Some patients with type 2 diabetes may benefit from intensive glycaemic and blood pressure control: A post-hoc machine learning analysis of ACCORD trial data.

AIM: The action to control cardiovascular risk in diabetes (ACCORD) trial showed a neutral average treatment effect of intensive blood glucose and blood pressure (BP) controls in preventing major adverse cardiovascular events (MACE) in individuals with type 2 diabetes. Yet, treatment effects across patient subgroups have not been well understood. We aimed to identify patient subgroups that might benefit from intensive glucose or BP controls for preventing MACE. MATERIALS AND METHODS: As a post-hoc analysis of the ACCORD trial, we included 10 251 individuals with type 2 diabetes. We applied causal forest and causal tree models to identify participant characteristics that modify the efficacy of intensive glucose or BP controls from 68 candidate variables (demographics, comorbidities, medications and biomarkers) at the baseline. The exposure was (a) intensive versus standard glucose control [glycated haemoglobin (HbA1c) <6.0% vs. 7.0%-7.9%], and (b) intensive versus standard BP control (systolic BP <120 vs. <140 mmHg). The primary outcome was MACE. RESULTS: Compared with standard glucose control, intensive one reduced MACE in those with baseline HbA1c <8.5% [relative risk (RR): 0.79, 95% confidence interval (CI): 0.67-0.93] and those with estimated glomerular filtration rate ≥106 ml/min/1.73 m2 (RR: 0.74, 95% CI: 0.55-0.99). Intensive BP control reduced MACE in those with normal high-density lipoprotein levels (women >55 mg/dl, men >45 mg/dl; RR: 0.51, 95% CI: 0.34-0.74). Risk reductions were not significant in other patient subgroups. CONCLUSIONS: Our findings suggest heterogeneous treatment effects of intensive glucose and BP control and could provide biomarkers for future clinical trials to identify more precise HbA1c and BP treatment goals for individualized medicine.

Physical Examination of the Thyroid: Accuracy in Detecting Thyroid Nodules and Frequency of Additional Findings.

OBJECTIVE: Thyroid palpation is a common clinical practice to detect thyroid abnormalities. However, its accuracy and potential for additional findings remain unclear. This study aimed to assess the diagnostic accuracy of physical exams in detecting thyroid nodules. METHODS: A retrospective observational study was conducted on a random sample of adult patients who underwent their first-time thyroid ultrasound between January 2015 and September 2017, following a documented thyroid physical exam. The study assessed the performance of thyroid palpation in detecting 1 or multiple thyroid nodules, as well as the proportion of additional findings on ultrasounds due to false positive thyroid palpation. RESULTS: We included 327 patients, mostly female (65.1%), white (84.1%), and treated in a primary care setting (54.4%) with a mean age of 50.8 years (SD 16.9). For solitary thyroid nodules, the physical exam had a sensitivity of 20.3%, specificity of 79.1%, an accuracy of 68.5%, negative predictive value of 81.8%, and positive predictive value of 17.6%. For detecting a multinodular goiter, physical exams demonstrated a sensitivity of 10.8%, specificity of 96.5%, accuracy of 55.4%, negative predictive value of 53.9, and positive predictive value of 73.9%. Among 154 cases with palpable nodules, 60% had additional nodules found in subsequent thyroid ultrasound. CONCLUSION: Thyroid physical exam has limited diagnostic performance and leads to additional findings when followed by a thyroid ultrasound. Future efforts should be directed at improving the accuracy of thyroid physical exams or re-evaluating its routine use.

Implementation strategies to support ultrasound thyroid nodule risk stratification: A systematic review.

