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Objectives To understand commonalities and differences in injured patient experiences of accessing and receiving quality injury care across three lower-income and middle-income countries.Design A qualitative interview study. The interviews were audiorecorded, transcribed and thematically analysed.Setting Urban and rural settings in Ghana, South Africa and Rwanda.Participants 59 patients with musculoskeletal injuries.Results We found five common barriers and six common facilitators to injured patient experiences of accessing and receiving high-quality injury care. The barriers encompassed issues such as service and treatment availability, transportation challenges, apathetic care, individual financial scarcity and inadequate health insurance coverage, alongside low health literacy and information provision. Facilitators included effective information giving and informed consent practices, access to health insurance, improved health literacy, empathetic and responsive care, comprehensive multidisciplinary management and discharge planning, as well as both informal and formal transportation options including ambulance services. These barriers and facilitators were prevalent and shared across at least two countries but demonstrated intercountry and intracountry (between urbanity and rurality) variation in thematic frequency.Conclusion There are universal factors influencing patient experiences of accessing and receiving care, independent of the context or healthcare system. It is important to recognise and understand these barriers and facilitators to inform policy decisions and develop transferable interventions aimed at enhancing the quality of injury care in sub-Saharan African nations.

Objectives To use verbal autopsy (VA) data to understand health system utilisation and the potential avoidability associated with fatal injury. Then to categorise any evident barriers driving avoidable delays to care within a Three-Delays framework that considers delays to seeking (Delay 1), reaching (Delay 2) or receiving (Delay 3) quality injury care.Design Retrospective analysis of existing VA data routinely collected by a demographic surveillance site.Setting Karonga Health and Demographic Surveillance Site (HDSS) population, Northern Malawi.Participants Fatally injured members of the HDSS.Primary and secondary outcome measures The primary outcome was the proportion of fatal injury deaths that were potentially avoidable. Secondary outcomes were the delay stage and corresponding barriers associated with avoidable deaths and the health system utilisation for fatal injuries within the health system.Results Of the 252 deaths due to external causes, 185 injury-related deaths were analysed. Deaths were predominantly among young males (median age 30, IQR 11–48), 71.9% (133/185). 35.1% (65/185) were assessed as potentially avoidable. Delay 1 was implicated in 30.8% (20/65) of potentially avoidable deaths, Delay 2 in 61.5% (40/65) and Delay 3 in 75.4% (49/65). Within Delay 1, ‘healthcare literacy’ was most commonly implicated barrier in 75% (15/20). Within Delay 2, ‘communication’ and ‘prehospital care’ were the most commonly implicated in 92.5% (37/40). Within Delay 3, ‘physical resources’ were most commonly implicated, 85.7% (42/49).Conclusions VA is feasible for studying pathways to care and health system responsiveness in avoidable deaths following injury and ascertaining the delays that contribute to deaths. A large proportion of injury deaths were avoidable, and we have identified several barriers as potential targets for intervention. Refining and integrating VA with other health system assessment methods is likely necessary to holistically understand an injury care health system.

Background The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.Methods The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×106 GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m2) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m2). The phase II segment focused on patients with NB at the dose 3 level of 160×106 GD2BATs/kg/infusion.Results Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2–3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines.Conclusions This study demonstrated the safety of GD2BATs up to 160×106 cells/kg/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.

Objective In men with a raised prostate-specific antigen (PSA), MRI increases the detection of clinically significant cancer and reduces overdiagnosis, with fewer biopsies. MRI as a screening tool has not been assessed independently of PSA in a formal screening study. We report a systematic community-based assessment of the prevalence of prostate MRI lesions in an age-selected population.Methods and analysis Men aged 50–75 were identified from participating general practice (GP) practices and randomly selected for invitation to a screening MRI and PSA. Men with a positive MRI or a raised PSA density (≥0.12 ng/mL2) were recommended for standard National Health Service (NHS) prostate cancer assessment.Results Eight GP practices sent invitations to 2096 men. 457 men (22%) responded and 303 completed both screening tests. Older white men were most likely to respond to the invitation, with black men having 20% of the acceptance rate of white men.One in six men (48/303 men, 16%) had a positive screening MRI, and an additional 1 in 20 men (16/303, 5%) had a raised PSA density alone. After NHS assessment, 29 men (9.6%) were diagnosed with clinically significant cancer and 3 men (1%) with clinically insignificant cancer.Two in three men with a positive MRI, and more than half of men with clinically significant disease had a PSA

