Medication affordability discussions with older adults in primary care.

Introduction: Cost is a major barrier to medication accessibility. While a minority of adults experience problems affording their medications, older adults are particularly vulnerable due to increased polypharmacy and fixed incomes.Clinicians can help reduce cost-related non-adherence and improve medication affordability; however, opportunities to improve affordability are often missed due to failure of the patient or clinician to discuss the issue. Objective: Identify the incidence and resolution of cost-related conversations between patients and clinicians during primary care visits. Methods: We conducted this quality improvement project at a primary care office. Student pharmacists observed in-person encounters with patients ≥65 years of age and documented the incidence of cost-related conversations and who initiated the conversation. After the visit, they asked if the patient had affordability issues. Patients and clinicians were blinded to the study purpose and hypothesis. Results: Students observed 79 primary care visits. Cost conversations (medication or non-medication related) occurred in 37% (29/79) of visits. Having concerns about affordability did not impact the likelihood of conversation about non-medication related healthcare costs (RR = 1.21 95% CI 0.35-4.19, p = 0.67) or medication related costs (RR = 0.86 95% CI 0.13-5.65, p = 1.0). Conclusion: Our results indicated that cost conversations did not routinely occur at our site. Failure to discuss costs, especially for patients with underlying cost concerns, may lead to cost related non-adherence and worse outcomes.

Interventions supporting cost conversations between patients and clinicians: A systematic review.

BACKGROUND AND AIM: Discussing cost during medical encounters may decrease the financial impact of medical care on patients and align their treatment plans with their financial capacities. We aimed to examine which interventions exist and quantify their effectiveness to support cost conversations. METHODS: Several databases were queried (Embase; Ovid MEDLINE(R); Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; the Cochrane databases; and Scopus) from their inception until January 31, 2020 using terms such as "clinician*", "patient*", "cost*", and "conversation*". Eligibility assessment, data extraction and risk of bias assessment were performed independently and in duplicate. We extracted study setting, design, intervention characteristics and outcomes related to patients, clinicians and quality metrics. RESULTS: We identified four studies (1327 patients) meeting our inclusion criteria. All studies were non-randomised and conducted in the United States. Three were performed in a primary care setting and the fourth in an oncology. Two studies used decision aids that included cost information; one used a training session for health care staff about cost conversations, and the other directly delivered information regarding cost conversations to patients. All interventions increased cost-conversation frequency. There was no effect on out-of-pocket costs, satisfaction, medication adherence or understanding of costs of care. CONCLUSION: The body of evidence is small and comprised of studies at high risk of bias. However, an increase in the frequency of cost conversations is consistent. Studies with higher quality are needed to ascertain the effects of these interventions on the acceptability, frequency and quality of cost conversations.

A deeper analysis in thyroid research: A meta-epidemiological study of the American Thyroid Association clinical guidelines.

BACKGROUND: The American Thyroid Association (ATA) uses the GRADE or the American College of Physicians (ACP) system to develop recommendations. Recommendations based on low-quality evidence should spur for the conduction of clinical studies, if feasible. The extent to which recommendations by the ATA based on low-quality of evidence are being actively researched remains unknown. METHODS: Clinical guidelines produced by the ATA using the GRADE or the ACP system to classify evidence were deemed eligible. Reviewers, in duplicate and independently, extracted therapeutic recommendations based on low-quality evidence, whereas recommendations with higher quality of evidence, aimed at diagnosis, or best practice statements were excluded. Eligible recommendations based on low-quality evidence were deconstructed to their components using the PICO format. We then searched on clinicaltrials.gov to identify ongoing research. Trials were deemed eligible if they addressed the PICO question with at least one of the intended outcomes. RESULTS: A total of 543 recommendations were retrieved, of which 305 (56%) were based on low-quality of evidence and only 90 were deemed eligible. Of these, we found that 33 (37%) recommendations were actively being researched in 53 clinical trials. Most of the trials were randomized and funded by non-profit organizations. Many clinical trials studied thyroid nodules and differentiated thyroid cancer (26/53; 49%), whereas few studied were aimed at anaplastic thyroid cancer (2/53; 4%). CONCLUSION: One out of three of gaps in evidence, identified as low quality during the development of ATA guidelines, are currently actively researched. This finding calls for the need to develop a better research infrastructure and funding to support thyroid research.

