Neonatal withdrawal syndrome following in utero exposure to antidepressants: a disproportionality analysis of VigiBase, the WHO spontaneous reporting database.

BACKGROUND: Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs). METHODS: In our case/non-case pharmacovigilance study, based on VigiBase®, the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared. RESULTS: A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45-7.01, IC: 2.07, 95% CI 1.92-2.21). Signals were found for TCAs (10.55, 95% CI 8.02-13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74-7.36) and SSRIs (ROR: 4.68, 95% CI 4.04-5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms (n = 106), irritability/agitation (n = 75), tremor (n = 52) and feeding problems (n = 40). CONCLUSIONS: Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class.

Global Cushing's disease epidemiology: a systematic review and meta-analysis of observational studies.

PURPOSE: Cushing's disease (CD), 70% of endogenous hypercortisolism cases, is a rare disease caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. To date, no systematic reviews and meta-analyses on its global epidemiology have been published. We provide a systematic review and meta-analysis of CD global epidemiology, also evaluating the quality of study reporting for the identified studies. METHODS: MEDLINE and EMBASE databases were searched for studies on CD epidemiology from inception until November 30th, 2020, including original observational studies in English about CD prevalence and/or incidence for well-defined geographic areas. Two reviewers independently extracted data and assessed reporting quality. CD prevalence/incidence pooled estimates were derived from a random-effects meta-analysis. Reporting quality was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases, heterogeneity using the Cochran's Q-test and its derived measure of inconsistency (I2). RESULTS: Thirteen studies were included. The pooled CD prevalence was 2.2 [95% CI 1.1-4.8] per 100,000, while the incidence rate was 0.24 [95% CI 0.15-0.33] per 100,000 person-years. For both parameters, considerable between-studies heterogeneity was found (I2 = 78.8% and 87.8%, respectively). The quality of study reporting was rated as medium for 11 (84.6%) studies and as low for 2 (15.4%). CONCLUSION: Overall, our systematic meta-analysis demonstrated CD epidemiology to be similarly reported across different areas of the world, with some exceptions regarding regional differences or observation period intervals. Keeping into account the methodological differences between each paper, large-scale studies on CD epidemiology are warranted. Setting up national specific registries, based on standardized diagnostic and clinical parameters, with clearly defined selection and analysis criteria, and a strong cooperation between the scientific national societies for endocrinology is crucial to exclude other causes of variability (i.e. geographical differences due to other factors like (epi)genetic changes), and to support public health decision making.

Prognostic Value of 18F-Fluorocholine PET Parameters in Metastatic Castrate-Resistant Prostate Cancer Patients Treated with Docetaxel.

Background and Aim: The availability of new treatments for metastatic castrate-resistant prostate cancer (mCRPC) patients increases the need for reliable biomarkers to help clinicians to choose the better sequence strategy. The aim of the present retrospective and observational work is to investigate the prognostic value of 18F-fluorocholine (18F-FCH) positron emission tomography (PET) parameters in mCRPC. Materials and Methods: Between March 2013 and August 2016, 29 patients with mCRPC were included. They all received three-weekly docetaxel after androgen deprivation therapy, and they underwent 18F-FCH PET/computed tomography (CT) before and after the therapy. Semi-quantitative indices such as maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) with partial volume effect (PVC-SUV) correction, metabolically active tumour volume (MATV), and total lesion activity (TLA) with partial volume effect (PVC-TLA) correction were measured both in pre-treatment and post-treatment 18F-FCH PET/CT scans for each lesion. Whole-body indices were calculated as sum of values measured for each lesion (SSUVmax, SPVC-SUV, SMATV, and STLA). Progression-free survival (PFS) and overall survival (OS) were considered as clinical endpoints. Univariate and multivariate hazard ratios for whole-body 18F-FCH PET indices were performed, and p < 0.05 was considered as significant. Results: Cox regression analysis showed a statistically significant correlation between PFS, SMATV, and STLA. No correlations between OS and 18F-FCH PET parameters were defined probably due to the small sample size. Conclusions: Semi-quantitative indices such as SMATV and STLA at baseline have a prognostic role in patients treated with docetaxel for mCRPC, suggesting a potential role of 18F-FCH PET/CT imaging in clinical decision-making.

PETC/CT with 18F-Choline localizes hyperfunctioning parathyroid adenomas equally well in normocalcemic hyperparathyroidism as in overt hyperparathyroidism.

