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AIM: This paper is a report of a study to develop a social outreach model of care, including the role of a link worker in developing collaborative care pathways, for marginalized groups with tuberculosis. BACKGROUND: Social risk factors such as homelessness and substance misuse are associated with poor treatment outcomes. Models of interprofessional practice to address the health and social care of patients are needed to improve outcomes. METHODS: A process evaluation involving a prospective cohort study of 100 patients and interviews with eight agencies involved in their care was conducted in London between January 2003 and April 2005. Outcome measures included a profile of patient need to guide service development; referrals to care providers; goal attainment; social improvement and treatment outcomes; and agencies' views on the benefits of link working. FINDINGS: The median age of the sample was 32.4 years and 62% were males. Reasons for referral to the link worker included housing need (56%); welfare benefits (42%); immigration (29%) and clinical management issues (28%). One-third of the patients were referred to other agencies. Goals, as agreed in the care plan, were attained totally or partially for 88% (59/67) of patients and 78% of patients successfully completed treatment. Barriers to attaining goals included service criteria which excluded some groups of patients and, in some cases, a patient's inability to follow a course of action. CONCLUSION: Link workers can mitigate some of the social risk factors that complicate the treatment of tuberculosis by enabling integrated health and social care. [ABSTRACT FROM AUTHOR]

Aim. This paper is a report of a study to examine the impact of social factors on the management of tuberculosis including engagement with services, hospitalization and extended treatment. Background. Rates of tuberculosis in major European cities have increased greatly in the last 10 years. The changing epidemiology of the disease, concentrated in marginalized groups, presents new challenges to the control of tuberculosis. Methods. A prospective cohort study of 250 newly diagnosed tuberculosis patients was conducted in London between January 2003 and January 2005. Data were collected by means of a risk assessment tool and from medical records. Outcome measures included missed appointments, frequency and duration of hospitalization and length of treatment. Results. The median age of the study sample was 33.82 (range 16.4-92.5) and 56.8% were male. Thirty-two per cent were hostel/street homeless or temporarily sharing accommodation with friends or relatives. Thirty-nine per cent were in receipt of welfare benefits and 13.2% had no income. Over a third anticipated difficulties taking their medicines and 30.3% had noone to remind them of this. Increased hospitalization was associated with hostel/street homelessness, drug or alcohol use and having noone to remind them to take their medicines (all P

Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by national TB programmes, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma-reduction efforts is limited by the need for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague, The Netherlands, stigma experts discussed and proposed a research agenda around four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?; 2) consequences: how consequential are TB stigmas and how are negative impacts most felt?; 3) burden: what is the global prevalence and distribution of TB stigma(s) and what explains any variation? 4): intervention: what can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma 'cure'. Nevertheless, these challenges should not hinder investments in the measurement and reduction of TB stigma. We believe it is time to focus on how, and not whether, the global community should measure and reduce TB stigma.