Women's Values and Preferences Regarding Osteoporosis Treatments: A Systematic Review.

BACKGROUND: Several treatments are available to reduce the risk of fragility fractures associated with osteoporosis. The choice of treatment requires knowledge of patients' values and preferences. The aim of the present study was to summarize what is known about the values and preferences relevant to the management of osteoporosis in women. METHODS: We conducted a comprehensive search of several databases for studies reported in any language that had included women who had already started or were about to start any pharmacological therapy for osteoporosis. Pairs of reviewers independently selected the studies and extracted the data. The results were synthesized narratively. RESULTS: We included 26 studies reporting on 15,348 women (mean age, 66 years). The women considered the effectiveness and adverse events equally, followed by the convenience of taking the drug and its effect on daily routine (less frequent dosing was preferred, the oral route was preferred, and the injectable route was preferred over oral if given less frequently). The treatment cost and duration were less important factors for decision making. Fear of breast cancer and fear of resuming uterine bleeding were common reasons for not choosing estrogen therapy. Calcium and vitamin D were viewed as safe and natural. Across the studies, the preferences were not affected by age, previous drug exposure, or employment status. CONCLUSIONS: Women starting osteoporosis medications value effectiveness and side effects equally and prefer medications given less frequently. Injectable drugs appear acceptable if given less frequently. More research on patient values and preferences is needed to guide decision making in osteoporosis.

Multimodal Postoperative Pain Control Is Effective and Reduces Opioid Use After Laparoscopic Roux-en-Y Gastric Bypass.

BACKGROUND: Opioids have been the mainstay for postoperative pain relief for many decades. Recently, opioid-related adverse events and death have been linked to postoperative dependency. Multimodal approaches to postoperative pain control may be part of the solution to this health care crisis. The safety and effectiveness of multimodal pain control regimens after laparoscopic Roux-en-Y gastric bypass (LRYGB) has not been well studied. The primary aim of our study was to determine if an evidence-based, multimodal pain regimen during hospitalization could decrease the total oral morphine equivalent (TME) use after LRYGB. STUDY DESIGN: We conducted a retrospective cohort study comparing outcomes prior to the implementation of a multimodal pain protocol (December 2010-December 2012) to those after implementation (April 2013-July 2015). The protocol utilized oral celecoxib and scheduled oral acetaminophen for pain control, with opioids used only as needed for breakthrough pain. Data was extracted from an electronic medical record and an institutionally maintained database of all patients undergoing bariatric surgery at a single center. RESULTS: Compared to controls, the multimodal pain regimen significantly reduced TME used and maximum pain scores with no change in mean pain scores. Multimodal pain protocol patients had a shorter length of stay with no increase in bleeding complications or marginal ulcer rates. CONCLUSIONS: An opioid-sparing multimodal pain regimen adequately controls pain while reducing TME use. The regimen appears to be safe and was associated with a reduced length of stay in patients undergoing LRYGB.

Impact of decision aids used during clinical encounters on clinician outcomes and consultation length: a systematic review.

