High Prescribing and State-Level Variation in Z-Drug Use Among Medicare Patients.

BACKGROUND: Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences. This study also aimed to determine prescribing patterns of Z-drugs to Medicare patients. METHODS: Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions per provider within each specialty was also determined. RESULTS: Zolpidem was the most prescribed Z-drug (95.0%). Prescriptions per 100 enrollees were significantly high in Utah (28.2) and Arkansas (26.7) and significantly low in Hawaii (9.3) relative to the national average (17.5). Family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly high among psychiatrists. DISCUSSION: Contrary to the Beers criteria, Z-drugs are prescribed to older adults at high rates.

Multimodal assessment of sustained threat in adolescents with nonsuicidal self-injury.

Nonsuicidal self-injury (NSSI) is a common but poorly understood phenomenon in adolescents. This study examined the Sustained Threat domain in female adolescents with a continuum of NSSI severity (N = 142). Across NSSI lifetime frequency and NSSI severity groups (No + Mild NSSI, Moderate NSSI, Severe NSSI), we examined physiological, self-reported and observed stress during the Trier Social Stress Test; amygdala volume; amygdala responses to threat stimuli; and resting-state functional connectivity (RSFC) between amygdala and medial prefrontal cortex (mPFC). Severe NSSI showed a blunted pattern of cortisol response, despite elevated reported and observed stress during TSST. Severe NSSI showed lower amygdala-mPFC RSFC; follow-up analyses suggested that this was more pronounced in those with a history of suicide attempt for both moderate and severe NSSI. Moderate NSSI showed elevated right amygdala activation to threat; multiple regressions showed that, when considered together with low amygdala-mPFC RSFC, higher right but lower left amygdala activation predicted NSSI severity. Patterns of interrelationships among Sustained Threat measures varied substantially across NSSI severity groups, and further by suicide attempt history. Study limitations include the cross-sectional design, missing data, and sampling biases. Our findings highlight the value of multilevel approaches in understanding the complexity of neurobiological mechanisms in adolescent NSSI.

Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Implementation of the North Carolina HIV Bridge Counseling Program to Facilitate Linkage and Reengagement in Care for Individuals Infected with HIV/AIDS.

BACKGROUND Statewide interventions are critical to meeting the goals of the National HIV/AIDS Strategy in this country. In 2012, the North Carolina Division of Public Health developed the North Carolina State Bridge Counselor program to improve linkage to and reengagement in care for newly diagnosed persons and persons living with HIV who were out-of-care.METHODS We reviewed the planning process for the North Carolina State Bridge Counselor program, which involved a review of existing strengths-based counseling models for persons living with HIV, implementation of these models, and communication strategies with other providers. State bridge counselor responsibilities were delineated from the role of disease intervention specialists while retaining the fieldwork capability of disease intervention specialists to conduct outreach and provide services for persons living with HIV throughout the state.RESULTS Program implementation required extensive planning with stakeholders, incorporation of strengths-based counseling models, development of performance standards, and utilization of CAREWare, an HIV care software program to document referrals and data-sharing between state bridge counselors and clinics. By the end of 2014, state bridge counselor services were provided to approximately 60 of the 400 persons living with HIV (15%) who are diagnosed each quarter in North Carolina, with increasing utilization of the program.LIMITATIONS We assessed the development of this intervention specific to the North Carolina Division of Public Health, which may limit its generalizability. However, the State Bridge Counselor program was implemented in both urban and rural areas throughout the state, which increases its applicability to different public health programs throughout the country.CONCLUSION We demonstrated that a statewide State Bridge Counselor program for linkage and reengagement activities can be implemented by leveraging existing infrastructures, electronic medical records, HIV care networks, and fieldwork activities.

Seeking help in times of economic hardship: access, experiences of services and unmet need.

