Subacute thyroiditis and COVID-19 vaccines: a case/non-case study.

PURPOSE: Some case reports have suggested a possible association between COVID-19 vaccines and subacute thyroiditis (SAT), however, to our knowledge, no study has analyzed this possible relationship. This study aimed to analyze whether a disproportionate number of cases of SAT were reported in the EudraVigilance database for four COVID-19 vaccines (BNT162b2, mRNA-1273 ChAdOx1-S or Ad26.COV2.S). METHODS: A case/non-case study was conducted to assess the association between SAT and COVID-19 vaccines, calculating the reporting odds ratios (RORs) up to December 2, 2021. Cases were selected using the preferred term 'subacute thyroiditis'. First, cases involving COVID-19 vaccines were compared with those involving all other drugs. Secondly, the RORs for COVID-19 vaccines compared with other viral vaccines (overall and influenza vaccines only) were obtained. RESULTS: Until December 2, 2021, of 1,221,582 spontaneous cases of adverse reactions with the four vaccines, we found 162 SAT cases: BNT162b2 (n = 103), mRNA-1273 (n = 27), ChAdOx1-S (n = 31) and Ad26.COV2.S (n = 1). SAT cases were found to be reported more frequently in association with BNT162b2, mRNA-1273, and ChAdOx1-S vaccines than with other drugs. Moreover, we found a signal of disproportionate reporting for SAT with BNT162b2 and mRNA-1273 vaccines comparing with other viral vaccines (BNT162b2 ROR 3.58, 95% CI 1.92-6.66; mRNA-1273 ROR 3.44, 95% CI 1.71-6.94). However, this association was absent when these COVID-19 vaccines were compared with influenza vaccines. CONCLUSIONS: In EudraVigilance, SAT is relatively more frequently reported in association with mRNA COVID-19 vaccines than with other viral vaccines. Well designed observational studies are needed to confirm these results.

SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database.

The association between sodium-glucose cotransporter 2 inhibitors (SGLT2is) and cancer risk is unclear. The objective of this study was to analyze whether a disproportionate number of cases of bladder cancer are reported for SGLT2is in EudraVigilance. A case/noncase study was conducted to assess the association between bladder cancer and SGLT2is, calculating reporting odds ratios (RORs) from November 11, 2012 (approval date for the first SGLT2i, dapagliflozin) to May 19, 2020. First, cases involving SGLT2is were compared with those involving all other drugs; and similar analysis was performed for each SGLT2i. Second, to reduce the risk of confounding by indication, the RORs for SGLT2is compared with other antidiabetics were obtained. Besides, 2 measures were taken to evaluate a possible notoriety bias: a sensitivity analysis excluding pioglitazone was performed and the evolution of the ROR over time for SGLT2is was measured. There were 6602 cases of bladder cancer in the 4,213,637 reports during the study period. SGLT2is were involved in 155 cases. The ROR for pooled SGLT2is was 3.97 (95% confidence interval [CI], 3.39-4.66), disproportionality also being observed for each SGLT2i separately. The association was strongest for dapagliflozin (ROR, 7.02; 95%CI, 5.69-8.66). Nonetheless, this association disappeared when comparing SGLT2is with other antidiabetic drugs (ROR, 0.20; 95%CI, 0.17-0.24). But when excluding pioglitazone from the analysis, a safety signal for SGLT2is compared with other antidiabetics emerged (ROR, 6.84; 95%CI 5.41-8.65). Our study found a disproportionately high number of cases of bladder cancer among users of SGLT2is. However, observational analytical studies will be needed to confirm these results.

Food groups, diet quality and colorectal cancer risk in the Basque Country.

BACKGROUND: The results obtained to date concerning food groups, diet quality and colorectal cancer (CRC) risk vary according to criteria used and the study populations. AIM: To study the relationships between food groups, diet quality and CRC risk, in an adult population of the Basque Country (North of Spain). METHODS: This observational study included 308 patients diagnosed with CRC and 308 age- and sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic and health status information was collected. Adherence to the dietary recommendations was evaluated utilizing the Healthy Eating Index for the Spanish Diet and the MedDietScore. Conditional logistic regressions were used to evaluate the associations of food group intakes, diet quality scores, categorized in tertiles, with CRC risk. RESULTS: The adjusted models for potential confounding factors showed a direct association between milk and dairy products consumption, in particular high-fat cheeses [odds ratio (OR) third tertile vs first tertile = 1.87, 95% confidence intervals (CI): 1.11-3.16], and CRC risk. While the consumption of fiber-containing foods, especially whole grains (OR third tertile vs first tertile = 0.62, 95%CI: 0.39-0.98), and fatty fish (OR third tertile vs first tertile = 0.53, 95%CI: 0.27-0.99) was associated with a lower risk for CRC. Moreover, higher MD adherence was associated with a reduced CRC risk in adjusted models (OR third tertile vs first tertile = 0.40, 95%CI: 0.20-0.80). CONCLUSION: Direct associations were found for high-fat cheese, whereas an inverse relation was reported for fiber-containing foods and fatty fish, as well as adherence to a Mediterranean dietary pattern.

Gene-Diet Interactions in Colorectal Cancer: Survey Design, Instruments, Participants and Descriptive Data of a Case-Control Study in the Basque Country.

Epidemiologic studies have revealed inconsistent evidence of gene-diet interaction in relation to colorectal cancer (CRC). The aim of this study was to analyze them in a sample of cases and controls from the population-based bowel cancer screening program of the Osakidetza/Basque Health Service. This study analyzed dietetic, genetic, demographic, socioeconomic factors and lifestyles. In the present manuscript, the survey design, sampling, instruments, measurements and related quality management were presented. Moreover, we analyze differences between cases and controls in some data, especially those related to diet. The participants were 308 cases and 308 age- and sex-matched subjects as controls. Cases were more likely than controls to have overweight/obesity (67.5% vs. 58.1%, p < 0.05), a lower intake of vitamin B2 (0.86 ± 0.23 vs. 0.92 ± 0.23 mg/1000 kcal, p < 0.01) and calcium:phosphorus ratio (0.62 ± 0.12 vs. 0.65 ± 0.13, p < 0.01). A higher proportion of cases than controls did not meet the Nutritional Objectives for saturated fatty acids (85.7% vs. 67.5%, p < 0.001) or cholesterol (35.4% vs. 25.0%, p < 0.01). In conclusion, the present study provides valuable data for analyzing the complexity of gene-diet interaction in relation to CRC. The results presented here suggest that overweight/obesity and a high intake of certain dietary components, especially saturated fatty acids and cholesterol, are more frequent in cases than in controls.

Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population.

Given the significant population diversity in genetic variation, we aimed to investigate whether single nucleotide polymorphisms (SNPs) previously identified in studies of colorectal cancer (CRC) susceptibility were also relevant to the population of the Basque Country (North of Spain). We genotyped 230 CRC cases and 230 healthy controls for 48 previously reported CRC-susceptibility SNPs. Only the rs6687758 in DUPS10 exhibited a statistically significant association with CRC risk based on the crude analysis. The rs6687758 AG genotype conferred about 2.13-fold increased risk for CRC compared to the AA genotype. Moreover, we found significant associations in cases between smoking status, physical activity, and the rs6687758 SNP. The results of a Genetic Risk Score (GRS) showed that the risk alleles were more frequent in cases than controls and the score was associated with CRC in crude analysis. In conclusion, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the GRS was associated with CRC. However, further experimental validations are needed to establish the role of this SNP, the function of the gene identified, as well as the contribution of the interaction between environmental factors and this locusto the risk of CRC.

Antipsychotics and pituitary tumors: an analysis of the European pharmacovigilance database (EudraVigilance).

One of the possible long-term consequences of antipsychotic-induced hyperprolactinemia is the development of pituitary tumors - prolactinomas. So far, two pharmacovigilance studies of spontaneous adverse event report databases have suggested an increased risk, whereas a longitudinal study carried out with risperidone showed no evidence of increased risk of tumors with mass effect. Besides, information on amisulpride and paliperidone is lacking. Thus, in this study, we aimed to analyze the European pharmacovigilance database (EudraVigilance) to shed light on this issue. We searched for all suspected spontaneous cases of pituitary tumors associated with antipsychotics in EudraVigilance up to 23 March 2017. To assess the association between pituitary tumor cases and each antipsychotic, we calculated the proportional reporting ratios. Among 4 964 866 events of all types recorded in EudraVigilance, we found 292 cases of pituitary tumors associated with antipsychotics. All atypical antipsychotics except clozapine fulfilled the criteria to generate a safety signal. The highest proportional reporting ratio values were found for amisulpride 51.57 (36.3-73.2), risperidone 21.83 (18.4-25.8), and paliperidone 19.95 (14.7-27.1). Sulpiride and haloperidol showed a higher risk among typical antipsychotics 12.4 (5.89-26.1) and 7.0 (4.35-11.3). Notably, we found that a mass effect was present in 16% of the cases. Besides, 18 cases occurred in patients aged below 18 years. Our analysis of the data in EudraVigilance confirms the safety signal detected by previous studies. Interestingly, for the first time, we show that the association seems to be the strongest for amisulpride and that a mass effect was present in around 16% of the cases.

Adverse reactions to antipsychotics in Parkinson disease: an analysis of the Spanish pharmacovigilance database.

PURPOSE: Although antipsychotics are well known for causing a plethora of adverse drug reactions (ADRs), the main concern when used to treat psychosis in Parkinson disease (PD) has traditionally been motor function worsening. The limited number of patients included in clinical trials contributes to underreport less common ADR. The aims of this study were to describe ADR to antipsychotics occurring in patients with PD notified to the Spanish Pharmacovigilance System and to contrast them with published reports. METHODS: All notifications from the Spanish Pharmacovigilance System for the last 30 years (1984-2014) where an antipsychotic was considered suspicious of the ADR in patients who were also on dopaminergic therapy were reviewed. In addition, a systematic search of MEDLINE (1966-2014) was conducted with the following Medical Subject Headings (MeSH) terms: "Parkinson disease" and "antipsychotic agents" or "psychotic disorders" and "drug-related side effects" or "adverse reactions." RESULTS: Forty-four notifications were selected for evaluation. Quetiapine was the most frequently implicated drug since 2002, and previously clozapine was the drug implied in higher number of notifications. The most severe ADR was neuroleptic malignant syndrome, which was described in 5 patients (3 cases related to quetiapine, one to haloperidol, and another to olanzapine). CONCLUSIONS: Some previously unreported ADRs caused by antipsychotic drugs in patients with PD have been described for the first time in this study, although there are in general well-known antipsychotic adverse effects. It is remarkable that some notifications involve the use of drugs not recommended in these patients.

Possible interaction between letrozole and long-acting injectable zuclopenthixol.

Mrs A, a 68-year-old woman with paranoid schizophrenia, was on long-term psychiatric treatment with long-acting intramuscular zuclopenthixol, quetiapine and alprazolam when, in April 2012, she was diagnosed with right breast infiltrating ductal carcinoma. After starting treatment with letrozole on 4 July, Mrs A progressively developed extrapyramidal symptoms and these were particularly evident after each zuclopenthixol administration. On 9 January, both quetiapine and alprazolam were stopped due to excessive lethargy. After the administration of the last dose of zuclopenthixol on 26 January, she presented with sedation, sialorrhea, festinant gait, axial dystonia and dysphagia, all of which were severe. The introduction of letrozole was the only change that had been made to her pharmacotherapeutic regimen in that period. The rest of the findings on neurological examination were normal. Renal function was adequate. Slow symptom onset and progressive worsening until full-blown clinical presentation after 6 months, and the dramatic improvement in the clinical picture achieved 2 days after treatment with biperiden, suggests a long-term insidious interaction leading to zuclopenthixol accumulation. To the best of our knowledge, this is the first report of a possible interaction between letrozole and zuclopenthixol. We consider that it warrants further investigation. In the meanwhile, physicians should be aware of the occurrence of this potentially serious drug-drug interaction.

La elaboración de interpretaciones en evaluación clínica / The development of interpretations in clinical evaluation

Este trabajo de revisión teórica tiene como objetivo estudiar las cogniciones interpretativas del evaluador clínico. Se investiga analíticamente la naturaleza y requisitos científicos de las cogniciones y metacogniciones que componen la tarea de interpretar. Se analizan las inferencias de distinto nivel implicadas, sus posibilidades y alcance, así como sus limitaciones, errores y sesgos principales. Finalmente, para orientar la mejora de la calidad de las interpretaciones que ha de efectuar el clínico, se aportan algunas recomendaciones de carácter práctico.

