Cabergoline treatment for surgery-naïve non-functioning pituitary macroadenomas.

PURPOSE: The treatment strategy of non-functioning pituitary adenomas (NFPAs) includes surgery, radiotherapy, medical therapy, or observation without intervention. Cabergoline, a dopaminergic agonist, was suggested for the treatment of NFPA remnants after trans-sphenoidal surgery. This study investigates the efficacy of cabergoline in surgery-naive patients with NFPA. METHODS: Retrospective cohort study including surgery-naive patients with NFPA ≥ 10 mm, treated with cabergoline at a dose of ≥ 1 mg/week for at least 24 months. Patients with chiasmal damage were excluded. Data collected included symptoms, in particular visual disturbances, hormonal levels, tumor characteristics and size evaluated by MRI. Tumor growth was defined as an increase in maximal diameter of ≥ 2 mm, and shrinkage as reduction of ≥ 2 mm. RESULTS: Our cohort included 25 patients treated with cabergoline as primary therapy. Mean age was 63.3 ± 17.3 years, 56% (14/25) were males. Mean tumor size at diagnosis was 18.6 ± 6.3 mm (median 17 mm, range 10-36), and the average follow-up period with cabergoline was 4.6 ± 3.4 years. Out of the 25 tumors, five tumors (20%) decreased in size (mean decrease of 5.0 ± 3.0 mm), 12 tumors (48%) remained stable, and eight (32%) increased in size (mean growth of 5.0 ± 3.3 mm) with cabergoline treatment. During the first two years of cabergoline treatment, the median tumor size exhibited a reduction of 0.5 mm. Patients with an increase in tumor size had larger adenomas at diagnosis and a longer follow-up. Two patients (8%) underwent surgery due to tumor enlargement. CONCLUSION: Primary treatment with cabergoline is a reasonable approach for selected patients with NFPAs without visual threat.

Dynamics of Patient-Based Benefit-Risk Assessment of Medicines in Chronic Diseases: A Systematic Review.

Background: A critical gap exits in understanding the dynamics of patient-based benefit-risk assessment (BRA) of medicines in chronic diseases during the disease journey. Purpose: To systematically review and synthesize current evidence on the changes of patients' preferences about the benefits and risks of medicines during their disease journey including the influence of disease duration and severity, and previous treatment experience. Methods: A systematic review of studies identified in PubMed and Embase, from inception to November 2020, was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Articles were eligible if they analyzed adult patient-based BRA of medicines with a chronic disease, based on at least one of the pre-specified dimensions: disease severity, disease duration, or previous treatment experience. Results: A total of 26,228 articles were identified and 105 were eligible for inclusion. Of these, 85 detected a variation in patient-based BRA of medicines with at least one of the pre-specified criteria. Patients with higher disease severity and more treatment experience have increased risk tolerance. It remains inconclusive whether disease duration directly affects the relative importance of a patient's preference. Conclusion: Factors important for patients' BRA of their medicines during a chronic disease journey vary more with their clinical situation and previous treatment experience than with time since diagnosis. Due to the importance of these factors on patients' perspectives and potential impact on their decision-making and eventually their clinical outcomes, there is a need for more studies to assess the dynamics of patients' BRA in every disease.

Patient-based benefit-risk assessment of medicines: development, refinement, and validation of a content search strategy to retrieve relevant studies.

Introduction: Poor indexing and inconsistent use of terms and keywords may prevent efficient retrieval of studies on the patient-based benefit-risk assessment (BRA) of medicines. We aimed to develop and validate an objectively derived content search strategy containing generic search terms that can be adapted for any search for evidence on patient-based BRA of medicines for any therapeutic area. Methods: We used a robust multistep process to develop and validate the content search strategy: (1) we developed a bank of search terms derived from screening studies on patient-based BRA of medicines in various therapeutic areas, (2) we refined the proposed content search strategy through an iterative process of testing sensitivity and precision of search terms, and (3) we validated the final search strategy in PubMed by firstly using multiple sclerosis as a case condition and secondly computing its relative performance versus a published systematic review on patient-based BRA of medicines in rheumatoid arthritis. Results: We conceptualized a final search strategy to retrieve studies on patient-based BRA containing generic search terms grouped into two domains, namely the patient and the BRA of medicines (sensitivity 84%, specificity 99.4%, precision 20.7%). The relative performance of the content search strategy was 85.7% compared with a search from a published systematic review of patient preferences in the treatment of rheumatoid arthritis. We also developed a more extended filter, with a relative performance of 93.3% when compared with a search from a published systematic review of patient preferences in lung cancer.

True hyperprolactinemia in men without visible pituitary adenoma.