BACKGROUND: Economic recessions are often accompanied by increased levels of psychological distress and suicidal behaviour in affected populations. Little is known about the experiences of people seeking help for employment, financial and benefit-related difficulties during recessions. We investigated the experiences of people struggling financially in the aftermath of the Great Recession (2008-9) - including some who had self-harmed - and of the frontline support staff providing assistance. METHODS: Interviews were conducted with three groups of people in two cities: i) people who had self-harmed due to employment, financial or benefit concerns (n = 19) ('self-harm'); ii) people who were struggling financially drawn from the community (n = 22), including one focus group) ('community'); iii) and frontline staff from voluntary and statutory sector organisations (e.g., Job Centres, Debt Advice and counselling agencies) providing support services to the groups (n = 25, including 2 focus groups) ('service providers'). Data were analysed using the constant comparison method. RESULTS: Service provision was described by people as confusing and difficult to access. The community sample reported considerably more knowledge and access to debt advice than the participants who had self-harmed - although both groups sought similar types of help. The self-harm group exhibited greater expectation that they should be self-reliant and also reported lower levels of informal networks and support from friends and relatives. They had also experienced more difficult circumstances such as benefit sanctions, and most had pre-existing mental health problems. Both self-harm and community groups indicated that practical help for debt and benefit issues would be the most useful - a view supported by service providers - and would have particularly helped those who self-harmed. CONCLUSION: Interventions to identify those in need and aid them to access practical, reliable and free advice from support agencies could help mitigate the impact on mental health of benefit, debt and employment difficulties for vulnerable sections of society.

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Protocol for a multicentre, parallel-arm, 12-month, randomised, controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN).

INTRODUCTION: Femoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome. METHODS: We will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02). ETHICS AND DISSEMINATION: Ethical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, including Health Technology Assessment, and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN64081839; Pre-results.

Understanding vulnerability to self-harm in times of economic hardship and austerity: a qualitative study.

OBJECTIVE: Self-harm and suicide increase in times of economic recession, but little is known about why people self-harm when in financial difficulty, and in what circumstances self-harm occurs. This study aimed to understand events and experiences leading to the episode of self-harm and to identify opportunities for prevention or mitigation of distress. SETTING: Participants' homes or university rooms. PARTICIPANTS: 19 people who had attended hospital following self-harm in two UK cities and who specifically cited job loss, economic hardship or the impact of austerity measures as a causal or contributory factor. PRIMARY AND SECONDARY OUTCOME MEASURES: Semistructured, in-depth interviews. Interviews were audio recorded, transcribed and analysed cross-sectionally and as case studies. RESULTS: Study participants described experiences of severe economic hardship; being unable to find employment or losing jobs, debt, housing problems and benefit sanctions. In many cases problems accumulated and felt unresolvable. For others an event, such as a call from a debt collector or benefit change triggered the self-harm. Participants also reported other current or past difficulties, including abuse, neglect, bullying, domestic violence, mental health problems, relationship difficulties, bereavements and low self-esteem. These contributed to their sense of despair and worthlessness and increased their vulnerability to self-harm. Participants struggled to gain the practical help they felt they needed for their economic difficulties or therapeutic support that might have helped with their other co-existing or historically damaging experiences. CONCLUSIONS: Economic hardships resulting from the recession and austerity measures accumulated or acted as a 'final straw' to trigger self-harm, often in the context of co-existing or historically damaging life-experiences. Interventions to mitigate these effects should include providing practical advice about economic issues before difficulties become insurmountable and providing appropriate psychosocial support for vulnerable individuals.

Magnetic resonance imaging and spectroscopy assessment of lower extremity skeletal muscles in boys with Duchenne muscular dystrophy: a multicenter cross sectional study.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines are often not able to be quantified in clinical trials for DMD until after age 7. In this study, we hypothesized that (1)H2O T2 derived using (1)H-MRS and MRI-T2 will be sensitive to muscle involvement at a young age (5-7 years) consistent with increased inflammation and muscle damage in a large cohort of DMD subjects compared to controls. METHODS: MR data were acquired from 123 boys with DMD (ages 5-14 years; mean 8.6 SD 2.2 years) and 31 healthy controls (age 9.7 SD 2.3 years) using 3-Tesla MRI instruments at three institutions (University of Florida, Oregon Health & Science University, and Children's Hospital of Philadelphia). T2-weighted multi-slice spin echo (SE) axial images and single voxel 1H-MRS were acquired from the lower leg and thigh to measure lipid fraction and (1)H2O T2. RESULTS: MRI-T2, (1)H2O T2, and lipid fraction were greater (p<0.05) in DMD compared to controls. In the youngest age group, DMD values were different (p<0.05) than controls for the soleus MRI-T2, (1)H2O T2 and lipid fraction and vastus lateralis MRI-T2 and (1)H2O T2. In the boys with DMD, MRI-T2 and lipid fraction were greater (p<0.05) in the oldest age group (11-14 years) than the youngest age group (5-6.9 years), while 1H2O T2 was lower in the oldest age group compared to the young age group. DISCUSSION: Overall, MR measures of T2 and lipid fraction revealed differences between DMD and Controls. Furthermore, MRI-T2 was greater in the older age group compared to the young age group, which was associated with higher lipid fractions. Overall, MR measures of T2 and lipid fraction show excellent sensitivity to DMD disease pathologies and potential therapeutic interventions in DMD, even in the younger boys.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

BACKGROUND: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. METHODS: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). CONCLUSIONS: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Assessment of intramuscular lipid and metabolites of the lower leg using magnetic resonance spectroscopy in boys with Duchenne muscular dystrophy.

