Does the rapid initiation of antiretroviral therapy at HIV diagnosis impact virological response in a real-life setting? A single-centre experience in Northern Italy.

Rapid initiation of antiretroviral therapy (ART) has been proven efficacious and safe, but more investigations are needed to define feasibility of rapid ART approach in real-life settings.We conducted a retrospective, observational study on newly HIVdiagnosed patients referred to our Infectious Diseases Department from September 1st, 2015, to July 31st, 2019. According to the timing of ART initiation, we distinguished 3 groups of patients (rapid, intermediate and late group) and represented the trend of virological response during a 400-days-period. The hazard ratios of each predictor on viral suppression were estimated through the Cox proportional hazard model.The median time from HIV diagnosis to the first medical referral was 15 days and the median time from the first care access to therapy start was 24 days. Among patients, 37.6% started ART within 7 days, 20.6% between 8 and 30 days, and 41.8% after 30 days. Longer time to ART start and higher baseline viral load were associated with a lower probability of viral suppression. After one year, all groups showed a high viral suppression rate (99%). In a high-income setting the rapid ART approach seems useful to accelerate viral suppression which is great over time regardless of ART initiation timing.

Ixekizumab and brodalumab indirect comparison in the treatment of moderate to severe psoriasis: Results from an Italian single-center retrospective study in a real-life setting.

Eleven biologic drugs are currently approved for psoriasis management. Real-life studies are needed to guide clinicians in choosing a tailored-tail therapy. The aim of our retrospective study is to indirectly compare the efficacy and safety of ixekizumab and brodalumab in psoriasis patients. A single-centre real-life retrospective study was performed enrolling moderate-to-severe psoriatic patients under biologic treatment with ixekizumab or brodalumab. For each patient, clinical and demographic data were collected and the effectiveness and safety of brodalumab and ixekizumab treatment were evaluated at weeks 4, 12, and 24. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) were used for psoriasis severity. A total of 139 patients were included in the study: 98(70.5%) and 41(29.5%) patients received ixekizumab and brodalumab, respectively. Mean PASI and BSA significantly reduced at each follow up for both ixekizumab and brodalumab groups. Even if ixekizumab reached higher rates of PASI90 and PASI100 than brodalumab (PASI90: 43.8% vs. 39.0% PASI100: 20.4% vs. 17.1% at week4 and PASI90: 83.6% vs. 75.6% PASI100: 71.5% vs. 60.9% at week24), these results were not statistically significant. Adverse events, mainly mild, were registered in 25.5% of ixekizumab and 26.8% of brodalumab group, respectively. Discontinuation rate was higher for brodalumab (17.1% vs. 9.1%), without statistical significance. Our study showed comparable efficacy and safety for ixekizumab and brodalumab.

Smoking cessation by combined medication and counselling: a feasibility study in lung cancer patients.

PURPOSE: Smoking cessation in patients with diagnosed lung cancer has positive effects on cancer therapy and overall prognosis. Despite this, knowledge on smoking cessation in lung cancer patients is sparse. METHODS: This is an observational single centre, 12-week, prospective, single-arm trial at a tertiary lung cancer centre. Responsive patients were enrolled following confirmed lung cancer diagnosis. Smoking cessation intervention included counselling as well as pharmacotherapy. The primary endpoint was the point prevalence abstinence rate at week 12 based on biochemical verification. Secondary endpoints were the abstinence rate at week 26, quality of life and side effects. RESULTS: 80 patients were enrolled. Mean age was 62.6 ± 7.9 years. Most patients (63%) were treated with chemotherapy or radiochemotherapy. 39 patients used nicotine replacement therapy, 35 varenicline whereas six patients did not use pharmacotherapy. During the study period 13 patients died. Data were available in 72 patients after 12 weeks and 57 patients at week 24. Point prevalence abstinence rates were 37.5% (95% CI 26.4-49.7%) at week 12 and 32.8% (95% CI 21.8-45.4%) at week 26, respectively. Quality of life and side effects were not significantly affected by pharmacotherapy. CONCLUSION: In conclusion, our results suggest that smoking cessation is feasible in patients with newly diagnosed lung cancer. The observed abstinence rate is comparable to other patient cohorts. Furthermore, pharmacotherapy in addition to cancer therapy was safe and did not show novel side effects in these seriously ill patients. Thus, smoking cessation should be an integral part of lung cancer treatment. Trial registration The study was conducted in accordance with good clinical practice standards (GCP) and approved by the local ethics committee (16/3/14), the European PAS registry (EUPAS8748) and the German BfArM (NIS-Studien-Nr. 5508). All patients provided written informed consent before study enrollment.

