ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe.

BACKGROUND: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. DESIGN AND METHODS: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. RESULTS: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. CONCLUSIONS: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

Cancer and breast cancer awareness interventions in an intellectual disability context: A review of the literature.

BACKGROUND: Women with an intellectual disability (ID) have a similar risk of developing breast cancer as women in the general population yet present with later stage breast cancers, which have poorer outcomes. AIM: To identify whether there is a need to develop a breast cancer awareness intervention for women with an ID. METHODS: Interventions aimed at increasing cancer awareness and breast cancer awareness for people with an ID were identified and critically appraised. RESULTS: Five interventions to increase cancer awareness or breast cancer awareness in people with an ID were identified. CONCLUSION: The review highlighted the paucity of theoretically underpinned breast cancer awareness interventions specifically aimed at women with an ID. Facilitating breast cancer awareness for women with an ID could potentially lead to earlier presentation of potential symptoms of breast cancer, earlier treatment, better prognosis and ultimately, improved survival. This article establishes that there is a need for an intervention underpinned by theory to increase breast cancer awareness in women with an ID.

Is psychosocial and cognitive dysfunction misattributed to the virus in hepatitis C infection? Select psychosocial contributors identified.

Chronic hepatitis C is associated with health-related quality of life and cognitive impairments, even in mild disease. Recent evidence demonstrating hepatitis C virus (HCV) neurotropism has strengthened a neuropathophysiological hypothesis. However, sample heterogeneity confounds study outcomes. A uniquely homogeneous cohort of Irish women, following an iatrogenic HCV outbreak, offers a rare opportunity to control for HCV chronicity and the virus' purported impact on quality of life and cognition. A multi site, three-group, cross-sectional design was employed. Noncirrhotic, iatrogenically infected women, developing either acute or chronic infection, were recruited from prospective tertiary-care liver clinics and the community. Well-matched healthy controls were also recruited. All participants completed a psychosocial survey and were invited to undergo a comprehensive neuropsychological test battery. Significantly distressed psychosocial symptom profiles were observed in those with an iatrogenic HCV exposure history, which was independent of viral chronicity. Chronic and cleared HCV cohorts were not differentiated from each other. Two distinct subgroups, demarcated along 'impaired' vs 'nonimpaired' quality-of-life reports, were clearly identified and logistic regression analysis identified depressed mood and cognitive fatigue, rather than viral status, as statistically significant predictors of group membership. Compared with matched controls, significant cognitive impairments were not observed in either HCV cohort. Our findings provide strong evidence of nonviral factors accounting for quality of life impairment in chronic HCV and they also appear to question existing reports of cognitive dysfunction in mild disease. Depressed mood and cognitive fatigue appear to be critical psychosocial mediators of reduced quality-of-life and we hypothesize that metabolite abnormalities reported in HCV samples may also be confounded by these factors, given the associated literature.

Low incidence of Pneumocystis jirovecii pneumonia in an unprophylaxed liver transplant cohort.

BACKGROUND: Liver transplant recipients are managed with a range of immunosuppressive regimens that place them at heightened risk of life-threatening opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). No routine PJP prophylaxis is used at out institution. We reviewed the incidence of PJP in this cohort of unprophylaxed liver transplant recipients. METHODS: We examined all liver transplants performed between January 2000 and January 2012 in Ireland's National Liver Transplant Centre, St. Vincent's University Hospital, Dublin. Cases were identified through a computerized database and through the histopathology and microbiology registration system. The diagnosis of PJP was confirmed by identification of Pneumocystis cysts in bronchoalveolar lavage (BAL) fluid or on autopsy specimens using Grocott-Gomori methenamine-silver nitrate or modified Wright-Giemsa staining methods. RESULTS: During the study period, 687 liver transplants were performed. We found 7 cases of PJP with an incidence rate of 0.84 per 1000 person transplant years. Five cases occurred within 12 months of transplant with 2 cases occurring at 56 and 60 months, respectively. Two cases were diagnosed at postmortem; 1 previously had negative cytology from BAL, while the other could not be bronchoscoped because of rapid deterioration in the clinical condition. Three of the 5 treated patients died. CONCLUSIONS: The incidence of PJP in this cohort was very low, but the case fatality rate was high. Two cases occurred well after the usual recommended period of prophylaxis. In institutions with a very low risk of infection, targeted rather than universal prophylaxis may be reasonable.

