Long-term Randomized Studies Research Articles

Treatment of bladder dysfunction with solifenacin: is there a risk of dementia or cognitive impairment?

The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.

Comparing the Effectiveness of Herbal and Conventional Dentifrices in Reducing Dental Plaque and Gingivitis: A Systematic Review.

ABSTRACTIntroduction:The important cause of chronic gingivitis was proved to be dental plaque, which is a well-organized biofilm. However, self-care efforts or mechanical control of dental plaque by toothbrushing was important; these alone will not be enough to prevent gingivitis.Aim:The aim of the present systematic review was to compare the effectiveness of herbal and conventional toothpastes on reduction of dental plaque and gingivitis.Materials and Methods:Data from original scientific papers published in PubMed, Cochrane, Lilacs, and Google Scholar were taken for review up to November 2020. Randomized controlled trials and clinical trials compare the effectiveness of herbal and non-herbal toothpastes on reduction of dental plaque and gingivitis. Articles published in English language only were included. References from the identified publications were manually searched to identify additional relevant articles. Seven publications fulfilled all the inclusion criteria and were finally selected for systematic review. Outcome measurements for gingivitis were gingival index and dental plaque index.Results:As all the studies were randomized controlled trials, level of evidence was II. Among all studies, green tea dentifrice toothpastes showed significant reduction when compared with conventional dentifrice, and ayurvedic toothpaste and Carica papaya leaf extract were also effective.Conclusion:Herbal toothpaste seems to be powerful similar to non-herbal toothpaste; however, it is no longer extra superior to fluoride toothpaste. Further, long-term randomized studies of >6 months are needed to investigate the beneficial effects of intervention alone.

Oral health-related quality of life and satisfaction in edentulous patients rehabilitated with implant-supported full dentures all-on-four concept: a systematic review.

Address oral health-related quality of life (OHRQoL) and patient satisfaction rehabilitated by the all-on-four concept as the primary outcome. A search was performed in the PubMed/MEDLINE, Web of Science, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria (PRISMA). The PICO question was used to address the following specific question: "What is the level of oral health-related quality of life and satisfaction in edentulous patients and with atrophic jaws who received dental implants for full-arch implant-supported restorations following the all-on-four in the mandible or maxilla?" Eleven studies including 693 patients aged 55 to 71 years were selected. The shortest follow-up period was 3 months and the longest, 7 years. Regarding the OHRQoL assessment method and patient satisfaction, the oral health impact profile (OHIP) and the visual analog scale (VAS) were the most used. OHRQoL and satisfaction in patients whose rehabilitation was based on the all-on-four concept were high. However, the current evidence is still limited by the quality of the available studies, making long-term randomized studies necessary to establish the real effectiveness of this surgical-prosthetic approach. Carefully analyze the aspects related to satisfaction and oral health-related quality of life of rehabilitated patients with implant-supported total prostheses made according to the all-on-four concept, aiming to achieve success through procedures with greater predictability and less complexity, as these are directly associated with recovery oral health of edentulous individuals with less morbidity and minimized costs.

The Impact of Restrictive and Non-restrictive Dietary Weight Loss Interventions on Neurobehavioral Factors Related to Body Weight Control: the Gaps and Challenges.

Restrictive diets, such as low-calorie diets, are difficult to maintain in the long term. For this reason, their popularity has decreased compared to non-restrictive approaches, which instead promote healthy eating strategies. Since both strategies may entail different neurobiological mechanisms, this review will examine the current evidence on the effects of restrictive and non-restrictive interventions on neurobehavioral factors. Restrictive diets appear to improve eating behaviors, and the evidence reviewed argues against the notion that they may worsen the severity of binge eating. Moreover, they may lead to short-term changes in brain structure and improvements in cerebrovascular markers which, in turn, could impact eating behaviors. Non-restrictive interventions may have a positive effect on weight management and eating behaviors. However, evidence of their neural effects is scarce. Small sample sizes, short follow-ups, and the absence of control groups are limitations of the studies targeting both interventions. Rigorous long-term randomized studies are needed to examine the neurobehavioral effects of restrictive and non-restrictive approaches.

