Alien Registration- Richardson, Martha L. (Bangor, Penobscot County)

https://digitalmaine.com/alien_docs/11140/thumbnail.jp

Cluster Randomised Trials in Cochrane Reviews: Evaluation of Methodological and Reporting Practice

Objective Systematic reviews can include cluster-randomised controlled trials (C-RCTs), which require different analysis compared with standard individual-randomised controlled trials. However, it is not known whether review authors follow the methodological and reporting guidance when including these trials. The aim of this study was to assess the methodological and reporting practice of Cochrane reviews that included C-RCTs against criteria developed from existing guidance. Methods Criteria were developed, based on methodological literature and personal experience supervising review production and quality. Criteria were grouped into four themes: identifying, reporting, assessing risk of bias, and analysing C-RCTs. The Cochrane Database of Systematic Reviews was searched (2nd December 2013), and the 50 most recent reviews that included C-RCTs were retrieved. Each review was then assessed using the criteria. Results The 50 reviews we identified were published by 26 Cochrane Review Groups between June 2013 and November 2013. For identifying C-RCTs, only 56% identified that C-RCTs were eligible for inclusion in the review in the eligibility criteria. For reporting C-RCTs, only eight (24%) of the 33 reviews reported the method of cluster adjustment for their included C-RCTs. For assessing risk of bias, only one review assessed all five C-RCT-specific risk-of-bias criteria. For analysing C-RCTs, of the 27 reviews that presented unadjusted data, only nine (33%) provided a warning that confidence intervals may be artificially narrow. Of the 34 reviews that reported data from unadjusted C-RCTs, only 13 (38%) excluded the unadjusted results from the meta-analyses. Conclusions The methodological and reporting practices in Cochrane reviews incorporating C-RCTs could be greatly improved, particularly with regard to analyses. Criteria developed as part of the current study could be used by review authors or editors to identify errors and improve the quality of published systematic reviews incorporating C-RCTs

Rapid diagnostic tests for plague

Background Plague is a severe disease associated with high mortality. Late diagnosis leads to advance stage of the disease with worse outcomes and higher risk of spread of the disease. A rapid diagnostic test (RDT) could help in establishing a prompt diagnosis of plague. This would improve patient care and help appropriate public health response. Objectives To determine the diagnostic accuracy of the RDT based on the antigen F1 (F1RDT) for detecting plague in people with suspected disease. Search methods We searched the CENTRAL, Embase, Science Citation Index, Google Scholar, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov up to 15 May 2019, and PubMed (MEDLINE) up to 27 August 2019, regardless of language, publication status, or publication date. We handsearched the reference lists of relevant papers and contacted researchers working in the field. Selection criteria We included cross‐sectional studies that assessed the accuracy of the F1RDT for diagnosing plague, where participants were tested with both the F1RDT and at least one reference standard. The reference standards were bacterial isolation by culture, polymerase chain reaction (PCR), and paired serology (this is a four‐fold difference in F1 antibody titres between two samples from acute and convalescent phases). Data collection and analysis Two review authors independently selected studies and extracted data. We appraised the methodological quality of each selected studies and applicability by using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. When meta‐analysis was appropriate, we used the bivariate model to obtain pooled estimates of sensitivity and specificity. We stratified all analyses by the reference standard used and presented disaggregated data for forms of plague. We assessed the certainty of the evidence using GRADE. Main results We included eight manuscripts reporting seven studies. Studies were conducted in three countries in Africa among adults and children with any form of plague. All studies except one assessed the F1RDT produced at the Institut Pasteur of Madagascar (F1RDT‐IPM) and one study assessed a F1RDT produced by New Horizons (F1RDT‐NH), utilized by the US Centers for Disease Control and Prevention. We could not pool the findings from the F1RDT‐NH in meta‐analyses due to a lack of raw data and a threshold of the test for positivity different from the F1RDT‐IPM. Risk of bias was high for participant selection (retrospective studies, recruitment of participants not consecutive or random, unclear exclusion criteria), low or unclear for index test (blinding of F1RDT interpretation unknown), low for reference standards, and high or unclear for flow and timing (time of sample transportation was longer than seven days, which can lead to decreased viability of the pathogen and overgrowth of contaminating bacteria, with subsequent false‐negative results and misclassification of the target condition). F1RDT for diagnosing all forms of plague F1RDT‐IPM pooled sensitivity against culture was 100% (95% confidence interval (CI) 82 to 100; 4 studies, 1692 participants; very low certainty evidence) and pooled specificity was 70.3% (95% CI 65 to 75; 4 studies, 2004 participants; very low‐certainty evidence). The performance of F1RDT‐IPM against PCR was calculated from a single study in participants with bubonic plague (see below). There were limited data on the performance of F1RDT against paired serology. F1RDT for diagnosing pneumonic plague Performed in sputum, F1RDT‐IPM pooled sensitivity against culture was 100% (95% CI 0 to 100; 2 studies, 56 participants; very low‐certainty evidence) and pooled specificity was 71% (95% CI 59 to 80; 2 studies, 297 participants; very low‐certainty evidence). There were limited data on the performance of F1RDT against PCR or against paired serology for diagnosing pneumonic plague. F1RDT for diagnosing bubonic plague Performed in bubo aspirate, F1RDT‐IPM pooled sensitivity against culture was 100% (95% CI not calculable; 2 studies, 1454 participants; low‐certainty evidence) and pooled specificity was 67% (95% CI 65 to 70; 2 studies, 1198 participants; very low‐certainty evidence). Performed in bubo aspirate, F1RDT‐IPM pooled sensitivity against PCR for the caf1 gene was 95% (95% CI 89 to 99; 1 study, 88 participants; very low‐certainty evidence) and pooled specificity was 93% (95% CI 84 to 98; 1 study, 61 participants; very low‐certainty evidence). There were no data providing data on both F1RDT and paired serology for diagnosing bubonic plague. Authors' conclusions Against culture, the F1RDT appeared highly sensitive for diagnosing either pneumonic or bubonic plague, and can help detect plague in remote areas to assure management and enable a public health response. False positive results mean culture or PCR confirmation may be needed. F1RDT does not replace culture, which provides additional information on resistance to antibiotics and bacterial strains

