Safety Issues In Patients Research Articles

Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial.

Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were -1.38%±0.08%, -1.03%±0.08%, and -0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Model Generalizability Investigation for GFCE-MRI Synthesis in NPC Radiotherapy Using Multi-Institutional Patient-Based Data Normalization.

Recently, deep learning has been demonstrated to be feasible in eliminating the use of gadoliniumbased contrast agents (GBCAs) through synthesizing gadolinium-free contrast-enhanced MRI (GFCE-MRI) from contrast-free MRI sequences, providing the community with an alternative to get rid of GBCAs-associated safety issues in patients. Nevertheless, generalizability assessment of the GFCE-MRI model has been largely challenged by the high inter-institutional heterogeneity of MRI data, on top of the scarcity of multi-institutional data itself. Although various data normalization methods have been adopted to address the heterogeneity issue, it has been limited to single-institutional investigation and there is no standard normalization approach presently. In this study, we aimed at investigating generalizability of GFCE-MRI model using data from seven institutions by manipulating heterogeneity of MRI data under five popular normalization approaches. Three state-of-the-art neural networks were applied to map from T1-weighted and T2-weighted MRI to contrast-enhanced MRI (CE-MRI) for GFCE-MRI synthesis in patients with nasopharyngeal carcinoma. MRI data from three institutions were used separately to generate three uni-institution models and jointly for a tri-institution model. The five normalization methods were applied to normalize the data of each model. MRI data from the remaining four institutions served as external cohorts for model generalizability assessment. Quality of GFCE-MRI was quantitatively evaluated against ground-truth CE-MRI using mean absolute error (MAE) and peak signal-to-noise ratio(PSNR). Results showed that performance of all uni-institution models remarkably dropped on the external cohorts. By contrast, model trained using multi-institutional data with Z-Score normalization yielded the best model generalizability improvement.

Understanding the medication safety challenges for patients with mental illness in primary care: a scoping review

BackgroundMental illness and medication safety are key priorities for healthcare systems around the world. Despite most patients with mental illness being treated exclusively in primary care, our understanding of medication safety challenges in this setting is fragmented.MethodSix electronic databases were searched between January 2000-January 2023. Google Scholar and reference lists of relevant/included studies were also screened for studies. Included studies reported data on epidemiology, aetiology, or interventions related to medication safety for patients with mental illness in primary care. Medication safety challenges were defined using the drug-related problems (DRPs) categorisation.ResultsSeventy-nine studies were included with 77 (97.5%) reporting on epidemiology, 25 (31.6%) on aetiology, and 18 (22.8%) evaluated an intervention. Studies most commonly (33/79, 41.8%) originated from the United States of America (USA) with the most investigated DRP being non-adherence (62/79, 78.5%). General practice was the most common study setting (31/79, 39.2%) and patients with depression were a common focus (48/79, 60.8%). Aetiological data was presented as either causal (15/25, 60.0%) or as risk factors (10/25, 40.0%). Prescriber-related risk factors/causes were reported in 8/25 (32.0%) studies and patient-related risk factors/causes in 23/25 (92.0%) studies. Interventions to improve adherence rates (11/18, 61.1%) were the most evaluated. Specialist pharmacists provided the majority of interventions (10/18, 55.6%) with eight of these studies involving a medication review/monitoring service. All 18 interventions reported positive improvements on some medication safety outcomes but 6/18 reported little difference between groups for certain medication safety measures.ConclusionPatients with mental illness are at risk of a variety of DRPs in primary care. However, to date, available research exploring DRPs has focused attention on non-adherence and potential prescribing safety issues in older patients with dementia. Our findings highlight the need for further research on the causes of preventable medication incidents and targeted interventions to improve medication safety for patients with mental illness in primary care.

A Retrospective Real-Life Multicenter Study on Concurrent Oral Preventive Treatments in Patients with Chronic Migraine Treated with OnabotulinumtoxinA.