BACKGROUND: Ultrasound risk stratification can improve the care of patients with thyroid nodules by providing a structured and systematic approach for the evaluation of thyroid nodule features and thyroid cancer risk. The optimal strategies to support implementation of high quality thyroid nodule risk stratification are unknown. This study seeks to summarise strategies used to support implementation of thyroid nodule ultrasound risk stratification in practice and their effects on implementation and service outcomes. METHODS: This is a systematic review of studies evaluating implementation strategies published between January 2000 and June 2022 that were identified on Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane, Scopus, or Web of Science. Screening of eligible studies, data collection and assessment for risk of bias was completed independently and in duplicate. Implementation strategies and their effects on implementation and service outcomes were evaluated and summarised. RESULTS: We identified 2666 potentially eligible studies of which 8 were included. Most implementation strategies were directed towards radiologists. Common strategies to support the implementation of thyroid nodule risk stratification included: tools to standardise thyroid ultrasound reports, education on thyroid nodule risk stratification and use of templates/forms for reporting, and reminders at the point of care. System based strategies, local consensus or audit were less commonly described. Overall, the use of these strategies supported the implementation process of thyroid nodule risk stratification with variable effects on service outcomes. CONCLUSIONS: Implementation of thyroid nodule risk stratification can be supported by development of standardised reporting templates, education of users on risk stratification and reminders of use at the point of care. Additional studies evaluating the value of implementation strategies in different contexts are urgently needed.

Drivers of Thyroid Ultrasound Use: A Retrospective Observational Study.

OBJECTIVE: Excessive use of thyroid ultrasound (TUS) contributes to the overdiagnosis of thyroid nodules and thyroid cancer. In this study, we evaluated drivers of and clinical trajectories following TUS orders. METHODS: We conducted a retrospective review of 500 adult patients who underwent an initial TUS between 2015 and 2017 at Mayo Clinic in Rochester, MN. A framework was employed to classify the indication for TUS, and it was characterized as inappropriate when ordered without a guideline-based indication. Medical records were reviewed for up to 12 months following the TUS, and clinical outcomes were evaluated. RESULTS: The mean age mean age (SD) was 53.6 years (16.6), 63.8% female, and 86.6% white. TUS orders were triggered by incidental findings on unrelated imaging (31.6%), thyroid symptoms (20.4%), thyroid abnormalities on routine physical examination (17.2%), and thyroid dysfunction workup (11.8%). In females and males, the most common reason were incidental findings on imaging (female, 91/319, 28.5% and male, 67/181, 37.0%). In primary care practice, TUS orders were mostly triggered by symptoms (71/218, 32.5%), while thyroid dysfunction workup was the primary reason in endocrinology (28/100, 28.0%). We classified 11.2% (56/500) TUS orders as likely to have been ordered inappropriately based on current guidelines. Finally, 119 patients (119/500, 23.8%) had a thyroid biopsy with 11.8% had thyroid cancer (14/119. 11.8%). CONCLUSIONS: Incidental findings on imaging, symptoms, and routine physical exam findings in asymptomatic patients were the most prevalent drivers of TUS. Furthermore, 1 in 10 TUS were likely inappropriately ordered based on current practice guidelines.

Concomitant use of levothyroxine and interacting medications in U.S. ambulatory care visits.

BACKGROUND: Levothyroxine (LT4) is the third most commonly prescribed medication in the United States. It is a narrow therapeutic index medication, and thus can be impacted by drug-drug interactions, which are primarily available over-the-counter. The prevalence and associated factors with concomitant interacting drugs with LT4 is limited since over-the-counter products are not routinely captured in many drug databases. OBJECTIVE: This study aimed to characterize the concomitant use of LT4 with interacting drugs at ambulatory care visits in the United States. DESIGN: A cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) from 2006 to 2018 was completed. SETTING AND PARTICIPANTS: Ambulatory care visits in the United States involving adult patients with a LT4 prescription were included in the analysis. OUTCOME MEASURES: The primary outcome was initiation or continuation of a selected concomitant interacting drug which impacts LT4 absorption (e.g., proton pump inhibitor) in a patient visit in conjunction with LT4. RESULTS: The authors analyzed 372,942,000 visits (weighted from a sample of 14,880) with a reported LT4 prescription. Concomitant use of interacting drugs with LT4 occurred in 24.4% of visits in which 80% of interacting drugs were proton pump inhibitors. Ages 35-49 years (adjusted odds ratio [aOR], 1.59), 50-64 years (aOR, 2.27), and ≥65 years (aOR, 2.87) compared to 18-34 years, female (aOR 1.37) versus males, and visits in 2014 or later (aOR, 1.27) versus 2006-2009 were associated with increased odds of concomitant interacting drug use in multivariable analysis. CONCLUSION: At ambulatory care visits between 2006 and 2018, concomitant use of LT4 and interacting drugs impacted one-quarter of patient visits. Increased age, females, and visits later in the study period were associated with increased odds for concomitant interacting drugs. Additional work is needed to identify downstream consequences of concomitant use.