PURPOSE: Identification of pathologic parathyroid glands in primary hyperparathyroidism, traditionally based on neck ultrasound (US) and/or 99mTc-Sestamibi scintigraphy, can be challenging. PET/CT with 18F-Fluorocholine (18F-FCH) might improve the detection of pathologic parathyroid glands. We aimed at comparing the diagnostic performance of 18F-FCH-PET/CT with that of dual-phase dual-isotope parathyroid scintigraphy and neck US. METHODS: Thirty-four consecutive patients with primary hyperparathyroidism were prospectively enrolled, 7 had normocalcemic hyperparathyroidism, and 27 had classic hypercalcemic hyperparathyroidism. All patients underwent high-resolution neck US, dual-phase dual-isotope 99mTc-Pertechnetate/99mTc-Sestamibi scintigraphy, and 18F-FCH-PET/CT. RESULTS: In the whole patients' group, the detection rates of the abnormal parathyroid gland were 68% for neck US, 71% for 18F-FCH-PET/CT, and only 15% for 99mTc-Sestamibi scintigraphy. The corresponding figures in normocalcemic and hypercalcemic hyperparathyroidism were 57 and 70% for neck US, 70 and 71% for 18F-FCH-PET/CT, and 0 and 18% for 99mTc-Sestamibi scintigraphy, respectively. In the 17 patients in whom the abnormal parathyroid gland was identified, either at surgery or at fine needle aspiration cytology/biochemistry, the correct detection rate was 82% for neck US, 89% for 18F-FCH-PET/CT, and only 17% for 99mTc-Sestamibi scintigraphy. CONCLUSIONS: 18F-FCH-PET/CT can be considered a first-line imaging technique for the identification of pathologic parathyroid glands in patients with normocalcemic and hypercalcemic hyperparathyroidism, even when the parathyroid volume is small.

The economic burden of preventable adverse drug reactions: a systematic review of observational studies.

INTRODUCTION: Adverse drug reactions (ADRs) are an important cause of morbidity and mortality worldwide. They are associated with healthcare costs due to hospital admissions or prolonged length of stay, as well as additional interventions. The aim of this study was to conduct a systematic review of observational studies to evaluate the economic impact of preventable ADRs. AREAS COVERED: Published observational research investigating the cost of preventable ADRs in Western countries (limited to the USA and European countries). EXPERT OPINION: Several reviews have been carried out in the field of the ADR epidemiology but fewer reviews have investigated the economic impact of ADRs, and at the time of writing, none has focused on preventable ADRs. The reason why future research should focus on the costs of preventable ADRs is that both the costs and the negative clinical outcomes are preventable, and as such, are a key point of public health policy action. Nevertheless, the present review highlights an important and sobering limitation of published research on the cost of preventable ADRs, of which the major limitation is the heterogeneity in methods and in reporting which limit what can be known through the summarizing work of a systematic review.

Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-life investigation from Italy.

PURPOSE: The study aimed to fill existing knowledge gaps on the safety of antidepressant drugs (ADs) by estimating the risk of hospitalization for arrhythmia associated with use of selective serotonin reuptake inhibitors (SSRIs) and newer atypical ADs (NAAs) among elderly with previous cardiovascular (CV) events. METHODS: The cohort was composed by 199,569 individuals aged ≥ 65 years from five Italian healthcare territorial units who were discharged for cardiovascular outcomes in the years 2008-2010. The 17,277 patients who experienced hospital admission for arrhythmia during follow-up were included as cases. Odds of current ADs use among cases (i.e., 14 days before hospital admission) was compared with (i) odds of current use of 1:5 matched controls (between-patients case-control) and with (ii) odds of previous use during 1:5 matched control periods (within-patient case-crossover). The risk of arrhythmia associated with ADs current use was modelled fitting a conditional logistic regression. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS: Current users of SSRIs and NAAs were at increased risk of arrhythmia with case-control odds ratios (OR) of 1.37 (95% confidence interval, CI 1.18 to 1.58) and 1.41 (1.16 to 1.71) and case-crossover OR of 1.48 (1.20 to 1.81) and 1.72 (1.31 to 2.27). An increased risk of arrhythmia was associated with current use of trazodone (NAA) consistently in case-control and case-crossover designs. CONCLUSIONS: Evidence that current use of SSRIs and NAAs is associated to an increased risk of arrhythmia among elderly with CV disease was consistently supplied by two observational approaches.

Use of antihistamines and risk of ventricular tachyarrhythmia: a nested case-control study in five European countries from the ARITMO project.