'They don't actually join the dots': An exploration of organizational change in Irish opiate community treatment services.

BACKGROUND: People who use community-based drug treatment services spend a considerable amount of their time in treatment in direct contact with frontline staff. These staff are also fundamental to supporting the implementation of change to meet service user needs. Yet, very little is known about staff perspectives on the process and internal dynamics of drug treatment services, their views about what makes services work effectively, and how services can more effectively adopt to changes in practice. AIM AND METHOD: Conducted across Irish community opiate prescribing services and drawing on data from 12 in-depth qualitative interviews with frontline staff. This paper examines the narratives of staff about the factors which influence the dynamics and process of treatment services, particularly in relation to the implantation of change. FINDINGS: Change itself was described both in respect of how a service responded to immediate service user needs or supported planned change. Little distinction was made in respect of service attributes which facilitated a response in either context. Overwhelmingly, staff contextualised current service effectiveness, historical change, and desired change in how effectively their services met service user needs, which was also viewed as a significant motivation for change. Differences in operational standards across services in terms of practices, policy implementation, job roles, divisions between professional groups, and recruitment and retention of staff inhibited change adoption. Factors which were identified in terms of inhibiting or facilitating planned change were consistent with the wider literature on change implementation but provided unique insights in the context of substance misuse services. CONCLUSIONS: A range of interdependent factors which influence an 'eco-system' of service delivery were identified. Effective policy implementation in Ireland remains aspirational, but findings reported in this paper have important implications for future planning and design of services for people who use drugs, and provide a good basis for further investigation.

Chronic hepatitis C infection blocks the ability of dendritic cells to secrete IFN-α and stimulate T-cell proliferation.

Dendritic cells (DCs) are likely to play a key role in the compromised T-cell function associated with hepatitis C Virus (HCV) infection. However, studies of DC function in HCV-infected patients to date have yielded conflicting findings possibly because of patient and virus heterogeneity. Here, we report the characterization of monocyte-derived DCs obtained from a homogenous cohort of women who were infected with HCV genotype 1b following exposure to contaminated anti-D immunoglobulin from a single donor source. Patients included in the study had not received anti-viral therapy and all had mild liver disease. We show that phenotypically normal monocyte-derived dendritic cells (MDDCs) (CD11c(+) HLA(-) DR(+) CD1a(+) CD14(lo) ) can be obtained from these patients. These cells respond to both Poly(I:C) and LPS, by up-regulating expression of CD86. They secrete high levels of IL-8 and CCL5 in response to LPS, an indication that the MyD88-dependent and MyD88-independent signalling pathways downstream of TLR4 ligation are functioning normally. However, these cells are poor stimulators of T-cell proliferation in allogeneic mixed lymphocyte reactions. Furthermore, patient MDDCs fail to secrete IFN-α in response to poly(I:C) or IFN-ß stimulation. Altered DC function may contribute to impaired cellular immune responses and chronicity of disease following HCV infection in this cohort. An effective therapeutic vaccine for chronic HCV infection will most likely need to target DCs to elicit an appropriate cellular response; therefore, it is important to resolve how the DCs of different patient cohorts respond to stimulation via TLRs.

Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease.

Overwhelming evidence supports the theory that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic predispositions of multiple genes, combined with an abnormal interaction with environmental factors. It is becoming apparent that epigenetic factors can have a significant contribution in the pathogenesis of disease. Changes in the methylation state of IBD-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We have explored the role of DNA methylation in IBD pathogenesis. DNA methylation profiles (1505 CpG sites of 807 genes) of matched diseased (n = 26) and non-diseased (n = 26) intestinal tissues from 26 patients with IBD [Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were profiled using the GoldenGate™ methylation assay. After an initial identification of a panel of 50 differentially methylated CpG sites from a training set (14 non-diseased and 14 diseased tissues) and subsequent validation with a testing set (12 non-diseased and 12 diseased tissues), we identified seven CpG sites that are differentially methylated in intestinal tissues of IBD patients. We have also identified changes in DNA methylation associated with the two major IBD subtypes, CD and UC. This study reports IBD-associated changes in DNA methylation in intestinal tissue, which may be disease subtype-specific.

