Summary Background CTX0E03 is an immortalised human neural stem-cell line from which a drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent improvement in sensorimotor function ...in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients. Methods We did an open-label, single-site, dose-escalation study. Men aged 60 years or older with stable disability (National Institutes of Health Stroke Scale NIHSS score ≥6 and modified Rankin Scale score 2–4) 6–60 months after ischaemic stroke were implanted with single doses of 2 million, 5 million, 10 million, or 20 million cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging data were collected over 2 years. The primary endpoint was safety (adverse events and neurological change). This trial is registered with ClinicalTrials.gov , number NCT01151124. Findings 13 men were recruited between September, 2010, and January, 2013, of whom 11 (mean age 69 years, range 60–82) received CTX-DP. Median NIHSS score before implantation was 7 (IQR 6–8) and the mean time from stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven had right-hemisphere infarcts. No immunological or cell-related adverse events were seen. Other adverse events were related to the procedure or comorbidities. Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients. At 2 years, improvement in NIHSS score ranged from 0 to 5 (median 2) points. Interpretation Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function. Our observations support further investigation of CTX-DP in stroke patients. Funding ReNeuron Limited.
Summary Background Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on ...the child. Methods We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22–24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com , number ISRCTN14568373. Findings Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons OR 0·86, 95% CI 0·61–1·22) or neonatal outcome (OR 0·62, 0·38–1·03), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97·3 SD 17·9 vs 97·7 17·5; difference in means −0·48, 95% CI −2·77 to 1·81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0·27). Interpretation Vaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age. Funding Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales.
Recently, studies have examined the underlying patient and practice factors for missed appointments, but less is known about the impact on patient health. People with one or more long-term conditions ...who fail to attend appointments may be at risk of premature death. This is the first study to examine the effect of missed primary healthcare appointments on all-cause mortality in those with long-term mental and physical health conditions.
We used a large, nationwide retrospective cohort (n = 824,374) extracted from routinely collected general practice data across Scotland over a 3-year period from September 2013 until September 2016. This data encompasses appointment history for approximately 15% of the Scottish population, and was linked to Scottish deaths records for patients who had died within a 16-month follow-up period. We generated appointment attendance history, number of long-term conditions and prescriptions data for patients. These factors were used in negative binomial and Cox's proportional hazards modelling to examine the risk of missing appointments and all-cause mortality.
Patients with a greater number of long-term conditions had an increased risk of missing general practice appointments despite controlling for number of appointments made, particularly among patients with mental health conditions. These patients were at significantly greater risk of all-cause mortality, and showed a dose-based response with increasing number of missed appointments. Patients with long-term mental health conditions who missed more than two appointments per year had a greater than 8-fold increase in risk of all-cause mortality compared with those who missed no appointments. These patients died prematurely, commonly from non-natural external factors such as suicide.
Missed appointments represent a significant risk marker for all-cause mortality, particularly in patients with mental health conditions. For these patients, existing primary healthcare appointment systems are ineffective. Future interventions should be developed with a particular focus on increasing attendance by these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Purpose We set out to compare patients' expectations, consultation characteristics, and outcomes in areas of high and low socioeconomic deprivation, and to examine whether the same factors ...predict better outcomes in both settings. Methods Six hundred fifty-nine patients attending 47 general practitioners in high- and low-deprivation areas of Scotland participated. We assessed patients' expectations of involvement in decision making immediately before the consultation and patients' perceptions of their general practitioners' empathy immediately after. Consultations were video recorded and analyzed for verbal and nonverbal physician behaviors. Symptom severity and related well-being were measured at baseline and 1 month post-consultation. Consultation factors predicting better outcomes at 1 month were identified using backward selection methods. Results Patients in deprived areas had less desire for shared decision-making ( P <.001). They had more problems to discuss ( P = .01) within the same consultation time. Patients in deprived areas perceived their general practitioners (GPs) as less empathic ( P = .02), and the physicians displayed verbal and nonverbal behaviors that were less patient centered. Outcomes were worse at 1 month in deprived than in affluent groups (70% response rate; P <.001). Perceived physician empathy predicted better outcomes in both groups. Conclusions Patients' expectations, GPs' behaviors within the consultation, and health outcomes differ substantially between high- and low-deprivation areas. In both settings, patients' perceptions of the physicians' empathy predict health outcomes. These findings are discussed in the context of inequalities and the “inverse care law.”
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to test the hypothesis that invasive coronary function testing at time of angiography could help stratify management of angina patients without obstructive coronary artery ...disease.