İzole Koroner Ektazide Kopeptin Düzeyi

Introduction: The level of copeptin was investigated in patients who underwent coronary angiography for suspected coronary artery disease and diagnosed with isolated coronary artery ectasia (CAE). Patients and Methods: A total of 308 patients were diagnosed as having coronary ectasia out of 3412 patients who underwent coronary angiography between May 2015 and July 2016. The evaluations were performed by two experienced physicians who were aware of the study design. Among these patients, 41 patients who did not have severe coronary artery disease (CAD) and who were diagnosed as having isolated CAE were included in the study. The control group comprised 33 age- and gender-matched individuals diagnosed as having normal coronary arteries following coronary angiography for suspected CAD. Patients with a previous coronary revascularization for severe CAD, known congestive heart disease and severe cardiac valve disease, and a left ventricular ejection fraction below 50% were excluded from the study. Blood samples were obtained from both groups and the serum copeptin levels were compared with each other. Results: Among patients with CAE, the frequency of isolated CAE was 14.9%. Among the total coronary angiography series, the frequency of isolated CAE was 1.34%. Most patients with isolated CAE were men (70%; women: 30%), and the mean age of the patients was 58 ± 9.2 years. In patients with isolated CAE, the frequencies of type I, type II, type III, and type IV CAE were found to be 4.3%, 17.4%, 32.6%, and 45.6%, respectively, according to Markis classification. The level of copeptin was found to be 7.8 ± 0.9 pmol/L in patients with normal coronary arteries and 9.7 ± 1.6 pmol/L in patients with isolated CAE (p< 0.028). Conclusion: The level of copeptin is increased in patients with isolated CAE. However, our results have to be supported by long-term randomized studies on isolated CAE patients with and high copeptin levels.

Natural products - alpha-lipoic acid and acetyl-L-carnitine - in the treatment of chemotherapy-induced peripheral neuropathy.

Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of anticancer agents. Yet, CIPN pathophysiology is poorly understood, and there is a lack of well-tolerated pharmacological remedies helpful to prevent or treat it. Therefore, new safe and effective compounds are highly warranted, namely if based on an adequate understanding of the pathogenic mechanisms. Herein we reviewed and discussed scientific data related to the beneficial role of some non-conventional treatments able to counteract CIPN, focusing our attention on alpha-lipoic acid (ALA) and L-acetyl-carnitine (LAC), two natural products that have been demonstrated to be promising preventive drugs. Although a growing body of in vitro and in vivo studies support ALA as a molecule able to counteract CIPN symptoms, mostly due to its antioxidant and anti-inflammatory properties, only two randomized clinical trials evaluated ALA usefulness in preventing chemotherapy-related neuropathy. Unfortunately, these studies were inconclusive and clinical outcomes showed to be highly dependent on the route of administration (oral versus or intravenous injection). LAC has demonstrated beneficial effects on both in vitro and in animal studies. Yet, some controversies aroused from randomized clinical trials. Indeed, while CIPN-patients treated with Taxane showed no benefit from LAC treatment, CIPN-patients treated with platinum compounds exhibit significant improvement of CIPN-related symptoms. Therefore, LAC treatment should be used, and thoroughly investigated only in patients treated with chemotherapy protocols Taxanes-free. Mechanisms of toxicity triggered by each single drug need to be deeply explored to better identify effective compounds to prevent or treat them. Moreover, additional experiments are mandatory to establish effective doses and length of treatment for each clinical situation in order to perform large and long-term randomized studies.

