Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis

Objective Reliable biomarkers for amyotrophic lateral sclerosis ( ALS ) are needed, given the clinical heterogeneity of the disease. Here, we provide proof‐of‐concept for using multimodal magnetic resonance imaging ( MRI ) as a diagnostic biomarker for ALS . Specifically, we evaluated the added diagnostic utility of proton magnetic resonance spectroscopy ( MRS ) to diffusion tensor imaging ( DTI ). Methods Twenty‐nine patients with ALS and 30 age‐ and gender‐matched healthy controls underwent brain MRI which used proton MRS including spectral editing techniques to measure γ‐aminobutyric acid ( GABA ) and DTI to measure fractional anisotropy of the corticospinal tract. Data were analyzed using logistic regression, t ‐tests, and generalized linear models with leave‐one‐out analysis to generate and compare the resulting receiver operating characteristic ( ROC ) curves. Results The diagnostic accuracy is significantly improved when the MRS data were combined with the DTI data as compared to the DTI data only (area under the ROC curves ( AUC ) = 0.93 vs. AUC  = 0.81; P  = 0.05). The combined MRS and DTI data resulted in sensitivity of 0.93, specificity of 0.85, positive likelihood ratio of 6.20, and negative likelihood ratio of 0.08 whereas the DTI data only resulted in sensitivity of 0.86, specificity of 0.70, positive likelihood ratio of 2.87, and negative likelihood ratio of 0.20. Interpretation Combining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106065/1/acn330.pd

Exploring the Feasibility of Service Integration in a Low-Income Setting: A Mixed Methods Investigation into Different Models of Reproductive Health and HIV Care in Swaziland.

Integrating reproductive health (RH) with HIV care is a policy priority in high HIV prevalence settings, despite doubts surrounding its feasibility and varying evidence of effects on health outcomes. The process and outcomes of integrated RH-HIV care were investigated in Swaziland, through a comparative case study of four service models, ranging from fully integrated to fully stand-alone HIV services, selected purposively within one town. A client exit survey (n=602) measured integrated care received and unmet family planning (FP) needs. Descriptive statistics were used to assess the degree of integration per clinic and client demand for services. Logistic regression modelling was used to test the hypothesis that clients at more integrated sites had lower unmet FP needs than clients in a stand-alone site. Qualitative methods included in-depth interviews with clients and providers to explore contextual factors influencing the feasibility of integrated RH-HIV care delivery; data were analysed thematically, combining deductive and inductive approaches. Results demonstrated that clinic models were not as integrated in practice as had been claimed. Fragmentation of HIV care was common. Services accessed per provider were no higher at the more integrated clinics compared to stand-alone models (p>0.05), despite reported demand. While women at more integrated sites received more FP and pregnancy counselling than stand-alone models, they received condoms (a method of choice) less often, and there was no statistical evidence of difference in unmet FP needs by model of care. Multiple contextual factors influenced integration practices, including provider de-skilling within sub-specialist roles; norms of task-oriented routinised HIV care; perceptions of heavy client loads; imbalanced client-provider interactions hindering articulation of RH needs; and provider motivation challenges. Thus, despite institutional support, factors related to the social context of care inhibited provision of fully integrated RH-HIV services in these clinics. Programmes should move beyond simplistic training and equipment provision if integrated care interventions are to be sustained

Changes in practice patterns affecting in-hospital and post-discharge survival among ACS patients

BACKGROUND: Adherence to clinical practice guidelines for the treatment of specific illnesses may result in unexpected outcomes, given that multiple therapies must often be given to patients with diverse medical conditions. Yet, few studies have presented empirical evidence that quality improvement (QI) programs both change practice by improving adherence to guidelines and improve patient outcomes under the conditions of actual practice. Thus, we focus on patient survival, following hospitalization for acute coronary syndrome in three successive patient cohorts from the same community hospitals, with a quality improvement intervention occurring between cohorts two and three. METHODS: This study is a comparison of three historical cohorts of Acute Coronary Syndrome (ACS) patients in the same five community hospitals in 1994–5, 1997, 2002–3. A quality improvement project, the Guidelines Applied to Practice (GAP), was implemented in these hospitals in 2001. Study participants were recruited from community hospitals located in two Michigan communities during three separate time periods. The cohorts comprise (1) patients enrolled between December 1993 and April 1995 (N = 814), (2) patients enrolled between February 1997 and September 1997 (N = 452), and (3) patients enrolled between January 14, 2002 and April 13, 2003 (N = 710). Mortality data were obtained from Michigan's Bureau of Vital Statistics for all three patient cohorts. Predictor variables, obtained from medical record reviews, included demographic information, indicators of disease severity (ejection fraction), co-morbid conditions, hospital treatment information concerning most invasive procedures and the use of ace-inhibitors, beta-blockers and aspirin in the hospital and as discharge recommendations. RESULTS: Adjusted in-hospital mortality showed a marked improvement with a HR = 0.16 (p < 0.001) comparing 2003 patients in the same hospitals to those 10 years earlier. Large gains in the in-hospital mortality were maintained based on 1-year mortality rates after hospital discharge. CONCLUSION: Changes in practice patterns that follow recommended guidelines can significantly improve care for ACS patients. In-hospital mortality gains were maintained in the year following discharge