The purpose of this study was to use proton magnetic resonance spectroscopy to assess intramuscular lipid and metabolites of lower leg muscles in boys with Duchenne muscular dystrophy (DMD) and determine its relationship with strength and functional ability. Spectroscopic measurements were obtained from four muscles of the lower leg in 25 boys with DMD (9.2±3.1 years) and 10 healthy boys (10.2±2.6 years). Lipid fractions and metabolite concentrations were also determined. Muscle strength, a timed functional test, and the Modified Brooke Lower Extremity Functional Scale were also determined. Lipid fractions were higher (p<0.01) for the DMD group than healthy subjects for all muscles, and lipid fraction was found to be greater in the older DMD boys. The peroneal muscle demonstrated a significant difference in lipid fraction in all DMD age groups. Lipid fractions in all muscles correlated with functional measures (r=0.52-0.70, p<0.001), with smaller inverse correlations with the strength measure (r=-0.36 to -0.56, p<0.05). These findings provide quantifiable information regarding intramuscular lipid and metabolite levels of different muscles across various age groups in boys with DMD and may be used in determining the effect of interventions in future clinical trials.

Does the cancer drugs fund lead to faster uptake of cost-effective drugs? A time-trend analysis comparing England and Wales.

BACKGROUND: The Cancer Drugs Fund (CDF) provides £200 million annually in England for 'anti-cancer' drugs. METHODS: We used a controlled pre-/post-intervention design to compare IMS Health dispensing data for 15 cancer drugs (2007-2012) in England vs Wales, stratified by pre-CDF NICE drug approval status (rejected, mixed recommendations, recommended, not appraised). RESULTS: The CDF was associated with increased prescribing in England for three of five drugs rejected or with mixed NICE recommendations. The prescribing volume ratios (PVR) ranged from 1.29 (95% CI 1.00, 1.67) for sorafenib to 3.28 (2.59, 4.14) for bevacizumab (NICE rejected) and 0.93 (0.81, 1.06) and 1.35 (1.21, 1.49) for sunitinib and imatinib respectively (mixed recommendations). Post CDF prescribing in England increased for both drugs awaiting NICE appraisal pre-CDF (lapatinib PVR=7.44 (5.81, 9.54), panitumumab PVR=5.40 (1.20, 24.42)) and subsequently rejected. The CDF was not associated with increased prescribing in England of NICE-recommended drugs. The three most recently launched, subsequently recommended drugs were adopted faster in Wales (from pazopanib PVR=0.51 (0.28, 0.96) to abiraterone PVR=0.78 (0.61-0.99)). INTERPRETATION: These data indicate that the CDF is used to access drugs deemed not cost-effective by NICE. The CDF did not expedite access to new cost-effective cancer agents prior to NICE approval.

Participation and quality of life in children with Duchenne muscular dystrophy using the International Classification of Functioning, Disability, and Health.

BACKGROUND: Duchenne muscular dystrophy (DMD) is characterized by muscle damage and progressive loss of muscle function in male children. DMD is one of the most devastating genetically linked neuromuscular diseases for which there is currently no cure. Most clinical studies for DMD utilize a standard protocol for measurement exploring pathophysiology, muscle strength and timed tasks. However, we propose that examining broader components of health as emphasized by the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) may be of great value to children and their families, and important outcomes for future clinical trials. METHODS: Fifty boys with DMD and 25 unaffected age-matched boys completed two self-report measures: the Children's Assessment of Participation and Enjoyment and the Pediatric Quality of Life InventoryTM 4.0. We investigated differences between the two groups with regard to participation in life activities and perceived quality of life (QoL). Additionally, we compared participation in activities and QoL in both cohorts of younger and older boys. RESULTS: Participation in physical activities was significantly lower in boys with DMD than unaffected boys. Perceived QoL was markedly diminished in children with DMD relative to unaffected controls, except in the emotional domain. The amount of time boys engage in an activity, as well as participation in social activities, declined for our older boys with DMD but no changes were observed for our older unaffected boys. For both groups, QoL remained constant over time. CONCLUSIONS: The ICF-CY provides a conceptual framework and specific terminology that facilitates investigation of the consequences of impairment in children and youth. Our study is one of the first to explore participation in a cohort of boys with DMD. It was not surprising that activities of choice for boys with DMD were less physical in nature than unaffected boys their age, but the consequences of less social engagement as the boys with DMD age is of great concern. Results from our study underscore the need to further evaluate activities that children elect to participate in, with special emphasis on facilitators and barriers to participation and how participation changes throughout the course of a disease.