Virtual Reality May Soon Become Clinical Reality in Psychosis Care

Virtual Reality May Soon Become Clinical Reality in Psychosis Care

Functional outcomes of percutaneous pinning augmented by Joshi's clamp in displaced extra-articular distal radius fractures

Aim: Fractures of the distal radius in adults are a common injury, particularly in the elderly people. Closed reduction of displaced extra-articular fractures and percutaneous pinning is a well-established treatment option. The aim of the study was to assess the functional outcomes of percutaneous pinning augmented by Joshi's clamp in patients with displaced extra-articular distal radius fractures. Materials and Methods: Twenty adult patients with displaced fractures requiring manipulation were recruited prospectively over a 1-year period. There were 13 (65%) females and 7 (35%) males, with a mean age of 36.45 years (range; 20–55 years). All the procedures were performed in the operating room by a single surgeon. External plaster support was not needed. Immediate postoperative active wrist mobilization was started. The patients were followed at 2, 6, and 8 weeks, and then monthly for a minimum of 6 months, looking for clinical and radiological union, Cooney's wrist score, and any complication. Results: None of the patients was lost to follow-up. According to the Cooney's score, 9 patients (45%) had good results, 9 patients (45%) had fair results, and poor results in 2 patients (10%). Fracture consolidation was achieved at an average of 43 days (range; 36–50). With regards to complications, 2 patients (10%) had a painful scar and 2 patients (10%) had a pin-tract infection. Conclusion: This technique is a viable alternative option. It allowed minimal soft-tissue injury, adequate stability, and early rehabilitation in our patients. Long-term comparative randomized studies are still warranted.

Comparison of Freeze-Dried and Solvent-Dehydrated Acellular Dermal Matrix for Root Coverage: A Randomized Controlled Trial.

The prevalence of gingival recession has been estimated at around 22.5% in people aged older than 29 years. Classic treatment approaches include the use of connective tissue grafts in combination with coronally advanced flaps (CAFs). To reduce morbidity and the need for a secondary surgical site, allograft materials are currently being used. Nevertheless, long-term randomized studies testing the efficacy of these materials are lacking. Hence, the aim of the present randomized controlled clinical trial was to compare two acellular dermal matrix (ADM) materials produced by different processing techniques, freeze-dried (FDADM) and solvent-dehydrated ADM (SDADM). At 12 months, both groups showed significant improvement in attachment level, recession depth, and recession width. A mean improvement in attachment level of 2.0 ± 1.08 mm for FDADM and 2.0 ± 0.70 mm for both SDADM was achieved (P = .002). Root coverage after 12 months was 80.66 ± 22.90% for FDADM and 80.97 ± 18.08% for SDADM. Hence, it was concluded that both FDADM and SDADM grafting materials can successfully achieve root coverage in Miller Class I and II recession defects for up to 12 months when used in combination with CAFs.

Robotic-Assisted Thoracic Surgery for Early-Stage Lung Cancer: A Review

This review evaluates the benefits and disadvantages associated with the use of robotic-assisted technology in performing lobectomies in patients with early-stage lung cancer. The author conducted a literature search of Ovid®, MEDLINE®, PubMed®, and CINAHL® for articles published from 2005 to 2013. Search criteria included key terms such as robot, robotic, robotic-assisted lobectomy, and lung cancer. Of 922 articles, the author included a total of 12 research-based published studies in the analysis and incorporated the findings into an evidence table. Results showed that robotic-assisted lobectomies are feasible safe procedures for patients with stage 1A or 1B lung cancer; however, there is a steep learning curve and long-term randomized studies evaluating robotic-assisted lobectomy and conventional posterolateral thoracotomy or video-assisted thoracic lobectomy are needed. For patient safety, perioperative nurses should be aware of the length of time and experience required to perform these procedures, the costs, techniques, benefits, and disadvantages.

Potential interactions of prescription and over-the-counter medications having antioxidant capabilities with radiation and chemotherapy.

Oncology patients undergoing radiation treatment and chemotherapy routinely use prescription and/or over-the counter medications either as part of pre-existing comorbid conditions or in the context of conventional treatment management. A growing amount of data suggest that commonly used pharmaceuticals possess antioxidant properties, which may also partially explain some of their therapeutic efficacy. Clinical research is continuing on how such agents interact during chemotherapy and radiation when oxidative mechanisms of action are involved. Historically, such discussions centered on the category of dietary supplements, natural health products, fruits and vegetables, along with established protectant medications. Evidence confirms that some pharmaceutical agents exhibit antioxidant properties similar to dietary supplements, protectants, and may hence hinder the efficacy of chemotherapy and radiation treatment. Awareness by both healthcare providers and patients in this area is often lacking. After reviewing some of the more common and well-established pharmaceuticals, which include those prescribed during cancer treatment, caution needs to be advised especially in regards to the use of corticosteroids, as long-term randomized outcome studies ensuring safety in this area are still outstanding.

