Network analysis characterizes key associations between subjective fatigue and specific depressive symptoms in early relapsing-remitting multiple sclerosis.

BACKGROUND: Fatigue is common and disabling in multiple sclerosis (MS), yet its mechanisms are poorly understood. In particular, overlap in measures of fatigue and depression complicates interpretation. We applied a multivariate network approach to quantify relationships between fatigue and other variables in early MS. METHODS: Data were collected from patients with newly diagnosed immunotherapy-naïve relapsing-remitting MS at baseline and month 12 follow-up in FutureMS, a Scottish nationally representative cohort. Subjective fatigue was assessed by Fatigue Severity Scale. Detailed phenotyping included measures assessing each of physical disability, affective disorders, cognitive performance, sleep quality, and structural brain imaging. Network analysis was conducted to estimate partial correlations between variables. Baseline networks were compared between those with persistent and remitted fatigue at one-year follow up. RESULTS: Data from 322 participants at baseline, and 323 at month 12, were included. At baseline, 154 patients (47.8%) reported clinically significant fatigue. In the network analysis, fatigue severity showed strongest connections with depression, followed by Expanded Disability Status Scale. Conversely, fatigue severity was not linked to objective cognitive performance or brain imaging variables. Even after controlling for measurement of "tiredness" in our measure of depression, four specific depressive symptoms remained linked to fatigue. Results were consistent at baseline and month 12. Overall network strength was not significantly different between groups with persistent and remitted fatigue (4.89 vs 2.90, p = 0.11). CONCLUSIONS: Our findings support robust links between subjective fatigue and depression in early relapsing-remitting MS. Shared mechanisms between specific depressive symptoms and fatigue could be key targets of treatment and research in MS-related fatigue.

Implications of lowering threshold of plasma troponin concentration in diagnosis of myocardial infarction: cohort study.

OBJECTIVE: To assess the relation between troponin concentration, assay precision, and clinical outcomes in patients with suspected acute coronary syndrome. DESIGN: Cohort study. SETTING: Tertiary centre in Scotland. PARTICIPANTS: 2092 consecutive patients admitted with suspected acute coronary syndrome were stratified with a sensitive troponin I assay into three groups (<0.012, 0.012-0.049, and ≥0.050 µg/L) based on the 99th centile for troponin concentration (0.012 µg/L; coefficient of variation 20.8%) and the diagnostic threshold (0.050 µg/L; 7.2%). MAIN OUTCOME MEASURE: One year survival without events (recurrent myocardial infarction, death) in patients grouped by troponin concentration. RESULTS: Troponin I concentrations were <0.012 µg/L in 988 patients (47%), 0.012-0.049 µg/L in 352 patients (17%), and ≥0.050 µg/L in 752 patients (36%). Adoption of the 99th centile would increase the number of people receiving a diagnosis of myocardial infarction from 752 to 1104: a relative increase of 47%. At one year, patients with troponin concentrations of 0.012-0.049 µg/L were more likely to be dead or readmitted with recurrent myocardial infarction than those with troponin concentrations <0.012 µg/L (13% v 3%, P<0.001; odds ratio 4.7, 95% confidence interval 2.9 to 7.9). Compared with troponin ≥0.050 µg/L, patients with troponin 0.012-0.049 µg/L had a higher risk profile but were less likely to have a diagnosis of, or be investigated and treated for, acute coronary syndrome. CONCLUSION: Lowering the diagnostic threshold to the 99th centile and accepting greater assay imprecision would identify more patients with acute coronary syndrome at risk of recurrent myocardial infarction and death but would increase the diagnosis of myocardial infarction by 47%. It remains to be established whether reclassification of these patients and treatment for myocardial infarction would improve outcome.

Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome.