Systematic review and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer

Background: Febrile neutropenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer. Many biomarkers have been proposed as predictors of adverse events. We aimed to undertake a systematic review and meta-analysis to summarize evidence on the discriminatory ability of initial serum biomarkers of febrile neutropenic episodes in children and young people. Methods: This review was conducted in accordance with the Center for Reviews and Dissemination Methods, using three random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100485. Results: We found that 25 studies exploring 14 different biomarkers were assessed in 3,585 episodes of febrile neutropenia. C-reactive protein (CRP), pro-calcitonin (PCT), and interleukin-6 (IL6) were subject to quantitative meta-analysis, and revealed huge inconsistencies and heterogeneity in the studies included in this review. Only CRP has been evaluated in assessing its value over the predictive value of simple clinical decision rules. Conclusions: The limited data available describing the predictive value of biomarkers in the setting of pediatric febrile neutropenia mean firm conclusions cannot yet be reached, although the use of IL6, IL8 and procalcitonin warrant further study

Multidetector computed tomography angiography for assessment of in-stent restenosis: meta-analysis of diagnostic performance

<p>Abstract</p> <p>Background</p> <p>Multi-detector computed tomography angiography (MDCTA)of the coronary arteries after stenting has been evaluated in multiple studies.</p> <p>The purpose of this study was to perform a structured review and meta-analysis of the diagnostic performance of MDCTA for the detection of in-stent restenosis in the coronary arteries.</p> <p>Methods</p> <p>A Pubmed and manual search of the literature on in-stent restenosis (ISR) detected on MDCTA compared with conventional coronary angiography (CA) was performed. Bivariate summary receiver operating curve (SROC) analysis, with calculation of summary estimates was done on a stent and patient basis. In addition, the influence of study characteristics on diagnostic performance and number of non-assessable segments (NAP) was investigated with logistic meta-regression.</p> <p>Results</p> <p>Fourteen studies were included. On a stent basis, Pooled sensitivity and specificity were 0.82(0.72–0.89) and 0.91 (0.83–0.96). Pooled negative likelihood ratio and positive likelihood ratio were 0.20 (0.13–0.32) and 9.34 (4.68–18.62) respectively. The exclusion of non-assessable stents and the strut thickness of the stents had an influence on the diagnostic performance. The proportion of non-assessable stents was influenced by the number of detectors, stent diameter, strut thickness and the use of an edge-enhancing kernel.</p> <p>Conclusion</p> <p>The sensitivity of MDTCA for the detection of in-stent stenosis is insufficient to use this test to select patients for further invasive testing as with this strategy around 20% of the patients with in-stent stenosis would be missed. Further improvement of scanner technology is needed before it can be recommended as a triage instrument in practice. In addition, the number of non-assessable stents is also high.</p