Tuberculosis (TB)-related stigma is an important social determinant of health. Research generally highlights how stigma can have a considerable impact on individuals and communities, including delays in seeking health care and adherence to treatment. There is scant research into the assessment of TB-related stigma in low incidence countries. This study aimed to systematically map out the research into stigma. A particular emphasis was placed on the methods employed to measure stigma, the conceptual frameworks used to understand stigma, and whether structural factors were theorized. Twenty-two studies were identified; the majority adopted a qualitative approach and aimed to assess knowledge, attitudes, and beliefs about TB. Few studies included stigma as a substantive topic. Only one study aimed to reduce stigma. A number of studies suggested that TB control measures and representations of migrants in the media reporting of TB were implicated in the production of stigma. The paucity of conceptual models and theories about how the social and structural determinants intersect with stigma was apparent. Future interventions to reduce stigma, and measurements of effectiveness, would benefit from a stronger theoretical underpinning in relation to TB stigma and the intersection between the social and structural determinants of health., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To identify whether parliamentary scrutiny, in the form of Written Parliamentary Questions (WPQs), has any significant impact on the UK government's stated aid priorities and whether, by refining the approach that MPs with an interest in TB take to scrutinising the government on its aid priorities, more resources could be secured for TB., Methods: We downloaded 19,234 Written Parliamentary Questions directed at the Department for International Development posed by Members of Parliament between June 2001 and September 2014. We categorised questions by theme, party of questioner, geographical area, date and government. We then identified questions which specifically referenced HIV, TB and Malaria, or the Global Fund to Fight Aids, TB and Malaria. Analyses were conducted on each of these categorisations to identify trends which could account for differences in government funding between the three diseases., Results: A significantly greater number of questions were posed on HIV than on TB and Malaria. These questions were more likely to reference a specific geographical area, and come from a wider group of MPs. A broadly equivalent number of questions were asked on TB and Malaria although there were differences between the parties of the MPs tabling questions. We also identified a significant fall in the number of WPQs tabled from the Labour government of 2005-2010 and the Coalition Government of the present day., Conclusion: High volumes of WPQs targeting specific policy areas or geographical locations can play a role in increasing political commitment within government towards a certain disease or condition, however other factors, including high-level MP champions and party policy, can play an equally significant role. Nonetheless, evidence suggests that a broad base of political support (as manifested through WPQs) is important to motivating a government response to a health issue and that the TB community should devote more effort to mobilising this wide political support., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: There is scant qualitative research into the experiences of tuberculosis (TB) treatment in urban risk groups with complex health and social needs in the UK. This study aimed to describe the social context of adherence to treatment in marginalized groups attending a major TB centre in London., Methods: A qualitative cross-sectional study was performed using semi-structured interviews with patients receiving treatment for TB. Analytical frameworks aimed to reflect the role of broader social structures in shaping individual health actions., Results: There were 17 participants; the majority were homeless and had complex medical and social needs, including drug and alcohol use or immigration problems affecting entitlement to social welfare. Participants rarely actively chose not to take their medication, but described a number of social and institutional barriers to adherence and their need for practical support. Many struggled with the physical aspects of taking medication and the side effects. Participants receiving directly observed therapy (DOT) reported both positive and negative experiences, reflecting the type of DOT provider and culture of the organization., Conclusions: There is a need for integrated care across drug, alcohol, HIV, and homeless services in order to address the complex clinical co-morbidities and social needs that impact on the patient's ability to sustain a course of treatment., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Tuberculosis awareness, grounded in social cognition models of health care seeking behaviour, relies on the ability of individuals to recognise symptoms, assess their risk and access health care (passive case finding). There is scant published research into the health actions of 'hard-to-reach' groups with tuberculosis, who represent approximately 17% of the London TB caseload. This study aimed to analyse patients' knowledge of tuberculosis, their experiences of symptoms and their health care seeking behaviours., Methods: Qualitative interviews were conducted with 17 participants, predominantly homeless and attending a major tuberculosis centre in London, UK. Most had complex medical and social needs including drug and alcohol use or immigration problems affecting entitlement to social welfare. Analytical frameworks aimed to reflect the role of broader social structures in shaping individual health actions., Results: Although participants demonstrated some knowledge of tuberculosis their awareness of personal risk was low. Symptoms commonly associated with tuberculosis were either not recognised or were attributed to other causes for which participants would not ordinarily seek health care. Many accessed health care by chance and, for some, for health concerns other than tuberculosis., Conclusions: Health education, based on increasing awareness of symptoms, may play a limited role in tuberculosis care for populations with complex health and social needs. The findings support the intensification of outreach initiatives to identify groups at risk of tuberculosis and the development of structured care pathways which support people into prompt diagnosis and treatment.

