Francesco Lapi

Inhaled corticosteroids in COPD and the risk of serious pneumonia.

Background Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use. Methods We formed a new-user cohort of patients with COPD treated during 1990–2005. Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia. A nested case–control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity. Results The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year). Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75). The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17). The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26). Conclusions ICS use by patients with COPD increases the risk of serious pneumonia. The risk is particularly elevated and dose related with fluticasone. While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials.

Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study.

Objectives To assess whether a double therapy combination consisting of diuretics, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers with addition of non-steroidal anti-inflammatory drugs (NSAIDs) and the triple therapy combination of two of the aforementioned antihypertensive drugs to which NSAIDs are added are associated with an increased risk of acute kidney injury. Design Retrospective cohort study using nested case-control analysis. Setting General practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. Participants A cohort of 487 372 users of antihypertensive drugs. Main outcome measures Rate ratios with 95% confidence intervals of acute kidney injury associated with current use of double and triple therapy combinations of antihypertensive drugs with NSAIDs. Results During a mean follow-up of 5.9 (SD 3.4) years, 2215 cases of acute kidney injury were identified (incidence rate 7/10 000 person years). Overall, current use of a double therapy combination containing either diuretics or angiotensin converting enzyme inhibitors or angiotensin receptor blockers with NSAIDs was not associated with an increased rate of acute kidney injury. In contrast, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). In secondary analyses, the highest risk was observed in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46). Conclusions A triple therapy combination consisting of diuretics with angiotensin converting enzyme inhibitors or angiotensin receptor blockers and NSAIDs was associated with an increased risk of acute kidney injury. The risk was greatest at the start of treatment. Although antihypertensive drugs have cardiovascular benefits, vigilance may be warranted when they are used concurrently with NSAIDs.

Androgen Deprivation Therapy and Risk of Acute Kidney Injury in Patients With Prostate Cancer

IMPORTANCE The use of androgen deprivation therapy (ADT) in the treatment of advanced prostate cancer has been shown to delay the clinical progression of the disease. However, the testosterone suppression associated with this therapy may lead to a hypogonadal condition that can have detrimental effects on renal function, thus raising the hypothesis that ADT-induced hypogonadism could potentially lead to acute kidney injury (AKI). OBJECTIVE To determine whether the use of ADT is associated with an increased risk of AKI in patients newly diagnosed with prostate cancer. DESIGN AND SETTING A nested case-control analysis using medical information extracted from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. PARTICIPANTS Men newly diagnosed with nonmetastatic prostate cancer between January 1, 1997, and December 31, 2008, were selected and followed up until December 31, 2009. Cases were patients with incident AKI during follow-up who were randomly matched with up to 20 controls on age, calendar year of prostate cancer diagnosis, and duration of follow-up. MAIN OUTCOMES AND MEASURES Conditional logistic regression was used to estimate odds ratios (ORs) with 95% CIs of AKI associated with the use of ADT. ADT was categorized into 1 of 6 mutually exclusive groups: gonadotropin-releasing hormone agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, estrogens, and combination of the above. RESULTS A total of 10,250 patients met the study inclusion criteria. During a mean follow-up of 4.1 (SD, 2.9) years, 232 incident cases of AKI were identified (rate, 5.5/1000 person-years). Overall, current use of any ADT was associated with an increased risk of AKI when compared with never use (OR, 2.48 [95% CI, 1.61-3.82]), generating a rate difference of 4.43/1000 persons per year (95% CI, 1.54-7.33). This association was mainly driven by a combined androgen blockade consisting of gonadotropin-releasing hormone agonists with oral antiandrogens (OR, 4.50 [95% CI, 2.61-7.78]), estrogens (OR, 4.00 [95% CI, 1.06-15.03]), other combination therapies (OR, 4.04 [95% CI, 1.88-8.69]), and gonadotropin-releasing hormone agonists (OR, 1.93 [95% CI, 1.20-3.10]). CONCLUSIONS AND RELEVANCE In a cohort of patients with newly diagnosed nonmetastatic prostate cancer, the use of ADT was significantly associated with an increased risk of AKI. These findings require replication in other well-designed studies as well as further investigation of their clinical importance.