BACKGROUND: Clinicians' satisfaction with encounter decision aids is an important component in facilitating implementation of these tools. We aimed to determine the impact of decision aids supporting shared decision making (SDM) during the clinical encounter on clinician outcomes. METHODS: We searched nine databases from inception to June 2017. Randomised clinical trials (RCTs) of decision aids used during clinical encounters with an unaided control group were eligible for inclusion. Due to heterogeneity among included studies, we used a narrative evidence synthesis approach. RESULTS: Twenty-five papers met inclusion criteria including 22 RCTs and 3 qualitative or mixed-methods studies nested in an RCT, together representing 23 unique trials. These trials evaluated healthcare decisions for cardiovascular prevention and treatment (n=8), treatment of diabetes mellitus (n=3), treatment of osteoporosis (n=2), treatment of depression (n=2), antibiotics to treat acute respiratory infections (n=3), cancer prevention and treatment (n=4) and prenatal diagnosis (n=1). Clinician outcomes were measured in only a minority of studies. Clinicians' satisfaction with decision making was assessed in only 8 (and only 2 of them showed statistically significantly greater satisfaction with the decision aid); only three trials asked if clinicians would recommend the decision aid to colleagues and only five asked if clinicians would use decision aids in the future. Outpatient consultations were not prolonged when a decision aid was used in 9 out of 13 trials. The overall strength of the evidence was low, with the major risk of bias related to lack of blinding of participants and/or outcome assessors. CONCLUSION: Decision aids can improve clinicians' satisfaction with medical decision making and provide helpful information without affecting length of consultation time. Most SDM trials, however, omit outcomes related to clinicians' perspective on the decision making process or the likelihood of using a decision aid in the future.

Comparison of audio vs. audio + video for the rating of shared decision making in oncology using the observer OPTION5 instrument: an exploratory analysis.

BACKGROUND: How non-verbal data may influence observer-administered ratings of shared decision making is unknown. Our objective for this exploratory analysis was to determine the effect of mode of data collection (audio+video vs. audio only) on the scoring of the OPTION5 instrument, an observer rated measure of shared decision making. METHODS: We analyzed recordings of 15 encounters between cancer patients and clinicians in which a clinical decision was made. Audio+video or audio only recordings of the encounters were randomly assigned to four trained raters, who reviewed them independently. We compared the adjusted mean scores of audio+video and audio only. RESULTS: Forty-one unique decisions were identified within the 15 encounters. The mean OPTION5 score for audio+video was 17.5 (95% CI 13.5, 21.6) and for audio only was 21.8 (95% CI 17.2, 26.4) with a mean difference of 4.28 (95% CI = 0.36, 8.21; p = 0.032). CONCLUSION: A rigorous and well established measure of shared decision making performs differently when the data source is audio only. Data source may influence rating of observer administered measures of shared decision making. This potential bias needs to be confirmed as video recording to examine communication behaviors becomes more common.

Efficacy of menopausal hormone therapy on sleep quality: systematic review and meta-analysis.

Sleep complaints are reported by 40-60 % of menopausal women. Poor sleep is a risk factor for cardiovascular disease, diabetes, and obesity. The effect of menopausal hormone therapy on sleep quality is unclear. A systematic review and meta-analysis were conducted to summarize the efficacy of menopausal hormone therapy on self-reported sleep quality. Electronic databases (PubMed, Scopus, Ovid MEDLINE, EMBASE, EBM Reviews CENTRAL, and PsycInfo) were searched from 2002 to October 2015. Randomized trials assessing the effect of menopausal hormone therapy with a minimum follow up of 8 weeks were included. Titles, abstracts, and full texts were screened independently and in duplicate. Primary outcome included sleep items within a questionnaire, scale or diary. Standardized mean differences across trials were pooled using random-effects models. The search identified 424 articles, from which 42 trials were included. Seven trials at a moderate to high risk of bias enrolling 15,468 women were pooled in meta-analysis. Menopausal hormone therapy improved sleep quality in women who had vasomotor symptoms at baseline [standardized mean difference -0.54 (-0.91 to -0.18), moderate quality evidence]. No difference was noted when women without such symptoms were analyzed separately or combined. Across 31 sleep quality questionnaires, daytime dysfunction was the most evaluated sleep domain. Menopausal hormone therapy improves sleep in women with concomitant vasomotor symptoms. Heterogeneity of trials regarding study population, formulations, and sleep scales; limit overall certainty in the evidence. Future menopausal hormone therapy trials should include assessment of self-reported sleep quality using standardized scales and adhere to reporting guidelines.

Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model. RESULTS: We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81. CONCLUSIONS: Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.

Diagnostic accuracy of ultrasound-guided fine needle aspiration biopsy for thyroid malignancy: systematic review and meta-analysis.