Objectives: This article discusses how hard-to-reach population groups were conceptualized into a search filter. The objectives of this article were to (1) discuss how the authors designed a multistranded population search filter and (2) retrospectively test the effectiveness of the search filter in capturing all relevant populations (eg, homeless people, immigrants, substance misusers) in a public health systematic review., Study Design and Setting: Systematic and retrospective analysis via a case study. Retrospective analysis of the search filter was conducted by comparing the MEDLINE search results retrieved without using the search filter against those retrieved with the search filter. A total of 5,465 additional results from the unfiltered search were screened to the same criteria as the filtered search., Results: No additional populations were identified in the unfiltered sample. The search filter reduced the volume of MEDLINE hits to screen by 64%, with no impact on inclusion of populations., Conclusions: The results demonstrate the effectiveness of the filter in capturing all relevant UK populations for the review. This suggests that well-planned search filters can be written for reviews that analyze imprecisely defined population groups. This filter could be used in topic areas of associated comorbidities, for rapid clinical searches, or for investigating hard-to-reach populations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The psychosocial support needs of parents considering a gastrostomy feeding tube for their disabled child are often overlooked, yet there is a growing body of evidence that attests to the decisional conflicts parents, often mothers, experience. This may be in addition to the stress associated with feeding a disabled child. The support needs of families and caregivers should be assessed, including the values parents attach to oral and tube feeding. Structured support should be embedded within the care pathway and both professionals, and service users, with appropriate training should be identified to ensure parental information needs, and any emotional, practical and financial issues are addressed.

Objective: To examine the benefits/barriers for HIV positive parents of communicating their status to seronegative children in low/middle income countries in order to inform policy and practice in Jamaica., Methods: The authors carried out a systematic search of published literature on parental disclosure in low/middle income countries written in the English language between January 1991 and September 2012, identified from databases: Academic Search Complete, CINAHL, EBSCOhostEJS, Gender Studies Database, Health Policy Reference Centre, MEDLINE (includes the West Indian Medical Journal), PsycARTICLES , PsycINFO , SocINDEX, AMED, Global Health, Embase, Social Policy and Practice, Maternity and Infant Care. The authors also refer to articles on parental disclosure in high income countries which appeared in peer-reviewed journals and conducted a local search in Jamaica for articles on HIV disclosure in the Caribbean region., Results: Global estimates of parental disclosure rates were 20-97% in high income countries and 11-44% in resource constrained countries. Mean age of children at disclosure was age 10-18 years. Mothers were more likely to disclose to older children, female children, and when they had strong support networks. Barriers included fear of stigma/discrimination, not knowing how to tell the child, fear of the child disclosing to others and believing a child was too young to cope. Of the 16 articles identified which met the search criteria, 10 studies and three reviews noted positive benefits of disclosure on parental health and the parent-child relationship., Conclusion: Significant differences in attitudes and rates of maternal disclosure in low/middle income countries compared to high income countries reflect the impact of cultural, structural, economic and social factors and highlight the need for culturally-specific research. Implications for policy and practice in Jamaica are discussed.

Determining how growth and differentiation are coordinated is key to understanding normal development, as well as disease states such as cancer, where that control is lost. We have previously shown that growth and neuronal differentiation are coordinated by the insulin receptor/target of rapamycin (TOR) kinase (InR/TOR) pathway. Here we show that the control of growth and differentiation diverge downstream of TOR. TOR regulates growth by controlling the activity of S6 kinase (S6K) and eIF4E. Loss of s6k delays differentiation, and is epistatic to the loss of tsc2, indicating that S6K acts downstream or in parallel to TOR in differentiation as in growth. However, loss of eIF4E inhibits growth but does not affect the timing of differentiation. We also show, for the first time in Drosophila, that there is crosstalk between the InR/TOR pathway and epidermal growth factor receptor (EGFR) signaling. InR/TOR signaling regulates the expression of several EGFR pathway components including pointedP2 (pntP2). In addition, reduction of EGFR signaling levels phenocopies inhibition of the InR/TOR pathway in the regulation of differentiation. Together these data suggest that InR/TOR signaling regulates the timing of differentiation through modulation of EGFR target genes in developing photoreceptors.

Using the findings of a small-scale qualitative investigation based on in-depth interviews with mothers attending a tertiary paediatric referral centre in London, this paper explores professional and parental discourses in relation to gastrostomy tube feeding and disabled children. Detailed accounts are given of women's struggles to negotiate their identities, and those of their children, within dominant discourses of mothering and child-centredness. Constructions of feeding practices as coercive conflict with normative expectations of 'good mothering' and the 'idealised autonomous' child. Although notions of 'stigmatised identities' featured in women's accounts of feeding children, both orally and by tube, stigma fails to explain why mothers are rendered culpable within expert discourses. Prevailing theories of stigma and coping are interrogated and judged to be more descriptive than explanatory. Felt stigma is posited as an aspect of governmentality.