OnabotulinumtoxinA (BoNTA) is a relatively safe and effective treatment for chronic migraine. The local mode of action of BoNTA favors the combination of oral treatments with systemic action. However, little is known about the possible interactions with other preventive treatments. The objective of the study was to describe the use of oral preventive treatments in patients with chronic migraine treated with BoNTA in routine clinical care and discuss the tolerability and efficacy according to the presence or absence of concomitant oral treatments. In this multicenter, observational, retrospective, cohort study, we collected data from patients with chronic migraine receiving prophylactic treatment with BoNTA. Patients were eligible if aged ≥18 years, diagnosed with chronic migraine according to the International Classification of Headache Disorders, Third Edition criteria, and treated with BoNTA according to the PREEMPT paradigm. We documented the proportion of patients with at least one concomitant treatment prescribed specifically for migraine (CT+M) and their side effects during four BoNTA treatment cycles. Additionally, we collected monthly headache days and monthly acute medication days from the patients' headache diaries. Patients with CT+M were compared to those without concomitant treatment (CT-) using a nonparametric approach. Our cohort included 181 patients taking BoNTA, of whom 77 (42.5%) received a CT+M. The most frequently prescribed concomitant treatments were antidepressants and antihypertensive drugs. Side effects in the CT+M group occurred in 14 patients (18.2%). Only in three of them (3.9%), the side effects had a significant interference with the patient's functioning (all in topiramate 200-mg/day users). Both CT+M and CT- groups had a significant reduction in monthly headache days of respectively -6 (95% confidence interval -9, -3; p < 0.001; w = 0.200) during cycle 4 compared with baseline versus -9 (95% confidence interval -13, -6; p < 0.001; w = 0.469). However, the reduction in monthly headache days was significantly smaller in patients with CT+M after the fourth treatment cycle compared with patients with CT- (p = 0.004). Prescription of oralconcomitant preventive treatment is common in patients with chronic migraine receiving BoNTA. We did not identify any unexpected safety or tolerability issues in patients receiving BoNTA and a CT+M. However, patients with a CT+M experienced a smaller reduction in monthly headache days when compared with those with CT-, which might be associated with a higher resistance to treatment in that subgroup of patients.

Characteristics and Cost of Unscheduled Hospitalizations in Patients Treated with New Oral Anticancer Drugs in Germany: Evidence from the Randomized AMBORA Trial.

Drug-related problems (e.g., adverse drug reactions, ADR) are serious safety issues in patients treated with oral anticancer therapeutics (OAT). The previously published randomized AMBORA trial showed that an intensified clinical pharmacological/pharmaceutical care program within the first 12 weeks of treatment reduces the number and severity of ADR as well as hospitalization rates in 202 patients. The present investigation focused on unscheduled hospitalizations detected within AMBORA and analyzed the characteristics (e.g., frequency, involved OAT) and cost of each hospital stay. To estimate the potential savings of an intensified care program in a larger group, the absolute risk for OAT-related hospitalizations was extrapolated to all insureds of a leading German statutory health insurance company (AOK Bayern). Within 12 weeks, 45 of 202 patients were hospitalized. 50% of all unscheduled hospital admissions were OAT-related (20 of 40) and occurred in 18 patients. The mean cost per inpatient stay was EUR 5873. The intensified AMBORA care program reduced the patients' absolute risk for OAT-related hospitalization by 11.36%. If this care program would have been implemented in the AOK Bayern collective (3,862,017 insureds) it has the potential to reduce hospitalization rates and thereby cost by a maximum of EUR 4.745 million within 12 weeks after therapy initiation.

Safety and efficacy of the SGLT2 inhibitor dapagliflozin in patients with systemic lupus erythematosus: a phase I/II trial

ObjectiveSodium-glucose cotransporter-2 inhibitors have been identified profound renal/cardiac protective effects in different diseases. Here, we assessed the safety and efficacy of dapagliflozin among adult patients with systemic lupus erythematosus (SLE).MethodsWe...