Introduction Multiparametric MRI (mpMRI) has transformed the prostate cancer diagnostic pathway, allowing for improved risk stratification and more targeted subsequent management. However, concerns exist over the interobserver variability of images and the applicability of this model long term, especially considering the current shortage of radiologists and the growing ageing population. Artificial intelligence (AI) is being integrated into clinical practice to support diagnostic and therapeutic imaging analysis to overcome these concerns. The following report details a protocol for a systematic review and meta-analysis investigating the accuracy of AI in predicting primary prostate cancer on mpMRI.Methods and analysis A systematic search will be performed using PubMed, MEDLINE, Embase and Cochrane databases. All relevant articles published between January 2016 and February 2023 will be eligible for inclusion. To be included, articles must use AI to study MRI prostate images to detect prostate cancer. All included articles will be in full-text, reporting original data and written in English. The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. The QUADAS-2 score will assess the quality and risk of bias across selected studies.Ethics and dissemination Ethical approval will not be required for this systematic review. Findings will be disseminated through peer-reviewed publications and presentations at both national and international conferences.PROSPERO registration number CRD42021293745.

Introduction Amid clinicians’ challenges in staying updated with medical research, artificial intelligence (AI) tools like the large language model (LLM) ChatGPT could automate appraisal of research quality, saving time and reducing bias. This study compares the proficiency of ChatGPT3 against human evaluation in scoring abstracts to determine its potential as a tool for evidence synthesis.Methods We compared ChatGPT’s scoring of implant dentistry abstracts with human evaluators using the Consolidated Standards of Reporting Trials for Abstracts reporting standards checklist, yielding an overall compliance score (OCS). Bland-Altman analysis assessed agreement between human and AI-generated OCS percentages. Additional error analysis included mean difference of OCS subscores, Welch’s t-test and Pearson’s correlation coefficient.Results Bland-Altman analysis showed a mean difference of 4.92% (95% CI 0.62%, 0.37%) in OCS between human evaluation and ChatGPT. Error analysis displayed small mean differences in most domains, with the highest in ‘conclusion’ (0.764 (95% CI 0.186, 0.280)) and the lowest in ‘blinding’ (0.034 (95% CI 0.818, 0.895)). The strongest correlations between were in ‘harms’ (r=0.32, p

Objectives We used the process mapping method and Three Delays framework, to identify and visually represent the relationship between critical actions, decisions and barriers to access to care following injury in the Karonga health system, Northern Malawi.Design Facilitated group process mapping workshops with summary process mapping synthesis.Setting Process mapping workshops took place in 11 identified health system facilities (one per facility) providing injury care for a population in Karonga, Northern Malawi.Participants Fifty-four healthcare workers from various cadres took part.Results An overall injury health system summary map was created using those categories of action, decision and barrier that were sometimes or frequently reported. This provided a visual summary of the process following injury within the health system. For Delay 1 (seeking care) four barriers were most commonly described (by 8 of 11 facilities) these were ‘cultural norms’, ‘healthcare literacy’, ‘traditional healers’ and ‘police processes’. For Delay 2 (reaching care) the barrier most frequently described was ‘transport’—a lack of timely affordable emergency transport (formal or informal) described by all 11 facilities. For Delay 3 (receiving quality care) the most commonly reported barrier was that of ‘physical resources’ (9 of 11 facilities).Conclusions We found our novel approach combining several process mapping exercises to produce a summary map to be highly suited to rapid health system assessment identifying barriers to injury care, within a Three Delays framework. We commend the approach to others wishing to conduct rapid health system assessments in similar contexts.

Introduction Type 2 diabetes is prevalent among US adults. Lifestyle interventions that modify health behaviours prevent or delay progression to diabetes among individuals at high risk. Despite the well-documented influence of individuals’ social context on their health, evidence-based type 2 diabetes prevention interventions do not systematically incorporate participants’ romantic partners. Involving partners of individuals at high risk for type 2 diabetes in primary prevention may improve engagement and outcomes of programmes. The randomised pilot trial protocol described in this manuscript will evaluate a couple-based lifestyle intervention to prevent type 2 diabetes. The objective of the trial is to describe the feasibility of the couple-based intervention and the study protocol to guide planning of a definitive randomised clinical trial (RCT).Methods and analysis We used community-based participatory research principles to adapt an individual diabetes prevention curriculum for delivery to couples. This parallel two-arm pilot study will include 12 romantic couples in which at least one partner (ie, ‘target individual’) is at risk for type 2 diabetes. Couples will be randomised to either the 2021 version of the CDC’s PreventT2 curriculum designed for delivery to individuals (six couples), or PreventT2 Together, the adapted couple-based curriculum (six couples). Participants and interventionists will be unblinded, but research nurses collecting data will be blinded to treatment allocation. Feasibility of the couple-based intervention and the study protocol will be assessed using both quantitative and qualitative measures.Ethics and dissemination This study has been approved by the University of Utah IRB (#143079). Findings will be shared with researchers through publications and presentations. We will collaborate with community partners to determine the optimal strategy for communicating findings to community members. Results will inform a subsequent definitive RCT.Trial registration number NCT05695170