Clinical comparision of intravesical hyaluronic acid and hyaluronic acid-chondroitin sulphate therapy for patients with bladder pain syndrome/interstitital cystitis.

Patients with a history of bladder pain syndrome/interstitial cystitis (BPS/IC) and who responded poorly or unsatisfactorily with previous treatment were compared taking intravesical hyaluronic acid (HA) or hyaluronic acid-chondroitin sulphate (HA-CS). Patients were treated with intravesical instillation with 50 mL sterile sodium hyalurinic acid (Hyacyst, Syner-Med, Surrey, UK) (n = 32) and sodium hyaluronate 1.6% sodium chondroitin sulphate 2% (Ialuril, Aspire Pharma, UK) (n = 33). Intravesical instillations were performed weekly in first month, every 15 days in the second month and monthly in third and fourth months, for a total of 8 doses. Patients were evaluated using a visual analog pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, cystometric bladder capacity and voided volume at the beginning and at 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann-Whitney U tests were used for statistical analysis. In total, 53 patients met the study criteria. There were 30 patients in the HA-CS group (mean age: 48.47) and 23 patients in the HA group (mean age: 49.61) (p > 0.05). The initial PST was positive in 71.7% patients (38/53) overall with no difference between groups (p > 0.05). Responses for VAS, ICCS, ICPS, 24-hour frequency/nocturia statistically improved in both groups at 6 months. There was no significant difference in symptomatic improvement (p > 0.05). Eight patients had mild adverse events. HA and HA/CS instillation can be effective in BPS/IC patients who do not respond to conservative treatment. An important limitation of our study is that the HA dosage of the 2 treatment arms were different. It would be more appropriate with same HA dosage in both groups; however, there was no commercially available glycosaminoglycan (GAG) substance with same HA dosage for single and combination therapy. Large, long-term randomized studies are required to determine if there is a difference between these treatments.

Oral Health and menopause: A comprehensive review on current knowledge and associated dental management

The menopause is physiological changes in women that give rise to adaptive changes at both systemic and oral level. As we all begin to reach an older age, dental health and hygiene becomes a major concern. The dentist is often the first person to appreciate numerous changes that are experienced throughout the body during menopause. The teeth and gums are extremely susceptible to any hormonal changes that take place just before menopause and readily decrease body's ability to fight off minor infections or maintain a healthy balance of useful and harmful bacteria within the oral environment. This review aimed to develop better understanding for major oro-dental complications observed in women during menopause, and schematic approach towards the different dental management protocols used during these periods. Various internets based popular search engines were used to explore related data from literature, which includes PubMed, PubMed Central, Cochrane, Google, Medknow, Ebsco, Science Direct, and IndMed. Upon compilation of relevant data, it was observed that periodontal health is most severely affected (up to 60%) followed by dry mouth (25%) and burning mouth (glossodynia; 15%) which, in turn, may increase the occurrence of oral mucosal and dental diseases, such as candidiasis. Though, the usage of hormone replacement therapy is effective but it does not necessarily prevent or help women with oral symptoms. Therefore, well controlled long-term randomized studies are needed to establish more authentic clinical guidelines for successful management of such conditions.