Basal metabolism of twenty-five Kansas college women between twenty-five and thirty years of age

Typescript, etc.Digitized by Kansas State University Librarie

A survey of first grade children's likes and dislikes in a basal reader

Thesis (Ed.M.)--Boston Universit

GenoType® MTBDRsl assay for resistance to second-line anti-tuberculosis drugs

Background Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. Objectives To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. Search methods We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. Selection criteria We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Data collection and analysis Two review authors independently extracted data and assessed quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We synthesized data for versions 1.0 and 2.0 separately. We estimated MTBDRsl sensitivity and specificity for fluoroquinolone resistance, SLID resistance, and extensively drug-resistant tuberculosis when the test was performed indirectly or directly (smear-positive specimen for version 1.0, smear-positive or -negative specimen for version 2.0). We explored the influence on accuracy estimates of individual drugs within a drug class and of different reference standards. We performed most analyses using a bivariate random-effects model with culture-based DST as reference standard. Main results We included 27 studies. Twenty-six studies evaluated version 1.0, and one study version 2.0. Of 26 studies stating specimen country origin, 15 studies (58%) evaluated patients from low- or middle-income countries. Overall, we considered the studies to be of high methodological quality. However, only three studies (11%) had low risk of bias for the reference standard; these studies used World Health Organization (WHO)-recommended critical concentrations for all drugs in the culture-based DST reference standard. MTBDRsl version 1.0 Fluoroquinolone resistance: indirect testing, MTBDRsl pooled sensitivity and specificity (95% confidence interval (CI)) were 85.6% (79.2% to 90.4%) and 98.5% (95.7% to 99.5%), (19 studies, 2223 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 86.2% (74.6% to 93.0%) and 98.6% (96.9% to 99.4%), (nine studies, 1771 participants, moderate quality evidence). SLID resistance: indirect testing, MTBDRsl pooled sensitivity and specificity were 76.5% (63.3% to 86.0%) and 99.1% (97.3% to 99.7%), (16 studies, 1921 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 87.0% (38.1% to 98.6%) and 99.5% (93.6% to 100.0%), (eight studies, 1639 participants, low quality evidence). Extensively drug-resistant tuberculosis: indirect testing, MTBDRsl pooled sensitivity and specificity were 70.9% (42.9% to 88.8%) and 98.8% (96.1% to 99.6%), (eight studies, 880 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 69.4% (38.8% to 89.0%) and 99.4% (95.0% to 99.3%), (six studies, 1420 participants, low quality evidence). Similar to the original Cochrane review, we found no evidence of a significant difference in MTBDRsl version 1.0 accuracy between indirect and direct testing for fluoroquinolone resistance, SLID resistance, and extensively drug-resistant tuberculosis. MTBDRsl version 2.0 Fluoroquinolone resistance: direct testing, MTBDRsl sensitivity and specificity were 97% (83% to 100%) and 98% (93% to 100%), smear-positive specimen; 80% (28% to 99%) and 100% (40% to 100%), smear-negative specimen. SLID resistance: direct testing, MTBDRsl sensitivity and specificity were 89% (72% to 98%) and 90% (84% to 95%), smear-positive specimen; 80% (28% to 99%) and 100% (40% to 100%), smear-negative specimen. Extensively drug-resistant tuberculosis: direct testing, MTBDRsl sensitivity and specificity were 79% (49% to 95%) and 97% (93% to 99%), smear-positive specimen; 50% (1% to 99%) and 100% (59% to 100%), smear-negative specimen. We had insufficient data to estimate summary sensitivity and specificity of version 2.0 (smear-positive and -negative specimens) or to compare accuracy of the two versions. A limitation was that most included studies did not consistently use the World Health Organization (WHO)-recommended concentrations for drugs in the culture-based DST reference standard. Authors' conclusions In people with rifampicin-resistant or multidrug-resistant tuberculosis, MTBDRsl performed on a culture isolate or smear-positive specimen may be useful in detecting second-line drug resistance. MTBDRsl (smear-positive specimen) correctly classified around six in seven people as having fluoroquinolone or SLID resistance, although the sensitivity estimates for SLID resistance varied. The test rarely gave a positive result for people without drug resistance. However, when second-line drug resistance is not detected (MTBDRsl result is negative), conventional DST can still be used to evaluate patients for resistance to the fluoroquinolones or SLIDs. We recommend that future work evaluate MTBDRsl version 2.0, in particular on smear-negative specimens and in different settings to account for different resistance-causing mutations that may vary by strain. Researchers should also consider incorporating WHO-recommended critical concentrations into their culture-based reference standards