Introduction Persistent inequalities in cancer care and cancer outcomes exist within and between countries. However, the evidence pertaining to the root causes driving cancer inequalities is mixed. This may be explained by the inadequate attention paid to experiences of patients with cancer living at the intersection of multiple social categories (eg, social class, ethnicity). This is supported by the intersectionality framework. This framework offers an alternative lens through which to analyse and understand how these interlocking systems of oppression uniquely shape the experiences of patients with cancer and drive inequalities. In this protocol, we outline a scoping review that will systematically map what is known about the relationship between intersectionality and inequalities in care experience and cancer outcomes of patients with cancer; and to determine how the intersectionality framework has been applied in studies across the cancer care pathway and across countries.Methods and analysis This study will be guided by Arksey and O’Malley’s, and Levac et al’s frameworks for scoping reviews. We will identify and map the evidence on cancer inequalities and intersectionality from 1989 to present date. Electronic databases (EMBASE, PsychINFO, CINAHL, Medline, Web of Science, ProQuest) and a systematic search strategy using a combination of keywords and Boolean operators AND/OR will be used to identify relevant studies. Screening of eligible papers and data extraction will be conducted by two independent reviewers, and disagreements resolved by discussion with the research team. We will use an iterative process to data charting using a piloted form. Findings will be collated into a narrative report.Ethics and dissemination Ethical approval is not required since data used are from publicly available secondary sources. Findings will be disseminated through peer-reviewed journals, conferences and stakeholder meetings. Further, findings will inform the next phases of a multistage research project aimed at understanding inequalities among patients with breast cancer.

Injuries in low-income and middle-income countries are prevalent and their number is expected to increase. Death and disability after injury can be reduced if people reach healthcare facilities in a timely manner. Knowledge of barriers to access to quality injury care is necessary to intervene to improve outcomes. We combined a four-delay framework with WHO Building Blocks and Institution of Medicine Quality Outcomes Frameworks to describe barriers to trauma care in three countries in sub-Saharan Africa: Ghana, South Africa and Rwanda. We used a parallel convergent mixed-methods research design, integrating the results to enable a holistic analysis of the barriers to access to quality injury care. Data were collected using surveys of patient experiences of injury care, interviews and focus group discussions with patients and community leaders, and a survey of policy-makers and healthcare leaders on the governance context for injury care. We identified 121 barriers across all three countries. Of these, 31 (25.6%) were shared across countries. More than half (18/31, 58%) were predominantly related to delay 3 (‘Delays to receiving quality care’). The majority of the barriers were captured using just one of the multiple methods, emphasising the need to use multiple methods to identify all barriers. Given there are many barriers to access to quality care for people who have been injured in Rwanda, Ghana and South Africa, but few of these are shared across countries, solutions to overcome these barriers may also be contextually dependent. This suggests the need for rigorous assessments of contexts using multiple data collection methods before developing interventions to improve access to quality care.

Introduction There is an increasing body of evidence to suggest that visibility of prostate cancer on magnetic resonance (MRI) may be related to likelihood of adverse pathological outcomes. Biochemical recurrence (BCR) after radical prostatectomy remains a significant clinical challenge and a means of predicting likelihood of this prior to surgery could inform treatment choice. It appears that MRI could be a potential candidate strategy for BCR prediction, and as such, there is a need to review extant literature on the prognostic capability of MRI. Here, we describe a protocol for a systematic review and meta-analysis of the utility of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) in predicting BCR following radical prostatectomy for prostate cancer treatment.Methods and analysis PubMed, MEDLINE, Embase and Cochrane databases will be searched and screening will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In order to meet the inclusion criteria, papers must be English-language articles involving patients who have had bpMRI or mpMRI for suspected prostate cancer and have undergone radical prostatectomy as definitive therapy. Patients must have had prostate-specific antigen monitoring before and after surgery. All relevant papers published from July 1977 to October 2020 will be eligible for inclusion. The Newcastle-Ottawa score will be used to determine the quality and bias of the studies. This protocol is written in-line with the PRISMA protocol 2015 checklist.Ethics and dissemination There are no relevant ethical concerns. Dissemination of this protocol will be via peer-reviewed journals as well as national and international conferences.PROSPERO registration number CRD42020206074.