Thyroid Cancer Risk Communication in Patients with Thyroid Nodules.

The objective of this study is to evaluate thyroid cancer risk clinician-patient communication among patients receiving usual counseling and counseling enhanced by a conversation aid. A secondary analysis of clinical visit recordings and post-visit surveys obtained during a trial assessing the impact of a conversation aid for patients with thyroid nodules was conducted. We assessed how thyroid cancer risk was communicated, different risk communication strategies between groups, and predictors of accurate cancer risk perception. Fifty-nine patients were analyzed. Most were women (90%) and middle-aged (median 57 years). A verbal description of thyroid cancer risk was present most frequently (83%) and was more frequent in the conversation aid than the usual care group (100% vs. 63%, p < 0.001). A numerical description using percentages was present in 41% of visits and was more frequent in the conversation aid group (59% vs. 19%, p = 0.012). Natural frequencies (7%) and positive/negative framing (10%) were utilized less commonly. Uncertainty about risks was not discussed. No predictors of accurate risk perception were identified. Clinicians most commonly present a verbal description of thyroid cancer risk. Less commonly, natural frequencies, negative/positive framing, or uncertainty is discussed. Clinicians caring for patients with thyroid nodules should be aware of different strategies for communicating thyroid cancer risk.

Development and pilot testing of a conversation aid to support the evaluation of patients with thyroid nodules.

OBJECTIVE: To support patient-centred care and the collaboration of patients and clinicians, we developed and pilot tested a conversation aid for patients with thyroid nodules. DESIGN, PATIENT AND MEASUREMENTS: We developed a web-based Thyroid NOdule Conversation aid (TNOC) following a human-centred design. A proof of concept observational pre-post study was conducted (TNOC vs. usual care [UC]) to assess the impact of TNOC on the quality of conversations. Data sources included recordings of clinical visits, post-encounter surveys and review of electronic health records. Summary statistics and group comparisons are reported. RESULTS: Sixty-five patients were analysed (32 in the UC and 33 in the TNOC cohort). Most patients were women (89%) with a median age of 57 years and were incidentally found to have a thyroid nodule (62%). Most thyroid nodules were at low risk for thyroid cancer (71%) and the median size was 1.4 cm. At baseline, the groups were similar except for higher numeracy in the TNOC cohort. The use of TNOC was associated with increased involvement of patients in the decision-making process, clinician satisfaction and discussion of relevant topics for decision making. In addition, decreased decisional conflict and fewer thyroid biopsies as the next management step were noted in the TNOC cohort. No differences in terms of knowledge transfer, length of consultation, thyroid cancer risk perception or concern for thyroid cancer diagnosis were found. CONCLUSION: In this pilot observational study, using TNOC in clinical practice was feasible and seemed to help the collaboration of patients and clinicians.

Ultrasound Image Classification of Thyroid Nodules Using Machine Learning Techniques.

Background and Objectives: Thyroid nodules are lumps of solid or liquid-filled tumors that form inside the thyroid gland, which can be malignant or benign. Our aim was to test whether the described features of the Thyroid Imaging Reporting and Data System (TI-RADS) could improve radiologists' decision making when integrated into a computer system. In this study, we developed a computer-aided diagnosis system integrated into multiple-instance learning (MIL) that would focus on benign-malignant classification. Data were available from the Universidad Nacional de Colombia. Materials and Methods: There were 99 cases (33 Benign and 66 malignant). In this study, the median filter and image binarization were used for image pre-processing and segmentation. The grey level co-occurrence matrix (GLCM) was used to extract seven ultrasound image features. These data were divided into 87% training and 13% validation sets. We compared the support vector machine (SVM) and artificial neural network (ANN) classification algorithms based on their accuracy score, sensitivity, and specificity. The outcome measure was whether the thyroid nodule was benign or malignant. We also developed a graphic user interface (GUI) to display the image features that would help radiologists with decision making. Results: ANN and SVM achieved an accuracy of 75% and 96% respectively. SVM outperformed all the other models on all performance metrics, achieving higher accuracy, sensitivity, and specificity score. Conclusions: Our study suggests promising results from MIL in thyroid cancer detection. Further testing with external data is required before our classification model can be employed in practice.