Smell impairment in patients with chronic rhinosinusitis: a real-life study.

OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequently occurring condition involving type 2 inflammation. It has a global prevalence of approximately 4% and has a major effect on the quality of life of those affected by it. CRSwNP is a complex condition for otorhinolaryngologists to manage, since its precise pathogenic basis has not been established, treatment is challenging and the condition often recurs. It is common to find abnormalities in smelling in those with CRSwNP. MATERIALS AND METHODS: This cross-sectional study enrolled patients suffering from CRS. Three groups were compared: 1812 patients with CRS, 571 with CRSwNP, and 120 with CRSwNP treated by FESS. The Sniffin' Sticks® olfactory test was used to measure olfactory function in all patients. RESULTS: Olfactory dysfunction was a common symptom in patients with CRS, ranging in frequency from 56 to 74%. In patients with CRSwNP, impairment of sense of smell affected 64% of subjects (42% with anosmia, 10% with hyposmia, and 12% with cacosmia). After surgery, there was a significant improvement in the ability to smell normally. CONCLUSION: The present study confirms that impairment of smell is a common symptom in patients with chronic rhinosinusitis, mainly in subjects with nasal polyps. FESS reduces the prevalence of olfactory dysfunction.

Characteristics of COPD patients treated with single­inhaler triple therapy in real-life clinical practice.

BACKGROUND: Inflammation associated with chronic obstructive pulmonary disease (COPD) causes narrowing of the airways and destruction of the lung parenchyma. The triple therapy (ICS+LABA+LAMA) may improve lung function, patient­reported outcomes, and exacerbation risk in a specified subset of GOLD group D patients. A better understanding of the factors leading to the single­inhaler triple therapy (SITT) prescription in real-life scenario is still an unmet need. METHODS: We assessed the characteristics of 838 GOLD group D patients treated with SITT and way of how those patients had been routinely managed before in their outpatient settings. The cross-sectional observational survey was based on an assessment of routine practice patterns and retrospective collection of anonymous medical data. RESULTS: Severe and very severe forms of airflow obstruction were experienced by 52 % and 34 % of patients, respectively. The mean number of exacerbations during the 12­month period antecedent to SITT prescription was 2.01. Before starting SITT, various combinations of COPD medications were prescribed: LABA (95 %), followed by ICS and LAMA. Compared to patients with 0-1 exacerbation, the patients with ≥2 exacerbations had higher levels of mMRC and CAT scores (2.47 vs 2.69 and 16.02 vs 19.31, respectively, both p <0.001), worse treatment adherence and higher need for rescue medication (4.7 vs 3.9 units, p=0.0011). The driver for switching the treatment to SITT was an expected improvement in lung function followed by reduction in dyspnoea and number of exacerbations. CONCLUSIONS: Despite current treatment, the burden of COPD remains significant in GOLD group D patients. The lung function, symptoms burden and exacerbation history are among the most important factors involved in the decision for stepping up to SITT with potential roles of both bronchodilator and anti-inflammatory components (Tab. 2, Fig. 9, Ref. 66).

Turbinate Hypertrophy, Allergic Rhinitis, and Otitis Media.