Evaluating meta-ethnography: systematic analysis and synthesis of qualitative research.

BACKGROUND: Methods for reviewing and synthesising findings from quantitative research studies in health care are well established. Although there is recognition of the need for qualitative research to be brought into the evidence base, there is no consensus about how this should be done and the methods for synthesising qualitative research are at a relatively early stage of development. OBJECTIVE: To evaluate meta-ethnography as a method for synthesising qualitative research studies in health and health care. METHODS: Two full syntheses of qualitative research studies were conducted between April 2002 and September 2004 using meta-ethnography: (1) studies of medicine-taking and (2) studies exploring patients' experiences of living with rheumatoid arthritis. Potentially relevant studies identified in multiple literature searches conducted in July and August 2002 (electronically and by hand) were appraised using a modified version of the Critical Appraisal Skills Programme questions for understanding qualitative research. Candidate papers were excluded on grounds of lack of relevance to the aims of the synthesis or because the work failed to employ qualitative methods of data collection and analysis. RESULTS: Thirty-eight studies were entered into the medicine-taking synthesis, one of which did not contribute to the final synthesis. The synthesis revealed a general caution about taking medicine, and that the practice of lay testing of medicines was widespread. People were found to take their medicine passively or actively or to reject it outright. Some, in particular clinical areas, were coerced into taking it. Those who actively accepted their medicine often modified the regimen prescribed by a doctor, without the doctor's knowledge. The synthesis concluded that people often do not take their medicines as prescribed because of concern about the medicines themselves. 'Resistance' emerged from the synthesis as a concept that best encapsulated the lay response to prescribed medicines. It was suggested that a policy focus should be on the problems associated with the medicines themselves and on evaluating the effectiveness of alternative treatments that some people use in preference to prescribed medicines. The synthesis of studies of lay experiences of living with rheumatoid arthritis began with 29 papers. Four could not be synthesised, leaving 25 papers (describing 22 studies) contributing to the final synthesis. Most of the papers were concerned with the everyday experience of living with rheumatoid arthritis. This synthesis did not produce significant new insights, probably because the early papers in the area were substantial and theoretically rich, and later papers were mostly confirmatory. In both topic areas, only a minority of the studies included in the syntheses were found to have referenced each other, suggesting that unnecessary replication had occurred. LIMITATIONS: We only evaluated meta-ethnography as a method for synthesising qualitative research, but there are other methods being employed. Further research is required to investigate how different methods of qualitative synthesis influence the outcome of the synthesis. CONCLUSIONS: Meta-ethnography is an effective method for synthesising qualitative research. The process of reciprocally translating the findings from each individual study into those from all the other studies in the synthesis, if applied rigorously, ensures that qualitative data can be combined. Following this essential process, the synthesis can then be expressed as a 'line of argument' that can be presented as text and in summary tables and diagrams or models. Meta-ethnography can produce significant new insights, but not all meta-ethnographic syntheses do so. Instead, some will identify fields in which saturation has been reached and in which no theoretical development has taken place for some time. Both outcomes are helpful in either moving research forward or avoiding wasted resources. Meta-ethnography is a highly interpretative method requiring considerable immersion in the individual studies to achieve a synthesis. It places substantial demands upon the synthesiser and requires a high degree of qualitative research skill. Meta-ethnography has great potential as a method of synthesis in qualitative health technology assessment but it is still evolving and cannot, at present, be regarded as a standardised approach capable of application in a routinised way. FUNDING: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Clinical trial: prolonged beneficial effect of Helicobacter pylori eradication on dyspepsia consultations - the Bristol Helicobacter Project.