Management of Hypothyroidism in Patients with Acute Myocardial Infarction.

Background and Objectives: Thyroid hormones (TH) affect cardiac function through effects on cardiac contractility and systemic vascular resistance. While TH replacement for patients with hypothyroidism might be necessary for restoration of cardiac output after an acute myocardial infarction (AMI), it could theoretically lead to excessively rapid restoration of the metabolic rate. The appropriate management of hypothyroidism in patients with AMI is unknown. We describe the practice patterns in the management of hypothyroidism in the setting of AMI as well as patients' clinical outcomes. Material and Methods: Retrospective study of patients that were admitted to a tertiary care hospital with AMI and newly diagnosed or uncontrolled hypothyroidism (TSH ≥ 10 mIU/L) between 2011-2018. Eligible patients were identified using diagnosis codes for AMI and laboratory values, followed by medical record review. We categorized patients according to treatment status with TH and by degree of hypothyroidism. Clinical outcomes included: 30-day mortality/readmission, bleeding, stroke, arrhythmia, sudden cardiac death, and new or worsening heart failure. Summary statistics and group comparisons are presented. Results: Sixty-four patients were included, their median age was 64 years and 61% (n = 39) were women. Most of the patients (59%) had a documented history of hypothyroidism. Of these, all were restarted on levothyroxine (LT4) during the index admission when compared to patients without a history of hypothyroidism, of which 54% received LT4 treatment (p = 0.001). The median TSH in those treated with LT4 was higher (25 mIU/L) when compared to those who were not (12 mIU/L), (p = 0.007). Patients who received intravenous LT4 had higher TSH levels and other variables suggesting worse clinical presentation, but these differences were not statistically significant. No statistically significant differences were noted on clinical outcomes according to LT4 treatment status. Conclusion: A history of hypothyroidism and the degree of TSH elevation seem to guide the management of hypothyroidism in patients with AMI. The clinical effect of correcting hypothyroidism in this setting requires further evaluation.

Patient Experiences and Perceptions Associated with the Use of Desiccated Thyroid Extract.

Background and objectives: It is unclear why many patients with hypothyroidism prefer the use of desiccated thyroid extract (DTE) as a thyroid hormone replacement formulation over levothyroxine (LT4) treatment, as recommended by clinical practice guidelines. We analyzed patient-reported information from patient online forums to better understand patient preferences for and attitudes toward the use of DTE to treat hypothyroidism. Materials and Methods: We conducted a mixed-methods study by evaluating the content of online posts from three popular hypothyroidism forums from patients currently taking DTE (n = 673). From these posts, we extracted descriptive information on patient demographics and clinical characteristics and qualitatively analyzed posts' content to explore patient perceptions on DTE and other therapies further. Results: Nearly half (46%) of the patients reported that a clinician initially drove their interest in trying DTE. Patients described many reasons for switching from a previous therapeutic approach to DTE, including lack of improvement in hypothyroidism-related symptoms (58%) and the development of side effects (22%). The majority of patients described DTE as moderately to majorly effective overall (81%) and more effective than the previous therapy (77%). The most frequently described benefits associated with DTE use were an improvement in symptoms (56%) and a change in overall well-being (34%). One-fifth of patients described side effects related to the use of DTE. Qualitative analysis of posts' content supported these findings and raised additional issues around the need for individualizing therapy approaches for hypothyroidism (e.g., a sense of each patient has different needs), as well as difficulties obtaining DTE (e.g., issues with pharmacy availability). Conclusions: Lack of individualized treatment and a feeling of not been listened to were recurrent themes among DTE users. A subset of patients may prefer DTE to LT4 for many reasons, including perceived better effectiveness and improved overall well-being, despite the risks associated with DTE.

Eliciting the Patient's Agenda- Secondary Analysis of Recorded Clinical Encounters.