Dosage compensation in mammalian females is achieved by the random inactivation of one X chromosome early in development; however, inactivation is not complete. In addition to a majority of pseudoautosomal loci, there are genes that are expressed from both the active and the inactive X chromosomes, and which are interspersed among other genes subject to regular dosage compensation. The patterns of X-linked gene expression in different tissues are of great significance for interpreting their impact on sex differences in development. We have examined the suitability and sensitivity of a microarray approach for determining the inactivation status of X-linked genes. Biotinylated cRNA from six female and six male lymphocyte samples were hybridised to Affymetrix HG-U133A microarrays. A total of 36 X-linked targets detected significantly higher levels of female transcripts, suggesting that these corresponded to sequences from loci that escaped, at least partly, from inactivation. These included genes for which previous experimental evidence, or circumstantial evidence, existed for their escape, and some novel candidates. Six of the targets were represented by more than one probe set, which gave independent support for the conclusions reached.

The author reviews and continues the debate initiated by her recent paper in this journal. The paper was critical of certain aspects of palliative medicine, and caused Ashby and Stoffell to modify the framework they proposed in 1991. It now takes account of the need for artificial hydration to satisfy thirst, or other symptoms due to lack of fluid intake in the terminally ill. There is also a more positive attitude to the emotional needs and ethical views of the patient's family and care-givers. However, clinical concerns about the general reluctance to use artificial hydration in terminal care remain, and doubts persist about the ethical and legal arguments used by some palliative medicine specialists and others, to justify their approach. Published contributions to the debate to date, in professional journals, are reviewed. Key statements relating to the care of sedated terminally ill patients are discussed, and where necessary criticised.

This paper explores ethical issues relating to the management of patients who are terminally ill and unable to maintain their own nutrition and hydration. A policy of sedation without hydration or nutrition is used in palliative medicine under certain circumstances. The author argues that this policy is dangerous, medically, ethically and legally, and can be disturbing for relatives. The role of the family in management is discussed. This issue requires wide debate by the public and the profession.

Fifty cases of orthostatic hypotension in the elderly are analysed. Three main modes of presentation were identified: (1) falls or mobility problems; (2) mental confusion or dementia; or (3) predominantly cardiac symptoms. Selected case histories are given to illustrate diagnostic difficulties. Medication was responsible for orthostatic hypotension in 66% of patients and striking examples of polypharmacy were encountered. However, 34% of cases were not iatrogenic. Only 14% of patients had overtly postural symptoms. A high index of suspicion is needed to diagnose orthostatic hypotension in the elderly and the condition is often overlooked. The paper provides useful diagnostic clues for clinicians.

Serum zinc and C-reactive protein (CRP) levels were measured in two groups of acutely ill geriatric hospital in-patients. Serum CRP levels were greater than 10 mg/l in 62% of the first group and 47% of the second. There was a significant negative correlation between zinc and CRP in both groups (r = -0.33, P less than 0.001, n = 103) and (r = -0.29, P less than 0.001, n = 135 respectively). The serum CRP was raised in 30% of long stay patients (n = 50) and 23% of a control group of elderly hospital patients with a normal serum albumin (n = 71), but there was no correlation between zinc and CRP in these patient groups. The results indicate that an acute phase response influences serum zinc levels in acutely ill geriatric patients. There is reason to believe that a distinction should be made between true zinc deficiency and a low serum zinc secondary to acute zinc redistribution during an inflammatory response. Measurement of CRP may help to distinguish between these two situations. We advise that if the serum zinc is low and CRP is significantly raised, zinc supplements should be avoided and a source of infection should be sought. Following recovery from severe infection low serum zinc levels return to normal while elevated CRP levels fall.