PURPOSE: After regulatory restrictions for terfenadine and astemizole in '90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. METHODS: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997-2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. RESULTS: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6-7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7-7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1-14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1-10.8) and PHARMO (ORadj, 4.6; 1.3-16.2). CONCLUSIONS: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

Adverse drug reactions associated with off-label use of ketorolac, with particular focus on elderly patients. An analysis of the Italian pharmacovigilance database and a population based study.

OBJECTIVE: This study aims to evaluate the frequency of off-label use of ketorolac in Italy and the related suspected adverse drug reactions (ADRs) reported. METHODS: All the suspected cases associated with ketorolac recorded in the Italian Pharmacovigilance database were retrieved. Case evaluations were carried out in order to identify the off-label use of ketorolac. Moreover, an analysis of the inappropriate use of ketorolac was conducted using the 'Arianna' database of Caserta local health unit. RESULTS: Up to December 2014, 822 reports of suspected ADRs related to ketorolac were retrieved in the database. The use of ketorolac was classified as off-label for 553 reports and on-label for 269. Among the off-label cases, 58.6% were serious compared to 39.0% of on-label cases. Gastrointestinal events were more frequently reported with off-label use. The analysis of Arianna database showed that 37,729 out of 61,910 patients, were treated off-label. CONCLUSIONS: The off-label use of ketorolac is widespread in Italy. This use increases the risk of serious ADR, especially in in case of prolonged duration of treatment and in elderly patients. The Italian Medicine Agency has decided to accurately monitor the appropriate use of the drug in Italy and, if necessary, take measures in order to minimize the risks.

Disorders of glucose metabolism in Prader-Willi syndrome: Results of a multicenter Italian cohort study.

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS) is characterized by a high incidence of altered glucose metabolism (AGM). However, epidemiological data on impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) are still discordant. METHODS AND RESULTS: We performed a multicenter study based on 274 PWS patients [144 females, aged 20.3 ± 10.4 yrs (range: 8.1-50.1 years)] evaluating the prevalence for AGM in the entire group, and according to age (children <10 yrs; adolescents 10-18 yrs, and adults >18 yrs), Body Mass Index (BMI = kg/m(2)), gender, genotypes (deletion or uniparental disomy for chromosome 15), and GH therapy (GHT) (untreated, previously or currently treated). Altogether, AGM was detected in 67 (24.4%) of patients (0.7% IFG, 10.2% IGT, 13.5% T2DM). The prevalence of AGM was correlated to age (p = 0.001), BMI (p = 0.001) and HOMA-IR (p = 0.001). However, gender, genotype, and GHT did not influence AGM development in univariate analysis. These data were confirmed as positive predictors when inserted in a multivariate analysis model. CONCLUSION: This study is the first report on the prevalence of AGM in a large population of PWS. Overall, PWS subjects show a high prevalence of AGM that appears more common in obese and adult subjects. Our data confirm the main role of obesity on the individual metabolic risk clustering in PWS, and thus reinforce the concept that improvement in weight control remains the most important goal of any PWS treatment program.

Incretin-based therapy and acute cholecystitis: a review of case reports and EudraVigilance spontaneous adverse drug reaction reporting database.

WHAT IS KNOWN AND OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists delay gastric and bowel emptying. A similar inhibitory effect of GLP-1 on gallbladder motility has been suggested, possibly leading to an increased risk of cholecystitis related to incretin-based medications, which include GLP-1 antagonists. Our objective was to review evidence in EudraVigilance, the European spontaneous reporting database and the scientific literature on this issue. COMMENT: Increasing evidence suggests an association of incretins with gallbladder adverse events. Pharmacovigilance data from EudraVigilance includes 200 serious ADR reports concerning cholecystitis related to the use of incretin-based therapies. Several mechanisms may explain this increased risk of cholecystitis, including rapid weight loss, inhibition of gallbladder contraction and emptying, reduced bile acids production, modulation of inflammation. WHAT IS NEW AND CONCLUSIONS: The available data suggest the possibility of gallbladder disease in diabetic subjects treated with incretins and highlight the importance of evaluating risk factors for cholelithiasis and gallbladder diseases in patients with diabetes before starting this therapy.

Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study.