PURPOSE: Men with mild to moderate hyperprolactinemia rarely present with normal pituitary on MRI with no visible adenoma, a condition entitled also "idiopathic hyperprolactinemia" or "non-tumoral hyperprolactinemia". We have characterized a cohort of hyperprolactinemic men with normal pituitary imaging. DESIGN: We have identified 13 men with true hyperprolactinemia and normal pituitary MRI. Baseline clinical and hormonal characteristics and response to medical treatment were retrospectively retrieved from medical records. RESULTS: Mean age at diagnosis was 51 ± 16 years (range, 20-77); mean serum prolactin level at presentation was 91 ng/ml (range, 28-264), eight men presented with low baseline testosterone. Initial complaints leading to diagnosis included sexual dysfunction in ten men and gynecomastia in five. All patients were treated with cabergoline, except for one who was given bromocriptine; none required pituitary surgery. All patients normalized prolactin and testosterone with subsequent clinical improvement reported by most men. Currently, after a mean follow-up of 72 months, ten patients continue treatment with caborgoline (median weekly dose, 0.25 mg), whereas three men discontinued treatment. CONCLUSIONS: Men with symptomatic hyperprolactinemia may rarely present with normal pituitary imaging. Medical treatment can lead to hormonal improvement with clinical benefit.

Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm may be a barrier to use. METHODS: In a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes. RESULTS: There were 1547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling. CONCLUSION: Consumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.

Does the Continuous Performance Test Predict ADHD Symptoms Severity and ADHD Presentation in Adults?

Objective: Our study aimed to provide empirical evidence on the usefulness of one of the most popular neuropsychological tests, the Continuous Performance Test (CPT), as a marker of ADHD severity and presentations among adults. Method: ADHD participants were recruited in a specialized center for the diagnosis and treatment of adults suffering from ADHD (n = 201). Measures included the CPT3™ and ADHD symptoms using a clinical interview and self-reported measures. Results: Only 51.7% of the participants were classified as likely to have a disorder characterized by attention deficit, such as ADHD, by the CPT. The relationships between CPT variables and ADHD symptoms were small. The classification error was 80.3% for the inattentive presentation and 22.5% for the hyperactive presentation when using the CPT to identify ADHD presentations. Conclusion: There was no evidence of the clinical utility of the CPT to assess or monitor ADHD in adult populations diagnosed and treated for ADHD.

Impact of pharmacy-led medication reconciliation on admission to internal medicine service: experience in two tertiary care teaching hospitals.

BACKGROUND: The Institute for Healthcare Improvement identifies medication reconciliation as the shared responsibility of nurses, pharmacists, and physicians, where each has a defined role. The study aims to assess the clinical impact of pharmacy-led medication reconciliation performed on day one of hospital admission to the internal medicine service. METHODS: This is a pilot prospective study conducted at two tertiary care teaching hospitals in Lebanon. Student pharmacists who were properly trained and closely supervised, collected the medication history, and pharmacists at the corresponding sites performed the reconciliation process. Interventions related to the unintended discrepancies were relayed to the medical team. The main outcome was the number of unintended discrepancies identified. The time needed for medication history, and the information sources used to complete the Best Possible Medication History were also assessed. The unintended discrepancies were classified by medication class and route of medication administration, by potential severity, and by proximal cause leading to the discrepancy. For the bivariate and multivariable analysis, the dependent variable was the incidence of unintended discrepancies. The "total number of unintended discrepancies" was dichotomized into yes (≥ 1 unintended discrepancy) or no (0 unintended discrepancies). Independent variables tested for their association with the dependent variable consisted of the following: gender, age, creatinine clearance, number of home medications, allergies, previous adverse drug reactions, and number of information sources used to obtain the BPMH. Results were assumed to be significant when p was < 0.05. RESULTS: During the study period, 204 patients were included, and 195 unintended discrepancies were identified. The most common discrepancies consisted of medication omission (71.8%), and the most common agents involved were dietary supplements (27.7%). Around 36% of the unintended discrepancies were judged as clinically significant, and only 1% were judged as serious. The most common interventions included the addition of a medication (71.8%) and the adjustment of a dose (12.8%). The number of home medications was significantly associated with the occurrence of unintended discrepancies (ORa = 1.11 (1.03-1.19) p = 0.007). CONCLUSIONS: Pharmacy-led medication reconciliation upon admission, along with student pharmacist involvement and physician communication can reduce unintended discrepancies and improve medication safety and patient outcomes.

Hyperprolactinemia diagnosis in elderly men: a cohort of 28 patients over 65 years.