PURPOSE OF REVIEW: Otitis media (OM) is a disease with high prevalence in infancy; it has a substantial burden on healthcare resources, and a relevant impact on the quality of life of families. The link between OM and allergic rhinitis (AR) is still debated. However, there is agreement about the relevance of type 2 inflammation on turbinate hypertrophy (TH) generation. There is also evidence that TH is associated with middle ear dysventilation: a pathogenic factor promoting OM. Therefore, a vicious circle among AR, TH, and OM may occur. RECENT FINDINGS: There are some recent studies exploring this issue through different approaches, such as epidemiological, mechanistic, and therapeutic. Identifying allergy as a pathogenic factor for OM could improve the management of OM patients. Vice versa, suspecting AR in OM patients, could be reasonable in selected patients. The current narrative review provides an overview of the evidence concerning the potential role of AR, and associated TH, in OM patients.

Turbinate Hypertrophy, Allergic Rhinitis, and Otitis Media.

PURPOSE OF REVIEW: Otitis media (OM) is a disease with high prevalence in infancy; it has a substantial burden on healthcare resources and a relevant impact on the quality of life of families. The link between OM and allergic rhinitis (AR) is still debated. However, there is agreement about the relevance of type 2 inflammation on turbinate hypertrophy (TH) generation. There is also evidence that TH is associated with middle ear dysventilation: a pathogenic factor promoting OM. Therefore, a vicious circle among AR, TH, and OM may occur. RECENT FINDINGS: There are some recent studies exploring this issue through different approaches, such as epidemiological, mechanistic, and therapeutic. Identifying allergy as a pathogenic factor for OM could improve the management of OM patients. Vice versa, suspecting AR in OM patients could be reasonable in selected patients. The current narrative review provides an overview of the evidence concerning the potential role of AR, and associated TH, in OM patients.

Effect of coffee and cocoa-based confectionery containing coffee on markers of cardiometabolic health: results from the pocket-4-life project.

PURPOSE: Coffee is an important source of bioactive compounds, including caffeine, trigonelline, and phenolic compounds. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic (CM) diseases, but the impact of different coffee dosages on markers of CM risk in a real-life setting has not been fully understood. This study aimed to investigate the effect of coffee and cocoa-based confectionery containing coffee consumption on several CM risk factors in healthy subjects. METHODS: In a three-arm, crossover, randomized trial, 21 volunteers were assigned to consume in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee, twice per day. At the last day of each treatment, blood samples were collected and used for the analysis of inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, and markers of glucose/insulin metabolism. Moreover, anthropometric parameters and blood pressure were measured. Finally, food consumption during the interventions was monitored. RESULTS: After 1 month, energy intake did not change among treatments, while significant differences were observed in the intake of saturated fatty acids, sugars, and total carbohydrates. No significant effect on CM markers was observed following neither the consumption of different coffee dosages nor after cocoa-based products containing coffee. CONCLUSIONS: The daily consumption of common dosages of coffee and its substitution with cocoa-based products containing coffee showed no effect on CM risk factors in healthy subjects. TRIAL REGISTRATION NUMBER: Registered at clinicaltrials.gov as NCT03166540, May 21, 2017.

Dabrafenib-trametinib combination in 'field-practice': an Italian experience.

AIM: This observational study investigates the effectiveness and safety of dabrafenib/trametinib combination in patients with metastatic melanoma. PATIENTS & METHODS: Seventy-six patients treated with dabrafenib/trametinib (150 mg twice daily/2 mg once daily) were included. RESULTS: Median progression-free survival was 9 months (95% CI: 7-11) and median overall survival was 14 months (11-16); disease control rate was 72%. Nine patients (12%) experienced a complete response. Of these, seven presented one metastatic site, none had lung or CNS metastasis, and none had elevated baseline lactate dehydrogenase (LDH) levels. Overall, subgroup analysis for patients with adverse prognostic features led to similar results. No new safety signals were reported. CONCLUSION: Dabrafenib/trametinib combination can be effective and well-tolerated also in a heterogeneous 'real life' population comprising patients with adverse prognostic features.

Telemonitoring to improve nutritional status in community-dwelling elderly: design and methods for process and effect evaluation of a non-randomized controlled trial.

