The impact of consent on observational research: a comparison of outcomes from consenters and non consenters to an observational study

Background Public health benefits from research often rely on the use of data from personal medical records. When neither patient consent nor anonymisation is possible, the case for accessing such records for research purposes depends on an assessment of the probabilities of public benefit and individual harm. Methods In the late 1990s, we carried out an observational study which compared the care given to affluent and deprived women with breast cancer. Patient consent was not required at that time for review of medical records, but was obtained later in the process prior to participation in the questionnaire study. We have re-analysed our original results to compare the whole sample with those who later provided consent. Results Two important findings emerged from the re-analysis of our data which if presented initially would have resulted in insufficient and inaccurate reporting. Firstly, the reduced dataset contains no information about women presenting with locally advanced or metastatic cancer and we would have been unable to demonstrate one of our initial key findings: namely a larger number of such women in the deprived group. Secondly, our re-analysis of the consented women shows that significantly more women from deprived areas (51 v 31%, p = 0.018) received radiotherapy compared to women from more affluent areas. Previously published data from the entire sample demonstrated no difference in radiotherapy treatment between the affluent and deprived groups. Conclusion The risk benefit assessment made regarding the use of medical records without consent should include the benefits of obtaining research evidence based on 100% of the population and the possibility of inappropriate or insufficient findings if research is confined to consented populations

A systematic map of evidence on the contribution of forests to poverty alleviation

This is the final version. Available from the publisher via the DOI in this record.Background: Forests provide an essential resource to the livelihoods of an estimated 20% of the global population. The contribution of forest ecosystems and forest-based resources to poverty reduction is increasingly emphasized in international policy discourse and conservation and development investments. However, evidence measuring the effect of forest-based activities on poverty outcomes remains scattered and unclear. Lack of systematic understanding of forest-poverty relationships, in turn, inhibits research, policymaking, and efficient financial resource allocation. Methods: To identify relevant studies for inclusion in this systematic map we searched six bibliographic databases, 15 organizational websites, eight systematic evidence syntheses (reviews and maps), and solicited information from key informants. Search results were screened for relevance against predefined inclusion criteria at title, abstract, and full text levels, according to a published protocol. Included articles were coded using a predefined framework. Trends in the evidence, knowledge gaps and relatively well-researched sub-topics are reported in a narrative synthesis. Occurrence and extent of existing evidence about links between interventions and outcomes are presented in a visual heatmap. Data are available through the open access Evidence for Nature and People Data Portal (http://www.natureandpeopleevidence.org). Results: A total of 242 articles were included in the systematic map database. Included articles measured effects of 14 forest-based intervention types on 11 poverty dimensions. The majority of the evidence base (72%) examined links between productivity-enhancement strategies (e.g. forest management, agroforestry, and habitat management) and monetary income and/or social capital outcomes. Other areas with high occurrence of articles include linkages between interventions involving governance, individual rights/empowerment or linked enterprises/livelihood alternatives with impacts on monetary income from direct sale of goods. A key knowledge gap was on the impacts of investment-based interventions (i.e. enhancing produced, human, and social capitals). Another was the impacts of forest-based interventions on financial capital (savings, debt), non-monetary benefits, and health. Conclusions: The evidence base on forest-based productive activities and poverty alleviation is growing but displays a number of biases in the distribution of articles on key linkages. Priorities for future systematic reviews and evaluations include in-depth examinations into the impacts of rights-based activities (e.g. governance, empowerment) on poverty dimensions; and productivity-enhancing activities on social capital. More comprehensive and robust evidence is needed to better understand the synergies and trade-offs among the different objectives of forest conservation and management and variation in outcomes for different social groups in different social-ecological contexts

Emergence and Persistence of Minor Drug-Resistant HIV-1 Variants in Ugandan Women after Nevirapine Single-Dose Prophylaxis