The pharmacoepidemiology of potential drug-drug interactions in patients with psychiatric disorders

Actuality. Drug safety issues in patients with psychiatric disorders are relevant due to specifics of clinical pharmacology of the medicinal products used, possible treatment-resistance of mental illnesses and concomitant use of multiple antipsychotic drugs. One of the aspects of treatment safety is a prediction of drug-drug interactions.The aim of the study was to analyze potential drug-drug interactions in patients with psychiatric disorders.Materials and methods. The study enrolled 500 patients with psychiatric disorders in two age-related groups. Drug therapy was analyzed to reveal potential cases of drug-drug interactions.Results. A total of 1 031 cases of the use of drug combinations leading to drug-drug interactions of various clinical significance were revealed in 72.4 % of patients. There were significant differences between two age-related groups in respect of the specifics of medications use and clinical significance of drug combinations.Conclusion. Prediction of drug-drug interactions is likely to ensure improved drug safety in patients with psychiatric disorders.

In which patients the best efficacy of secukinumab? Update of a real-life analysis after 136 weeks of treatment with secukinumab in moderate-to-severe plaque psoriasis

ABSTRACTBackground: There is limited long-term, real-world evidence on the efficacy and safety in patients with plaque psoriasis treated with secukinumab. We present results at 136 weeks in a real-world setting with focus on special populations.Research design and methods: Retrospective analysis of 151 patients with chronic plaque psoriasis who initiated treatment with secukinumab between September 2015 and May 2019. Secukinumab 300 mg was administered once weekly for 5 weeks followed by once monthly.Main outcome measures: Clinical and laboratory assessments were performed up to 136 weeks.Results: At 16 weeks, 90%, 79%, and 63% of patients achieved Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100, respectively, compared with 79%, 72%, and 55% of patients after 136 weeks of therapy with secukinumab. Fifteen of the 151 patients experienced an adverse event, the most common of which was candida infection (4%). Biological treatment naïve was significantly associated with response to therapy at 1 and 2 years (P < 0.0001). There were no safety issues in patients with infection with HBV, HCV or mycobacterium tuberculosis.Conclusions: Our results confirm the rapidity of action of secukinumab as well as its long-lasting efficacy and good safety in real-world clinical practice.

Beta-blockers in cirrhosis: Evidence-based indicationsandlimitations.

SummaryNon-selective beta-blockers (NSBBs) are the mainstay of treatment for portal hypertension in the setting of liver cirrhosis. Randomised controlled trials demonstrated their efficacy in preventing initial variceal bleeding and subsequent rebleeding. Recent evidence indicates that NSBBs could prevent liver decompensation in patients with compensated cirrhosis. Despite solid data favouring NSBB use in cirrhosis, some studies have highlighted relevant safety issues in patients with end-stage liver disease, particularly with refractory ascites and infection. This review summarises the evidence supporting current recommendations and restrictions of NSBB use in patients with cirrhosis.

Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension

ObjectiveEvaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE).MethodsDuring the...

Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials

ObjectivesTo investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs).MethodsPubMed, Embase and Cochrane...

Factors Affecting Diagnostic Timeliness and Safety in Symptomatic Patients Subsequently Diagnosed With Bladder and Kidney Cancer: A Systematic Review