BACKGROUND: A good nutritional status is key for maintaining health and quality of life in older adults. In the Netherlands, 11 to 35% of the community-dwelling elderly are undernourished. Undernutrition or the risk of it should be signalled as soon as possible to be able to intervene at an early stage. However, in the context of an ageing population health care resources are scarce, evoking interest in health enabling technologies such as telemonitoring. This article describes the design of an intervention study focussing at telemonitoring and improving nutritional status of community-dwelling elderly. METHODS: The PhysioDom Home Dietary Intake Monitoring intervention was evaluated using a parallel arm pre-test post-test design including 215 Dutch community-dwelling elderly aged > 65 years. The six-month intervention included nutritional telemonitoring, television messages, and dietary advice by a nurse or a dietician. The control group received usual care. Measurements were performed at baseline, after 4.5 months, and at the end of the study, and included the primary outcome nutritional status and secondary outcomes behavioural determinants, diet quality, appetite, body weight, physical activity, physical functioning, and quality of life. Furthermore, a process evaluation was conducted to provide insight into intervention delivery, feasibility, and acceptability. DISCUSSION: This study will improve insight into feasibility and effectiveness of telemonitoring of nutritional parameters in community-dwelling elderly. This will provide relevant insights for health care professionals, researchers, and policy makers. TRIAL REGISTRATION: The study was retrospectively registered at Clinical-Trials.gov (identifier NCT03240094 ) since August 3, 2017.

Effect, process, and economic evaluation of a combined resistance exercise and diet intervention (ProMuscle in Practice) for community-dwelling older adults: design and methods of a randomised controlled trial.

BACKGROUND: Exercise and nutrition are important for older adults to maintain or to regain their muscle mass, function, strength, and ultimately quality of life. The effectiveness of combined resistance exercise and diet interventions is commonly evaluated in controlled clinical studies, but evidence from real-life settings is lacking. This article describes the effectiveness, process, and economic evaluation design of a combined nutrition and exercise intervention for community-dwelling older adults in a Dutch real-life setting. METHODS: The ProMuscle in Practice study is a randomised controlled multicentre intervention study, conducted in five municipalities in the Netherlands. Two hundred community-dwelling older adults (≥65 years) who are frail or pre-frail based on Fried frailty criteria or who experience strength loss are randomised over an intervention and control group by municipality. In the first 12-week intensive support intervention, participants in the intervention group perform resistance exercise training guided by a physiotherapist twice a week and increase protein intake by consuming protein-rich products under the supervision of a dietitian. Afterwards, they continue with a 12-week moderate support intervention. The control group receives only regular care during the two 12-week periods. Effect outcomes are measured at all locations at baseline, 12 weeks, 24 weeks, 36 weeks and only at three locations at 52 weeks. The primary outcome is physical functioning (Short Physical Performance Battery). Secondary outcomes include leg muscle strength, lean body mass, activities of daily living, social participation, food intake, and quality of life. Qualitative and quantitative implementation process data are collected during the intervention. Healthcare use and intervention costs are registered for the economic evaluation. DISCUSSION: Evaluating the effects, implementation, and costs of this combined intervention provides valuable insight into the feasibility of this intervention for community-dwelling older adults and into the intervention's ability to improve or to maintain physical functioning and quality of life. TRIAL REGISTRATION: Netherlands Trial Register ( NTR6038 ) since 30 August 2016.

Determinants of weight outcomes in type 2 diabetes prevention intervention in primary health care setting (the DE-PLAN project).