The Alvarado score for predicting acute appendicitis: a systematic review

Background: The Alvarado score can be used to stratify patients with symptoms of suspected appendicitis; the validity of the score in certain patient groups and at different cut points is still unclear. The aim of this study was to assess the discrimination (diagnostic accuracy) and calibration performance of the Alvarado score. Methods: A systematic search of validation studies in Medline, Embase, DARE and The Cochrane library was performed up to April 2011. We assessed the diagnostic accuracy of the score at the two cut-off points: score of 5 (1 to 4 vs. 5 to 10) and score of 7 (1 to 6 vs. 7 to 10). Calibration was analysed across low (1 to 4), intermediate (5 to 6) and high (7 to 10) risk strata. The analysis focused on three sub-groups: men, women and children. Results: Forty-two studies were included in the review. In terms of diagnostic accuracy, the cut-point of 5 was good at 'ruling out' admission for appendicitis (sensitivity 99% overall, 96% men, 99% woman, 99% children). At the cut-point of 7, recommended for 'ruling in' appendicitis and progression to surgery, the score performed poorly in each subgroup (specificity overall 81%, men 57%, woman 73%, children 76%). The Alvarado score is well calibrated in men across all risk strata (low RR 1.06, 95% CI 0.87 to 1.28; intermediate 1.09, 0.86 to 1.37 and high 1.02, 0.97 to 1.08). The score over-predicts the probability of appendicitis in children in the intermediate and high risk groups and in women across all risk strata. Conclusions: The Alvarado score is a useful diagnostic 'rule out' score at a cut point of 5 for all patient groups. The score is well calibrated in men, inconsistent in children and over-predicts the probability of appendicitis in women across all strata of risk

Imaging in assessing hepatic and peritoneal metastases of gastric cancer: a systematic review

<p>Abstract</p> <p>Background</p> <p>Hepatic and peritoneal metastases of gastric cancer are operation contraindications. Systematic review to provide an overview of imaging in predicting the status of liver and peritoneum pre-therapeuticly is essential.</p> <p>Methods</p> <p>A systematic review of relevant literatures was performed in Pubmed/Medline, Embase, The Cochrane Library and the China Biological Medicine Databases. QUADAS was used for assessing the methodological quality of included studies and the bivariate model was used for this meta-analysis.</p> <p>Results</p> <p>Totally 33 studies were included (8 US studies, 5 EUS studies, 22 CT studies, 2 MRI studies and 5 18F-FDG PET studies) and the methodological quality of included studies was moderate. The result of meta-analysis showed that CT is the most sensitive imaging method [0.74 (95% CI: 0.59-0.85)] with a high rate of specificity [0.99 (95% CI: 0.97-1.00)] in detecting hepatic metastasis, and EUS is the most sensitive imaging modality [0.34 (95% CI: 0.10-0.69) ] with a specificity of 0.96 (95% CI: 0.87-0.99) in detecting peritoneal metastasis. Only two eligible MRI studies were identified and the data were not combined. The two studies found that MRI had both high sensitivity and specificity in detecting liver metastasis.</p> <p>Conclusion</p> <p>US, EUS, CT and ¹⁸F-FDG PET did not obtain consistently high sensitivity and specificity in assessing liver and peritoneal metastases of gastric cancer. The value of laparoscopy, PET/CT, DW-MRI, and new PET tracers such as ¹⁸F-FLT needs to be studied in future.</p

Persistent frequent attenders in primary care: costs, reasons for attendance, organisation of care and potential for cognitive behavioural therapeutic intervention

<p><b>Abstract</b></p> <p>Background</p> <p>The top 3% of frequent attendance in primary care is associated with 15% of all appointments in primary care, a fivefold increase in hospital expenditure, and more mental disorder and functional somatic symptoms compared to normal attendance. Although often temporary if these rates of attendance last more than two years, they may become persistent (persistent frequent or regular attendance). However, there is no long-term study of the economic impact or clinical characteristics of regular attendance in primary care. Cognitive behaviour formulation and treatment (CBT) for regular attendance as a motivated behaviour may offer an understanding of the development, maintenance and treatment of regular attendance in the context of their health problems, cognitive processes and social context.</p> <p>Methods/design</p> <p>A case control design will compare the clinical characteristics, patterns of health care use and economic costs over the last 10 years of 100 regular attenders (≥30 appointments with general practitioner [GP] over 2 years) with 100 normal attenders (6–22 appointments with GP over 2 years), from purposefully selected primary care practices with differing organisation of care and patient demographics. Qualitative interviews with regular attending patients and practice staff will explore patient barriers, drivers and experiences of consultation, and organisation of care by practices with its challenges. Cognitive behaviour formulation analysed thematically will explore the development, maintenance and therapeutic opportunities for management in regular attenders. The feasibility, acceptability and utility of CBT for regular attendance will be examined.</p> <p>Discussion</p> <p>The health care costs, clinical needs, patient motivation for consultation and organisation of care for persistent frequent or regular attendance in primary care will be explored to develop training and policies for service providers. CBT for regular attendance will be piloted with a view to developing this approach as part of a multifaceted intervention.</p