Objectives This study aimed to evaluate the epidemiology of injury as well as patient-reported health system responsiveness following injury and how this compares with non-injured patient experience, in older individuals in rural Burkina Faso.Design Cross-sectional household survey. Secondary analysis of the CRSN Heidelberg Ageing Study dataset.Setting Rural Burkina Faso.Participants 3028 adults, over 40, from multiple ethnic groups, were randomly sampled from the 2015 Nouna Health and Demographic Surveillance Site census.Primary and secondary outcome measures Primary outcome was incidence of injury. Secondary outcomes were incidence of injury related disability and patient-reported health system responsiveness following injury.Results 7.7% (232/3028) of the population reported injury in the preceding 12 months. In multivariable analyses, younger age, male sex, highest wealth quintile, an abnormal Generalised Anxiety Disorder score and lower Quality of Life score were all associated with injury. The most common mechanism of injury was being struck or hit by an object, 32.8%. In multivariable analysis, only education was significantly negatively associated with odds of disability (OR 0.407, 95% CI 0.17 to 0.997). Across all survey participants, 3.9% (119/3028) reported their most recent care seeking episode was following injury, rather than for another condition. Positive experience and satisfaction with care were reported following injury, with shorter median wait times (10 vs 20 min, p=0.002) and longer consultation times (20 vs 15 min, p=0.002) than care for another reason. Injured patients were also asked to return to health facilities more often than those seeking care for another reason, 81.4% (95% CI 73.1% to 87.9%) vs 54.8% (95% CI 49.9% to 53.6%).Conclusions Injury is an important disease burden in this older adult rural low-income and middle-income country population. Further research could inform preventative strategies, including safer rural farming methods, explore the association between adverse mental health and injury, and strengthen health system readiness to provide quality care.

Background The large burden of injuries falls disproportionately on low/middle-income countries (LMICs). Health system interventions improve outcomes in high-income countries. Assessing LMIC trauma systems supports their improvement. Evaluating systems using a Three Delays framework, considering barriers to seeking (Delay 1), reaching (Delay 2) and receiving care (Delay 3), has aided maternal health gains. Rapid assessments allow timely appraisal within resource and logistically constrained settings. We systematically reviewed existing literature on the assessment of LMIC trauma systems, applying the Three Delays framework and rapid assessment principles.Methods We conducted a systematic review and narrative synthesis of articles assessing LMIC trauma systems. We searched seven databases and grey literature for studies and reports published until October 2018. Inclusion criteria were an injury care focus and assessment of at least one defined system aspect. We mapped each study to the Three Delays framework and judged its suitability for rapid assessment.Results Of 14 677 articles identified, 111 studies and 8 documents were included. Sub-Saharan Africa was the most commonly included region (44.1%). Delay 3, either alone or in combination, was most commonly assessed (79.3%) followed by Delay 2 (46.8%) and Delay 1 (10.8%). Facility assessment was the most common method of assessment (36.0%). Only 2.7% of studies assessed all Three Delays. We judged 62.6% of study methodologies potentially suitable for rapid assessment.Conclusions Whole health system injury research is needed as facility capacity assessments dominate. Future studies should consider novel or combined methods to study Delays 1 and 2, alongside care processes and outcomes.

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).Results Of 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.

A rising number of non-tuberculous mycobacterial (NTM) isolates are being identified in UK clinical practice. There are many uncertainties around the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD), including its epidemiology, diagnosis, treatment and prevention. Regional variations in how patients with NTM-PD are managed reflects the lack of standardised pathways in the UK. Service optimisation and multidisciplinary working can improve the quality of care for patients with NTM-PD, including (1) better identification of patients at risk of NTM-PD and modification of risk factors where applicable; (2) standardisation of reference laboratory testing to offer clinicians access to accurate and prompt information on NTM species and drug sensitivities; (3) development of recognised specialist NTM nursing care; (4) standardisation of NTM-PD imaging strategies for monitoring of treatment and disease progression; (5) establishment of a hub-and-spoke model of care, including clear referral and management pathways, dedicated NTM-PD multidisciplinary teams, and long-term patient follow-up; (6) formation of clinical networks to link experts who manage diseases associated with NTM; (7) enabling patients to access relevant support groups that can provide information and support for their condition; and (8) development of NTM research groups to allow patient participation in clinical trials and to facilitate professional education.