BACKGROUND: Real life implementation studies performed in different settings have proved that lifestyle interventions in the prevention of type 2 diabetes (DM2) can be effective, although the weight reduction results are typically modest compared to randomized control trials. Our objective was to identify the factors that predict successful weight loss in a less intensive, lower budget, real life setting lifestyle diabetes prevention intervention. METHODS: Study participants (n = 175) with increased DM2 risk (Finnish Diabetes Risk Score (FINDRISC) > 14) but no diabetes at baseline received ten group lifestyle counselling sessions, physical activity and motivation sessions during a ten-month intervention. Stepwise regression analysis was used to determine demographic, clinical, and lifestyle predictors of successful weight reduction defined as a reduction of ≥5% of the initial body weight. RESULTS: At 12 months following the initiation of the intervention, 23.4% of study participants lost ≥5% weight (mean loss of 7.9 kg, SD = 5.8). Increased physical activity (44% vs 25%, p = 0.03), decreased total fat consumption (88% vs 65%, p = 0.006) and adherence to four-five lifestyle goals (71% vs 46%, p = 0.007) were more often reported among those who managed to lose ≥5% weight versus those who did not. In a multivariate analysis, meeting the ≥5% weight loss goal was most effective in individuals with a higher baseline BMI (OR 1.1, 95%CI 1.0-1.2), baseline and medium versus higher education (OR 5.4, 95% CI 1.2-24.7) and a history of increased glucose (OR 2.6, 95%CI 1.1-1.3). A reduction of total fat in the diet was an independent lifestyle predictor, increasing the probability of successful weight loss by 3.8 times (OR 3.8, 95% CI 1.2-11.4). CONCLUSION: Baseline higher BMI, lower education and a history of increased glucose predicted the successful weight loss among individuals with a high risk for the DM2 following lifestyle intervention in a real life primary health care setting. People who manage to lose weight more often adhere to lifestyle changes, while the reduction of total fat in diet independently predicts successful weight loss. Further studies exploring the predictors of success in implementation studies in DM2 prevention should help health care providers redesign interventions to improve their effectiveness and outcomes. TRIAL REGISTRATION: ISRCTN, ID ISRCTN96692060 , registered 03.08.2016 retrospectively.

Real-life clinical practice results with vinflunine in patients with relapsed platinum-treated metastatic urothelial carcinoma: an Italian multicenter study (MOVIE-GOIRC 01-2014).

BACKGROUND: Vinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice. METHODS: This was a retrospective multicenter study. Italian cancer centers were selected if, according to the Registry of the Italian Medicines Agency (AIFA), at least four patients had been treated with vinflunine between February 2011 and June 2014, after first- or second-line platinum-based chemotherapy. The primary objective was to test whether the efficacy measured by overall survival (OS) in the registration study could be confirmed in routine clinical practice. Multivariate analysis was carried out using Cox proportional hazard model. RESULTS: A total of 217 patients were treated in 28 Italian centers. Median age was 69 years (IQR 62-76) and 84% were male; Eastern Cooperative Oncology Group performance status (ECOG PS) was ≥ 1 in 53% of patients. The median number of cycles was 4 (IQR 2-6); 29%, 35%, and 36% received an initial dose of 320 mg/m2, 280 mg/m2 or a lower dose, respectively. Median progression-free survival (PFS) and OS for the entire population was 3.2 months (2.6-3.7) and 8.1 months (6.3-8.9). A complete response was observed in six patients, partial response in 21, stable disease in 60, progressive disease in 108, with a disease control rate of 40%. Multivariate analysis showed that ECOG PS, number of metastatic sites and liver involvement were unfavorable prognostic factors for OS. Toxicity was mild, and grade 3-4 adverse effects were mainly: neutropenia (9%), anemia (6%), asthenia/fatigue (7%) and constipation (5%). CONCLUSIONS: In routine clinical practice the results obtained with VFL seem to be better than the results of the registration trial and reinforce evidence supporting its use after failure of a platinum-based chemotherapy.

Translation of a tailored nutrition and resistance exercise intervention for elderly people to a real-life setting: adaptation process and pilot study.