Background: Timely diagnosis of cancer is important for good clinical outcomes and patient experience. Bladder and kidney cancer, being two relatively common cancers, can pose diagnostic challenges. Symptoms such as hematuria and urinary tract infections in some patients have a higher than 3% positive predictive value for cancer, a threshold above which English GPs are advised to consider the referral of patients for, under the 2015 NICE guidelines. However, the majority of patients with these symptoms will end up not having cancer. Therefore, the decision to perform further investigations or refer patients with these common urinary symptoms may differ despite the existence of guidelines. Studying in whom, and why, some patients may experience a longer than average time to diagnosis is important to understanding how avoidable diagnostic delay can be reduced, so that targeted interventions to improve early diagnosis can be developed to improve, ultimately, the outcome of these cancers. Aim: A systematic review was therefore performed to identify the factors that affect the diagnostic timeliness and safety of patients with urological symptoms that may be suggestive of kidney and bladder cancer. Methods: We searched Embase and Medline (Ovid) between 2000 and January 2018, for publications on symptoms/conditions including hematuria and urinary tract infection (UTI). We focused on clinical features that are listed in the English 2015 NICE guidelines for suspected cancer to examine the population that are most likely to have cancer, and in whom a timely diagnosis is the most crucial for outcomes. We also included symptoms that might be suggestive of a UTI (including dysuria, urinary frequency, urgency, incontinence and nocturia) to be overinclusive in our search. Results: Our initial search identified 7787 articles. Following title and abstract screening, 37 full texts were assessed for eligibility. A final 23 relevant studies were included. Our preliminary findings include evidence on patient, clinician and system factors contributing to diagnostic timeliness and safety issues (such as completeness of evaluation/investigations and referrals) in patients with possible urological cancer. These include patient sociodemographic factors (age, gender, ethnicity), clinician type (generalist, urologist vs gynecologist) and experience, and system factors such as delay in specialist appointment scheduling and patient no-shows. Conclusion: Our findings will provide a granular understanding of the factors contributing to avoidable diagnostic delay of patients with possible urological cancers globally. This is particularly important so that targeted interventions can be developed to help clinicians and health systems to better identify and manage at-risk patients with symptoms, so as to improve early diagnosis and outcomes of urological cancers.

Safety of biologic DMARDs in RA patients in real life: A systematic literature review and meta-analyses of biologic registers

ObjectivesIn daily practice, safety in rheumatoid arthritis (RA) patients receiving biological treatment is an important issue. Unlike randomized controlled trials, biologic registers provide long-term real life safety data. To identify all biologic registers worldwide, to extract and analyze data regarding safety in RA patients under biologics. MethodSystematic review was performed independently by 2 rheumatologists using PUBMED, COCHRANE Library and EMBASE databases, up to December 2014. Worldwide biologic registers and related publications were identified. Data on safety issues in RA patients were extracted for meta-analyses. Random-effect meta-analyses were performed to estimate risk ratios (RRs) of mortality, cardiovascular events, cancer, including lymphoma and melanoma and serious infections between (1) biological and non-biological DMARD (cDMARD), (2) between biologics when data were available. ResultsForty-three biological registers were identified worldwide and 27 publications were included for safety meta-analyses on anti-TNFs. Compared to cDMARD, mortality and cardiovascular events were significantly decreased in patients treated with anti-TNFs: RR=0.60 [95% CI 0.38–0.94] and RR=0.62 [0.44–0.88], respectively. Anti-TNFs did not increase the risk of solid cancer in patients without or with prior malignancy (RR=0.84 [0.60–1.18] and RR=0.77 [0.29–2.03], respectively), lymphoma (RR=0.90 [0.62–1.31]) and melanoma (RR=1.17 [0.86–1.59]). As expected, serious infections were significantly increased during anti-TNF treatment (RR=1.48 [1.18–1.85]) compared to cDMARD. No significant difference was found between soluble receptor to TNF and monoclonal antibodies (RR=0.55 [0.22–1.35]). ConclusionsBy reducing dramatically chronic inflammation in RA patients, anti-TNFs decrease mortality, cardiovascular events without increase significantly the risk of cancer, compared to cDMARDs.

The Effects and Risks of High Intensity Interval Aerobic Exercise in Cardiac Rehabilitation Programme-A Critical Evaluation of Research

This review intends to explore the impact of high interval level of exercise intensity on physical fitness in cardiac rehabilitation. Specifically, this paper aims to determine if a high-intensity interval aerobic exercise is as effective as a moderately intense aerobic exercise programme for producing improvements in fitness level. Although numerous studies have emerged in the past decade revealing the advantages of high-intensity interval aerobic exercise for cardiac rehabilitation, this paper will review this question and will also provide novel information related to its effect and safety issues in patients with cardiovascular disease. Information gained from this review is believed to allow for more individualised and appropriate exercise prescription for cardiac rehabilitation programmes, as well as promote greater consistency and clarity related to the fitness of varying levels of exercise intensity.

