Inappropriate prescription of allopurinol and febuxostat and risk of adverse events in the elderly: results from the REPOSI registry.

PURPOSE: To investigate the prevalence of xanthine oxidase (XO) inhibitors prescription at admission and discharge in elderly hospital in-patients, to analyze the appropriateness of their use in relation to evidence-based indications, to evaluate the predictors of inappropriate prescription at discharge and the association with adverse events 3 months after hospital discharge. METHODS: This cross-sectional study, based upon a prospective registry, was held in 95 Italian internal medicine and geriatric hospital wards. The sample included 4035 patients aged 65 years or older at admission and 3502 at discharge. The prescription of XO inhibitors was considered appropriate in patients with diagnosis of gout, gout nephropathy, uric acid nephrolithiasis, tophi, and chemotherapy-induced hyperuricemia. In order to evaluate the predictors of inappropriate prescription of XO inhibitors, we compared the characteristics of patients considered inappropriately treated with those appropriately not treated. RESULTS: Among the 4035 patients eligible for the analysis, 467 (11.6 %) were treated with allopurinol or febuxostat at hospital admission and 461 (13.2 %) among 3502 patients discharged. At admission, 39 (8.6 %) of patients receiving XO inhibitors and 43 (9.4 %) at discharge were appropriately treated. Among those inappropriately treated, hyperuricemia, polytherapy, chronic renal failure, diabetes, obesity, ischemic cardiomyopathy, heart failure, and cardiac dysrhythmias were associated with greater prescription of XO inhibitors. Prescription of XO inhibitors was associated with a higher risk of adverse clinical events in univariate and multivariate analysis. CONCLUSIONS: Prevalence of inappropriate prescription of XO inhibitors remained almost the same at admission and discharge. Inappropriate use of these drugs is principally related to treatment of asymptomatic hyperuricemia and various cardiovascular diseases.

Medication non-adherence among elderly patients newly discharged and receiving polypharmacy.

BACKGROUND: Poor adherence may have a major impact on clinical outcome, contributing to substantial worsening of disease, increased health care costs and even death. With increasing numbers of medications, low adherence is a growing concern, seriously undermining the benefits of current medical care. Little is known about medication adherence among older adults living at home and requiring complex medication regimens. OBJECTIVE: The aim of this study was to describe adherence to drug prescriptions in a cohort of elderly patients receiving polypharmacy, discharged from an internal medicine ward. METHODS: A sample of elderly patients (65 years of age or older) discharged from an internal medicine ward in Italy throughout 2012 were enrolled. They were followed for 3 months after discharge with a structured telephone interview to collect information on drug regimens and medication adherence 15-30 days (first follow-up) and 3 months (second follow-up) after discharge. Demographic variables including age, sex, marital status and caregiver were collected. RESULTS: Among 100 patients recruited, information on medication adherence was available for, respectively, 89 and 79 patients at the first and second follow-ups. Non-adherence was reported for 49 patients (55.1 %) at the first follow-up and for 55 (69.6 %) 3 months from discharge. Voluntary withdrawal of a drug and change of dosage without medical consultation were the main reasons for non-adherence at both follow-ups. The number of drugs prescribed at discharge was related to medication non-adherence at both follow-up interviews. No association was found between age and non-adherence. Only 25 patients (28.1 %) at the first follow-up and 20 (25.3 %) at the second understood the reasons for their medications. CONCLUSIONS: Low medication adherence is a real, complex problem for older patients receiving polypharmacy. We found that the increasing number of drugs prescribed at hospital discharge is correlated to non-adherence and a high percentage of patients did not understand the purpose of their medications. Simplification of drug regimens and reduction of pill burdens as well as better explanations of the reason for the medications should be targets for intervention.

[A peculiar lead poisoning: a concern of team achievement]. / Un caso di intossicazione anomala da piombo: l'importanza di un'intervento multidisciplinare.

We describe a case of lead poisoning in a worker after hand and forearm trauma with fracture of radius and multiple fractures of metacarpal bones and hand phalanges and tissue infiltration of lead oxide (PbO) paste. Orthopedic surgery was immediately performed. After 20 days the patient had abdominal colic pain episodes and severe stipsis and blood lead level (BLL) was 60 mcg/mL with urinary lead level (ULL) of 238 mcg/24 h. After mobilization test with calcium disodium edetate were observed a high increase of BLL (180 mcg/dL) and UBL (17,000 mcg/24h). An initial anemia was observed and became severe (Hb 7.6 g/dL). A NMR exam and echography showed forearm subcutaneous lead paste infiltration and the patient underwent to a second surgical debridement with local low temperature (5 degrees C) irrigation of saline and CaNa2EDTA made the removal of the hardened lead paste. The day after, oral succimer (DMSA) chelation treatment was started with recovery of lead poison.

Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults.

Most autoinflammatory disorders typically come out in the pediatric population, although a limited number of patients may experience disease onset during adulthood. To date, a late disease onset has been described only in familial Mediterranean fever, caused by mutations in the MEFV gene, and in tumor necrosis factor receptor-associated periodic syndrome, caused by mutations in the TNFRSF1A gene. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. With the aim of improving the genetic diagnosis in adults with suspected autoinflammatory disorders, we recently identified a set of variables related to the probability of detecting gene mutations in MEFV and TNFRSF1A and, in addition, we have also proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. In the present study we evaluated the preliminary score sensitivity and specificity on a wider number of patients in order to validate the goodness of fit of the model. Two hundred and nineteen consecutive patients with a clinical history of periodic fever attacks were screened for mutations in MEFV and TNFRSF1A genes; detailed information about family/personal history and clinical manifestations were also collected. For the validation of the score we considered data both from the 110 patients used to build the preliminary diagnostic score and from the additional 219 patients enrolled in the present study, for a total number of 329 patients. Early age at disease onset, positive family history for recurrent fever episodes, thoracic pain, abdominal pain and skin rash, which are the variables that had previously been shown to be significantly associated with a positive genetic test result (12), were used for validation. On univariate analysis the associations with a positive genetic test were: age at onset (odds ratio [OR] 0.43, p=0.003), positive family history for recurrent fever episodes (OR 5.81, p<0.001), thoracic pain (OR 3.17, p<0.001), abdominal pain (OR 3.80, p<0.001) and skin rash (OR 1.58, p=0.103). The diagnostic score was calculated using the linear combination of the estimated coefficients of the logistic multivariate model (cut-off equals to 0.24) revealing good sensitivity (0.778) and good specificity (0.718). In conclusion, our score may serve in the diagnostic evaluation of adult patients presenting with recurrent fever episodes suspected of having an autoinflammatory disorder, helping identify the few subjects among them who may be carriers of mutations in MEFV and TNFRSF1A genes.

Diagnostic issues in the clinical management of pericarditis.

AIMS: To review the current major diagnostic issues on the diagnosis of acute and recurrent pericarditis. METHODS: To review the current available evidence, we performed a through search of several evidence-based sources of information, including Cochrane Database of Systematic Reviews, Clinical Evidence, Evidence-based guidelines from National Guidelines Clearinghouse and a comprehensive Medline search with the MeSH terms 'pericarditis', 'etiology' and 'diagnosis'. RESULTS: The diagnosis of pericarditis is based on clinical criteria including symptoms, presence of specific physical findings (rubs), electrocardiographical changes and pericardial effusion. Although the aetiology may be varied, most cases are idiopathic or viral, even after an extensive diagnostic evaluation. In such cases, the course is often benign following anti-inflammatory treatment, and management would be not affected by a more precise diagnostic evaluation. A triage of pericarditis can be safely performed on the basis of the clinical and echocardiographical presentation. Specific diagnostic tests are not warranted if no specific aetiologies are suspected on the basis of the epidemiological background, history and presentation. High-risk features associated with specific aetiologies or complications include: fever > 38 degrees C, subacute onset, large pericardial effusion, cardiac tamponade, lack of response to aspirin or a NSAID. CONCLUSIONS: A targeted diagnostic evaluation is warranted in acute and recurrent pericarditis, with a specific aetiological search to rule out tuberculous, purulent or neoplastic pericarditis, as well as pericarditis related to a systemic disease, in selected patients according to the epidemiological background, presentation and clinical suspicion.

Autoimmune diseases and infections: controversial issues.

The etiology and pathogenesis of certain types of disease remain controversial and stand like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Infection, for example, may initiate a disease, although it is the genetic regulation in the host, the interplay between virus or bacteria persistence and autoimmunity that produces the later phases of disease, the antigenic determinants responsible for inducing autoimmune disease, and the pathogenetic effector mechanisms. Infections agents cause pericarditis, but in 85% of cases it is "idiopathic". It has also been shown that persistent Clamydia pneumoniae, Porphyromonas gingivalis, and Helicobacter pylori infections cause host immunity and promote atherogenesis. A number of infectious agents have been suggested as potential triggers for primary biliary cirrhosis. Infections and vaccinations have also been linked to the pathogenesis of fibromyalgia syndrome, a common, chronic syndrome of widespread pain. Many factors are also responsible for fever of unknown origin such as: infections, autoimmunity disease, etc. However, it is difficult to determine a direct correlation between the infections agents in such a large group of diseases. The aim of this review is to analyze some of the controversies about the role of infections in autoimmune diseases.

Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs.

A consensus paper concerning the interaction of anti-rheumatic drugs and reproduction was published in 2006, representing data collected during the year 2004 and 2005. Because of an increasing use of biological agents in women of fertile age, the information was updated for the years 2006 and 2007. Experts disagree whether TNF-inhibitors should be stopped as soon as pregnancy is recognized or may be continued throughout pregnancy. Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy. LEF has not been proven to be a human teratogen. Registries of transplant recipients have shown that cyclosporin (CsA) and tacrolimus do not increase the rate of congenital anomalies, whereas mycophenolate mofetil (MMF) clearly carries a risk for congenital anomalies. Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. Data remain insufficient for gonadal toxicity of immunosuppressive drugs in men and for excretion of these drugs in human breast milk.

Progesterone supplement in pregnancy: an immunologic therapy?

One of the most interesting functions of the placenta is the regulation of the maternal immune response such that the fetal semi-allograft is tolerated during pregnancy. Trophoblasts are presumed to be essential to this phenomenon because they lie at the maternal-fetal interface, where they are in direct contact with cells of the maternal immune system. Trophoblasts do not express classic major histocompatibility complex (MHC) class II molecules. Surprisingly, cytotrophoblasts express more HLA-G, a MHC class Ib molecule, as they invade the uterus. Progesterone plays an important role in postovulatory regulation of the menstrual cycle. If fertilization occurs, progesterone supports implantation of the ovum and maintains the pregnancy. Progesterone has been named the 'hormone of pregnancy', because in preparing the endometrium for embryo implantation and facilitating endometrial development, it is critical to the very survival of a pregnancy. In addition, this key hormone inhibits the rejection of T cell-mediated tissue and also decreases myometrial activity and sensitivity throughout pregnancy. The cellular actions of progesterone are mediated through intracellular progesterone receptors (PRs), which are well studied gene regulators, not express classic major histocompatibility complex. The more used paradigm is relative to the alteration of relationship TH1/TH2, but the complexity of the respective distributions of cytokines at the materno-fetal interface, strongly suggest that, as useful as it certainly was for a while, the Th1/Th2 paradigm must now be considered as an oversimplification. Rather, the existing data point to sequential windows and are suggestive of a system where an extreme complexity is allied to very precise timing and tuning. They also suggest that the materno-fetal relationship is not simply maternal tolerance of a foreign tissue, but a series of intricate mutual cytokine interactions governing selective immune regulation and also control of the adhesion and vascularization processes during this dialogue. However, as shifting the immune response toward the Th2 pattern (IL-4, IL-5, IL-6) may benefit the fetus, whereas development of proinflammatory Th1 cells (secreting IL-2, IFN g, TNF a) may be harmful. Now we are working to open comprise the precise behaviour of NK populations, with the hope of obtaining a diagnostic test of the condition of abortion from 'immunological causes'.

Anti-mitochondrial type M5 and anti-cardiolipin antibodies in autoimmune disorders: studies on their association and cross-reactivity.

In a series of 42 positive sera, anti-mitochondrial type M5 antibodies (AMA-M5) were found most frequently in patients with SLE (24) and SLE-like syndromes. Patients with AMA-M5 displayed a higher prevalence of thrombocytopenia, thrombosis, biological false positive seroreactions for syphilis, lupus-like anticoagulant activity and anti-cardiolipin antibodies in comparison with a group of 43 SLE AMA-M5 negative patients. The strong association between anti-phospholipid and AMA-M5 antibodies cannot be explained entirely by cross-reactivity between these two groups of antibodies, as indicated by absorption experiments and studies using affinity purified antibody preparations. However, cardiolipin liposomes were able to reduce partially the titres of AMA-M5 sera, suggesting that a small population of AMA-M5 antibodies exists that cross-reacts with cardiolipin. The existence of this population was further substantiated by our demonstration that an IgM monoclonal antibody, from a patient with Waldenström's macroglobulinaemia, displayed both anti-cardiolipin and AMA-M5 activity, and AMA-M5 activity was completely inhibited by cardiolipin.