Regioselective bromination of 1,4-dimethoxy-2,3-dimethylbenzene and conversion into sulfur-functionalised benzoquinones

The NBS bromination of 1,4-dimethoxy-2,3-dimethylbenzene has been examined under a variety of conditions in both 1,1,1-trichloroethane and benzotrifluoride. Four different bromination products have been isolated including the previously unknown 1-bromo-4-bromomethyl-2,5-dimethoxy-3-methylbenzene whose single crystal X-ray structure is presented. The synthetically useful 2,3-bis(bromomethyl)-1,4-dimethoxybenzene is readily prepared using either solvent and it has been converted into new sulfur-containing quinone derivativesPostprintPeer reviewe

Creating an Online CME Module: Early Detection and Diagnosis of Dementia and Alzheimer’s Disease

Introduction. The number of individuals living with dementia and Alzheimer’s disease (AD) in the United States is growing annually; only 40% are properly diagnosed. Primary care providers should identify individuals with cognitive impairment and provide options for care; early diagnosis of dementia and AD helps patients and families plan for the future, increases quality of life, and allows for treatment options.https://scholarworks.uvm.edu/comphp_gallery/1192/thumbnail.jp

ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure

ACE inhibition or angiotensin receptor blockade: Impact on potassium in renal failure.BackgroundInhibition of the renin-angiotensin system is known to raise serum potassium [K+] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K+] in people with renal insufficiency.MethodsThe study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 ± 2 years. Mean baseline serum [K+] was 4.4 ± 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 ± 5 mL/min/1.73 m2, and blood pressure was 150 ± 2/88 ± 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods.ResultsFor the total group, serum [K+] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of ≤60 mL/min/1.73 m2 who received lisinopril demonstrated significant increases in serum [K+] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K+] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K+] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of ≤60 mL/min/1.73 m2. The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K+], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K+] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14).ConclusionsIn the presence of renal insufficiency, the ARB valsartan did not raise serum [K+] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K+] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K+] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency

Screening for Alzheimer’s Disease in Vermont Primary Care Practice

Introduction: • Alzheimer’s Disease (AD) is a form of progressive dementia that affects 5.3 million Americans and is the sixth leading cause of death in the US. • Age is a major risk factor for disease , and 1 in 8 Americans over 65 can expect to develop AD. • The U.S. healthcare system spends $172 billion/year on patients with AD and dementia, more than half of the Medicare budget. This cost is estimated to increase to over$1 trillion by 2050. • In 2003, the US Preventative Services Task Force (USPSTF) concluded that screening older adults for dementia is ineffective due to insufficient means of preventing or slowing its progression. • In 2011, the National Institute on Aging published new diagnostic criteria for AD. • In accordance with these guidelines the Centers for Medicare and Medicaid Services released rules for the new Annual Wellness Visit that include the detection of cognitive impairment. • Our goal was to identify the attitudes and practices of primary care physicians (PCPs) in Vermont (VT) related to screening for AD and dementia.https://scholarworks.uvm.edu/comphp_gallery/1063/thumbnail.jp