ObjectiveTo estimate the effectiveness of standardised self-management kits for children with type 1 diabetes.DesignPragmatic trial with randomisation ratio of two intervention: one control. Qualitative process evaluation.Setting11 diabetes clinics in England and Wales.ParticipantsBetween February 2010 and August 2011, we validly randomised 308 children aged 6–18 years; 201 received the intervention.InterventionWe designed kits to empower children to achieve glycaemic control, notably by recording blood glucose and titrating insulin. The comparator was usual treatment.Outcome measures at 3 and 6 monthsPrimary: Diabetes Pediatric Quality of Life Inventory (PedsQL). Secondary: HbA1c; General PedsQL; EQ-5D; healthcare resource use.ResultsOf the five Diabetes PedsQL dimensions, Worry showed adjusted scores significantly favouring self-management kits at 3 months (mean child-reported difference =+5.87; Standard error[SE]=2.19; 95% confidence interval [CI]) from +1.57 to +10.18; p=0.008); but Treatment Adherence significantly favoured controls at 6 months (mean child-reported difference=−4.68; SE=1.74; 95%CI from −8.10 to −1.25; p=0.008). Intervention children reported significantly worse changes between 3 and 6 months on four of the five Diabetes PedsQL dimensions and on the total score (mean difference=−3.20; SE=1.33; 95% CI from −5.73 to −0.67; p=0.020). There was no evidence of change in HbA1c; only 18% of participants in each group achieved recommended levels at 6 months. No serious adverse reactions attributable to the intervention or its absence were reported.Use of kits was poor. Few children or parents associated blood glucose readings with better glycaemic control. The kits, costing £185, alienated many children and parents.ConclusionsStandardised kits showed no evidence of benefit, inhibited diabetes self-management and increased worry. Future research should study relationships between children and professionals, and seek new methods of helping children and parents to manage diabetes.Trial registration numberISRCTN17551624.

Objective: This study aimed to evaluate the feasibility of completing a parallel-group randomized controlled trial to compare usual follow-up care for women who have completed treatment of gynecological cancer against a nurse-led telephone intervention, known as Optimal Personalised Care After Treatment-Gynaecological. Methods: The unblinded trial aimed to recruit patients who had completed treatment of cervical, endometrial, epithelial ovarian, or vulval cancer within the previous 3 months at 3 NorthWales hospitals.We randomized participants to either usual hospital-based follow-up or specialist nurseYled telephone education, empowerment, and structured needs assessment follow-up. The primary outcomes assessed the feasibility of running a larger trial including patient eligibility, recruitment and retention rates, and outcome measure completion. Secondary outcomes were generic and health-related quality of life and a patient self-report health service use (Client Service Receipt Inventory) data collected at 3 time points (baseline, 3 months, and 6 months). Results: Of the 58 women screened, 44 were eligible (76%) and 24 (55%) were recruited and randomized (12:12 to control and intervention, respectively). One participant was lost to follow-up. Recruited participants had a mean (SD) age of 60 (11.2) years and were approximately 5 months fromtheir initial diagnosis (mean [SD], 159 [58] days). Seventeen (71%) of the participants had an endometrial cancer diagnosis. All outcome measure completion rates exceeded 96%. Although not a core feasibility objective, analyses of outcome measures indicated positive changes in quality of life andwell-being within theOptimal Personalised Care AfterTreatmentVGynaecological group; exploratory cost consequence analysis indicated that the nurse-led intervention had a mean total service use cost of £27 per patient (bootstrapped 95% confidence interval, £290 to £240) lower than did the standard care group. Conclusion: Eligibility, recruitment, and retention rates as well as outcome measure completion showed that the trial is feasible. [ABSTRACT FROM AUTHOR]

The problem of resource allocation in health has stimulated much thought and research, in attempts to provide objective, rational methods by which necessary choices can be made. One such method was proposed in a paper in this journal. The authors argued for a utilitarian approach, which they claimed to demonstrate was acceptable to society at large. This paper argues that the evidence supporting such a claim was flawed; such a utilitarian approach is not socially acceptable, and is therefore not relevant. Rather more relevant directions for research are discussed, based on the assertion that a degree of realism is essential when considering the problems of resource allocation. [ABSTRACT FROM PUBLISHER]