BACKGROUND: Combining increased dietary protein intake and resistance exercise training for elderly people is a promising strategy to prevent or counteract the loss of muscle mass and decrease the risk of disabilities. Using findings from controlled interventions in a real-life setting requires adaptations to the intervention and working procedures of healthcare professionals (HCPs). The aim of this study is to adapt an efficacious intervention for elderly people to a real-life setting (phase one) and test the feasibility and potential impact of this prototype intervention in practice in a pilot study (phase two). METHODS: The Intervention Mapping approach was used to guide the adaptation in phase one. Qualitative data were collected from the original researchers, target group, and HCPs, and information was used to decide whether and how specified intervention elements needed to be adapted. In phase two, a one-group pre-test post-test pilot study was conducted (n = 25 community-dwelling elderly), to elicit further improvements to the prototype intervention. The evaluation included participant questionnaires and measurements at baseline (T0) and follow-up (T1), registration forms, interviews, and focus group discussions (T1). Qualitative data for both phases were analysed using an inductive approach. Outcome measures included physical functioning, strength, body composition, and dietary intake. Change in outcomes was assessed using Wilcoxon signed-rank tests. RESULTS: The most important adaptations to the original intervention were the design of HCP training and extending the original protein supplementation with a broader nutrition programme aimed at increasing protein intake, facilitated by a dietician. Although the prototype intervention was appreciated by participants and professionals, and perceived applicable for implementation, the pilot study process evaluation resulted in further adaptations, mostly concerning recruitment, training session guidance, and the nutrition programme. Pilot study outcome measures showed significant improvements in muscle strength and functioning, but no change in lean body mass. CONCLUSION: The combined nutrition and exercise intervention was successfully adapted to the real-life setting and seems to have included the most important effective intervention elements. After adaptation of the intervention using insights from the pilot study, a larger, controlled trial should be conducted to assess cost-effectiveness. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov NL51834.081.14 (April 22, 2015).

Sustained diabetes risk reduction after real life and primary health care setting implementation of the diabetes in Europe prevention using lifestyle, physical activity and nutritional intervention (DE-PLAN) project.

BACKGROUND: Real life implementation studies performed in different settings and populations proved that lifestyle interventions in prevention of type 2 diabetes can be effective. However, little is known about long term results of these translational studies. Therefore, the purpose of this study was to examine the maintenance of diabetes type 2 risk factor reduction achieved 1 year after intervention and during 3 year follow-up in primary health care setting in Poland. METHODS: Study participants (n = 262), middle aged, slightly obese, with increased type 2 diabetes risk ((age 55.5 (SD = 11.3), BMI 32 (SD = 4.8), Finnish Diabetes Risk Score FINDRISC 18.4 (SD = 2.9)) but no diabetes at baseline, were invited for 1 individual and 10 group lifestyle counselling sessions as well as received 6 motivational phone calls and 2 letters followed by organized physical activity sessions combined with counselling to increase physical activity. Measurements were performed at baseline and then repeated 1 and 3 years after the initiation of the intervention. RESULTS: One hundred five participants completed all 3 examinations (baseline age 56.6 (SD = 10.7)), BMI 31.1 (SD = 4.9)), FINDRISC 18.57 (SD = 3.09)). Males comprised 13% of the group, 10% of the patients presented impaired fasting glucose (IFG) and 14% impaired glucose tolerance (IGT). Mean weight of participants decreased by 2.27 kg (SD = 5.25) after 1 year (p = <0.001). After 3 years a weight gain by 1.13 kg (SD = 4.6) (p = 0.04) was observed. In comparison with baseline however, the mean total weight loss at the end of the study was maintained by 1.14 kg (SD = 5.8) (ns). Diabetes risk (FINDRISC) declined after one year by 2.8 (SD = 3.6) (p = 0.001) and the decrease by 2.26 (SD = 4.27) was maintained after 3 years (p = 0.001). Body mass reduction by >5% was achieved after 1 and 3 years by 27 and 19% of the participants, respectively. Repeated measures analysis revealed significant changes observed from baseline to year 1 and year 3 in: weight (p = 0.048), BMI (p = 0.001), total cholesterol (p = 0.013), TG (p = 0.061), fasting glucose level (p = 0.037) and FINDRISC (p = 0.001) parameters. The conversion rate to diabetes was 2% after 1 year and 7% after 3 years. CONCLUSIONS: Type 2 diabetes prevention in real life primary health care setting through lifestyle intervention delivered by trained nurses leads to modest weight reduction, favorable cardiovascular risk factors changes and decrease of diabetes risk. These beneficial outcomes can be maintained at a 3-year follow-up. TRIAL REGISTRATION: ISRCTN, ID ISRCTN96692060 , registered 03.08.2016 retrospectively.