Views and experiences of healthcare professionals towards the use of African traditional, complementary and alternative medicines among patients with HIV infection: the case of eThekwini health district, South Africa.

BackgroundMany patients with human immunodeficiency virus infection use traditional, complementary, and alternative medicines and other practices to combat the disease, with some also using prescribed antiretroviral therapy provided by the public health sector. This study aimed to establish the awareness of public sector biomedical health care providers on the use of traditional, complementary and alternative medicines by HIV-infected patients who also used highly active antiretroviral therapy, and to determine whether this was based on patients seen or cases being reported to them. Potential risks of interactions between the prescribed antiretroviral and non-prescribed medication therapies may pose safety and effectiveness issues in patients using both types of treatment.MethodsA descriptive cross-sectional study, using a researcher administered semi-structured questionnaire, was conducted from June to August 2013 at ten public sector antiretroviral clinics in five regional, three specialised and two district hospitals in eThekwini Health District, South Africa. Questionnaires were administered through face-to face interview to 120 eligible participants consisting of doctors, nurses, pharmacists and post-basic pharmacist assistants in HIV clinical practice. The results are presented as percent or proportion with standard error (SE), or as frequency.ResultsNinety-four respondents completed the questionnaire, yielding a response rate of 78.3 %. Almost half (48/94) were aware of patients using African traditional herbal medicines, over-the-counter supplements, unnamed complementary Ayurveda medicines and acupuncture. Twenty-three of the 94 respondents (24.4 %) said they had consulted patients who were using both antiretroviral therapy and certain types of non-prescribed medication in the previous three months.ConclusionsAwareness among healthcare providers on patient use of traditional, complementary and alternative medicines was relatively high. Few respondents had seen patients who used mostly African traditional medicines, over-the counter supplements, and negligible complementary Ayurveda medicines and acupuncture, with caution being advised in the interpretation of the former. Further research is needed to investigate communication between healthcare providers and patients in this regard, and levels of acceptance of traditional, complementary and alternative medicines by biomedical health care workers in HIV public sector practice.

Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double‐blind, placebo‐controlled study

This multicenter, double-blind, placebo-controlled study examined the efficacy and safety of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with metformin in Japanese patients with type 2 diabetes mellitus (T2DM). Patients were randomized in a 2: 1 ratio to 50 mg ipragliflozin (n = 112) or placebo (n = 56) once daily for 24 weeks, followed by a 28-week open-label extension in which all patients received 50 or 100 mg ipragliflozin, while continuing metformin. The primary outcome was the change in glycated haemoglobin (HbA1c) from baseline to week 24. HbA1c decreased significantly in the ipragliflozin group (−0.87%; adjusted mean difference from placebo: −1.30%; p < 0.001). The overall incidence of treatment-emergent adverse events was similar in both groups, although pollakiuria and constipation were more common in the ipragliflozin group; thus, ipragliflozin significantly improved glycaemic control and reduced body weight without major safety issues in Japanese patients with T2DM.

Application of a Self-Controlled Case Series Study to a Database Study in Children

Post-marketing surveillance activities are particularly important for safety issues in children, the elderly, and patients with severe comorbidities since these populations are usually excluded from clinical trials. In addition, using electronic databases for monitoring of safety of marketed products has been of considerable interest. This study aimed to clarify the advantages and difficulties of the self-controlled case series method relative to cohort studies in pharmacoepidemiological studies in children, using an administrative database, and to explore the impact on results of handling the period eligible for analysis and recurrent events in different ways. Datasets of only individuals who had the outcome of interest were derived from an anonymized hospital administrative database in Japan from April 2003 through August 2011. We calculated incidence rate ratios (IRRs) and their 95 % confidence intervals (CIs) for the risks of diarrhea, bronchitis, and eczema related to palivizumab treatment in young children. The analysis included 'first diagnosed' events or 'multiple' events during an eligible period. An eligible period was defined in two ways: first-time inpatient periods of more than 3 continuous days (EPA); and a continuous period in cases where the interval between visits was below the 75th percentile of the interval between visits for patients with the same diagnosis (EPB). We extracted data for 70,771 patients and identified 641 who were exposed to palivizumab. The age-adjusted IRRs for diarrhea, bronchitis, and eczema were 3.0 (95 % CI 1.7-5.4), 10.3 (95 % CI 8.0-13.2), and 16.9 (95 % CI 12-23), respectively, in multiple events and the EPB eligible period. The IRRs varied greatly between the two eligible periods. This method could be a useful tool in pharmacoepidemiological studies in children. Careful consideration in the handling of inpatient and outpatient periods, including sensitivity analyses, is necessary because this method is a within-individual comparison.