BACKGROUND: Nevirapine (NVP) single-dose is still a widely used antiretroviral prophylaxis for the prevention of vertical HIV-1 transmission in resource-limited settings. However, the main disadvantage of the Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) NVP is the rapid selection of NVP-resistant virus with negative implications for subsequent NNRTI-based long-term antiretroviral therapy (ART). Here, we analysed the emergence of drug-resistant HIV-1 including minor variants in the early phase after NVP single-dose prophylaxis and the persistence of drug-resistant virus over time. METHODS AND FINDINGS: NVP-resistant HIV-1 harbouring the K103N and/or Y181C resistance mutations in the HIV-1 reverse transcriptase gene was measured from 1 week up to 18 months after NVP single-dose prophylaxis in 29 Ugandan women using allele-specific PCR assays capable of detecting drug-resistant variants representing less than 1% of the whole viral population. In total, drug-resistant HIV-1 was identified in 18/29 (62%) women; rates increased from 18% to 38% and 44% at week 1, 2, 6, respectively, and decreased to 18%, 25%, 13% and 4% at month 3, 6, 12 and 18, respectively. The proportion of NVP-resistant virus of the total viral population was significantly higher in women infected with subtype D (median 40.5%) as compared to subtype A (median 1.3%; p = 0.032, Mann-Whitney U test). 33% of resistant virus was not detectable at week 2 but was for the first time measurable 6-12 weeks after NVP single-dose prophylaxis. Three (10%) women harboured resistant virus in proportions >10% still at month 6. CONCLUSIONS: Current WHO guidelines recommend an additional postnatal intake of AZT and 3TC for one week to avoid NVP resistance formation. Our findings indicate that a 1-week medication might be too short to impede the emergence of NVP resistance in a substantial proportion of women. Furthermore, subsequent NNRTI-based ART should not be started earlier than 12 months after NVP single-dose prophylaxis

Awareness of cancer symptoms and anticipated help seeking among ethnic minority groups in England

<p>Objective: Little is known about ethnic differences in awareness of cancer-warning signs or help-seeking behaviour in Britain. As part of the National Awareness and Early Diagnosis Initiative (NAEDI), this study aimed to explore these factors as possible contributors to delay in cancer diagnosis.</p> <p>Methods: We used quota sampling to recruit 1500 men and women from the six largest minority ethnic groups in England (Indian, Pakistani, Bangladeshi, Caribbean, African and Chinese). In face-to-face interviews, participants completed the newly developed cancer awareness measure (CAM), which includes questions about warning signs for cancer, speed of consultation for possible cancer symptoms and barriers to help seeking.</p> <p>Results: Awareness of warning signs was low across all ethnic groups, especially using the open-ended (recall) question format, with lowest awareness in the African group. Women identified more emotional barriers and men more practical barriers to help seeking, with considerable ethnic variation. Anticipated delay in help seeking was higher in individuals who identified fewer warning signs and more barriers.</p> <p>Conclusions: The study suggests the need for culturally sensitive, community-based interventions to raise awareness and encourage early presentation.</p&gt

Estimating the workload associated with symptoms-based ovarian cancer screening in primary care: an audit of electronic medical records

BACKGROUND: Ovarian cancer is the most lethal gynaecological malignancy in the United Kingdom (UK). Studies have found that many women with ovarian cancer have symptoms for several months before diagnosis. Using a symptoms-based tool to diagnose ovarian cancer (OC) earlier is appealing, but may increase general practitioner (GP) workload because the symptoms are typically vague and non-specific. This study aimed to provide estimates of the GP workload associated with offering symptoms-based ovarian cancer screening. METHODS: A cross-sectional analysis of electronic records from four general practices in England, UK. We downloaded anonymous data on women aged 45–74 who consulted over one week to estimate the proportion who would be offered ‘screening’ according to the UK National Institute for Health and Care Excellence (NICE) guidelines and a symptoms index (Index 2) over one year. We used previous consultations (censoring women with no prior symptom at the date of their last recorded consultation) to estimate the proportion of women presenting with a new (not recorded in previous 12 months) NICE symptom each year. RESULTS: Data were obtained from 19,558 women. The proportion presenting over one week varied between practices (5%-14%), however, the proportion with an OC symptom was similar (17% overall). Over one year, an estimated 51.8% (95% CI 44.0%-59.7%) would present with an OC symptom, 26.6% (95% CI 19.3%-35.1%) with a NICE symptom and 20.3% (95% CI 13.7%-28.5%) with an Index 2 symptom. Each year, an estimated 11.9% (95% CI 5.0%-18.3%) of women would present with a new NICE symptom. CONCLUSION: One in two women aged 45–74 present to primary care at least once a year with an OC symptom, 11.9% with a new NICE symptom. This would be comparable to 2 to 8 yearly screening (depending on what symptoms triggered testing)

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

Interpretation and expectation in childhood anxiety disorders: age effects and social specificity