Long-term treatment of chronic migraine with OnabotulinumtoxinA: efficacy, quality of life and tolerability in a real-life setting.

Botulinum toxin was shown to be effective in treatment of chronic migraine. We wanted to explore its efficacy and tolerability in chronic application under real-life conditions. For this, 27 consecutive patients (age 45.6 ± 10.8 years, 25 females, 2 males) received altogether 176 injection series (IS) with 189.7 ± 45.8MU onabotulinumtoxinA (Botox(®)) according to the PREEMPT scheme. During the study period altogether 6.5 ± 2.9 (min 4, max 13) IS were applied per patient (total treatment time of 73.1 ± 36.9 weeks). 96 % of the patients reported benefit. Monthly headache days were reduced from 18.9 ± 3.9 to 8.7 ± 4.5 (p < 0.001, -53.7 %), migraine days from 16.8 ± 4.9 to 7.4 ± 4.6 (p < 0.001, -55.1 %), autonomic days from 8.6 ± 7.5 to 2.7 ± 4.2 (p < 0.001, -71.9 %) and medication days from 14.2 ± 4.6 to 8.3 ± 4.2 (p < 0.001, -71.1 %). Health-related quality of life improved by 0.6-1.5 standard deviations (SD) (Short Form Health Survey), migraine-related quality of life by 1.4-2.0 SD (Migraine-Specific Quality of Life Questionnaire) and by 1.9 SD (Headache Impact Test), depression by 1.1 SD (Beck Depression Inventory). Subjective global clinical improvement was 2.6 ± 0.6 (Global Clinical Improvement Scale). All improvements were stable throughout the entire study period. Adverse effects were infrequent, mild and transient. Botulinum toxin provides highly effective and safe long-term treatment of chronic migraine.

Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting.

The chronic course of hepatitis E virus (HEV) infections in orthotopic liver transplant (OLT) recipients has been described previously, but prospectively collected data are rare. We aimed to study the role of chronic hepatitis E in OLT in a real-life setting. Therefore, 287 adult OLT recipients (169 male [59%], median age 56 years) were prospectively tested by HEV polymerase chain reaction assay (lower level of detection = 10 IU/mL), irrespective of their level of liver enzymes. In 4 patients (1.4%), chronic HEV infection was diagnosed. All 4 patients were male, and their age (median 48.5 years), the time since transplantation (median 45.5 months), and bilirubin level (median 0.6 mg/dL) did not differ significantly from the total cohort. However, alanine transaminase and aspartame transaminase levels were significantly higher in HEV-infected patients (75-646 U/L, median 216 U/L and 68-317 U/L, median 108 U/L) than in non-infected patients (6-617 U/L, median 41 and 6-355 U/L, median 36; P = 0.004 and 0.040, Mann-Whitney test). In 3 patients, liver biopsy was performed and revealed signs of inflammation and chronic liver disease, as enlarged densely infiltrated portal tracts with mild-to-moderate interface hepatitis. All infected patients were treated with ribavirin with the starting dose adjusted to renal function (400-800 mg/day). In 2 patients, dose reduction was necessary. Transaminases normalized in all 4 patients, and all patients cleared their infection within 3 months of ribavirin treatment. However, 1 patient experienced viral relapse 12 weeks after discontinuation. Ribavirin medication was re-started and viral clearance occurred within 8 weeks and persisted. Sequence analysis of the HEV genome of this patient revealed that he was infected with an HEV variant, which recently has been shown to have a reduced response to ribavirin in cell culture. The risk of chronic HEV infections in OLT recipients in low-endemic countries should not be overestimated. No case of chronic hepatitis E was observed in patients with normal liver enzymes, indicating that general screening of all OLT recipients is not necessary. However, if chronic hepatitis E develops, it can be treated efficiently with ribavirin.

