Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a gallery of artifacts

In spite of the facts that magnetic resonance spectroscopy (MRS) is applied as clinical tool in non-specialized institutions and that semi-automatic acquisition and processing tools can be used to produce quantitative information from MRS exams without expert information, issues of spectral quality and quality assessment are neglected in the literature of MR spectroscopy. Even worse, there is no consensus among experts on concepts or detailed criteria of quality assessment for MR spectra. Furthermore, artifacts are not at all conspicuous in MRS and can easily be taken for true, interpretable features. This article aims to increase interest in issues of spectral quality and quality assessment, to start a larger debate on generally accepted criteria that spectra must fulfil to be clinically and scientifically acceptable, and to provide a sample gallery of artifacts, which can be used to raise awareness for potential pitfalls in MRS.

A survey of paediatric HIV programmatic and clinical management practices in Asia and sub-Saharan Africa--the International epidemiologic Databases to Evaluate AIDS (IeDEA)

INTRODUCTION There are limited data on paediatric HIV care and treatment programmes in low-resource settings. METHODS A standardized survey was completed by International epidemiologic Databases to Evaluate AIDS paediatric cohort sites in the regions of Asia-Pacific (AP), Central Africa (CA), East Africa (EA), Southern Africa (SA) and West Africa (WA) to understand operational resource availability and paediatric management practices. Data were collected through January 2010 using a secure, web-based software program (REDCap). RESULTS A total of 64,552 children were under care at 63 clinics (AP, N=10; CA, N=4; EA, N=29; SA, N=10; WA, N=10). Most were in urban settings (N=41, 65%) and received funding from governments (N=51, 81%), PEPFAR (N=34, 54%), and/or the Global Fund (N=15, 24%). The majority were combined adult-paediatric clinics (N=36, 57%). Prevention of mother-to-child transmission was integrated at 35 (56%) sites; 89% (N=56) had access to DNA PCR for infant diagnosis. African (N=40/53) but not Asian sites recommended exclusive breastfeeding up until 4-6 months. Regular laboratory monitoring included CD4 (N=60, 95%), and viral load (N=24, 38%). Although 42 (67%) sites had the ability to conduct acid-fast bacilli (AFB) smears, 23 (37%) sites could conduct AFB cultures and 18 (29%) sites could conduct tuberculosis drug susceptibility testing. Loss to follow-up was defined as >3 months of lost contact for 25 (40%) sites, >6 months for 27 sites (43%) and >12 months for 6 sites (10%). Telephone calls (N=52, 83%) and outreach worker home visits to trace children lost to follow-up (N=45, 71%) were common. CONCLUSIONS In general, there was a high level of patient and laboratory monitoring within this multiregional paediatric cohort consortium that will facilitate detailed observational research studies. Practices will continue to be monitored as the WHO/UNAIDS Treatment 2.0 framework is implemented.

Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program

OBJECTIVES The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. BACKGROUND The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. METHODS We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. RESULTS The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). CONCLUSIONS The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

0 and Metacognition: Relations and individual differences in 2nd graders

Introduction. Prospective Memory (PM), defined as the ability to remember to perform intended activities at some point in the future (Kliegel & Jäger, 2007), is crucial to succeed in everyday life. PM seems to increase over the childhood years (Zimmermann & Meier, 2006), but yet little is known about PM competences in children in general, but also about factors that influence its development. Currently, a number of studies has focused on factors that might influence PM performance, with EF being potentially influencing mechanisms (Ford, Driscoll, Shum & Macaulay, 2012; Mahy & Moses, 2011). Also metacognitive processes (MC: monitoring and control) are assumed to be involved while learning or optimizing one’s performance (Krebs & Roebers, 2010; 2012; Roebers, Schmid, & Roderer, 2009). Yet, the empirical relation between PM, EF and MC remains rather unclear. We intend to examine relations and explain individual differences in PM performance. Method. An empirical cross-sectional study on 120 2nd graders will be presented. Participants completed six EF tasks (a Stroop, two Updating Tasks, two Shifting Tasks, a Flanker Task), a computerised event-based PM Task and a MC spelling task. Children were tested individually in two sessions of 30 minutes each. Each of the three EF components defined by Miyake, Friedman, Emerson, Witzki & Howerter (2002) was represented by two variables. PM performance was represented by PM accuracy. Metacognitive processes (control, monitoring) were represented separately. Results. Preliminary analyses (SEM) indicate a substantial association between EF (updating, inhibition) and PM. Further, MC seems to be significantly related only to EF. We will explore whether metacognitive monitoring is related to PM monitoring (Roebers, 2002; Mantylä, 2007). As to EF and MC, we expect the two domains to be empirically well distinguishable and nevertheless substantially interrelated. Discussion. The results are discussed on a broader and interindividual level.

Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability, d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis: A Prospective Management Study.

BACKGROUND Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE None.

Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the sole implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

Clinical primary flexor tendon repair and rehabilitation: The Bern Experience

In this chapter we present our experience with treatment of zone 2 flexor tendon repair using a six-strand repair technique combined with postoperative place-and-hold exercise. The six-strand Lim/Tsai repair technique combined with place-and-hold exercises demonstrated better digital function compared to a two-strand repair without place-and-hold exercises. Range of motion in the Lim/Tsai repair group appeared to be increased without a higher rate of ruptures but with a shorter rehabilitation period. The fact that the two groups differed in both suture techniques and rehabilitation programs made it impossible to know whether the better results in the group of Lim/Tsai were due to the six-strand repair or the place-and-hold exercises or both. Despite the obvious benefit of early active mobilization, an active motion protocol may not always be possible to apply in a substantial number of patients due to concomitant injuries, the quality of the surgical repair or patient factors (swelling, pain, limited compliance). Since August 2006 a staged rehabilitation program (“stop and go”) was introduced within our unit using early active controlled flexion (green), place-and-hold (yellow), or passive flexion exercises (red) introduced by Kleinert-Duran. Our experience using the six-strand suture repair technique and “stop and go” is outlined.