Ochroconis gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis.

Ochroconis gallopava has rarely been isolated in immunosuppressed patients. We report the first case to our knowledge of O. gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis. A 58-year-old man who had undergone cardiac transplant 8 years earlier alerted his dialysis nurses to the presence of black material in his catheter lumen. Fungal hyphae were seen on direct microscopy of the black material and from the dialysate effluent, and O. gallopava was cultured from both after 1 day. He was treated successfully with a single dose of intravenous voriconazole, followed by 2 weeks of oral voriconazole.

PhD Away Days: a component of PhD supervision.

AIM: This paper describes a peer-to-peer and supervisor support and mentoring process that was implemented in one PhD programme in nursing in the Republic of Ireland. BACKGROUND: PhD Away Days are held once per year and attended by all enrolled PhD students and their academic supervisors. Positive evaluations were obtained both from students and supervisors as collective learning occurred and group cohesiveness developed. All participants expressed interest in continuing the PhD Away Days as they learned from others' experiences. In addition, the range of topics provided learning on topics of concern across content areas, e.g. conceptual and theoretical developments, research design, challenges in data collection, and analysis and publication plans. Most importantly, there was a feeling of togetherness among students, thus decreasing the feeling of being alone with the challenges of PhD work. CONCLUSIONS: Plans for the future include the need to have the PhD Away Days continued structured around key topics of concern to both students and supervisors, and to implement content-specific modules in the PhD programme.

Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure.

BACKGROUND: Natural killer (NK) cells may be impaired in patients with persistent hepatitis C virus (HCV) infection, but studies to date have yielded inconsistent findings due to patient and virus heterogeneity and difficulties obtaining appropriate controls. AIMS: To overcome these variables, we have examined numbers, phenotypes, cytotoxic activities and cytokine profiles of circulating NK cells from Irish women who acquired infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source and matched controls. RESULTS: Comparing 29 women who developed persistent infection with 21 who spontaneously resolved infection and 26 controls, we found that NK cell numbers were consistently lower in the persistently infected group (p = 0.02 and 0.002). This decrease was due to depletions of NK cells expressing low levels of CD56 (CD56(dim) NK cells; p = 0.004 and 0.0001), whilst CD56(bright) NK cells were expanded (p = 0.004 and 0.0001). Compared to HCV resolvers, CD56(dim) NK cells from persistently infected patients less frequently expressed CD16 and more frequently expressed NKG2A/C/E. These phenotypic changes did not significantly affect natural or interleukin-2-induced cytotoxicity by peripheral blood mononuclear cells against K562 and Daudi targets. Greater frequencies of CD56(bright) NK cells from chronic HCV patients produced interferon-gamma compared with HCV responders (p = 0.05) and controls (p = 0.0001) after phorbol ester stimulation in vitro. CONCLUSIONS: Alterations in NK subset distributions in chronic HCV infection may explain why previous reports of impaired NK cell functions were difficult to confirm. Altered NK cell functions may contribute to impaired cellular immune responses and chronicity of disease following HCV infection.

The high prevalence of unrecognized anaemia in patients with diabetes and chronic kidney disease: a population-based study.

BACKGROUND: Anaemia occurs early in the course of diabetes-related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population. METHODS: Haemoglobin (Hb) was measured on all glycated haemoglobin (HbA1c) samples and the most recent (< 4 months) estimated glomerular filtration rate (eGFR) was obtained. Anaemia (at treatment level) was defined as Hb < 110 g/l or the use of erythropoetic stimulating agents (ESA). RESULTS: Twelve per cent (10-14%) of people had Hb < 110 g/l. The prevalence of anaemia increased progressively with worsening CKD. People with CKD stage 3 accounted for the largest number of people with anaemia; 18% (95% CI 13-24%) had Hb < 110 g/l. Those with eGFR < 60 ml/min/1.73 m2 and not on ESA or dialysis were four (2-7) times more likely than patients with better renal function to have Hb < 110 g/l. The relation between Hb and eGFR became approximately linear below an eGFR of 83 ml/min/1.73 m2, where, for every 1 ml/min/1.73 m2 fall in eGFR, there was a 0.4 (0.3-0.5) g/l fall in haemoglobin. CONCLUSIONS: This study demonstrates that anaemia, at levels where treatment is indicated, occurs commonly in people with diabetes and CKD stage 3 or worse. The screening for anaemia in current diabetes management should be extended.