Prebiotics and nucleotides in infant nutrition; review of the evidence

Most of the initiation and maintenance pediatric formulas commercialized in Spain contain prebiotics and/or nucleotides aiming at achieving beneficial effects on prevention of different pathologies and immune protection, similar to human breast milk. However, according to the current legislation, its inclusion is optional since sufficient scientific evidences supporting its mandatory inclusion is lacking. To systematically review the scientific evidence from randomized clinical studies with a control group allowing determining the beneficial role for infant health derived from the inclusion of prebiotics and/or nucleotides in pediatric formulas. We looked for and selected both original papers and reviews in Spanish and English language of placebo controlled randomized clinical studies published in the databases MEDLINE/PubMed, Scielo, Science Direct, and Scopus, until October of 2011. We found 43 randomized clinical trials meeting the inclusion criteria. More long-term randomized studies with higher number of patients, and standardized supplemental amounts and experimental conditions are needed to establish healthy statements with stronger scientific support regarding the addition of a mixture of prebiotics (GOS/FOS) and/or nucleotides in pediatric formulas. The current trend to include them in pediatric formulas may be justified based on the currently available evidence, as well as their safety and their presence in human breast milk.

Rate Control in Atrial Fibrillation.

Rate control may now be adopted as a first-choice therapy in a variety of patients, especially older relatively asymptomatic patients with hypertension or other underlying heart diseases. The goal of rate control therapy is to minimize symptoms, improve quality of life, decrease the risk of development of heart failure, and prevent thromboembolic complications. A lenient rate control approach may be the initial therapeutic strategy. If symptoms persist, a stricter rate control approach may be adopted. Although long-term randomized studies are lacking, the evidence available suggests that a β-blocker with or without digoxin is the first-choice rate control therapy.

Prostate cancer screening behaviour

Prostate cancer remains the most common non-cutaneous malignancy, and it is diagnosed by measurement of prostatespecific antigen (PSA), digital rectal examination (DRE), transrectal ultrasound and biopsies. Routine screening with measurement of PSA cannot be justified until long-term randomized studies demonstrate that PSA screening has a significant impact on morbidity and mortality.1 Hopefully, the results of the European Randomized Screening for Prostate Cancer Study among 190,000 men and of the Prostate, Lung, Colorectal and Ovary Screening Study of the US National Cancer Institute upon 74,000 Americans will be available for discussion in 2008.1 Furthermore, PSA screening may result in false-positive cases and diagnosis of clinically insignificant (non-life-threatening) cancers, while there is absence of definitive biopsy results. The controversy regarding routine screening reflects the uncertainty about treating all prostate cancer cases in terms of survival and quality of life. Last but not least is the public health issue of funding for prevention. The American Cancer Society guidelines suggest that men over the age of 50 years should be offered annual DRE and PSA screening (45 years for African Americans and those with a positive family history) as long as they are informed of the benefits and limitations of screening and have a life expectancy of at least 10 years.3 In the UK, the National Screening Committee has introduced a PSA informed choice programme entitled ‘Prostate Cancer Risk Management Programme’. The objective of this programme is to ensure that men receive clear and balanced information about the PSA screening test, and relevant information packs have been sent to general practitioners (GPs) to assist them with screening counselling. However, evidence is scarce regarding the psychological

Long‐term outcome of branched‐chain amino acid treatment in patients with liver cirrhosis

Clinical impact of protein-energy malnutrition (PEM) on the outcome of liver cirrhosis is well documented. As a candidate interventional modality to improve PEM in cirrhosis, effects of branched-chain amino acid (BCAA) supplementation on event-free survival and quality of life (QOL) was first reported by Yoshida et al. in 1989. Although critical arguments still continue regarding the effects of BCAA, several randomized trials in the last 5 years have brought positive results, and seem to have settled the discussion in a favorable direction for the efficacy of BCAA in liver cirrhosis. Actually, The European Society for Clinical Nutrition and Metabolism (ESPEN) upgraded the recommendation of BCAA supplementation in decompensated liver cirrhosis in the latest revision of its guidelines in 2006, by referring to the literatures from Italy and Japan. Particularly in these two long-term randomized studies with 1-2 years-supplementation, event-free survival was estimated by employing composite endpoints such as aggravation of hepatic failure (ascites, peripheral edema, hepatic encephalopathy, and jaundice), rupture of esophageal or gastric varices, development of liver cancer, and death from any cause. Both trials agreed on the effect of BCAA to reduce the incidence of hepatic failure, thus contributing to the rise in the event-free survival. Quality of life is another essential marker of outcome survey. Marchesini, Muto, and Nakaya reported the improved QOL in cirrhotics with BCAA supplementation. In particular, quantitative analysis of QOL measured by Short Form 36 (SF-36) questionnaire demonstrated a significant recovery of general heath perception score in BCAA supplemented patients in a randomized trial. In this article, the long-term outcome of BCAA treatment in liver cirrhosis will be reviewed with its action mechanisms. In addition, the effects of BCAA treatment on the incidence of liver cancer in obese patients with type C liver cirrhosis, significance of obesity as a risk factor for type C liver cancer, and a possible role of Body Mass Index to estimate the histological grade of fat deposition in the liver will be briefly discussed.