UNLABELLED: Analyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely ruled out. The observed tendency for decreased valvulopathy risk with cumulative duration of bisphosphonate use >6 months may even indicate a protective effect with prolonged use. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy. INTRODUCTION: A signal of cardiac valve disorders with use of bisphosphonates was identified in the literature and EudraVigilance database, which contains reports of suspected adverse drug reactions from worldwide sources. The aim of this study was to evaluate the association using population-based healthcare data. METHODS: This was a case-control study among users of bisphosphonates and other drugs for osteoporosis in six healthcare databases covering over 30 million individuals in Italy, Netherlands and the UK from 1996 to 2012. Prescriptions/dispensations were used to assess drug exposure. Newly diagnosed cases of cardiac valvulopathy were identified via disease codes/free-text search. Controls were matched to each case by age, sex, database and index date. Adjusted odds ratios (ORs) were estimated using conditional logistic regression for the pooled data and meta-analysis of individual database risk estimates. RESULTS: A small but statistically significant association was found between exposure to bisphosphonates as a class and risk of valvulopathy. Overall risk was 18 % higher (95 % CI 12-23 %) in those currently exposed to any bisphosphonate (mainly alendronate and risedronate) vs. those not exposed within the previous year. Risk of valve regurgitation was 14 % higher (95 % CI 7-22 %). Decreased valvulopathy risk was observed with longer cumulative duration of bisphosphonate use, compared to use of less than 6 months. Meta-analyses of database-specific estimates confirmed results from pooled analyses. CONCLUSIONS: The observed increased risks of cardiac valvulopathy with bisphosphonate use, although statistically significant, were quite small and unlikely to be clinically significant. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy and to investigate possible mechanisms for the association.

Medication is an additional source of phosphate intake in chronic kidney disease patients.

BACKGROUND AND AIMS: Hyperphosphatemia increases the risk of cardiovascular morbidity but the use of medicines as a source of phosphate has not been investigated yet. This study aims to explore the use of absorbable phosphate-containing drugs in CKD patients. METHODS AND RESULTS: Incident CKD patients were identified within the Arianna database (containing data from 158,510 persons in Caserta (Southern Italy) registered with 123 general practitioners) from 2005 to 2011. Drugs prescribed to these patients were classified as phosphate-containing based on the summary of product characteristics (SPC), PubChem and Micromedex. The number and duration of prescriptions for these drugs as well as the overall intake of phosphate were estimated. Out of 1989 CKD patients, 1381 (70%) were prescribed 266 medicinal products containing absorbable phosphate over a median follow-up of 6 years (interquartile range (IQR) = 5.2-6.0). Most patients were prescribed ATC A (650; 47.1%) and C (660; 47.8%) phosphate-containing drug products targeting the gastrointestinal and cardiovascular system for a median of 232 (IQR: 56-656) and 224 (IQR: 56-784) days respectively. CONCLUSIONS: Several medications, especially chronically prescribed ones, contain absorbable phosphate. This study's findings confirm the relevance of medicines as a phosphate source for the first time.

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

UNLABELLED: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. INTRODUCTION: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. METHODS: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out. RESULTS: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). CONCLUSION: In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

Parkinsonism and severe hypothyroidism in an elderly patient: a case of lithium toxicity due to pharmacological interactions.

WHAT IS KNOWN AND OBJECTIVE: Hypothyroidism is a common clinical side effect of lithium treatment, whereas parkinsonism is a very rare adverse event. A number of case series of clinical signs of reversible and permanent parkinsonism due to lithium toxicity have been previously published, but never in association with hypothyroidism. We describe a rare clinical case of concurrent reversible parkinsonism and severe hypothyroidism due to lithium toxicity. CASE SUMMARY: The patient was a 74-year-old woman chronically treated with carbonate lithium (300 mg, twice daily) and clomipramine (75 mg, once daily); she also received valsartan (160 mg) plus hydrochlorothiazide (12·5 mg), once daily. The patient was visited after a 1-week history of progressively worsening and disabling parkinsonism. Laboratory tests showed elevated values of lithium and thyroid stimulating hormone (TSH) serum concentrations as well as reduced circulating thyroid hormone serum concentrations. Lithium treatment was discontinued; treatment with levothyroxine and saline solution i.v. was readily performed, and valsartan plus hydrochlorothiazide were replaced with amlodipine (5 mg, once daily). Within a few days, the patient showed a rapid improvement in overall clinical condition, but complete resolution of neurologic symptoms occurred only after about 5 months. WHAT IS NEW AND CONCLUSION: Lithium toxicity may present with concurrent hypothyroidism and parkinsonism. In the present case, interaction with valsartan and hydrochlorothiazide most likely played an important role. In patients who receive chronic therapy with lithium, prescribers should monitor lithium serum concentration both periodically and immediately at the onset of signs and symptoms, potentially related to lithium toxicity.