Medical therapy for angina guided by invasive coronary vascular function testing holds promise, but the longer-term effects on quality of life and clinical events are unknown among patients without obstructive disease.
A total of 151 patients with angina with symptoms and/or signs of ischemia and no obstructive coronary artery disease were randomized to stratified medical therapy guided by an interventional diagnostic procedure versus standard care (control group with blinded interventional diagnostic procedure results). The interventional diagnostic procedure–facilitated diagnosis (microvascular angina, vasospastic angina, both, or neither) was linked to guideline-based management. Pre-specified endpoints included 1-year patient-reported outcome measures (Seattle Angina Questionnaire, quality of life EQ-5D) and major adverse cardiac events (all-cause mortality, myocardial infarction, unstable angina hospitalization or revascularization, heart failure hospitalization, and cerebrovascular event) at subsequent follow-up.
Between November 2016 and December 2017, 151 patients with ischemia and no obstructive coronary artery disease were randomized (n = 75 to the intervention group, n = 76 to the control group). At 1 year, overall angina (Seattle Angina Questionnaire summary score) improved in the intervention group by 27% (difference 13.6 units; 95% confidence interval: 7.3 to 19.9; p < 0.001). Quality of life (EQ-5D index) improved in the intervention group relative to the control group (mean difference 0.11 units 18%; 95% confidence interval: 0.03 to 0.19; p = 0.010). After a median follow-up duration of 19 months (interquartile range: 16 to 22 months), major adverse cardiac events were similar between the groups, occurring in 9 subjects (12%) in the intervention group and 8 (11%) in the control group (p = 0.803).
Stratified medical therapy in patients with ischemia and no obstructive coronary artery disease leads to marked and sustained angina improvement and better quality of life at 1 year following invasive coronary angiography. (Coronary Microvascular Angina CorMicA; NCT03193294)
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Background The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has ...been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD. Study Design Randomized patient-blinded crossover trial. Settings & Participants 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom. Intervention 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa. Outcomes Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters. Measurements Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire. Results There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 IQR, 0-240 vs 30 IQR, 0-210 minutes, respectively; P = 0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk RR, 1.52; 95% CI, 1.2-1.9; P < 0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P = 0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3 g/dL; P < 0.001). Health-related quality-of-life scores were equivalent. Limitations Single center; mean achieved HDF convection volume, 20.6 L. Conclusions Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.
Objective To define an optimal model for the decline in circulating antimüllerian hormone (AMH) with age and develop a validated age-related nomogram. Design Cohort study with validation of linear, ...biphasic linear, differential, power, and quadratic equations undertaken in two additional cohorts. Setting United Kingdom infertility clinics. Patient(s) Training cohort of 4,590 infertile women. Two separate validation cohorts; 4,588 infertile women, and 423 women with confirmed ovulation and normal pelvic ultrasound who have a male partner with severe oligospermia. Intervention(s) Serum AMH measurement. Main Outcome Measure(s) Optimal fit and age-related AMH nomogram. Result(s) The linear model had the largest sum of absolute and squared residuals and provided a less adequate fit than the four nonlinear models. Of these, the R2 ranged from 19.45% to 19.48% in the training dataset, from 21.30% to 21.36% in the validation dataset, and from 13.29% to 13.75% in the partners of oligospermic males. The parameters of the differential model were difficult to estimate, and the goodness-of-fit of the power model was slightly inferior to the quadratic model. Conclusion(s) Circulating AMH concentrations decline with increasing reproductive age in a manner optimally described by a quadratic equation. This validated age-related AMH nomogram will enable counseling of infertility patients regarding reproductive performance.
Interventions to promote positive parenting are often reported to offer good outcomes for children but they can consume substantial resources and they require rigorous appraisal.
Evaluations of the ...Triple P parenting program were subjected to systematic review and meta-analysis with analysis of biases. PsychInfo, Embase and Ovid Medline were used as data sources. We selected published articles reporting any child-based outcome in which any variant of Triple P was evaluated in relation to a comparison condition. Unpublished data, papers in languages other than English and some book chapters were not examined. Studies reporting Eyberg Child Behavior Inventory or Child Behavior Checklist scores as outcomes were used in the meta-analysis.