CONTEXT: Although troponin assays have become increasingly more sensitive, it is unclear whether further reductions in the threshold of detection for plasma troponin concentrations will improve clinical outcomes in patients with suspected acute coronary syndrome (ACS). OBJECTIVE: To determine whether lowering the diagnostic threshold for myocardial infarction (MI) with a sensitive troponin assay could improve clinical outcomes. DESIGN, SETTING, AND PATIENTS: All consecutive patients admitted with suspected ACS to the Royal Infirmary of Edinburgh, Edinburgh, Scotland, before (n = 1038; February 1-July 31, 2008, during the validation phase) and after (n = 1054; February 1-July 31, 2009, during the implementation phase) lowering the threshold of detection for myocardial necrosis from 0.20 to 0.05 ng/mL with a sensitive troponin I assay were stratified into 3 groups (<0.05 ng/mL, 0.05-0.19 ng/mL, and ≥0.20 ng/mL). During the validation phase, only concentrations above the original diagnostic threshold of 0.20 ng/mL were reported to clinicians. MAIN OUTCOME MEASURE: Event-free survival (recurrent MI and death) at 1 year in patients grouped by plasma troponin concentrations. RESULTS: Plasma troponin concentrations were less than 0.05 ng/mL in 1340 patients (64%), 0.05 to 0.19 ng/mL in 170 patients (8%), and 0.20 ng/mL or more in 582 patients (28%). During the validation phase, 39% of patients with plasma troponin concentrations of 0.05 to 0.19 ng/mL were dead or had recurrent MI at 1 year compared with 7% and 24% of those patients with troponin concentrations of less than 0.05 ng/mL (P < .001) or 0.20 ng/mL or more (P = .007), respectively. During the implementation phase, lowering the diagnostic threshold to 0.05 ng/mL was associated with a lower risk of death and recurrent MI (from 39% to 21%) in patients with troponin concentrations of 0.05 to 0.19 ng/mL (odds ratio, 0.42; 95% confidence interval, 0.24-0.84; P = .01). CONCLUSIONS: In patients with suspected ACS, implementation of a sensitive troponin assay increased the diagnosis of MI and identified patients at high risk of recurrent MI and death. Lowering the diagnostic threshold of plasma troponin was associated with major reductions in morbidity and mortality.

Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease.

OBJECTIVE: Variant Creutzfeldt-Jakob disease (vCJD), a novel form of human prion disease, was recognized in 1996. The disease affected a younger cohort than sporadic CJD, and the early clinical course was dominated by psychiatric and sensory symptoms. In an attempt to aid diagnosis and establish standardization between surveillance networks, diagnostic criteria were established. These were devised from the features of a small number of cases and modified in 2000 as the clinical phenotype was established. Since then, only minor changes have been introduced; revalidation of the criteria in the current format is overdue. METHODS: Included in this study are autopsy/cerebral biopsy-proven cases of vCJD referred to the National CJD Surveillance Unit (NCJDSU) between 1995 and 2004 and suspect cases in which an alternative diagnosis was identified following autopsy/cerebral biopsy. RESULTS: Over the 10-year period, 106 definite cases of vCJD and 45 pathologically confirmed "noncases" were identified from the archives of the NCJDSU. The median age at onset of the cases was significantly younger than that of the noncases (27 years [range, 12-74 years] vs 43 years [range, 10-64 years]), and the median duration of illness was significantly shorter (14 months [range, 6-39 months] vs 22 months [range, 2-139 months]). The most commonly identified core clinical feature in cases was dementia; persistent painful sensory symptoms were the least frequent. Eighty-eight of 106 (83%) vCJD cases were retrospectively classified as probable in life, 6 cases were classified as possible. Most cases were classified as probable on the basis of core clinical features and brain magnetic resonance imaging. To date, the diagnostic criteria remain 100% specific, with no autopsy/cerebral biopsy-proven noncases classified as probable in life. INTERPRETATION: This study confirms that the diagnostic criteria for vCJD are sensitive and specific and provide a useful standard framework for case classification in a surveillance setting.

Routine mortality monitoring for detecting mass murder in UK general practice: test of effectiveness using modelling.

BACKGROUND: The Shipman Inquiry recommended mortality rate monitoring if it could be 'shown to be workable' in detecting a future mass murderer in general practice. AIM: To examine the effectiveness of cumulative sum (CUSUM) charts, cross-sectional Shewhart charts, and exponentially-weighted, moving-average control charts in mortality monitoring at practice level. DESIGN OF STUDY: Analysis of Scottish routine general practice data combined with estimation of control chart effectiveness in detecting a 'murderer' in a simulated dataset. METHOD: Practice stability was calculated from routine data to determine feasible lengths of monitoring. A simulated dataset of 405,000 'patients' was created, registered with 75 'practices' whose underlying mortality rates varied with the same distribution as case-mix-adjusted mortality in all Scottish practices. The sensitivity of each chart to detect five and 10 excess deaths was examined in repeated simulations. The sensitivity of control charts to excess deaths in simulated data, and the number of alarm signals when control charts were applied to routine data were estimated. RESULTS: Practice instability limited the length of monitoring and modelling was consequently restricted to a 3-year period. Monitoring mortality over 3 years, CUSUM charts were most sensitive but only reliably achieved >50% successful detection for 10 excess deaths per year and generated multiple false alarms (>15%). CONCLUSION: At best, mortality monitoring can act as a backstop to detect a particularly prolific serial killer when other means of detection have failed. Policy should focus on changes likely to improve detection of individual murders, such as reform of death certification and the coroner system.

To what extent are carers involved in the care and rehabilitation of patients with hip fracture?