Economics of Early Warning Scores for identifying clinical deterioration-a systematic review.

AIM: In 2013, a National Early Warning System (EWS) was implemented in Ireland. Whilst evidence exists to support the clinical effectiveness of EWS in the acute health care setting, there is a paucity of information on their cost and cost effectiveness. The objective of this systematic literature review was to critically evaluate the economic literature on the use of EWS in adult patients in acute health care settings for the timely detection of physiological deterioration. METHODS: A systematic literature review was conducted to accumulate the economic evidence on the use of EWS in adult patients in acute health care settings. RESULTS: The search yielded one health technology assessment, two budget impact analyses and two cost descriptions. Three of the studies were Irish, and considered the national EWS system. A Dutch study reported financial consequences of a single parameter EWS, as part of a rapid response system, in a surgical ward. The fifth study examined an advanced triage system in a medical emergency admission unit in Wales. CONCLUSIONS: The economic evidence on the use of EWS amongst adult patients in acute health care settings for the timely detection of physiological deterioration is limited. Further research is required to investigate the cost effectiveness of EWS, and the appropriateness of using standard methods to do so. The recent implementation of a national EWS in Ireland offers a unique opportunity to bridge this gap in the literature to examine the costs and cost effectiveness of a nationally implemented EWS system.

Renal and liver transplantation for toxin-induced organ failure.

OBJECTIVE: Determine the number and outcome of renal (January 1987-June 2001, inclusive) and liver transplants (January 1993-June 2001) performed in Ireland for drug or toxin-induced organ failure and identify the toxins involved. METHODS: Retrospective review of national transplant coordinators' records and patient charts. RESULTS: Fourteen patients received renal transplants for nephropathy secondary to drugs or toxins. In 12 of these cases, renal failure was attributed to chronic toxicity, principally cyclosporin A therapy (seven cases). One-year patient and graft survival were 100%. Twenty-nine liver transplants were for toxin-induced organ failure, and 20 of these were for chronic ethanol induced liver disease. One-year patient and graft survival rates were 77% and 73%, respectively. CONCLUSIONS: Kidney and liver transplants were needed more often because of chronic toxicity than acute poisoning. Both groups had good outcomes at one year post-transplantation.

Improved survival outcomes for liver transplantation.

UNLABELLED: Liver transplantation is the treatment of choice for end stage liver disease and fulminant hepatic failure. Outcome of the procedure may be dependent on multiple factors including patient selection, donor selection, and centre experience. AIM: To determine whether the outcome for liver transplantation has improved over the time for the Irish National Liver Transplant Unit since its initial set up in 1993. METHODS: All patients who underwent liver transplantation between Jan 1993 to Oct 2004 were included. Patients were sub-divided into three sequential cohorts of 90 patients each. Survival outcomes were compared between the groups. RESULTS: 270 patients (male = 137) underwent 323 liver transplants (median age 49 yrs, range 16-68 yrs). Indications included primary biliary cirrhosis (14.1%), alcohol related liver disease (6.2%), fulminant hepatic failure (14.2%), primary sclerosing cholangitis (10.1%), chronic active hepatitis (9.5%), viral hepatitis (9.5%) and cryptogenic cirrhosis (7.1%). Most procedures (85.8%) were elective. Re-transplantation rates within the first 3 months of primary procedure were 9%, 5%, and 5% for the three chronological groups. Overall calculated 3-month, 1-year and 3 year survival rates for group 1 were 87%, 82% and 77%. For the groups 2 and 3 the figures were 86%, 81%, 77% and 89%, 89%, and 81% respectively. One- and 3-year survival rates were significantly better for group 3 compared to group 1 (p < 0.05). CONCLUSIONS: Survival outcome has improved significantly over the past 12 years and is likely attributed to increasing experience of the transplant centre.