Complex Sleep Apnea: It Isn't Really a Disease

Complex Sleep Apnea: It Isn't Really a Disease

Infliximab in Crohn's disease: early and long-term treatment

The natural history of Crohn's disease is characterized by a remitting and relapsing course that progresses to complications and surgery in the majority of patients. Current treatment guidelines advocate a stepwise approach according to disease location and severity at presentation, with goals mainly aimed at inducing and maintaining clinical remission. Major advances in the understanding of the pathogenesis of Crohn's disease offered significant opportunities for the development of new therapies over the past years. Infliximab and other biologic agents have shown impressive results in Crohn's disease patients refractory to standard therapy, suggesting a potential disease course-modifying action. These led to the proposal to reverse the traditional therapeutic algorithms using these agents early in the course of the disease. Preliminary data suggest that early intervention may be a more effective treatment strategy in some Crohn's disease patients. As yet, early and indiscriminate use of biologics remains to be supported by convincing evidence. Data on long-term treatment of Crohn's disease with infliximab or other biologics are even more scarce. Future studies aimed to identify predictors of complicated disease and long-term randomized studies aimed to compare "step-up" and "top-down" strategies in high-risk groups should help to answer if early introduction of biological therapy alters the natural history of Crohn's disease.

Secondary Prophylaxis in a Cohort of Adolescent and Adult Italian Hemophiliacs.

Although primary prophylaxis is a well-established and widely recommended practice for the management of patients with severe hemophilia, there are limited data in the literature documenting the benefit of secondary prophylaxis initiated in adolescence or adulthood. In order to address this issue we have conducted a retrospective study among the 10 Italian Hemophilia Centers on adolescent and adult patients with severe hemophilia switched from on-demand treatment to a long term secondary prophylaxis regimen. On the whole, we collected information on 73 consecutive patients with severe hemophilia (66 hemophilia A and 7 hemophilia B). Their median age started prophylaxis was 12 (range 10–17) for 23 adolescents and 30 (17.4–72) for the 50 adults and continued for a median of years 5.8 (2–14.7) in adolescents and 4 years (1.5–12) in adults. The clinical impact of secondary prophylaxis with respect to the last year on-demand regimen before switching is showed in the following table for each group of patients.Adolescents (n=23)Adults (n=50)On-DemandProphylaxisOn-DemandProphylaxisBleedings32.4(24.8)2.8 (3.2)42.7 (24.5)5.5 (5.2)Joint bleedings25.6 (22.1)1.9 (2.3)36.4 (24.5)4.2 (4.1)Orthopaedic score8.4 (7.5)3.7 (2.4)21.6 (12.2)17.7 (12.2)Pettersson score5.1 (3.4)5.0 (3.3)14.7 (13.8)15.2 (14.3)Work/school days lost35.1 (34.5)1.0 (1.5)33.8 (20.9)2 (0–17)Concentrate consumption U/Kg/y2449.8 (1761.9)3508.3(803.1)3222.6 (2241.8)4058.5 (952.3)Values are reported as mean (standard deviation)The decreased joint bleeding, better orthopaedic score, less work/school days lost, delayed progression of arthropathy and improved well-being observed with secondary prophylaxis show the benefit of this therapeutic approach and appear to counterbalance its higher clotting factor consumption. In conclusion large, prospective, long-term randomized studies are needed to definitevely assess the clinical impact of this strategy in adolescent and adult hemophiliacs and to identify those groups of patients who would benefit from this therapeutic approach.