BACKGROUND: Eliciting patient concerns and listening carefully to them contributes to patient-centered care. Yet, clinicians often fail to elicit the patient's agenda and, when they do, they interrupt the patient's discourse. OBJECTIVE: We aimed to describe the extent to which patients' concerns are elicited across different clinical settings and how shared decision-making tools impact agenda elicitation. DESIGN AND PARTICIPANTS: We performed a secondary analysis of a random sample of 112 clinical encounters recorded during trials testing the efficacy of shared decision-making tools. MAIN MEASURES: Two reviewers, working independently, characterized the elicitation of the patient agenda and the time to interruption or to complete statement; we analyzed the distribution of agenda elicitation according to setting and use of shared decision-making tools. KEY RESULTS: Clinicians elicited the patient's agenda in 40 of 112 (36%) encounters. Agendas were elicited more often in primary care (30/61 encounters, 49%) than in specialty care (10/51 encounters, 20%); p = .058. Shared decision-making tools did not affect the likelihood of eliciting the patient's agenda (34 vs. 37% in encounters with and without these tools; p = .09). In 27 of the 40 (67%) encounters in which clinicians elicited patient concerns, the clinician interrupted the patient after a median of 11 seconds (interquartile range 7-22; range 3 to 234 s). Uninterrupted patients took a median of 6 s (interquartile range 3-19; range 2 to 108 s) to state their concern. CONCLUSIONS: Clinicians seldom elicit the patient's agenda; when they do, they interrupt patients sooner than previously reported. Physicians in specialty care elicited the patient's agenda less often compared to physicians in primary care. Failure to elicit the patient's agenda reduces the chance that clinicians will orient the priorities of a clinical encounter toward specific aspects that matter to each patient.

Reflecting on shared decision making: A reflection-quantification study.

BACKGROUND: Reflecting ("stop-and-think") before rating may help patients consider the quality of shared decision making (SDM) and mitigate ceiling/halo effects that limit the performance of self-reported SDM measures. METHODS: We asked a diverse patient sample from the United States to reflect on their care before completing the 3-item CollaboRATE SDM measure. Study 1 focused on rephrasing CollaboRATE items to promote reflection before each item. Study 2 used 5 open-ended questions (about what went well and what could be improved upon, signs that the clinician understood the patient's situation, how the situation will be addressed, and why this treatment plan makes sense) to invite reflection before using the whole scale. A linear analogue scale assessed the extent to which the plan of care made sense to the patient. RESULTS: In Study 1, 107 participants completed surveys (84% response rate), 43 (40%) rated a clinical decision of which 27 (63%) after responding to reflection questions. Adding reflection lowered CollaboRATE scores ("less" SDM) and reduced the proportion of patients giving maximum (ceiling) scores (not statistically significant). In Study 2, 103 of 212 responders (49%) fully completed the version containing reflection questions. Reflection did not significantly change the distribution of CollaboRATE scores or of top scores. Participants indicated high scores on the sense of their care plan (mean 9.7 out of 10, SD 0.79). This rating was weakly correlated with total CollaboRATE scores (rho = .4, P = .0001). CONCLUSION: Reflection-before-quantification interventions may not improve the performance of patient-reported measures of SDM with substantial ceiling/halo effects.

Effects of increasing levothyroxine on pregnancy outcomes in women with uncontrolled hypothyroidism.

OBJECTIVE: Uncontrolled hypothyroidism has been associated with an increased risk of adverse pregnancy outcomes. We aimed to assess the effectiveness of increasing levothyroxine (LT4) dose on reducing the risk of adverse outcomes for pregnant women with TSH level greater than the recommended 1st trimester limit. DESIGN, PATIENTS, MEASUREMENTS: We reviewed the electronic medical records of pregnant women evaluated from January 2011 to December 2013, who had history of LT4-treated hypothyroidism and were found to have TSH > 2·5 mIU/l in 1st trimester. Women were divided into two groups: group A - LT4 dose was increased within two weeks from the TSH test, group B - LT4 dose remained stable. We compared the frequency of pregnancy loss (primary outcome) and other prespecified pregnancy-related adverse outcomes between groups. RESULTS: There were 85 women in group A (median TSH: 5·0, interquartile range 3·8-6·8 mIU/l) and 11 women in group B (median TSH: 4·5, interquartile range 3·2-4·9 mIU/l). The groups were not different in baseline clinical and socioeconomic characteristics. The mean interval between TSH test and LT4 dose increase was 4·5 (SD 4·6) days. Pregnancy loss was significantly lower in group A (2/85, 2·4%) vs group B (4/11, 36·4%) (P = 0·001). Other pregnancy-related adverse outcomes were similar between groups. CONCLUSIONS: Increasing LT4 dose for women with uncontrolled hypothyroidism in the 1st trimester of pregnancy was associated with a decreased risk of pregnancy loss. Given the limitations of our study, this association awaits further confirmation from larger studies.