PURPOSE: To examine the carer's role regarding early hospital rehabilitation. METHOD: A qualitative study, using semi-structured interviews with 30 carers. A convenience sample was obtained through participants volunteering for the study. Interviews were of 30 - 45 minutes duration and were audiotaped. The transcripts were read in their entirety by all authors. Main themes were identified and coded. RESULTS: Twenty women and ten men were recruited, who cared for 22 women and eight men. A third of the interviewees reported other caring responsibilities. Carers performed a range of tasks for the patient and most revolved around the key activity of hospital visiting. A range of functions were undertaken, including: help with eating and drinking; providing the opportunity for social interaction; acting as a link between the external world and hospital; and offering emotional support. CONCLUSIONS: Carers not only provided practical help but also offered psychological support. Our study highlights the key role of carers in the rehabilitation of patients with hip fracture and provides support for the recommendation that family members should be provided with information regarding rehabilitation. Carers need to be regarded as a resource by hospital staff, given their key role in enhancing patient motivation.

Predicting vascular risk in Type 1 diabetes: stratification in a hospital based population in Scotland.

AIMS: To estimate the absolute cardiovascular risk of patients with Type 1 diabetes attending hospital diabetes clinics in Scotland and to develop a method for identifying those at highest risk, thus enabling therapy to be targeted. METHODS: Baseline information was collected for 2136 patients with Type 1 diabetes using the Royal College of Physicians of Edinburgh Diabetes Register. These records were then linked to diagnoses of macrovascular disease in databases of the Information Statistics Division of the Common Services Agency. RESULTS: During six to nine years of follow up 110 patients (5%) developed macrovascular disease. There were significant associations between baseline age (P < 0.00001), blood pressure (P < 0.00001), albuminuria (P < 0.0002), HbA1c (P < 0.001), cholesterol (P < 0.00001) and smoking status (P < 0.00001) with the development of macrovascular disease. A scoring system for future macrovascular risk was developed from a multivariate analysis of this data. CONCLUSIONS: The data confirm the high vascular risk of patients with Type 1 diabetes. The relationship with age is such that those patients above 50 years require only one additional risk factor to reach such a high vascular risk that intervention is indicated. Using these data many patients between the age of 40 and 49 years are also likely to be identified to be at high risk.

The relationship between UK hospital nurse staffing and emotional exhaustion and job dissatisfaction.

AIM: To explore the relationship between nurse outcomes (dissatisfaction and emotional exhaustion) and nurse workload, nurse characteristics and hospital variables. BACKGROUND: Concern about the impact of restructuring of nurse staffing, and reports of nurse shortages, on nurse and patient outcomes led to the research being reported on in this article. METHODS: A questionnaire survey of registered nurses in Scotland and England. A questionnaire survey of the hospitals in which these nurses worked. RESULTS: Respondents in the two countries were similar in terms of demographic, work and employment characteristics. Significant relationships were found using the combined English and Scottish data between nurse patient ratios and (1) emotional exhaustion and (2) dissatisfaction with current job reported by nurses. CONCLUSIONS: Increasing numbers of patients to nurses was associated with increasing risk of emotional exhaustion and dissatisfaction with current job.

Mortality after discharge from long-term psychiatric care in Scotland, 1977-94: a retrospective cohort study.

BACKGROUND: Recent United Kingdom strategies focus on preventable suicide deaths in former psychiatric in-patients, but natural causes of death, accidents and homicide may also be important. This study was intended to find the relative importance of natural and unnatural causes of death in people discharged from long-term psychiatric care in Scotland in 1977-1994. METHODS: People discharged alive from psychiatric hospitals in Scotland in 1977-94 after a stay of one year or longer were identified using routine hospital records. Computer record linkage was used to link hospital discharges to subsequent death records. Mortality was described using a person-years analysis, and compared to the general population rates. RESULTS: 6,776 people were discharged in the time period. 1,994 people (29%) died by the end of follow-up, 732 more deaths than expected. Deaths from suicide, homicide, accident and undetermined cause were increased, but accounted for only 197 of the excess deaths. Deaths from respiratory disease were four times higher than expected, and deaths from other causes, including cardiovascular disease, were also elevated. CONCLUSION: Suicide is an important cause of preventable mortality, but natural causes account for more excess deaths. Prevention activities should not focus only on unnatural causes of death.

Potential treatments and treatment strategies in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease is a rare neurodegenerative disease that follows a rapidly progressive course, leading to death, usually only a few months from onset. Over the last 30 years, many treatments have been tried for this condition, including a wide variety of antiviral agents and immunomodulating drugs. More recently, potential treatments have been devised that interfere with the pathological processes involved in the formation of the prion protein. Most of these experiments have been performed in in vitro and tissue culture models and have yet to be tried in human prion disease. As yet, no treatment has been of sustained benefit but, currently, a preliminary open-label trial of quinacrine is underway in the UK.