Eribulin mesylate in advanced breast cancer: retrospective review of a single institute experience.

AIM: EMA licensed eribulin mesylate in 2011 for women with advanced breast cancer already treated with at least two lines of chemotherapy, including anthracyclines and taxanes. Azienda Sanitaria Firenze experience is reported to assess the efficacy and safety of eribulin in the real-life setting. PATIENTS & METHODS: Eribulin was infused as per indication. All women treated in the last 2 years were reviewed. RESULTS: A total of 27 women received eribulin. All but one was pretreated with anthracyclines, 97% with taxanes and 87% with capecitabine. Median age was 63 years (range: 27-80). A median of four cycles of eribulin were infused (range: 2-10). Overall response rate was 30% with a 45% of clinical benefit (response plus stable disease for at least 24 weeks). Toxicities have been as expected. Severe toxicities were rare, with one patient experiencing sepsis and 18% developing grade 3 asthenia. CONCLUSION: Eribulin maintains its activity out of clinical trials, without unexpected toxicities.

Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease.

BACKGROUND: Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation between the initial cognitive response to ChEI treatment and the subsequent long-term course of cognition of AD patients. METHODS: The Frisian Alzheimer's Disease Cohort study is a retrospective longitudinal study of 576 community-dwelling AD patients treated with ChEIs in a "real-life" setting at a large memory clinic. A repeated measures analysis using a marginal model (population based averaged model) was applied to investigate whether there is a difference in the subsequent long-term course of cognition (Mini-Mental State Examination (MMSE)) between initial non-responders and responders. Absence of an initial response was defined as a lower MMSE score after the first six months of treatment compared to baseline, a positive response as the same or a higher MMSE score. RESULTS: At baseline, median age was 80 years and the median MMSE score 23. Non-responders showed a slower rate of cognitive decline in the three subsequent years than responders, with a mean annual MMSE decline of 0.9 points versus 1.2 points, respectively (p < 0.0001). CONCLUSIONS: Our results suggest that it is not appropriate to discontinue ChEI treatment solely based on the absence of an initial cognitive response.

Long-Term Efficacy Following Intra-articular Injection of Carboxymethyl-chitosan, a New Product Class for Knee Osteoarthritis: Results from an Observational Study in Germany.

INTRODUCTION: Evaluate the real-world efficacy of a single intra-articular injection of carboxymethyl-chitosan (CM-chitosan), a new product class for knee osteoarthritis (OA). METHODS: This post-marketing study included adult patients with knee OA, who received a single injection of 60 mg CM-chitosan (currently marketed as KioMedinevsone) according to the instructions for use. Follow-up was performed at weeks 1, 12, 24, and 36. Efficacy was evaluated using a Visual Analog Scale (VAS) score for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS), Patient's Global Assessment (PGA), and overall patient satisfaction. RESULTS: Forty-nine patients were included in the study. VAS pain score significantly decreased from a median of 49.0 mm at baseline to 24.0 mm at week 1 and to 18 mm at week 36. Pain improvement was stable since at week 36; 91.8% of patients confirmed pain reduction. All KOOS subscales (symptoms, pain, activities of daily living, sports and recreational activities, quality of life) improved significantly compared to baseline at all time points. KOOS pain improved progressively from a median of 58.3% at baseline (mean 56.2 ± 18.8%) to 86.1% (mean 74.1 ± 24%) at week 36 compared to baseline. Overall, more than 70% of patients reported a condition gain (PGA), matching well with the more than 75% of patients being satisfied with the treatment. At 6 months, 72.7% of the patients could be classified as responder according to the OMERACT-OARSI proposed set of responder criteria. CONCLUSION: CM-chitosan showed a rapid onset of pain relief after 1 week and with a duration of 9 months. In a real-world setting, treatment with CM-chitosan would appear to be a potentially effective option to reduce pain and improve physical function and global condition in patients with knee OA, opening new perspectives in patients who are considered as refractory to current symptomatic therapies and where the unmet need is high. TRIAL REGISTRATION NUMBER: NCT04757051 (ClinicalTrials.gov).