PURPOSE: To systematically appraise and summarize the available evidence about the diagnostic accuracy of ultrasound-guided fine needle aspiration biopsy (USFNA) for thyroid malignancy, and to explore the integration of these estimates with the probability of thyroid malignancy before USFNA. METHODS: A comprehensive search of multiple databases from each database's inception to August 2014 was performed. Eligible studies included those that evaluated patients with thyroid nodules who underwent USFNA and subsequent evaluation by histopathology or long-term follow-up. RESULTS: We identified 32 studies at moderate risk of bias evaluating the USFNA diagnostic characteristics for the diagnosis of thyroid malignancy. Results were imprecise and inconsistent across trials. The pooled likelihood ratio (LR) of thyroid malignancy for a benign USFNA result was 0.09 (95 % CI 0.06, 0.14; I (2) = 33 %), whereas the pooled LR for a malignant result was 197 (95 % CI, 68, 569; I (2) = 77 %). In the case of a suspicious for follicular neoplasm result, the pooled LR for malignancy was 0.6 (95 % CI, 0.4, 1.0; I (2) = 84 %) and 8.3 (95 % CI, 3.6, 19.2; I (2) = 89) for a result of suspicious for malignancy. CONCLUSION: The available evidence regarding the diagnostic accuracy of USFNA warrants only limited confidence due to risk of bias, imprecision, and inconsistency. However, some USFNA results (benign, malignant) are likely very helpful, by significantly changing the pre-test probability of thyroid cancer.

Outcomes of Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

BACKGROUND: Parathyroidectomy is a definitive treatment for primary hyperparathyroidism. Patients contemplating this intervention will benefit from knowledge regarding the expected outcomes and potential risks of the currently available surgical options. PURPOSE: To appraise and summarize the available evidence regarding benefits and harms of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE). DATA SOURCES: A comprehensive search of multiple databases (MEDLINE, EMBASE, and Scopus) from each database's inception to September 2014 was performed. STUDY SELECTION: Eligible studies evaluated patients with primary hyperparathyroidism undergoing MIP or BNE. DATA EXTRACTION: Reviewers working independently and in duplicate extracted data and assessed the risk of bias. DATA SYNTHESIS: We identified 82 observational studies and 6 randomized trials at moderate risk of bias. Most of them reported outcomes after MIP (n = 71). Using random-effects models to pool results across studies, the cure rate was 98 % (95 % CI 97-98 %, I (2) = 10 %) with BNE and 97 % (95 % CI 96-98 %, I (2) = 86 %) with MIP. Hypocalcemia occurred in 14 % (95 % CI 10-17 % I (2) = 93 %) of the BNE cases and in 2.3 % (95 % CI 1.6-3.1 %, I (2) = 87 %) with MIP (P < 0.001). There was a statistically significant lower risk of laryngeal nerve injury with MIP (0.3 %) than with BNE (0.9 %), but similar risk of infection (0.5 vs. 0.5 %) and mortality (0.1 vs. 0.5 %). LIMITATIONS: The available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency for some outcomes (cure rate, hypocalcemia). CONCLUSION: MIP and BNE are both effective surgical techniques for the treatment of primary hyperparathyroidism. The safety profile of MIP appears superior to BNE (lower rate of hypocalcemia and recurrent laryngeal nerve injury).

PREDICTORS OF BIOCHEMICAL REMISSION AND RECURRENCE AFTER SURGICAL AND RADIATION TREATMENTS OF CUSHING DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. METHODS: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). RESULTS: First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. CONCLUSION: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Diagnostic accuracy of thyroid nodule growth to predict malignancy in thyroid nodules with benign cytology: systematic review and meta-analysis.

