The pathogenesis of inflammatory muscle diseases: on the cutting edge among the environment,the genetic background,the immune response and the dysregulation of apoptosis

Inflammatory muscle diseases (IMD), including dermatomyositis (DM) and polymyositis (PM), affect skeletal muscle, leading to profound tissue modification. The etiology of IMD is unknown, but multiple steps of the disease pathogenesis have been identified. The main alterations involve the immune response. Cellular infiltrates found in the muscle provide strong evidence for the involvement of a preferential immune mechanism of muscle damage. The pathologic differences found between PM and DM indicate a different role played by cell-mediated and humoral immune alterations. It is well accepted that in the pathogenetic pathway both host genes and environmental factors are involved. Apoptosis, or programmed cell death, is a complex process that plays a key role in many physiological events. It regulates the turnover of immune cells and is one of the mechanisms involved in ensuring a competent, non-autoreactive repertoire of lymphocytes. Apoptosis as a mechanism of muscle fibre death has been described in several neuromuscular disorders and muscular dystrophies, and evidence of a lack of apoptosis in IMD suggests a failure of apoptotic clearance of inflammatory cells playing a role in the maintenance of chronic cytotoxic muscle fibre damage. Most likely, the failure of apoptosis seems to be the main hallmark of the pathogenesis of IMD.     

Nurse Decision-making for Suspected Urinary Tract Infections in Nursing Homes: Potential Targets to Reduce Antibiotic Overuse

ObjectivesTo determine what information is most important to registered nurses' (RNs) decisions to call clinicians about suspected urinary tract infections (UTIs) in nursing home residents.DesignWeb-based discrete choice experiment with 19 clinical scenarios.Setting and ParticipantsOnline survey with a convenience sample of RNs (N = 881) recruited from a health care research panel.MethodsClinical scenarios used information from 10 categories of resident characteristics: UTI risk, resident type, functional status, mental status, lower urinary tract status, body temperature, physical examination, urinalysis, antibiotic request, and goals of care. Participants were randomized into 2 deliberation conditions (self-paced, n = 437 and forced deliberation, n = 444). The degree to which evidence- and non–evidence-based information was important to decision-making was estimated using unconditional multinomial logistic regression.ResultsFor all nurses (22.8%) and the self-paced group (24.1%), lower urinary tract status had the highest importance scores for the decision to call a clinician about a suspected UTI. For the forced-deliberation group, body temperature was most important (23.7%), and lower urinary tract status was less important (21%, P = .001). The information associated with the highest odds of an RN calling about a suspected UTI was painful or difficult urination [odds ratio (OR) 4.85, 95% confidence interval (CI) 4.16–5.65], obvious blood in urine (OR 4.66, 95% CI 3.99–5.44), and temperature at 101.5° (OR 3.80, 95% CI 3.28–4.42). For the self-paced group, painful or difficult urination (OR 5.65, 95% CI 4.53–7.04) had the highest odds, whereas obvious blood in urine (OR 4.39, 95% CI 3.53–5.47) had highest odds for the forced-deliberation group.Conclusions and ImplicationsThis study highlighted the importance of specific resident characteristics in nurse decision-making about suspected UTIs. Future antimicrobial stewardship efforts should aim to not only improve the previously studied overprescribing practices of clinicians, but to improve nurses' assessment of signs and symptoms of potential infections and how they weigh resident information.     

A randomized trial of a primary care-based disease management program to improve cardiovascular risk factors and glycated hemoglobin levels in patients with diabetes

PURPOSE: To assess the efficacy of a pharmacist-led, primary care-based, disease management program to improve cardiovascular risk factors and glycated hemoglobin (A(1C)) levels in vulnerable patients with poorly controlled diabetes. METHODS: A randomized controlled trial of 217 patients with type 2 diabetes and poor glycemic control (A(1C) level >or=8.0%) was conducted at an academic general medicine practice from February 2001 to April 2003. Intervention patients received intensive management from clinical pharmacists, as well as from a diabetes care coordinator who provided diabetes education, applied algorithms for managing glucose control and decreasing cardiovascular risk factors, and addressed barriers to care. Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider. Outcomes were recorded at baseline and at 6 and 12 months. Primary outcomes included blood pressure, A(1C) level, cholesterol level, and aspirin use. Secondary outcomes included diabetes knowledge, satisfaction, use of clinical services, and adverse events. RESULTS: For the 194 patients (89%) with 12-month data, the intervention group had significantly greater improvement than did the control group for systolic blood pressure (-9 mm Hg; 95% confidence interval [CI]: -16 to -3 mm Hg) and A(1C) level (-0.8%; 95% CI: -1.7% to 0%). Change in total cholesterol level was not significant. At 12 months, aspirin use was 91% in the intervention group versus 58% among controls (P <0.0001). Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients. There were no significant differences in use of clinical services or adverse events. CONCLUSION: Our comprehensive disease management program reduced cardiovascular risk factors and A(1C) levels among vulnerable patients with type 2 diabetes and poor glycemic control.     

Clarifying values: an updated review

Background

Consensus guidelines have recommended that decision aids include a process for helping patients clarify their values. We sought to examine the theoretical and empirical evidence related to the use of values clarification methods in patient decision aids.