A total of 33 eligible studies was identified, most involving media-recruited families. Thirty-one of these 33 studies compared Triple P interventions with waiting list or no-treatment comparison groups. Most papers only reported maternal assessments of child behavior. Twenty-three papers were incorporated in the meta-analysis. No studies involved children younger than two-years old and comparisons of intervention and control groups beyond the duration of the intervention were only possible in five studies. For maternally-reported outcomes the summary effect size was 0.61 (95%CI 0.42, 0.79). Paternally-reported outcomes following Triple P intervention were smaller and did not differ significantly from the control condition (effect size 0.42 (95%CI -0.02, 0.87)). The two studies involving an active control group showed no between-group differences. There was limited evidence of publication bias, but there was substantial selective reporting bias, and preferential reporting of positive results in article abstracts. Thirty-two of the 33 eligible studies were authored by Triple-P affiliated personnel. No trials were registered and only two papers contained conflict of interest statements.
In volunteer populations over the short term, mothers generally report that Triple P group interventions are better than no intervention, but there is concern about these results given the high risk of bias, poor reporting and potential conflicts of interest. We found no convincing evidence that Triple P interventions work across the whole population or that any benefits are long-term. Given the substantial cost implications, commissioners should apply to parenting programs the standards used in assessing pharmaceutical interventions. See related commentary: http://www.biomedcentral.com/1741-7015/10/145.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Purpose The influence of multimorbidity on the clinical encounter is poorly understood, especially in areas of high socioeconomic deprivation where burdensome multimorbidity is concentrated. ...The aim of the current study was to examine the effect of multimorbidity on general practice consultations, in areas of high and low deprivation. Methods We conducted secondary analyses of 659 video-recorded routine consultations involving 25 general practitioners (GPs) in deprived areas and 22 in affluent areas of Scotland. Patients rated the GP's empathy using the Consultation and Relational Empathy (CARE) measure immediately after the consultation. Videos were analyzed using the Measure of Patient-Centered Communication. Multilevel, multi-regression analysis identified differences between the groups. Results In affluent areas, patients with multimorbidity received longer consultations than patients without multimorbidity (mean 12.8 minutes vs 9.3, respectively; P = .015), but this was not so in deprived areas (mean 9.9 minutes vs 10.0 respectively; P = .774). In affluent areas, patients with multimorbidity perceived their GP as more empathic ( P = .009) than patients without multimorbidity; this difference was not found in deprived areas ( P = .344). Video analysis showed that GPs in affluent areas were more attentive to the disease and illness experience in patients with multimorbidity ( P < .031) compared with patients without multimorbidity. This was not the case in deprived areas ( P = .727). Conclusions In deprived areas, the greater need of patients with multimorbidity is not reflected in the longer consultation length, higher GP patient centeredness, and higher perceived GP empathy found in affluent areas. Action is required to redress this mismatch of need and service provision for patients with multimorbidity if health inequalities are to be narrowed rather than widened by primary care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary Background Clinical use of criteria for metabolic syndrome to simultaneously predict risk of cardiovascular disease and diabetes remains uncertain. We investigated to what extent metabolic ...syndrome and its individual components were related to risk for these two diseases in elderly populations. Methods We related metabolic syndrome (defined on the basis of criteria from the Third Report of the National Cholesterol Education Program) and its five individual components to the risk of events of incident cardiovascular disease and type 2 diabetes in 4812 non-diabetic individuals aged 70–82 years from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). We corroborated these data in a second prospective study (the British Regional Heart Study BRHS) of 2737 non-diabetic men aged 60–79 years. Findings In PROSPER, 772 cases of incident cardiovascular disease and 287 of diabetes occurred over 3·2 years. Metabolic syndrome was not associated with increased risk of cardiovascular disease in those without baseline disease (hazard ratio 1·07 95% CI 0·86–1·32) but was associated with increased risk of diabetes (4·41 3·33–5·84) as was each of its components, particularly fasting glucose (18·4 13·9–24·5). Results were similar in participants with existing cardiovascular disease. In BRHS, 440 cases of incident cardiovascular disease and 105 of diabetes occurred over 7 years. Metabolic syndrome was modestly associated with incident cardiovascular disease (relative risk 1·27 1·04–1·56) despite strong association with diabetes (7·47 4·90–11·46). In both studies, body-mass index or waist circumference, triglyceride, and glucose cutoff points were not associated with risk of cardiovascular disease, but all five components were associated with risk of new-onset diabetes. Interpretation Metabolic syndrome and its components are associated with type 2 diabetes but have weak or no association with vascular risk in elderly populations, suggesting that attempts to define criteria that simultaneously predict risk for both cardiovascular disease and diabetes are unhelpful. Clinical focus should remain on establishing optimum risk algorithms for each disease. Funding Diabetes UK and British Heart Foundation.
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