BACKGROUND: Thyroid ultrasound to assess for nodular growth is commonly performed during the follow-up of patients with benign thyroid nodules, with the goal of identifying patients with a missed diagnosis of thyroid cancer. The objective of this study was to summarize the evidence regarding the diagnostic accuracy of growth during follow-up of benign thyroid nodules for thyroid cancer. METHODS: We searched multiple electronic databases using a search strategy designed by an experienced medical librarian from inception to March 2015. Eligible studies included patients with benign thyroid nodules assessed for growth during follow-up and evaluated for thyroid cancer either by surgical histology or a repeat fine needle aspiration biopsy. Reviewers working independently and in duplicate recorded data and assessed each study. RESULTS: The seven eligible studies lacked safeguards against bias and generated results that were imprecise with wide confidence intervals and inconsistent across studies. This warrants very low confidence in these results. The odds of nodule growth in patients with thyroid cancer on histopathology over these odds in patients without thyroid cancer (diagnostic odds ratio) was 0·58 (95% CI: 0·26-1·3); the diagnostic odds ratio was 2·2 (95% CI: 0·26-18) when an abnormal repeat biopsy was the reference standard. CONCLUSION: The body of evidence linking nodule growth with thyroid cancer during the follow-up of benign nodules warrants very low confidence. In the era of high-value health care, the commonplace practice of following benign thyroid nodules with serial ultrasound assessment of growth to diagnose cancer can be questioned, calling for imminent evaluation.

Restricting ultrasound thyroid fine needle aspiration biopsy by nodule size: which tumors are we missing? A population-based study.

Clinicians use nodule size to determine which thyroid nodules should receive cytological evaluation. The American Thyroid Association (ATA) has recommended against cytological evaluation for nodules <1 cm. It is unknown, however, if nodule size can accurately discriminate lesions that will represent tumors with favorable versus unfavorable prognosis. Also, the characteristics of thyroid cancers that would not be diagnosed if a strict 1 cm size cut off is used as the threshold for biopsy of intrathyroidal nodules are not well established. Using the Rochester Epidemiology Project, a population-based cohort, we identified all thyroid nodules in Olmsted County residents from 2003-2006. To assess the presence of favorable or unfavorable features for each nodule size cutoff, each patient found to have thyroid cancer was risk-stratified using the ATA risk score, which predicts risk of recurrence and persistent disease. Thyroid cancer cases in which a biopsy was done for factors other than thyroid nodule size or suspicious ultrasound features were excluded. We identified 485 thyroid nodules, 46 (9.5%) harbored thyroid cancer. Of the 46 thyroid cancers, 37 (7.6%) had ATA low risk; 8 (1.6%) had intermediate, and only 1 (0.2%) had an ATA high risk scores. The frequency of thyroid cancer and the distribution of ATA risk scores were similar across tumor sizes. In thyroid nodules of <1 cm, 92 (87%) were benign, while 13 (13%) were malignant (11% ATA low risk, 2% ATA intermediate risk) without extrathyroid extension, aggressive histology, or distant metastasis. For all thyroid cancer patients, no cases of persistent disease were found after a median follow-up of 7 years. In this population-based study, we showed that high risk thyroid cancers are rare; indeed, in this highly selected cohort of patients, the ATA's recommendation to avoid cytologic evaluation in thyroid nodules less than 1 cm would not miss any thyroid cancer with high risk features. However, thyroid nodule size at presentation did not accurately discriminate between tumors with favorable versus unfavorable clinicopathologic features. Thus, if further discrimination is desired, for example, to avoid overdiagnosis, features other than size at presentation need to be evaluated.

Accuracy of thyroid nodule sonography for the detection of thyroid cancer in children: systematic review and meta-analysis.

INTRODUCTION: Thyroid ultrasound (US) is a widely used tool for evaluating thyroid nodules. Various US features have been suggested as predictors of thyroid cancer in children. OBJECTIVE: To conduct a systematic review and meta-analysis to assess the diagnostic accuracy of different thyroid US features in detecting thyroid cancer in children. METHODS: We searched multiple online databases for cohort studies that enrolled paediatric patients with thyroid nodules (age <21 years) and evaluated the accuracy of 12 relevant ultrasound features. Diagnostic measures were pooled across studies using a random effects model. RESULTS: The search strategy yielded 1199 citations, of which 12 studies met the predefined inclusion criteria (750 nodules). The prevalence of thyroid cancer was 27·2% (40·8% in patients with a history of radiation exposure and 23·2% in patients without a history of exposure to radiation). The most common cancer was papillary thyroid cancer (86·7%). The presence of internal calcifications and enlarged cervical lymph nodes were the US features with the highest likelihood ratio [4·46 (95% CI: 1·87-10·64) and 4·96 (95% CI: 2·01-12·24), respectively] for thyroid cancer. A cystic nodule was the feature with highest likelihood ratio for benign nodules [1·96 (95% CI: 0·87-4·43)]. CONCLUSION: Thyroid US features are not highly accurate predictors of benign or malignant aetiology of thyroid nodules in children. Internal calcification may predict malignancy, and cystic appearance may suggest benign aetiology.