When and how should patients with multiple endocrine neoplasia type 1 be screened for thymic and bronchial carcinoid tumours?

Patients with multiple endocrine neoplasia type 1 (MEN1) are commonly evaluated for clinical manifestations of this syndrome with the rationale that early diagnosis and adequate treatment will result in improved survival and quality of life. Thymic and bronchial carcinoid tumours are uncommon but important manifestations of MEN1. Current practice guidelines recommend evaluation with computed tomography or magnetic resonance imaging scan of the chest every 1-2 years to detect these neoplasms. However, the certainty that patients will be better off (increased survival or quality of life) as a result of this case detection strategy is based on evidence at moderate-high risk of bias that yields only imprecise results of indirect relevance to these patients. In order to improve the care that patients with MEN1 receive, co-ordinated efforts from different stakeholders are required so that large, prospective, multicentre studies evaluating patient important outcomes are carried out.

Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 - case report and review of the literature.

OBJECTIVE: To report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature. BACKGROUND: Primary hyperparathyroidism (PHP) is the most common manifestation of MEN1. The occurrence of PC in patients with MEN1 is rare and the literature regarding the clinical manifestations - including the prevalence of the disease - is scarce. CONTEXT: Single tertiary care centre experience from 1977 to 2013. DESIGN: Electronic search of the medical records to identify a cohort of patients with MEN1. Literature review based on current case reports. PATIENTS: Single case of PC in a cohort of 348 patients with MEN1. Ten cases of PC in patients with MEN1 reported in the literature. MEASUREMENT: Clinical features of PC in patients with MEN1. RESULTS: The prevalence of PC in 348 patients with MEN1 was found to be 0·28% (95% CI, 0-1·4%). Based on the current published cases of PC in patients with MEN1, 54·5% were women, mean age at diagnosis was 48·3 years, and the serum PTH concentrations at least four times the upper limit of the reference range in 73% of the cases. CONCLUSION: PC in patients with MEN 1 is rare with a prevalence of 0·28%, and the clinical features are similar to PC in patients without MEN1.

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.

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.

Is the endocrine research pipeline broken? A systematic evaluation of the Endocrine Society clinical practice guidelines and trial registration.

BACKGROUND: Very low quality (VLQ) evidence translates into very low confidence in the balance of risk and benefits based on the estimates drawn from the body of evidence. Consequently, this assessment highlights gaps in the research evidence, i.e. knowledge gaps, for important clinical questions. In this way, expert guideline panels identify priority knowledge gaps that, arguably, should inform the research agenda and prioritize scarce research economical resources. The extent to which the research agenda reflects the knowledge gaps identified in clinical practice guidelines is unknown. METHODS: A systematic evaluation of the Endocrine Society (ES) clinical practice guidelines portfolio from 2008 to 2014 was conducted with the objectives to identify (1) recommendations in the ES clinical practice guidelines based on VLQ evidence reflecting knowledge gaps in endocrinology, and (2) active research designed to address these gaps by searching the clinical trial registry, clinicaltrials.gov, using terms describing patients (diseases), interventions, comparison, and outcomes. RESULTS: In 25 ES guidelines, we found 660 recommendations, of which 131 (20 %) were supported by VLQ evidence. Clinical trialists are attempting to answer 28 (21 %) of these knowledge gaps by performing 69 clinical trials. CONCLUSION: The research enterprise is addressing one in five knowledge gaps identified in clinical practice recommendations in endocrinology. These findings suggest an inefficiency in the allocation of very scarce research economical resources. Linking the research agenda to evidence gaps in clinical practice guidelines may improve both the efficiency of the research enterprise and the translation of evidence into more confident clinical practice.