The objective of this theoretical review paper is to study the cognitive interpretations of the clinical evaluator. This study investigates the analytical characteristics and scientific requirements of cognition and metacognition which comprise the task of interpreting. We analyze the inferences of different levels involved, their possibilities and extent, as well as their limitations, errors and biases. Finally, we provide some practical recommendations in an effort to guide and improve the quality of the interpretations made by the clinician.

Eosinophilia associated with bupropion.

CASE (DESCRIPTION): A 48-year-old woman started treatment with bupropion 150 mg once daily for depressive symptoms. After 19 days she presented to her family physician complaining of myalgia and non-productive cough. The physical examination was normal and laboratory investigations showed an eosinophil count of 4.7 × 10(9)/L (0-0.5). The results of a basal test before to bupropion intake were within normal range including eosinophils (0.2 × 10(9)/L). After ruling out other causes of eosinophilia, the physician decided to gradually discontinue bupropion, and a marked decrease in absolute eosinophil count was subsequently observed. CONCLUSION: To the best of our knowledge, this is the third published case of bupropion-related eosinophilia. Although, in light of the case presented, the prevalence of this adverse effect seems to be low, an awareness that bupropion can be a potential cause of eosinophilia may lead to the avoidance of unnecessary diagnostic tests or referral to other specialists.

Selective serotonin reuptake inhibitors and gastrointestinal bleeding: a case-control study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal (GI) bleeding. Given their worldwide use, even small risks account for a large number of cases. This study has been conducted with carefully collected information to further investigate the relationship between SSRIs and upper GI bleeding. METHODS: We conducted a case-control study in hospitals in Spain and in Italy. Cases were patients aged ≥18 years with a primary diagnosis of acute upper GI bleeding diagnosed by endoscopy; three controls were matched by sex, age, date of admission (within 3 months) and hospital among patients who were admitted for elective surgery for non-painful disorders. Exposures to SSRIs, other antidepressants and other drugs were defined as any use of these drugs in the 7 days before the day on which upper gastrointestinal bleeding started (index day). RESULTS: 581 cases of upper GI bleeding and 1358 controls were considered eligible for the study; no differences in age or sex distribution were observed between cases and controls after matching. Overall, 4.0% of the cases and 3.3% of controls used an SSRI antidepressant in the week before the index day. No significant risk of upper GI bleeding was encountered for SSRI antidepressants (adjusted odds ratio, 1.06, 95% CI, 0.57-1.96) or for whichever other grouping of antidepressants. CONCLUSIONS: The results of this case-control study showed no significant increase in upper GI bleeding with SSRIs and provide good evidence that the magnitude of any increase in risk is not greater than 2.

Factors predicting hospital readmissions related to adverse drug reactions.

OBJECTIVE: To analyse the contribution of adverse drug reactions (ADR) to hospital readmissions. METHODS: This was a case-control study in which unscheduled admissions of patients who had been admitted to the hospital during the two previous months were assessed during a 21-month period. The patient was considered a case when the main diagnosis of readmission complied with the World Health Organisation's definition of an ADR. For each case, two controls were selected from those patients that had been admitted for ADR without readmission (n = 177). Information on drugs and other risk factors was obtained from cases by interview and from controls by clinical record review. RESULTS: There were 26,559 unscheduled admissions of which 81 were readmissions associated with ADR (4.5% of the unscheduled readmissions). There were no statistically significant correlations with sex, age or medical history, with the exception of arterial hypertension. The main drug products causing readmission were acenocoumarol (15, 18.5%), antihypertensive-diuretics (14, 17.3%), anticancer drugs (11, 13.6%) and digoxin (seven, 8.6%). In the multivariate logistic analysis, the variables predicting readmission were acenocoumarol [odds ratio (OR) 12.2, 95% confidence interval (CI) 3.8-38.3, P < 0.0001], a record of diabetes mellitus (OR 2.6, 95% CI 1.3-5.5, P < 0.01), the number of drugs taken at the moment of ADR (OR 1.2, 95% CI 1.1-1.4, P < 0.001) and high blood pressure (OR 0.3, 95% CI 0.2-0.6, P < 0.001) even though the latter was a negative predictor, preventing readmission. Of the 81 readmissions associated with ADR, 28 (34.6%) were preventable. CONCLUSION: A medical record of diabetes mellitus, polypharmacy and acenocoumarol treatment were risk factors predicting hospital readmission related to ADR.