Acting on black box warnings requires a GRADE evidence table and an implementation guide: the case of teriparatide.

OBJECTIVES: To assess how well do the black box warnings present and communicate evidence in a way that is consistent with evidence-based patient-centered practice, through evaluating the boxed warning on teriparatide-induced osteosarcoma. STUDY DESIGN AND SETTING: We critically appraised teriparatide black box warning for osteosarcoma by reviewing human and animal studies that were used as basis for the warning. We also evaluated the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS: We found that this warning was based on very low-quality evidence that was derived primarily from animal studies. The quality of evidence was rated down because of high risk of bias in addition to inconsistency, indirectness, and imprecision of the estimates. The warning does not provide sufficient guidance for practice like an implementation tool or an evidence profile to clarify the limitations of the evidence. CONCLUSION: Black box warning for teriparatide-associated osteosarcoma does not explicitly present the quality of evidence, and therefore, it could be of limited use in evidence-based practice. We propose that black box warnings should include an evidence profile and an implementation guide to be more useful in evidence-based patient-centered practice.

The incremental benefit of functional imaging in pheochromocytoma/paraganglioma: a systematic review.

Computed tomography (CT) and magnetic resonance imaging (MRI) are the major imaging modalities used for the localization of catecholamine-producing tumors (pheochromocytoma and paraganglioma). Functional imaging (FI) offers an alternative approach to localize, evaluate, and stage these tumors. Our objective was to describe the additive benefit of FI studies for patients with pheochromocytoma and paraganglioma (PPG) who have undergone MRI or CT scan evaluation. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from database inception through June 2012 for studies that included patients with biochemically proven PPGs who underwent CT or MRI and additional FI for the localization of PPGs. We included 32 studies enrolling a total of 1,264 patients with a mean age of 43-years old. The studies were uncontrolled and evaluated six FI modalities. FI tests provided small additive value to CT/MRI, aiding in the localization of only 24/1,445 primary cases (1.4 %) and 28/805 metastatic cases (3.5 %). In metastatic cases, 6-[F-18]fluoro-L-dihydroxyphenylalanine (DOPA) and fluorodopamine-PET (FDA) were the FI tests most successful at identifying disease missed by CT/MRI, providing additional benefit in 6/60 (10 %) and 5/78 (6.4 %) cases, respectively. No clinically significant findings were observed in any of the predefined subgroups. No study evaluated the impact of FI on the completeness of surgical resection or other patient-important outcomes. Observational evidence suggests that FI tests have a limited additional role in patients with PPGs who have undergone CT/MRI evaluation. However, the role of FI tests in specific subgroups of patients with atypical presentations (metastatic, extra-adrenal) as well as the use of hybrid FI tests should be explored. Further research should also evaluate the impact of FI tests on patient-important outcomes.

Tumor necrosis factor-α and its role as a mediator in myocardial infarction: A brief review.

Tumor necrosis factor-α (TNF-α) contributes to myocardial infarction (MI) injury. Polymorphism of TNF-α gene promoter region and secretion and release of TNF-α and its transformation by a series of signaling pathways are all changed at different points of pathophysiological process in MI. Researches also investigated TNF-α antagonists and their potential therapeutic role in the setting of MI and heart failure at both molecular and clinical level. This article briefly reviews TNF-α and its mechanism as a mediator in MI.

Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review.

BACKGROUND: The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown. OBJECTIVE: To describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations. METHODS: We searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease. RESULTS: We included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (4·6%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members. CONCLUSIONS: The frequency of germline mutations in SPPs is approximately 11-13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear.