Leukocyte- and platelet-rich fibrin does not provide any additional benefit for tooth extraction in head and neck cancer patients post-radiotherapy: a randomized clinical trial.

BACKGROUND: One of the most important complications of radiotherapy (RT) for head and neck cancer (HNC) is osteoradionecrosis (ORN) of the jaws, arising mainly from tooth extractions. Thus, the present study aimed to evaluate the efficacy of leukocyte- and platelet-rich fibrin (L-PRF) in preventing ORN following tooth extraction in post-irradiated HNC patients, as well as other postoperative complications. MATERIAL AND METHODS: 23 patients previously submitted to conventionally fractionated 3D-conformational RT for HNC underwent atraumatic tooth extractions with perioperative antibiotic therapy. Besides, they were randomly assigned to receive L-PRF clots to fill and cover the extraction sockets (n=11, Test Group) or not (n=12, Control Group). A visual analog scale was used to quantify postoperative pain on the 3rd and 7th days. For ORN diagnosis, patients were clinically assessed for up to 180 days. Other postoperative complications (edema, alveolitis, suture dehiscence, continuous bleeding, and oroantral communication) were also evaluated within this period. RESULTS: No case of ORN or another surgical complication was observed and there were no differences in the postoperative pain scores between the groups on the 3rd and 7th days. CONCLUSIONS: L-PRF did not seem to provide any additional benefits than those achieved by the combination of the surgical and drug protocols used for tooth extractions in the post-irradiated HNC patients.

Artepillin C and phenolic compounds responsible for antimicrobial and antioxidant activity of green propolis and Baccharis dracunculifolia DC.

AIMS: This study investigates the antimicrobial activity in Staphylococcus aureus isolates (methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA)) and antioxidant activity of green propolis, Baccharis dracunculifolia DC extracts and Artepillin C™. METHODS AND RESULTS: The amount of Artepillin C in different extracts was determined by high performance liquid chromatography analysis. Minimum inhibitory concentration 90 (MIC90) was determined using 40 isolates of S. aureus inoculated in Müeller-Hinton agar culture medium containing the green propolis and B. dracunculifolia DC extracts. PVEE (green propolis ethanolic extract) and BDEH (B. dracunculifolia hexanic extract) showed the greatest antimicrobial activity with MIC90 values of 246·3 and 295·5 µg ml-1 respectively. Green propolis ethanolic and hexanic extracts (PVEE and PVEH respectively) showed the greatest antioxidant activity assessed by DPPH (1,1-diphenyl-2-picryl hydrazyl radical) with IC50 values of 13·09 and 95·86 µg ml-1 respectively. CONCLUSIONS: Green propolis ethanolic displays better antimicrobial and antioxidant activities compared to other extracts. These activities may be related to the presence of Artepillin C in synergism with the other constituents of the extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, the antimicrobial activity of the extracts of green propolis and B. dracunculifolia DC demonstrated in MRSA and MSSA clinical isolates indicated that they can be important tools to treat infections caused by these bacteria.

Prevalence and Risk Factors Associated with Use of QT-Prolonging Drugs in Hospitalized Older People.

AIMS: The objective of this study was to evaluate the prevalence of the prescription of QT-prolonging drugs at hospital admission and discharge and the risk factors associated with their use in older people (aged 65 years and older). METHODS: Data were obtained from the REPOSI (REgistro POliterapie SIMI [Società Italiana di Medicina Interna]) registry, which enrolled 4035 patients in 2008 (n = 1332), 2010 (n = 1380), and 2012 (n = 1323). Multivariable logistic regression was performed to determine the risk factors independently associated with QT-prolonging drug use. QT-prolonging drugs were classified by the risk of Torsades de Pointes (TdP) (definite, possible, or conditional) according to the Arizona Center for Education and Research on Therapeutics (AzCERT) classification. Specific drug combinations were also assessed. RESULTS: Among 3906 patients prescribed at least one drug at admission, 2156 (55.2%) were taking at least one QT-prolonging drug. Risk factors independently associated with the use of any QT-prolonging drugs were increasing age (odds ratio [OR] 1.02, 95% CI 1.01-1.03), multimorbidity (OR 2.69, 95% CI 2.33-3.10), hypokalemia (OR 2.79, 95% CI 1.32-5.89), atrial fibrillation (OR 1.66, 95% CI 1.40-1.98), and heart failure (OR 3.17, 95% CI 2.49-4.05). Furosemide, alone or in combination, was the most prescribed drug. Amiodarone was the most prescribed drug with a definite risk of TdP. Both the absolute number of QT-prolonging drugs (2890 vs. 3549) and the number of patients treated with them (2456 vs. 2156) increased at discharge. Among 1808 patients not prescribed QT-prolonging drugs at admission, 35.8% were prescribed them at discharge. CONCLUSIONS: Despite their risk, QT-prolonging drugs are widely prescribed to hospitalized older persons. The curriculum for both practicing physicians and medical students should be strengthened to provide more education on the appropriate use of drugs in order to improve the management of hospitalized older people.

Brain and kidney, victims of atrial microembolism in elderly hospitalized patients? Data from the REPOSI study.

BACKGROUND: It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. METHODS: We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. RESULTS: Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. CONCLUSIONS: Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality.

Risk of recurrence after a first unprovoked venous thromboembolism: external validation of the Vienna Prediction Model with pooled individual patient data.

BACKGROUND: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. OBJECTIVE: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. PATIENTS/METHODS: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. RESULTS: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P = 0.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12 months. CONCLUSIONS: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence.

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.

Gender-differences in disease distribution and outcome in hospitalized elderly: data from the REPOSI study.

BACKGROUND AND PURPOSE: Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people. METHODS: Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied. RESULTS: A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men. CONCLUSIONS: Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare.

Patient data meta-analysis of Post-Authorization Safety Surveillance (PASS) studies of haemophilia A patients treated with rAHF-PFM.

UNLABELLED: A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effectiveness of rAHF-PFM (ADVATE) use in haemophilia patients in routine clinical settings. The main aim of this project was to estimate the rate of inhibitors and other adverse events across ADVATE-PASS studies by meta-analysing individual patient data (IPD). Eligible Studies: PASS studies conducted in different countries, between 2003 and 2013, for which IPD were provided. Eligible patients: haemophilia A patients with baseline FVIII:C < 5%, with a known number of prior exposure days (EDs). PRIMARY OUTCOME: de novo inhibitors in severe, previously treated patients (PTPs) with > 150 EDs. SECONDARY OUTCOMES: de novo inhibitors according to prior exposure and disease severity; other adverse events; annualized bleeding rate (ABR). ANALYSIS: random-effects logistic regression. Five of seven registered ADVATE-PASS (Australia, Europe, Japan, Italy and USA) and 1188 patients were included (median follow-up 384 days). Among severe PTPs with > 150 EDs, 1/669 developed de novo inhibitors (1.5 per 1000; 95% confidence interval [CI] 0.2, 10.6 per 1000). Among all patients included in the PASS studies, 21 developed any type of inhibitors (2.0%, 95% CI: 0.8%, 4.7%). Less than 1% of patients presented with other serious adverse events possibly related to ADVATE. The overall median ABR was 3.83 bleeds/year (first, third quartiles: 0.60, 12.90); 1.66 (0, 4.78) in the 557 patients continuously on prophylaxis ≥ twice/week. Meta-analysing PASS data from different countries confirmed the overall favourable safety and effectiveness profile of ADVATE in routine clinical settings.

Prevalence of potentially inappropriate medications and risk of adverse clinical outcome in a cohort of hospitalized elderly patients: results from the REPOSI Study.

WHAT IS KNOWN AND OBJECTIVE: Inappropriate prescribing is highly prevalent for older people and has become a global healthcare concern because of its association with negative health outcomes including ADEs, hospitalization and resource utilization. Beers' criteria are widely utilized for evaluating the appropriateness of medications, and an up-to-date version has recently been published. To assess the prevalence of patients exposed to PIMs at hospital discharge according to the 2003 and 2012 versions of Beers' criteria and to evaluate the risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up. METHODS: This cross-sectional study was held in 66 Italian internal medicine and geriatric wards. The sample included 1380 inpatients aged 65 years or older. Prescriptions of PIM were analysed at hospital discharge. We considered all patients with complete 3-month follow-up. RESULTS AND DISCUSSION: The prevalence of patients receiving at least one PIM was 20·1% and 23·5% according to the 2003 and 2012 versions of the Beers' criteria, respectively. The 2012 Beers' criteria identified more patients with at least one PIM than the 2003 version, although a high percentage of those patients (72·2%) were also identified by the criteria updated in 2003. The main difference in the prevalence of patients receiving a PIM according to the two versions of Beers' criteria involved prescriptions of benzodiazepines for insomnia or agitation, chronic use of non-benzodiazepine hypnotics, prescription of antipsychotics in people with dementia and oral iron at dosage higher than 325 mg/day. Prescription of PIMs was not associated with a higher risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up in both univariate and multivariate analysis, after adjusting for age, sex and CIRS comorbidity index. WHAT IS NEW AND CONCLUSIONS: This study found no significant effect of inappropriate drug use according to Beers' criteria on health outcomes among older adults 3 month after discharge. Even though these criteria have been suggested as helpful in promoting appropriate prescribing, reducing drug-related adverse events and associated healthcare costs, to date there is no clear evidence that their application can achieve objective and quantifiable improvements in clinical outcomes. A possible explanation is that both versions of the Beers' criteria have several recognized limitations, one of the main ones being the restricted availability of some drugs in Europe or their limited prescription in everyday clinical practice.

Inhibitor development in previously treated hemophilia A patients: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: The development of neutralizing alloantibodies (inhibitors) is the most serious complication of factor VIII (FVIII) replacement therapy in patients with hemophilia A. Unlike previously untreated patients, no definite risk factors for inhibitor development are known for previously treated patients (PTPs). The investigation of the development of inhibitors in PTPs is hindered by several methodological limitations in the available literature. We conducted a systematic review to account for these limitations. METHODS: We considered the studies reporting on PTPs that were included in the Wight and Paisley meta-analysis and a systematic search of MEDLINE, EMBASE, and The Cochrane Library was conducted to identify studies published after 2003. Studies that investigated the development of inhibitors in hemophilia A PTPs who were treated with any type of FVIII concentrate and that included at least 25 patients with follow-up were included in the analysis. RESULTS: Thirty-three independent cohorts of PTPs with 4323 subjects and 43 incident de novo inhibitors were found and analyzed. The pooled incidence rate of inhibitor development for the 25 studies providing data on follow-up was 3 (95% confidence interval 1-4) per 1000 person-years. A significant association was not found between putative risk factors and inhibitor development in PTPs at meta-regression analysis and subgroup analysis, but the model was sensitive enough to the inclusion of the reports on the Belgian-Dutch experience with a highly immunogenic factor VIII. CONCLUSION: We confirmed a low overall rate of de novo inhibitors in PTPs, without any significant effect of putative predictors, including the type of factor VIII concentrate.

Comparison of disease clusters in two elderly populations hospitalized in 2008 and 2010.

BACKGROUND: As chronicity represents one of the major challenges in the healthcare of aging populations, the understanding of how chronic diseases distribute and co-occur in this part of the population is needed. OBJECTIVES: The aims of this study were to evaluate and compare patterns of diseases identified with cluster analysis in two samples of hospitalized elderly. METHODS: Data were obtained from the multicenter 'Registry Politerapie SIMI (REPOSI)' that included people aged 65 or older hospitalized in internal medicine and geriatric wards in Italy during 2008 and 2010. The study sample from the first wave included 1,411 subjects enrolled in 38 hospitals wards, whereas the second wave included 1,380 subjects in 66 wards located in different regions of Italy. To analyze patterns of multimorbidity, a cluster analysis was performed including the same diseases (19 chronic conditions with a prevalence >5%) collected at hospital discharge during the two waves of the registry. RESULTS: Eight clusters of diseases were identified in the first wave of the REPOSI registry and six in the second wave. Several diseases were included in similar clusters in the two waves, such as malignancy and liver cirrhosis; anemia, gastric and intestinal diseases; diabetes and coronary heart disease; chronic obstructive pulmonary disease and prostate hypertrophy. CONCLUSION: These findings strengthened the idea of an association other than by chance of diseases in the elderly population.

Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH).

BACKGROUND: In patients with unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulation is anchored on estimating the risk of disease recurrence. OBJECTIVES: We aimed to develop a score that could predict the recurrence risk following a first episode of unprovoked VTE, pooling individual patient data from seven prospective studies. METHODS: One thousand eight hundred and eighteen cases with unprovoked VTE treated for at least 3 months with a vitamin K antagonist were available for analysis. Optimism-corrected Cox regression coefficients were used to develop a recurrence score that was subsequently internally validated by bootstrap analysis. RESULTS: Abnormal D-dimer after stopping anticoagulation, age <50 years, male sex and VTE not associated with hormonal therapy (in women) were the main predictors of recurrence and were used to derive a prognostic recurrence score (DASH, D-dimer, Age, Sex, Hormonal therapy) showing a satisfactory predictive capability (ROC area =0.71). The annualized recurrence risk was 3.1% (95% confidence interval [CI], 2.3-3.9) for a score ≤ 1, 6.4% (95% CI, 4.8-7.9) for a score=2 and 12.3% (95% CI, 9.9-14.7) for a score ≥ 3. By considering at low recurrence risk those patients with a score ≤ 1, life-long anticoagulation might be avoided in about half of patients with unprovoked VTE. CONCLUSIONS: The DASH prediction rule appears to predict recurrence risk in patients with a first unprovoked VTE and may be useful to decide whether anticoagulant therapy should be continued indefinitely or stopped after an initial treatment period of at least 3 months.

Prevalence and characteristics of antidepressant drug prescriptions in older Italian patients.

BACKGROUND: During last few decades, the proportion of elderly persons prescribed with antidepressants for the treatment of depression and anxiety has increased. The aim of this study was to evaluate prevalence of antidepressant prescription and related factors in elderly in-patients, as well as the consistency between prescription of antidepressants and specific diagnoses requiring these medications. METHODS: Thirty-four internal medicine and four geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI study during 2008. In all, 1,155 in-patients, 65 years or older, were enrolled. Prevalence of the use of antidepressants was calculated at both admission and discharge. Logistic regression was used to evaluate the association between patients' characteristics (age, gender, Charlson Index, number of drugs, specific diseases, other psychotropic medications) and the prescription of antidepressants. RESULTS: The number of patients treated with antidepressant medication at hospital admission was 115 (9.9%) and at discharge 119 (10.3%). In a multivariate analysis, a higher number of drugs (OR = 1.2; 95% CI = 1.1-1.3), use of anxiolytic drugs (OR = 2.1; 95% CI = 1.2-3.6 and OR = 3.8; 95% CI = 2.1-6.8), and a diagnosis of dementia (OR = 6.1; 95% CI = 3.1-11.8 and OR = 5.8; 95% CI = 3.3-10.3, respectively, at admission and discharge) were independently associated with antidepressant prescription. A specific diagnosis requiring the use of antidepressants was present only in 66 (57.4%) patients at admission and 76 (66.1%) at discharge. CONCLUSIONS: Antidepressants are commonly prescribed in geriatric patients, especially in those receiving multiple drugs, other psychotropic drugs, and those affected by dementia. There is an inconsistency between the prescription of antidepressants and a specific diagnosis that the hospitalization only slightly improves.

In-hospital death according to dementia diagnosis in acutely ill elderly patients: the REPOSI study.

OBJECTIVE: The aim of the study was to explore the association of dementia with in-hospital death in acutely ill medical patients. METHODS: Thirty-four internal medicine and 4 geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI-study during 2008. One thousand three hundred and thirty two in-patients aged 65 years or older were enrolled. Logistic regression models were used to evaluate the association of dementia with in-hospital death. Socio-demographic characteristics, morbidity (single diseases and the Charlson Index), number of drugs, and adverse clinical events during hospitalization were considered as potential confounders. RESULTS: One hundred and seventeen participants were diagnosed as being affected by dementia. Patients with dementia were more likely to be women, older, to have cerebrovascular diseases, pneumonia, and a higher number of adverse clinical events during hospitalization. The percentage of patients affected by dementia who died during hospitalization was higher than that of patients without dementia (9.4 versus 4.9%). After multiadjustment, the diagnosis of dementia was associated with in-hospital death (OR = 2.1; 95% CI = 1.0-4.5). Having dementia and at least one adverse clinical event during hospitalization showed an additive effect on in-hospital mortality (OR = 20.7; 95% CI = 6.9-61.9). CONCLUSIONS: Acutely ill elderly patients affected by dementia are more likely to die shortly after hospital admission. Having dementia and adverse clinical events during hospital stay increases the risk of death.