Serum zinc levels measured by atomic absorption spectrophotometry were found to be low (less than 10.5 mumols/l) in 38% of acute geriatric admissions, 69% of long stay geriatric patients and 19% of a control group of elderly hospital patients with a normal serum albumin. There was a significant positive correlation between serum zinc and serum albumin in all groups. In acutely ill geriatric patients only, there was a weak but statistically significant positive correlation between serum zinc and alpha-2-macroglobulin (A2M) (r = 0.20), P less than 0.05). Serum transferrin was low in 46% of acute geriatric patients and 22% of long stay geriatric patients but there was no correlation between serum zinc and serum transferrin levels in any patient group. There were significant differences in serum zinc, A2M and transferrin levels between the acute and long stay geriatric patients. The differences in serum zinc levels between these patients groups could not be explained by changes in serum A2M, transferrin or albumin. Changes mediated by an acute phase response may have influenced results in the acute geriatric group of patients.

Two cases of sudden death due to perforation of a benign oesophageal ulcer into a major blood vessel are reported. In one man, anaemia and aspiration pneumonitis dominated the clinical picture. He had an oesophageal stricture and a chronic peptic ulcer associated with an incarcerated hiatus hernia. Death was due to haemorrhage caused by perforation of the ulcer into the thoracic aorta. The second patient presented with confusion and falls, backache and indigestion. She had a hiatus hernia and a large benign chronic oesophageal ulcer. Death was due to perforation of the ulcer into the left pulmonary vein. The cases are presented for their rarity, to illustrate the complex and late presentation of problems in geriatric medicine, and as a reminder that reflux oesophagitis can be dangerous.

1. A high incidence of vitamin B12 or folate deficiency, or both, may be found in the elderly, particularly those in hospital. This report concerns fifty cases detected in an inner-city-area geriatric unit during the course of routine clinical investigation. The majority had none of the classical haematological signs of vitamin B12 or folate deficiency, and all the patients reported had a mean corpuscular volume (MCV) of less than 100 fl. 2. There was a significant negative correlation between the MCV and the erythrocyte folate (P less than 0.01), supporting earlier published work using a low serum folate as an index of folate deficiency. 3. There was no correlation between the MCV and the serum vitamin B12. Published work differs on this point. 4. Serum iron, total Fe-binding capacity and percentage Fe saturation results were available in forty patients in this series. There was a significant positive correlation between the serum Fe and the MCV (P less than 0.01) and 34% of patients had haematological evidence of Fe deficiency. In the majority, however, there was no evidence that associated Fe deficiency had masked the haematological signs of vitamin B12 or folate deficiency. 5. More attention should be paid to the problem of 'masked' vitamin B12 and folate deficiency in the elderly. There is a case for routine screening of the elderly for vitamin B12 and folate deficiency irrespective of the MCV.

Circhoral pulsatile release of immunoreactive luteinising hormone (LH) and prostaglandin F2 alpha (PGF2 alpha) occur synchronously into the jugular vein in ovariectomised sheep. Following a 4-hour control period, intra-carotid injections of phentolamine or intramuscular injections of phenoxybenzamine were given to ovariectomised sheep and the pulsatile release of LH and PGF2 alpha was monitored for a further 6 to 8 hours. Phenoxybenzamine caused a fall in LH and PGF2 alpha in jugular venous plasma. Phentolamine also reduced LH significantly but in this case a marked rise in PGF2 alpha as measured by radioimmunoassay (RIA) occurred after very high doses of phentolamine. Interpretation of the latter results was complicated by the fact that phentolamine at high dose levels interfered with the RIA of PGF2 alpha in plasma. Experiments were repeated in ovariectomised sheep with cannulae placed in the lateral ventricles of the brain for sampling cerebrospinal fluid (CSF). In contrast to the previously observed rise in jugular venous PGF2 alpha following high doses of phentolamine, a fall in CSF levels of immunoreactive PGF2 alpha occurred following intracarotid phentolamine or phenoxybenzamine in 3 out of 7 experiments, while no change was observed in the remaining 4 animals. Phentolamine did not reduce LH significantly in animals with intraventricular cannulae. The work provides support for the view that circhoral pulses of immunoreactive PGF2 alpha in sheep are neural in origin and may be related to sympathetic neurotransmission.

Prostaglandin F2alpah (PGF2alpha) was given intravenously in a maximun dose of 24 mug per min to 6 normal male volunteers. There was no change in serum luteinizing hormone, follicle-stimulating hormone, or blood glucose. Plasma cortisol fluctrated but no substained rise was demonstrated.