We have previously shown that 5-HT may play a role in the post-prandial exacerbation of symptoms seen in female patients with d-lBS. As both progesterone (P) and oestrogen (O) can influence the 5-HT system, the aim of th s study was to compare plasma 5-HT concentrations in female patients with d-lBS (Rome II) with high and ow levels of P/O. Platelet depleted plasma (PDP) 5-HT concentration was therefore assessed for 2 h (60 min intervals) under fasting conditions and 4 h (30 min intervals) after a standard carbohydrate meal (457 kcal) in 39 patients (aged 19-52 yrs) with high P/O (studied either during the luteal phase of the menstrual cycle or while taking combined P/O oral contraception) and in 11 aged matched patients (aged 22-45 years) with Iow P/O levels (menses). 5-HT concentration was measured by reverse-phase high performance liquid chromatography with fluorimetric detection. In addition, symptomatology (0-4; 4 = severe) was assessed throughout the study. Results: Under fasting conditions there was no difference in PDP 5-HT concentration between patients with a high (5.41 ng/ml, (mean)) and Iow (4.98 ng/ml; difference high Iow (95%CI), 0.43 ng/ml (-0.69,1.55) ng/ml; p = 0.443) P/O status. Following meal ingestion, however, patients with high P/O levels have a significantly higher PDP 5-HT peak (13.99 ng/ml; (geometric mean) than those with Iow P/O levels (8.57 ng/ml; ratio high:low, 1.63 (1.02,2.62); p = 0.043). This difference was particularly evident in patients reporting post-prandial symptoms (patients with high P/O levels (n = 31): 15.60 ng/ml v patients with Iow P/O levels (n = 11): 8.57 ng/ml; ratio high:low, 1.82 (1.12, 2.96); p = 0.017) and was not related to a difference in symptom severity between the two groups (patients with high P/O levels: 0.70 (mean) v Iow P/E levels: 0.58; difference highIow, 0.12 (-0.28, 0.53); p = 0.547. Conclusions: Female sex hormones may play a role in the gastrointestinal tract 5-HT response to a meal in female... [ABSTRACT FROM AUTHOR]

Recent studies suggest that patients with irritable bowel syndrome lBS have elevated levels of plasma 5-HT following meal ingestion compared with healthy controls. Moreover, patients who exhibit postprandial symptoms have higher plasma 5-HT levels compared with those who do not, suggesting a possible relationship between Dost-prandial symptoms and abnormalities in 5-HT release. Given functional dyspepsia (FD) belongs to the same family of disorders as lBS, the aims of this study were to assess platelet depleted plasma (PDP) 5-HT concentrations under fasting and fed (760 kcal meal) conditions in 11 patients with FD (aged 30-61 years; 6 males) and 12 healthy volunteers (aged 20-48 years; 5 males) and assess any relationship to gender and epigastric pain/discomfort (p/d). Results: Under fasting conditions FD patients had similar levels of PDP 5-HT to controls (FD (n = 11): 4.65 ng/ml (geometric mean) vs controls (n = 12): 4.57ng/ml; ratio FD:controls (95%CI), 1.02 (0.14, 1.26)). However, under fed conditions, although the peak PDP 5-HT concentration for the whole group of FD patients was not significantly different from controls (11.19 ng/ml vs 8.43 ng/ml; 1.33(0.69, 2.54); p = 0.37, patients who reported post-prandial p/d had a higher PDP 5-HT peak (n = 8:14.74 ng/ml) than both patients who did not report p/d (5.36ng/ml; ratio with:without p/d 2.75(1.24, 6.10); p = 0.02) and controls (8.43 ng/ml; ratio FD with p/d:controls, 1.75 (0.79, 3.87); p = 0.14). This was as a consequence of a higher PDP 5-HT peak in the female FD patients with p/d (36.56 ng/ml), as all other females (FD and controls (n = 9): 7.71 ng/ml; ratio FD with p/d:FD and controls 4.74 (2.5, 9.0 p < 0.001) and all males (FD and contro s (n = 11): 8.07 ng/ml; ratio female FD with p/d: all males, 4.53 (2.19,9.35); p < 0.001) had lower PDP 5-HT peaks. Lastly, symptom severity tended to correlate with peak PDP 5-HT concentration (rho = 0.37; p = 0.08). Conclusions: These data provide evidence for a role... [ABSTRACT FROM AUTHOR]