS were linearly associated with BCVA; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 0.0058, 0.245, and 0.546, respectively (all P<0.0001). Gradients were not influenced by duration of follow-up. Models predicting distance, near, and composite NEIVFQ scores from BCVA were quadratic; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 5.08, 5.48, and 3.90, respectively (all P<0.0001). The BCVA predicted HRQoL scores more strongly than CS. CONCLUSIONS Clinically significant deterioration in clinical measures of vision is associated with small decreases in generic and vision-specific HRQoL. Our findings are important for further research modeling the cost effectiveness of current and future interventions for neovascular AMD.

Respiratory function during infancy in survivors of the INNOVO trial.

Despite encouraging reports suggesting that inhaled nitric oxide (iNO) appear to improve outcome in hypoxemic term and near term infants by improving oxygenation and reducing need for ECMO, the long‐term benefits of iNO remain unclear. This study aimed to compare lung function at approximately 1 year in infants who were and were not randomly allocated to iNO as part of their neonatal management for severe respiratory failure at birth. Furthermore, results were compared to lung function of healthy infants.

Verteporfin Photodynamic Therapy Cohort Study: Report 3: Cost Effectiveness and Lessons for Future Evaluations

PURPOSE To report (1) the costs of verteporfin photodynamic therapy (VPDT) in routine treatment of neovascular age-related macular degeneration (nAMD), (2) the relationship between health and social service costs and best-corrected visual acuity (BCVA), (3) the cost-effectiveness of VPDT versus a best supportive care (BSC) group who were assumed to have no active treatment, and (4) lessons for future cost-effectiveness analyses (CEAs). DESIGN The CEA of VPDT versus BSC that uses health-related quality of life (HrQoL), resource use, and visual acuity data from the United Kingdom (UK) VPDT Cohort Study. PARTICIPANTS Data on VPDT use were collected from patients attending 45 ophthalmology provider units in the UK National Health Service, 15 units collected data on self-reported use of services. METHODS Incremental costs of VPDT versus BSC were calculated from treatment costs, change in cost associated with declining BCVA, and difference in BCVA previously attributed to VPDT. Similarly, incremental quality-adjusted life years (QALYs) were calculated from change in HRQoL associated with declining BCVA, giving an incremental cost per QALY of VPDT versus BSC over 2 years. MAIN OUTCOME MEASURES Incremental costs (UK pounds [ pound]; United States dollars [

Verteporfin Photodynamic Therapy Cohort Study: Report 1: Effectiveness and Factors Influencing Outcomes

]); incremental QALYs; costs per QALY. RESULTS The treatment costs of VDPT were pound 3026 (

Impact of integrated services on HIV testing: a nonrandomized trial among Kenyan family planning clients.

4544) in year 1 and pound 845 (

Neonatal Ventilation With Inhaled Nitric Oxide Versus Ventilatory Support Without Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure: The INNOVO Multicentre Randomised Controlled Trial (ISRCTN 17821339)

1269) in year 2. For patients who used services, a 5-letter decrease in BCVA was associated with an increase in annual costs of approximately pound 110 (