Pulmonary sequestration: a (131)I whole body scintigraphy false-positive result.

A 35-year-old woman affected by a well-differentiated papillary thyroid carcinoma was referred to our hospital to perform a (131)Iodine ((131)I) whole body scintigraphy for restaging purpose. The patient had been previously treated with total thyroidectomy and three subsequent doses of (131)I for the ablation of a remnant jugular tissue and a suspected metastatic focus at the superior left hemi-thorax. In spite of the previous treatments with (131)I, planar and tomographic images showed the persistence of an area of increased uptake at the superior left hemi-thorax. This finding prompted the surgical resection of the lesion. Histological examination of the surgical specimen showed the presence of a pulmonary tissue consistent with pulmonary sequestration. Even though rare, pulmonary sequestration should be included in the potential causes of false-positive results of radioiodine scans.

Combining multiple healthcare databases for postmarketing drug and vaccine safety surveillance: why and how?

A growing number of international initiatives (e.g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e.g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives.

Lymphoscintigraphy in clinical routine practice: reproducibility and accuracy in melanoma patients with a long-term follow-up.

INTRODUCTION: The sentinel node status is the most important single factor determining overall survival for patients with localized melanoma. Preoperative lymphoscintigraphy (LS) is essential in locating the correct sentinel lymph node (SN) and the reproducibility of the method determines the accuracy of the sentinel node biopsy (SNB). This study aims at determining the reproducibility and accuracy of LS in routine clinical practice after long-term follow-up. PATIENTS AND METHODS: One hundred and eight melanoma patients with clinically unpredictable lymphatic drainage were prospectively enrolled to undergo two LS. The first LS was performed to determine the site and number of the lymphatic basins to plan SNB anesthesia and the second preoperative LS was to allow SN localization intra-operatively. RESULTS: Lymphatic drainage was demonstrated in all patients. In 84 of 108 cases, both LSs were concordant in terms of site and number of nodal basins visualized. After a median follow-up of 80 months, no nodal recurrence was observed in the five patients with a decreased number of lymph node basins. In the group with increased number of lymph node basins, one patient developed nodal metastases in the same regional lymph node basin visualized by both LS studies. CONCLUSION: LS is an accurate and reproducible method to determine the localization of the sentinel node in the day-to-day routine to clinical practice when primary melanoma is also located in body sites with variable lymphatic drainage.

Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

BACKGROUND: Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA). AIM: To identify whether and in whom either of these strategies should be preferred in daily practice. METHODS: A nested case-control study was conducted using three European primary care databases. We selected a cohort including all naive nsNSAID+GPA (≥80% GPA adherence) and coxib users (without GPA use) aged ≥50 years. Cases with an UGI event (i.e. symptomatic UGI ulcer or bleeding) were matched to cohort members without an UGI event on age, sex and number of individual UGI risk factors (i.e. UGI event history, age ≥65 years, concomitant use of anticoagulants, antiplatelets, or glucocorticoids) and calendar time. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% CI, while adjusting for potential confounders. RESULTS: Within the NSAID cohort (n = 617,220), 398 UGI cases were identified. The risk of UGI events was equivalent for coxib and nsNSAID+GPA (≥80% adherence) users (OR: 1.02; 95%CI: 0.77-1.37). In concurrent glucocorticoid users, the risk of UGI events was significantly elevated for nsNSAID+GPA (≥80% adherence) compared with coxib users (OR: 9.01; 95%CI: 1.61-50.50). CONCLUSIONS: The risk of UGI events was similar in nsNSAID+GPA (≥80% adherence) and coxibs users. In patients concurrently using glucocorticoids, a significant increase in the risk of UGI events for nsNSAID+GPA users was observed and coxibs should be preferred.

Overuse of prescription and OTC non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis and osteoarthritis.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to have significant cardiovascular and gastrointestinal toxicity; high dose of intake and concomitant use of multiple compounds or corticosteroids are factors that increase the risk of NSAID toxicity. In this paper we described our experience on NSAIDs misuse (both prescribing and OTC formulations), particularly relevant in the setting of rheumatoid arthritis (39.5 percent of patients) and osteoarthritis (47 percent of patients). We also evaluated causes underlying NSAIDs misuse (e.g. not satisfactory pain control, other painful conditions, etc).