PURPOSE: To characterize a cohort of elderly men with prolactinomas and their response to treatment. METHODS: We have identified 28 elderly men diagnosed after the age of 65 with prolactinomas at seven different endocrine clinics in Israel. A retrospective electronic chart review identified a control group of 76 younger men with macroprolactinomas treated in one of the centers. RESULTS: Mean age at diagnosis was 71.3 ± 5.6 (range 65-86) years, and current age 76.6 ± 7.5 years. Initial complaints leading to diagnosis included sexual dysfunction in 17 males (61%), headaches in two patients (7%), and visual abnormalities in two (7%). Three men presented with osteoporosis. Ten patients (36%) were diagnosed incidentally following brain imaging for unrelated reasons. Seventeen patients (61%) had macroadenoma, while eleven (39%) presented with a microadenoma or no visible adenoma. Mean prolactin (PRL) at presentation was 1594 (median 382; range 50-18,329) ng/ml. Testosterone was low in 21 men. Patients were treated with cabergoline (max dose, 1.1 ± 0.5 mg/week), except for one given bromocriptine; none required pituitary surgery or radiotherapy. Treatment normalized PRL in 24 patients, and in three men PRL suppressed to <2 ULN. Fifteen men normalized testosterone, three improved without normalization, and in three the normal baseline level increased. After a mean follow-up of 5.3 years, 14/15 patients harboring a macroadenoma showed significant adenoma shrinkage. Most patients reported improvement of low libido/erectile dysfunction. In the control group 60 men (79%) achieved PRL normalization. CONCLUSIONS: Elderly men with prolactinomas are diagnosed incidentally in 36% of cases. Long-term medical therapy is successful, achieving biochemical remission, adenoma shrinkage, and clinical improvement in almost all patients.

[CLINICAL CHARACTERISTICS OF MALE PATIENTS WITH OSTEOPOROSIS REFERRED TO THE ENDOCRINE CLINIC OF A TERTIARY HOSPITAL].

INTRODUCTION: Osteoporosis in men is underdiagnosed and undertreated. The prevalence of male osteoporosis increases with age and it becomes a significant public health burden. Currently, there are a few clinical studies on male osteoporosis with limited knowledge of effective therapeutic options. AIMS: Our study aimed to characterize men with osteoporosis in a referral metabolic clinic in Rabin Medical Center at the Beilinson Campus. METHODS: In this study we retrospectively analyzed the medical records of 270 consecutive male patients with osteoporosis diagnosed and treated in our clinic during 2013. RESULTS: A total of 270 of 1940 (14%) patients with osteoporosis in our clinic were males. The mean age of men with osteoporosis was 67.9 ± 13.6; 113 (40%) men suffered from osteoporotic fractures, 57 of them (51%) had vertebral fractures, 28 (25%) had more than one fracture. Osteoporotic fracture was the first presentation of osteoporosis in 82% of men with fractures (age of presentation 62.2 ± 14.5). Furthermore, 141 patients (52%) had vitamin D insufficiency (25OHD levels < 60 nmol/l, normal 75-250 nmol/l), and the mean level was 39.9±12.6 nmol/l. Secondary osteoporosis was identified in 166 (61%) men. The most common etiologies were chronic glucocorticoid treatment (45%), hypogonadism (36%), hypercalciuria (23.4%) and hyperparathyroidism (19%). Most men (223) received bisphosphonates as primary therapy and alendronate was the mostly commonly prescribed agent. CONCLUSIONS: Osteoporosis in men usually remains an underdiagnosed disorder until an osteoporotic fracture occurs. Secondary causes for osteoporosis are commonly encountered, of which glucocorticoid treatment and hypogonadism are the most prevalent etiologies. Increasing awareness of osteoporosis in men may prevent the deleterious consequences of this disabling, yet treatable disease.

Enzalutamide for patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To review and evaluate current literature on the US Food and Drug Administration (FDA)-approved drug enzalutamide (XTANDI(®)) in metastatic castration-resistant prostate cancer. DATA SOURCES: Literature search was done through PubMed using the terms enzalutamide, MDV3100, abiraterone, and castration-resistant prostate cancer. Data from FDA product labels were also used. STUDY SELECTION AND DATA EXTRACTION: Recent and relevant studies were included in the review. Collected clinical trials were screened and evaluated. DATA SYNTHESIS: Enzalutamide is an androgen receptor (AR) inhibitor with high selectivity and affinity to the AR. It was approved by the FDA to treat metastatic castration-resistant prostate cancer in patients previously treated with docetaxel, after a Phase III trial (AFFIRM) that showed a 4.8-month survival benefit in this population. Recently, the FDA expanded the approval of enzalutamide as first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) who did not receive chemotherapy. Moreover, enzalutamide is shown to be associated with an acceptable safety profile. CONCLUSION: Enzalutamide has been shown to be both safe and effective in improving overall survival in metastatic castration-resistant prostate cancer postchemotherapy with docetaxel and as a first line treatment before initiation of chemotherapy. However, additional studies and head-to-head trials are needed.