BACKGROUND: Chronic infection of the stomach with Helicobacter pylori is widespread throughout the world and is the major cause of peptic ulcer disease and gastric cancer. Short-term benefit results from community programmes to eradicate the infection, but there is little information on cumulative long-term benefit. AIM: To determine whether a community programme of screening for and eradication of H. pylori infection produces further benefit after an initial 2-year period, as judged by a reduction in GP consultations for dyspepsia. METHODS: A total of 1517 people aged 20-59 years, who were registered with seven general practices in Frenchay Health District, Bristol, had a positive (13)C-urea breath test for H. pylori infection and were entered into a randomized double-blind trial of H. pylori eradication therapy. After 2 years, we found a 35% reduction in GP consultations for dyspepsia (previously reported). In this extension to the study, we analysed dyspepsia consultations between two and 7 years after treatment. RESULTS: Between two and 7 years after treatment, 81/764 (10.6%) of participants randomized to receive active treatment consulted for dyspepsia, compared with 106/753 (14.1%) of those who received placebo, a 25% reduction, odds ratio 0.84 (0.71, 1.00), P = 0.042. CONCLUSIONS: Eradication of H. pylori infection in the community gives cumulative long-term benefit, with a continued reduction in the development of dyspepsia severe enough to require a consultation with a general practitioner up to at least 7 years. The cost savings resulting from this aspect of a community H. pylori eradication programme, in addition to the other theoretical benefits, make such programmes worthy of serious consideration, particularly in populations with a high prevalence of H. pylori infection.

In vitro culture combined with quantitative TaqMan PCR for the assessment of Toxoplasma gondii tissue cyst viability.

Toxoplasma gondii is a serious food-borne pathogen with a worldwide distribution. In order to assess the risk of contracting toxoplasmosis from certain foods, many studies rely on the molecular detection of T. gondii DNA. However, determining the viability of parasites in positive samples is much more problematic. In this paper we describe a novel viability assay that relies on semi-quantitative comparison of the amount of parasite DNA present in samples used to infect host cell monolayers in vitro, and the amount of DNA detected in the same monolayers after 23 days incubation. Our assay is robust, easy to perform and interpret and offers a viable alternative to bioassays, for use in epidemiological studies, or the evaluation of specific food safety treatments.

Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats.

The effects of acute and repeated intraparaventricular (iPVN) administration of human relaxin-3 (H3) were examined on food intake, energy expenditure, and the hypothalamo-pituitary thyroid axis in male Wistar rats. An acute high dose iPVN injection of H3 significantly increased food intake 1 h post-administration [0.4+/-0.1 g (vehicle) vs 1.6+/-0.5 g (180 pmol H3), 2.4+/-0.5 g (540 pmol H3) and 2.2+/-0.5 g (1,620 pmol H3), p<0.05 for all doses vs vehicle]. Repeated iPVN H3 injection (180 pmol/twice a day for 7 days) significantly increased cumulative food intake in ad libitum fed animals compared with vehicle [211.8+/-7.1 g (vehicle) vs 261.6+/-6.7 g (ad libitum fed H3), p<0.05]. Plasma leptin was increased in the H3 ad libitum fed group. Plasma thyroid stimulating hormone was significantly decreased after acute and repeated administration of H3. These data suggest H3 may play a role in long-term control of food intake.

Unmet need for joint replacement: a qualitative investigation of barriers to treatment among individuals with severe pain and disability of the hip and knee.

OBJECTIVE: To explore barriers to health-care utilization in respondents with moderate to severe hip/knee symptoms of pain and disability. METHODS: In-depth interviews were carried out with 27 participants who had high levels of hip/knee pain and disability (according to New Zealand scores). There were 10 men and 17 women; median age 76 yr (range 51-91). The data were analysed thematically using the constant comparison technique. RESULTS: Three types of barrier were identified: (i) people's own perceptions of need and reluctance to seek treatment, (ii) perceptions and experiences of primary care and (iii) experiences of treatment in secondary care. Pessimism about availability of treatments, and concerns about effectiveness and risks of surgery, made older people reluctant to seek medical help. Such views were often confirmed by GPs. Some of those referred to a hospital specialist were told that they were too young or too mobile for surgery. CONCLUSION: Barriers to treatment and unmet need for joint replacement exist in the UK, particularly amongst older people.

Who should have priority for a knee joint replacement?

OBJECTIVES: To explore patients' views on who should have priority for total knee replacement (TKR). METHODS: In-depth, semistructured interviews were conducted with 25 patients on the waiting list for a TKR. RESULTS: All participants were willing to comment on waiting lists and prioritization for TKR. Two major themes emerged: what they thought should happen, and what they thought did happen. They thought that priority should be based on length and degree of suffering, pain severity, immobility, paid employment, payment of National Insurance contributions, and caring for dependants. In contrast, they thought that what actually happened depended on age and weight, excessive complaining and access to private practice. CONCLUSIONS: The participants agreed with health professionals that pain and disability should be key criteria on which to prioritize people for a TKR. However, they also argued for a fair decision-making process that also included additional factors specific to the patient's circumstances. Criteria to aid prioritization for joint surgery need to accommodate the views of patients as well as professionals.