Using Healthcare Data in Embedded Pragmatic Clinical Trials among People Living with Dementia and Their Caregivers: State of the Art

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156003/1/jgs16617_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156003/2/jgs16617.pd

Diagnosed prevalence of Alzheimer’s disease and related dementias in Medicare Advantage plans

IntroductionOne- third of Medicare beneficiaries are enrolled in Medicare Advantage (MA). Yet, little is known about MA beneficiaries diagnosed with Alzheimer’s disease (AD) and AD- related dementias (AD/ADRD).MethodsWe calculated the prevalence of AD/ADRD diagnoses in 2014 and 2016 in three MA plans. We determined the demographic characteristics of beneficiaries diagnosed with AD/ADRD, and whether they disenrolled from the MA plan for any reason within 364 days from the index date.ResultsIn 2014 and 2016, the overall prevalence of AD/ADRD diagnoses was 5.6% and 6.5%, respectively. In 2016, AD/ADRD beneficiaries were on average 82.4 (SD = 7.4) years of age, 61.8% female, and had multiple comorbidities. By 364 days post- index date, 32% of beneficiaries with AD/ADRD had disenrolled from their plan. The demographic characteristics of 2014 beneficiaries with diagnosed AD/ADRD were similar to their 2016 counterparts.DiscussionThe prevalence of AD/ADRD diagnosis in MA is lower than rates reported in Medicare fee- for- service.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156169/2/dad212048.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156169/1/dad212048_am.pd

Factors influencing elderly women's mammography screening decisions: implications for counseling

<p>Abstract</p> <p>Background</p> <p>Although guidelines recommend that clinicians consider life expectancy before screening older women for breast cancer, many older women with limited life expectancies are screened. We aimed to identify factors important to mammography screening decisions among women aged 80 and older compared to women aged 65–79.</p> <p>Methods</p> <p>Telephone surveys of 107 women aged 80+ and 93 women aged 65–79 randomly selected from one academic primary care practice who were able to communicate in English (60% response rate). The survey addressed the following factors in regards to older women's mammography screening decisions: perceived importance of a history of breast disease, family history of breast cancer, doctor's recommendations, habit, reassurance, previous experience, mailed reminder cards, family/friend's recommendations or experience with breast cancer, age, health, and media. The survey also assessed older women's preferred role in decision making around mammography screening.</p> <p>Results</p> <p>Of the 200 women, 65.5% were non-Hispanic white and 82.8% were in good to excellent health. Most (81.3%) had undergone mammography in the past 2 years. Regardless of age, older women ranked doctor's recommendations as the most important factor influencing their decision to get screened. Habit and reassurance were the next two highly ranked factors influencing older women to get screened. Among women who did not get screened, women aged 80 and older ranked age and doctor's counseling as the most influential factors and women aged 65–79 ranked a previous negative experience with mammography as the most important factor. There were no significant differences in preferred role in decision-making around mammography screening by age, however, most women in both age groups preferred to make the final decision on their own (46.6% of women aged 80+ and 50.5% of women aged 65–79).</p> <p>Conclusion</p> <p>While a doctor's recommendation is the most important factor influencing elderly women's mammography screening decisions, habit and reassurance also strongly influence decision-making. Interventions aimed at improving clinician counseling about mammography, which include discussions around habit and reassurance, may result in better decision-making.</p

A systematic review of intravenous gamma globulin for therapy of acute myocarditis

BACKGROUND: Intravenous gamma globulin (IVGG) is commonly used in the management of acute myocarditis. The objective of this study was to systematically review the literature evaluating this practice. METHODS: We conducted a comprehensive search (electronic databases, trials registries, conference proceedings, reference lists, contact with authors) to identify studies evaluating the use of IVGG in adults and children with a clinical or histologically proven diagnosis of myocarditis of possible viral etiology and symptoms of less than six months duration. Two reviewers independently screened the searches, applied inclusion criteria, and graded the evidence. RESULTS: Results were described qualitatively; data were not pooled because only one randomized controlled trial (RCT) with 62 patients was identified. The RCT showed no benefit with respect to cardiac function, functional outcome, or event-free survival. A small, uncontrolled trial (n = 10) showed significant improvement in LVEF from a mean of 24% to 41% 12 months after IVGG in nine survivors. A retrospective cohort study of pediatric patients showed improvement in cardiac function and a trend towards improved survival in patients receiving IVGG (n = 21) versus historic controls (n = 25). Ten case reports and two case series (total n = 21) described improvement in cardiac function after administration of IVGG; two case reports showed no benefit of IVGG. One case of hemolytic anemia was attributed to IVGG. CONCLUSION: There is insufficient data from methodologically strong studies to recommend routine use of IVGG for acute myocarditis. Future randomized studies that take into account the etiology of acute myocarditis will be required to determine the efficacy of IVGG

A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype

Background Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis. Methods Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed. Results We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly. Conclusions Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial features—particularly when associated with markers of mitochondrial dysfunction and/or Irish ancestry—should suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations

In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: A case report

Background. The molecular characteristics and the clinical disease course of bladder cancer (BC) in young patients remain largely unresolved. All patients are monitored according to an intensive surveillance protocol and we aim to gain more insight into the molecular pathways of bladder tumors in young patients that could ultimately contribute to patient stratification, improve patient quality of life and reduce associated costs. We also determined whether a biomarker-based surveillance could be feasible. Case Presentation. We report a unique case of a 26-year-old Caucasian male with recurrent non-muscle invasive bladder tumors occurring at a high frequency and analyzed multiple tumors (maximal pTaG2) and urine samples of this patient. Analysis included FGFR3 mutation detection, FGFR3 and TP53 immunohistochemistry, mircosatellite analysis of markers on chromosomes 8, 9, 10, 11 and 17 and a genome wide single nucleotide polymorphism-array (SNP). All analyzed tumors contained a mutation in FGFR3 and were associated with FGFR3 overexpression. None of the tumors showed overexpression of TP53. We found a deletion on chromosome 9 in the primary tumor and this was confirmed by the SNP-array that showed regions of loss on chromosome 9. Detection of all recurrences was possible by urinary FGFR3 mutation analysis. Conclusions. Our findings would suggest that the BC disease course is determined by not only a patient's age, but also by the molecular characteristics of a tumor. This young patient contained typical genetic changes found in tumors of older patients and implies a clinical disease course comparable to older patients. We demonstrate that FGFR3 mutation analysis on voided urine is a simple non-invasive method and could serve as a feasible follow-up approach for this young patient presenting with an FGFR3 mutant tumor

Conducting High-Value Secondary Dataset Analysis: An Introductory Guide and Resources

Secondary analyses of large datasets provide a mechanism for researchers to address high impact questions that would otherwise be prohibitively expensive and time-consuming to study. This paper presents a guide to assist investigators interested in conducting secondary data analysis, including advice on the process of successful secondary data analysis as well as a brief summary of high-value datasets and online resources for researchers, including the SGIM dataset compendium (www.sgim.org/go/datasets). The same basic research principles that apply to primary data analysis apply to secondary data analysis, including the development of a clear and clinically relevant research question, study sample, appropriate measures, and a thoughtful analytic approach. A real-world case description illustrates key steps: (1) define your research topic and question; (2) select a dataset; (3) get to know your dataset; and (4) structure your analysis and presentation of findings in a way that is clinically meaningful. Secondary dataset analysis is a well-established methodology. Secondary analysis is particularly valuable for junior investigators, who have limited time and resources to demonstrate expertise and productivity

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Antibiotic susceptibility of Atopobium vaginae

BACKGROUND: Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV). Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV. METHODS: Nine strains of Atopobium vaginae, four strains of Gardnerella vaginalis, two strains of Lactobacillus iners and one strain each of Bifidobacterium breve, B. longum, L. crispatus, L. gasseri and L. jensenii were tested against 15 antimicrobial agents using the Etest. RESULTS: All nine strains of A. vaginae were highly resistant to nalidixic acid and colistin while being inhibited by low concentrations of clindamycin (range: < 0.016 μg/ml), rifampicin (< 0.002 μg/ml), azithromycin (< 0.016 – 0.32 μg/ml), penicillin (0.008 – 0.25 μg/ml), ampicillin (< 0.016 – 0.94 μg/ml), ciprofloxacin (0.023 – 0.25 μg/ml) and linezolid (0.016 – 0.125 μg/ml). We found a variable susceptibility for metronidazole, ranging from 2 to more than 256 μg/ml. The four G. vaginalis strains were also susceptible for clindamycin (< 0.016 – 0.047 μg/ml) and three strains were susceptible to less than 1 μg/ml of metronidazole. All lactobacilli were resistant to metronidazole (> 256 μg/ml) but susceptible to clindamycin (0.023 – 0.125 μg/ml). CONCLUSION: Clindamycin has higher activity against G. vaginalis and A. vaginae than metronidazole, but not all A. vaginae isolates are metronidazole resistant, as seemed to be a straightforward conclusion from previous studies on a more limited number of strains

Trends in the Ambulatory Management of Headache: Analysis of NAMCS and NHAMCS Data 1999–2010

BACKGROUND: Headache is a frequent complaint and among the most common reasons for visiting a physician. OBJECTIVE: To characterize trends from 1999 through 2010 in the management of headache. DESIGN: Longitudinal trends analysis. DATA: Nationally representative sample of visits to clinicians for headache from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, excluding visits with “red flags,” such as neurologic deficit, cancer, or trauma. MAIN MEASURES: Use of advanced imaging (CT/MRI), opioids/barbiturates, and referrals to other physicians (guideline-discordant indicators), as well as counseling on lifestyle modifications and use of preventive medications including verapamil, topiramate, amitriptyline, or propranolol (guideline-concordant during study period). We analyzed results using logistic regression, adjusting for patient and clinician characteristics, and weighted to reflect U.S. population estimates. Additionally, we stratified findings based on migraine versus non-migraine, acute versus chronic symptoms, and whether the clinician self-identified as the primary care physician. KEY RESULTS: We identified 9,362 visits for headache, representing an estimated 144 million visits during the study period. Nearly three-quarters of patients were female, and the mean age was approximately 46 years. Use of CT/MRI rose from 6.7 % of visits in 1999–2000 to 13.9 % in 2009–2010 (unadjusted p < 0.001), and referrals to other physicians increased from 6.9 % to 13.2 % (p = 0.005). In contrast, clinician counseling declined from 23.5 % to 18.5 % (p = 0.041). Use of preventive medications increased from 8.5 % to 15.9 % (p = 0.001), while opioids/barbiturates remained unchanged, at approximately 18 %. Adjusted trends were similar, as were results after stratifying by migraine versus non-migraine and acute versus chronic presentation. Primary care clinicians had lower odds of ordering CT/MRI (OR 0.56 [0.42, 0.74]). CONCLUSIONS: Contrary to numerous guidelines, clinicians are increasingly ordering advanced imaging and referring to other physicians, and less frequently offering lifestyle counseling to their patients. The management of headache represents an important opportunity to improve the value of U.S. healthcare. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-014-3107-3) contains supplementary material, which is available to authorized users