Lack of Heterogeneity in Bacteriocin Production Across a Selection of Commercial Probiotic Products.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Bacteriocin production has often been mooted as a desirable probiotic trait and, in specific cases, has been shown to promote probiotic survival within the gastrointestinal tract, contribute to the control of pathogens and even influence host gene expression in the gut. However, it is not clear what proportion of probiotic strains routinely found in commercial products produces bacteriocins, and additionally, it is not known which bacteriocins are produced most frequently. To address this, we conducted a culture-based assessment of the bacteriocinogenic ability of bacterial strains found in a variety of commercially available probiotic products. We detected eight bacteriocin-producing isolates from 16 tested products. Interestingly, in all cases, the isolates were Lactobacillus acidophilus, and the bacteriocin produced was identified as the narrow spectrum class II bacteriocin, lactacin B. The apparent absence of other bacteriocin-producing strains from across these products suggests a lack of heterogeneity in bacteriocin production within probiotic products and suggests that bacteriocin production is not being optimally harnessed as a probiotic trait.

MELD score as a prognostic model for listing acute liver failure patients for liver transplantation.

OBJECTIVES: The King's College Hospital (KCH) criteria are widely used for listing patients with acute liver failure (ALF) for liver transplantation (LT). Recent reports have suggested that the Model for End-Stage Liver Disease (MELD) score may be useful in assessing prognosis in ALF (nonparacetamol). This study compares prognostic accuracy of the two systems in patients with paracetamol (POD)-induced ALF treated in this unit. METHODS: Seventy-two patients (average age 38 years; F:M ratio 2:1) admitted from 1994 to 2005 with POD-related ALF were studied. Clinical and biochemical parameters were recorded. The effect of applying a MELD score of greater than 30 as listing criteria for LT was calculated and compared with the KCH criteria. Outcomes were defined as LT, death, or full recovery. RESULTS: Thirty-one patients (43%) recovered with medical therapy, 29 (40%) patients died, and 12 (17%) underwent LT. Sixty five percent of patients had a MELD > 30 and therefore could potentially be listed on admission; however, using KCH criteria only 24% patients were listed immediately. Sensitivity and negative predictive value of MELD was higher then KCH; however, we found KCH to have much higher specificity and positive predictive value. CONCLUSION: MELD has higher sensitivity and negative predictive value for POD-induced ALF than the KCH criteria. However, the high false-positive rate associated with MELD limits its clinical utility. The high negative predictive value of MELD score may allow it to be used in conjunction with KCH criteria to avoid unneeded LT in patients who will likely recover spontaneously.

Severe acute renal failure in adults: place of care, incidence and outcomes.

BACKGROUND: Department of Health guidelines recommend specialist critical care facilities for patients with severe single-organ failure such as acute renal failure (ARF). Prospective studies examining incidence, causes and outcomes of ARF outside of intensive care settings are lacking. AIM: To determine the incidence, causes, place of care and outcomes of severe single-organ ARF. DESIGN: Prospective observational study. METHODS: For 6 weeks in June-July 2003, renal physicians were contacted daily, and ICUs on alternate days, to identify cases of severe single-organ ARF in the Greater Manchester area. All patients with serum creatinine >or=500 micromol/l and not requiring other organ support were included. Patients with end-stage renal disease were excluded. Survivors were followed up at 90 days and 1 year from admission. Two independent consultant nephrologists assessed each case using anonymized summaries. RESULTS: Eighty-five patients had multi-organ ARF and 28 had severe single-organ ARF (380 and 125 pmp/year, respectively). Of those with single-organ ARF, 10 (36%) had known pre-existing chronic kidney disease. Renal replacement therapy (RRT) was required in 15 (54%). Total bed occupancy on ICUs relating to single-organ ARF was 59 days (range per patient 1-21). At 90 days, 18 (64%) were alive, and 17 (94%) had independent renal function. At 1 year, 4/18 had died, none receiving RRT at the time of death. Survivors all had independent renal function. In 13 (46%) cases there was an unacceptable delay in patient transfer and in 7 (25%), delays in assessment or commencement of RRT may have adversely affected patient outcome. DISCUSSION: The incidence of ARF treated with RRT is rising. Delays in transfer to renal services may result in inappropriate ICU bed use, and may adversely affect patient outcomes. There are serious problems regarding the appropriate use of expensive and limited medical resources in the critical care area, and in providing safe and effective treatment of patients with ARF.

Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment.

BACKGROUND: Abrupt discontinuation of long-term psychotropic medication can be followed by a high risk of early relapse. This study aimed to quantify the relapse risk over time in patients with schizophrenia following discontinuation of maintenance neuroleptic treatment. METHODS: Data on the timing of relapses in patients with schizophrenia after withdrawal from neuroleptic therapy were located by a computerized literature search, combined with new data, and evaluated by survival analysis. RESULTS: Data were found for 1210 schizophrenic subjects: 1006 (795 inpatients and 211 outpatients) were withdrawn abruptly from oral neuroleptic therapy, and 204 discontinued treatment gradually (> or = 3 weeks) or stopped treatment with depot neuroleptic drugs. After abrupt discontinuation of oral medication, the risk of relapse reached 50% within 30 weeks, with remarkably little additional risk thereafter to 3.7 years; inpatients relapsed more rapidly than did outpatients (10 vs 18 weeks to a 25% relapse risk). In studies including subjects whose drug therapy was withdrawn abruptly (n = 49) vs gradually (n = 58), relapse was earlier after abrupt discontinuation (25% risk in 6 vs 10 weeks), with a persistent difference for at least 6 months. CONCLUSIONS: The relapse risk was high within 6 months of discontinuing oral neuroleptic therapy, particularly in hospitalized patients. Most patients who remained stable for 6 months continued to do so for long periods without medication, indicating clinical heterogeneity. Drug-withdrawal stressors, related to long-term pharmacodynamic adaptations, are implicated. Since the risk was lower after gradually discontinuing oral neuroleptic therapy or stopping depot injections, early relapse may be spared by a slow removal of drugs.

One hundred years of schizophrenia: a meta-analysis of the outcome literature.

OBJECTIVE: This study was undertaken to assess the twentieth-century literature on outcome in schizophrenia for historical trends that might be associated with changes in diagnostic and therapeutic practice and to test the hypothesis that both improved biological treatment and changes in diagnostic criteria have influenced outcome. METHOD: Meta-analysis of the international literature on outcome in schizophrenia or dementia praecox from 1895 to 1992 identified 821 studies; 320 of these, with 51,800 subjects in 368 cohorts, met the inclusion criteria for the study. RESULTS: Only 40.2% of patients were considered improved after follow-ups averaging 5.6 years (range = 1-40). Outcome was significantly better when patients were diagnosed according to systems with broad criteria (46.5% were improved) or undefined criteria (41.0% were improved) rather than narrow criteria (27.3% were improved). The proportion of patients who improved increased significantly after mid-century (for 1956-1985 versus 1895-1955, 48.5% versus 35.4%), probably reflecting improved treatment as well as a broadened concept of schizophrenia. However, in the past decade, the average rate of favorable outcome has declined to 36.4%, perhaps reflecting the re-emergence of narrow diagnostic concepts. CONCLUSIONS: Overall, less than half of patients diagnosed with schizophrenia have shown substantial clinical improvement after follow-up averaging nearly 6 years. Despite considerable gains in improvement rates after mid-century, there has been a decline since the 1970s. These historical changes probably reflect improved treatment, shifts in diagnostic criteria, and selection bias related to changes in health care.

Meta-analysis of postmortem studies of Alzheimer's disease-like neuropathology in schizophrenia.

OBJECTIVE: To evaluate the hypothesis that patients with schizophrenia who have been treated with neuroleptics have a high rate of Alzheimer's disease-like neuropathology. METHOD: Neuropathological studies indicating the presence or absence of Alzheimer's disease-like neuropathology in the postmortem brains of patients with schizophrenia, normal comparison subjects, and comparison subjects who had affective disorder were evaluated with Mantel-Haenszel chi-square and odds ratio analyses. RESULTS: Ten studies with relevant data were reviewed; none of eight with comparisons indicated that Alzheimer's disease-like neuropathology was more likely to be found in the brains of patients with schizophrenia than in the brains of comparison subjects. CONCLUSIONS: Suggestions that cerebral plaques and neurofibrillary tangles are more common in schizophrenia in association with neuroleptic treatment were not supported.