Intensive Treatment With Recombinant Factor VIIa (NovoSeven®) To Prevent Joint Bleeding In 4 Patients With Haemophilia A With Inhibitors Undergoing a Regular Program Of Physical Therapy

IntroductionThe development of anti-factor VIII inhibitors is the main complication of modern therapy of hemophilia A (HA) occurring in 25%-30% of severe forms. Inhibitors affect the possibility of a primary prophylaxis and regular physiotherapy, which is an important therapeutic tool to preserve joint function. In patients with severe HA with inhibitors, a prospective randomized study (Konkle et al J Thromb Haemost 5:1904, 2007) and the PRO-PACT retrospective multicenter observational study of a large case series (Young et al Thromb Res 130:864, 2012) have demonstrated the feasibility and effectiveness of secondary prophylaxis with recombinant activated factor VII (rFVIIa, NovoSeven®) in reducing hemarthrosis.Aim of the study: This study describes the unique experience of Hemophilia Pediatric Center of Turin (Italy) in a case series of 4 children with severe hemophilia A, history of high-titer inhibitor and mild or severe artropathy, who underwent to regular rehabilitation programme despite presence of inhibitors. MethodsPostural evaluation and gait analysis have been performed for each patient to assess posture and gait performance and plan a tailored therapeutic-rehabilitative treatment.Each physiotherapy session lasted about 45 minutes. rFVIIa at a dose of 90-180 mcg/kg in a preparation for rehabilitative treatment was administered immediately prior to each session.During physiotherapy sessions, children carried out both active and passive rehabilitation exercises to maintain adequate muscle strength and preserve joint range of movement (ROM). Basal and final joints angles (in degree) were measured with a goniometer. Manual Muscle Testing (MMT) was applied for grading muscle strength. ResultsClinical characteristics and individual physiotherapy program are listed below: Patient 1A 10-years-old African child with 2 target joints (knees) and 1 bleeding episode/month, has performed 102 sessions of active and passive rehabilitation treatment (November 2010 to November 2012) while on immune tolerance therapy (ITI). Patient 2A 12-years-old Caucasian child with 3 target joints (left elbow, knees) has performed a total of 16 sessions (February 2011 to April 2011). Patient 3A 2-years-old Caucasian child with a target joint (knee) has performed a total of 20 sessions (February 2011 to August 2012) while on ITI. Patient 4A 8-years-old Caucasian child with 4 target joint (elbow, 2 ankles) has performed a total of 149 sessions (November 2009 to November 2012) after failed ITI.Within 72 hours after each session, no joint nor muscle bleeding have been observed as evidence of the potential role of rFVIIa in preventing bleeding.The 4 children had a total of 287 physiotherapy sessions, each of them preceded by a single administration of rFVIIa. Treatment provided adequate hemostasis in all patients; no bleeding was observed during the sessions and in the following 3 days. The rehabilitative program obtained a gain of ROM in most of the 9 joints assessed and an improvement in muscle strength was also observed, as described in table. Postural evaluation and gait analysis confirmed these results. We did not observe thrombotic events nor infectious episodes. ConclusionCombination of rFVIIa and physiotherapy improved joint ROM and muscle strength in hemophilic children with inhibitors. The rehabilitation program has not given rise to safety issues in these young patients. Disclosures:Messina:Pfizer: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Baxter: Honoraria; Bayer: Honoraria. Forneris:Novo Nordisk: Honoraria, the autor has received reimbursement for attending a symposium and fees for speaking by Novo Nordisk Other. Off Label Use: rFVIIa is not licensed for nonsurgical prophylaxis in Italy. The use of rFVIIa in prophylaxis as a preparation for physiotherapy treatment currently is considered off label in Italy.