The use of inhaled corticosteroids and the risk of adrenal insufficiency

Adrenal insufficiency is a potential complication of therapy with an inhaled corticosteroid (ICS). Although prior studies found the highest risk of adrenal insufficiency with fluticasone, a more potent ICS, these results might be explained by a channelling bias and concomitant exposure to oral corticosteroids. We re-examined the relationship between the use of ICSs and adrenal insufficiency by using a cohort of patients treated for respiratory conditions during 1990–2005, identified in the healthcare databases from the province of Quebec, Canada, with follow-up until 2007. A nested case–control analysis was performed within this cohort. Cases of adrenal insufficiency were matched with up to 10 controls. 392 cases were identified (incidence rate 1.1 per 10 000 person-years). Although the rate of adrenal insufficiency was not significantly higher among all current users of ICSs, patients receiving the highest dosages showed a greater risk (OR 1.84, 95% CI 1.16–2.90). Consistently, an increased risk was estimated for the highest tertile of ICS dose (OR 1.90, 95% CI 1.07–3.37) cumulated in the year before the event. ICS at high doses appear to be a significant independent risk factor for adrenal insufficiency. Physicians prescribing ICS at such dosages should be sensitive to the signs and symptoms of adrenal insufficiency in their patients.

Use of antidepressant serotoninergic medications and cardiac valvulopathy: a nested case-control study in the health improvement network (THIN) database

AIMS To quantify the risk of cardiac valvulopathy (CV) associated with the use of antidepressant serotoninergic medications (SMs). METHODS We conducted a case-control study nested in a cohort of users of antidepressant SMs selected from The Health Improvement Network database. Patients who experienced a CV event during follow-up were cases. Cases were ascertained in a random sample of them. Up to 10 controls were matched to each case by sex, age, month and year of the study entry. Use of antidepressant SMs during follow-up was defined as current (the last prescription for antidepressant SMs occurred in the 2 months before the CV event), recent (in the 2-12 months before the CV event) and past (>12 months before the CV event). We fitted a conditional regression model to estimate the association between use of antidepressant SMs and the risk of CV by means of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Sensitivity analyses were conducted to test the robustness of our results. RESULTS The study cohort included 752,945 subjects aged 18-89 years. Throughout follow-up, 1663 cases (incidence rate: 3.4 per 10,000 person-years) of CV were detected and were matched to 16,566 controls. The adjusted OR (95% CI) for current and recent users compared with past users of antidepressant SMs were 1.16 (0.96-1.40) and 1.06 (0.93-1.22), respectively. Consistent effect estimates were obtained when considering cumulative exposure to antidepressant SMs during follow-up. CONCLUSIONS These results would suggest that exposure to antidepressant SMs is not associated with an increased risk of CV.

Risk of severe upper gastrointestinal complications among oral bisphosphonate users.

Background Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed. Aim To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases. Methods A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty. Results The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations. Conclusions No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.

Vivere il lutto nella professione assistenziale. Sequele post-traumatiche e rischio di burn-out negli operatori sanitari

La morte durante la gravidanza o dopo il parto e un evento profondamente stressante, che puo compromettere l’equilibrio psichico della madre e della coppia genitoriale, e associarsi a disturbi psichici di lunga durata. L’assistenza ai genitori colpiti da lutto puo essere estremamente stressante anche per l’operatore, che molto spesso e impreparato nell’affrontare una gravidanza che si conclude con la morte del bambino. Spesso i genitori percepiscono la mancanza di assistenza psicologica come un trauma aggiuntivo alla perdita, ed i caregivers rivestono un importante ruolo nel determinare la qualita del percorso di elaborazione del lutto. L’associazione CiaoLapo ONLUS fornisce dal 2006 supporto psicologico ai genitori in lutto e promuove formazione e ricerca sui genitori e sugli operatori nel campo del lutto perinatale. In questo articolo sono presentati i risultati preliminari di uno studio condotto nell’Area Vasta di Firenze. Lo studio si e svolto in due fasi; una prima fase ha visto coinvolti 60 operatori dell’area materno-infantile e successivamente sono state arruolate 100 ostetriche della ASL 10 di Firenze. L’obiettivo era quello di approfondire l’impatto traumatico della morte intrauterina con particolare attenzione alla relazione tra esperienze professionali traumatiche (misurate con l’Impact of Event Scale IES) e sviluppo di sindrome da burn-out (misurata con la Maslach Burn-Out Inventory - MBI). I punteggi di entrambi i test sono risultati significativamente piu alti nelle ostetriche rispetto alle altre categorie professionali. Le ostetriche sembrano dunque piu esposte all’impatto traumatico della morte intrauterina rispetto agli altri colleghi coinvolti nella gestione della coppia affetta da morte in utero, e dovrebbero potersi avvalere di una formazione specifica sul lutto e di un supporto psicologico quando necessario.