Theory and treatment for childhood anxiety disorders typically implicates children’s negative cognitions, yet little is known about the characteristics of thinking styles of clinically anxious children. In particular, it is unclear whether differences in thinking styles between children with anxiety disorders and non-anxious children vary as a function of child age, whether particular cognitive distortions are associated with childhood anxiety disorders at different child ages, and whether cognitive content is disorder-specific. The current study addressed these questions among 120 7 - 12 year old children (53% female) who met diagnostic criteria for social anxiety disorder, other anxiety disorder, or who were not currently anxious. Contrary to expectations, threat interpretation was not inflated amongst anxious compared to non-anxious children at any age, although older (10 - 12 year old) anxious children did differ from non-anxious children on measures of perceived coping. The notion of cognitive-content specificity was not supported across the age-range. The findings challenge current treatment models of childhood anxiety, and suggest that a focus on changing anxious children’s cognitions is not warranted in mid-childhood, and in late childhood cognitive approaches may be better focussed on promoting children’s perceptions of control rather than challenging threat interpretations

Inter-Relationship between Testicular Dysgenesis and Leydig Cell Function in the Masculinization Programming Window in the Rat

The testicular dysgenesis syndrome (TDS) hypothesis proposes that maldevelopment of the testis, irrespective of cause, leads to malfunction of the somatic (Leydig, Sertoli) cells and consequent downstream TDS disorders. Studies in rats exposed in utero to di(n-butyl) phthalate (DBP) have strongly supported the TDS concept, but so far no direct evidence has been produced that links dysgenesis per se to somatic cell dysfunction, in particular to androgen production/action during the ‘masculinization programming window’ (MPW; e15.5–e18.5). Normal reproductive tract development and anogenital distance (AGD) are programmed within the MPW, and TDS disorders arise because of deficiencies in this programming. However, DBP-induced focal testicular dysgenesis (Leydig cell aggregation, ectopic Sertoli cells, malformed seminiferous cords) is not evident until after the MPW. Therefore, we used AGD as a read-out of androgen exposure in the MPW, and investigated if this measure was related to objectively quantified dysgenesis (Leydig cell aggregation) at e21.5 in male fetuses exposed to vehicle, DBP (500 or 750 mg/kg/day) or the synthetic glucocorticoid dexamethasone (Dex; alone or plus DBP-500) from e15.5–e18.5 (MPW), e13.5–e20.5 or e19.5–e20.5 (late window). Dysgenesis was found only in animals exposed to DBP during the MPW, and was negatively correlated (R2 = −0.5) with AGD at e21.5 and at postnatal day 8, irrespective of treatment period. Dysgenesis was also negatively correlated (R2 = –0.5) with intratesticular testosterone (ITT) at e21.5, but only when treatments in short windows (MPW, late window) were excluded; the same was true for correlation between AGD and ITT. We conclude that AGD, reflecting Leydig cell function solely within the MPW, is strongly related to focal dysgenesis. Our results point to this occurring because of a common early mechanism, targeted by DBP that determines both dysgenesis and early (during the MPW) fetal Leydig cell dysfunction. The findings provide strong validation of the TDS hypothesis

Prostaglandins, masculinization and its disorders:effects of fetal exposure of the rat to the cyclooxygenase inhibitor- indomethacin

Recent studies have established that masculinization of the male reproductive tract is programmed by androgens in a critical fetal ‘masculinization programming window’ (MPW). What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin (PG)-mediation of androgen-induced masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin (which blocks PG production by inhibiting cyclooxygenase activity) during this period and then examining if androgen production or action (masculinization) was affected. Pregnant rats were treated with indomethacin (0.8 mg/kg/day; e15.5–e18.5) to encompass the MPW. Indomethacin exposure decreased fetal bodyweight (e21.5), testis weight (e21.5) and testicular PGE2 (e17.5, e21.5), but had no effect on intratesticular testosterone (ITT; e17.5) or anogenital index (AGI; e21.5). Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p<0.001) in adulthood, an effect that is unexplained. Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced masculinization during the MPW in rats. The contrast with previous mouse studies is unexplained but may reflect a species difference

D-galactose-induced brain ageing model:A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices

Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent. To better understand the characteristics of the model and effects of d-galactose on neurobehavioral and neurochemical outcomes in rodents we performed a systematic review and meta-analysis. We applied random-effects meta-analysis to evaluate the effect of study features. Our results give an overview of the characteristics of the d-galactose rodent ageing model, including neurobehavioral and neurochemical outcomes. We found that few studies took measures to reduce risks of bias, and substantial heterogeneity in the reported effects of d-galactose in included studies. This highlights the need for improvements in the use of the d-galactose rodent ageing model if it is to provide useful in the development of drugs to treat human ageing