Pharmacovigilance as a tool for safety and monitoring: a review of general issues and the specific challenges with end-stage renal failure patients.

Pharmacovigilance is instrumental in helping to ensure patient safety for both newly released drugs and those that are well established in the market. However, while pharmacovigilance procedures are strictly regulated in the clinical trial setting, post-marketing adverse event reporting is not well implemented or enforced. As such, the underreporting of adverse events, in relation to drugs that are on the market, is estimated to be in the region of 90%. The identification of drug safety issues in patients with complex diseases and extensive comorbidities is therefore particularly challenging. Dialysis patients – those with end-stage renal disease and often other comorbidities such as diabetes, hypertension, and cardiovascular disease – are a population with significant treatment challenges. Patients receive dialysis using complex medical devices (eg, a peritoneal dialysis home cycler) and also receive a range of pharmaceutical agents as part of dialysis itself (eg, peritoneal dialysis solutions). Many of the pharmaceutical agents used to treat these patients have been developed in populations without these complications and, therefore, an extensive knowledge of potential problems and contraindications in the dialysis population is lacking. It is important that the nephrology community understands the concept of pharmacovigilance – the pharmacologic science relating to the detection, assessment, understanding, and prevention of adverse effects, particularly long-term and short-term side effects, of medicines. Health care professionals (HCPs) and providers, pharmaceutical companies, global regulatory agencies, and the patients themselves all play unique and critical roles in this process. This review defines the science of pharmacovigilance and the process of adverse event reporting, highlights the new directions that pharmacovigilance has taken, and provides insight for HCPs managing dialysis patients into the important role that they play in helping to shape the understanding of a drug’s safety profile in order to continually enhance patient safety.

Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope® in children requiring growth hormone treatment

To describe the rationale, design and first data from PATRO Children, a postmarketing surveillance of the long-term efficacy and safety of somatropin (Omnitrope(®)) for the treatment of children requiring growth hormone treatment. PATRO Children is a multicentre, open, longitudinal, noninterventional study being conducted in children's hospitals and specialised endocrinology clinics. The primary objective is to assess the long-term safety of Omnitrope(®) in routine clinical practice. Eligible patients are infants, children and adolescents (male or female) who are receiving treatment with Omnitrope(®) and who have provided informed consent. Patients who have been treated with another recombinant human growth hormone (rhGH) product before starting Omnitrope(®) are eligible for inclusion. All adverse events (AEs) are monitored and recorded, with particular emphasis on: long-term safety; the recording of malignancies; the occurrence and clinical impact of anti-hGH antibodies; the development of diabetes during Omnitrope(®) treatment in children short for gestational age (SGA); safety issues in patients with Prader-Willi syndrome (PWS). Efficacy assessments include auxological parameters, plus insulin-like growth factor-1 and insulin-like growth factor binding protein-3. As of September 2012, 1837 patients were enrolled in the study from 184 sites in 10 European countries. To date, efficacy data are reassuring and consistent with previous studies. In addition, there have been no confirmed cases of diabetes occurring under Omnitrope(®) treatment, no reports of malignancy and no safety issues in PWS patients. The efficacy and safety profile of Omnitrope(®) in the PATRO Children study so far are as expected. The ongoing study will extend the safety database for Omnitrope(®), and rhGH products more generally, in paediatric indications. Of particular interest, PATRO Children will add important information on the diabetogenic potential of rhGH in children born SGA, the risk of malignancies in children receiving rhGH, and AEs with a possible causal relationship to rhGH treatment in children with PWS.