Methods

Building on the International Patient Decision Aid Standards (IPDAS) Collaboration’s 2005 review of values clarification methods in decision aids, we convened a multi-disciplinary expert group to examine key definitions, decision-making process theories, and empirical evidence about the effects of values clarification methods in decision aids. To summarize the current state of theory and evidence about the role of values clarification methods in decision aids, we undertook a process of evidence review and summary.

Results

Values clarification methods (VCMs) are best defined as methods to help patients think about the desirability of options or attributes of options within a specific decision context, in order to identify which option he/she prefers. Several decision making process theories were identified that can inform the design of values clarification methods, but no single “best” practice for how such methods should be constructed was determined. Our evidence review found that existing VCMs were used for a variety of different decisions, rarely referenced underlying theory for their design, but generally were well described in regard to their development process. Listing the pros and cons of a decision was the most common method used. The 13 trials that compared decision support with or without VCMs reached mixed results: some found that VCMs improved some decision-making processes, while others found no effect.

Conclusions

Values clarification methods may improve decision-making processes and potentially more distal outcomes. However, the small number of evaluations of VCMs and, where evaluations exist, the heterogeneity in outcome measures makes it difficult to determine their overall effectiveness or the specific characteristics that increase effectiveness.

     

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.     

Dimensions of psychological dysfunction in patients with fibromyalgia: development of an Italian questionnaire

Our objective was to observe whether dysfunctional psychological dimensions of pain could be detected in fibromyalgia patients through the development of a new questionnaire. An original questionnaire composed of 51 items was given to 250 patients (185 females and 65 males, mean age 55±12.8 years) suffering from chronic fibromyalgia according to the criteria of the Multicenter Criteria Committee of the American College of Rheumatology. A Varimax computerized program of factorial analysis with orthogonal and oblique rotation of the axes was used to analyze the data. Five strong independent factors were identified: 1) catastrophizing and 2) external control beliefs (cognitive); 3) alexithymia (emotional); 4) restless behavior (behavioral); and 5) need for support (relational). Our questionnaire is a preliminary development of an Italian language psychological characterization of FM patients which may be a relevant and useful tool for the evaluation of the outcome of clinical/psychological treatment of FM.Abbreviations FM Fibromyalgia     

Comparing 3 Values Clarification Methods for Colorectal Cancer Screening Decision-Making: A Randomized Trial in the US and Australia

Purpose

To compare the effects of three methods of values clarification (VCM): balance sheet; rating and ranking; and a discrete choice experiment (DCE) on decision-making about colorectal cancer (CRC) screening among adults in the US and Australia.

Methods

Using online panels managed by a survey research organization in the US and Australia, we recruited adults ages 50–75 at average risk for CRC for an online survey. Those eligible were randomized to one of the three VCM tasks. CRC screening options were described in terms of five key attributes: reduction in risk of CRC incidence and mortality; nature of the screening test; screening frequency; complications from screening; and chance of requiring a colonoscopy (as initial or follow-up testing). Main outcomes included self-reported most important attribute and unlabeled screening test preference by VCM and by country, assessed after the VCM.

Results

A total of 920 participants were enrolled; 51 % were Australian; mean age was 59.0; 87.0 % were white; 34.2 % had a 4-year college degree; 42.8 % had household incomes less than $45,000 USD per year; 44.9 % were up to date with CRC screening. Most important attribute differed across VCM groups: the rating and ranking group was more likely to choose risk reduction as most important attribute (69.8 %) than the balance sheet group (54.7 %) or DCE (49.3 %), p < 0.0001; most important attribute did not vary by country (p = 0.236). The fecal occult blood test (FOBT)-like test was the most frequently preferred test overall (55.9 %). Unlabeled test choice did not differ meaningfully by VCM. Australians were more likely to prefer the FOBT (AU 66.2 % vs. US 45.1 %, OR 2.4, 95 % CI 1.8, 3.1). Few participants favored no screening (US: 9.2 %, AU: 6.2 %).

Conclusions

Screening test attribute importance varied by VCM, but not by country. FOBT was more commonly preferred by Australians than by Americans, but test preferences were heterogeneous in both countries.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-013-2701-0) contains supplementary material, which is available to authorized users.KEY WORDS: values clarification, colorectal cancer screening, patient decision support     

Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention–sponsored Summit

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.     

Cardiac amyloidosis: the heart of the matter

Amyloidosis comprises a unique group of diseases that share in common the extracellular deposition of insoluble fibrillar proteins in organs and tissue including the heart. Cardiac amyloidosis could be primary a part of systemic acquired amyloidosis, or a result of heredofamilial amyloidosis. Although the infiltration of the heart from different types of amyloid results in restrictive cardiomyopathy that manifests with refractory congestive heart failure and conduction abnormalities, unequivocal identification of the deposited amyloidogenic protein is mandatory in order to avoid misdiagnosis and inappropriate treatment. Recent developments in imaging techniques and extracardiac tissue biopsy have minimized the need for invasive endomyocardial biopsy for amyloidosis. Despite advances in treatment, the prognosis of a patient with amyloidosis is still poor and depends upon the underlying disease, and the type and degree of dysfunction of the involved organs. Thus, early diagnosis is mandatory because patients with advanced disease are usually too ill for intensive therapy. This review outlines current approaches to diagnosis, assessment of disease severity, and treatment of cardiac amyloidosis.