Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study.

INTRODUCTION: Current treatment for haemophilia A involves factor VIII replacement or non-replacement (emicizumab) therapies, neither of which permanently normalise factor VIII levels. Gene therapy using adeno-associated viral (AAV) vectors is an emerging long-term treatment strategy for people with severe haemophilia A (PwSHA) that is likely to be available for clinical use in the near future. AIM: This article proposes practical guidelines for the assessment, treatment, and follow-up of potential PwSHA candidates for AAV-based gene therapy. METHOD: Using the Delphi method, a working group of Italian stakeholders with expertise in and knowledge of the care of adults with haemophilia A analysed literature for AAV-based gene therapy and drafted a list of statements that were circulated to a panel of Italian peers. During two rounds of voting, panel members voted on their agreement with each statement to reach a consensus. RESULTS: The Delphi process yielded 40 statements regarding haemophilia A gene therapy, across five topics: (1) organisational model; (2) multidisciplinary team; (3) patient engagement; (4) laboratory surveillance; and (5) patient follow-up and gene therapy outcomes. The consensus was reached for all 40 statements, with the second round of voting needed for five statements. CONCLUSION: Use of the hub-and-spoke organisational model and multidisciplinary teams are expected to optimise patient selection for gene therapy, as well as the management of dosing and patient follow-up, patient engagement, laboratory surveillance, and patient expectations regarding outcomes. This approach should allow the benefits of AAV-based gene therapy for haemophilia A to be maximised.

[Results of a vertebral deformity screening in the students of the district of Florence (Tuscany Region, Central Italy)]. / Risultati di uno screening per le deformità vertebrali tra gli studenti delle scuole del comune di Firenze.

OBJECTIVES: to observe the prevalence of vertebral deformities in an adolescent population in the 178 schools of the District of Florence (Tuscany Region, Central Italy), correlating these results with clinical aspects as ligamentous laxity and verifying if these data are in agreement with what emerged in literature in studies of the same type. DESIGN: prevalence study. SETTING AND PARTICIPANTS: report of the results of a school screening for vertebral deformities in an adolescent population of 11,820 students of the Schools of District of Florence held between November 2010 and June 2013. MAIN OUTCOMES MEASURES: asymmetry of waist triangle; trunk imbalance using plumb-line from C7; leg length discrepancies; presence of gibbus and measurement of Angle of Trunk Rotation using Bunnell scoliometer; measure of thoracic kyphosis (a value of kyphosis> 50° was considered to be at high risk of hyperkyphosis making it necessary to request an X-ray); ligamuentuos laxity using Beighton Score. RESULTS: 11,820 students were screened; 85.95% of them had no significant spinal deformities; 14,05% of the students showed significant clinical signs of scoliosis; 28.46% of the students had a thoracic hyperkyphosis (>40°), 1.55% of those presented a non-reducible thoracic hyperkyphosis. Results show a statistically significant correlation between the severity of the deformities and the score of the Beighton Score. CONCLUSIONS: the results confirm the association between vertebral deformities and ligament laxity. The prevalence of vertebral deformities in the school age population of the Municipality of Florence is 14.05%, in accordance with what emerged in the literature from similar studies.

Lower limbs heterometry correction in patients with osteoporosis and increased risk of falls.

Osteoporotic fractures are associated with a significant increase in morbidity, mortality and medical costs. There is also a strong link between fractures and increased mortality. Among effective measures for the prevention of falls, instability treatment surely plays a crucial role. Several factors contribute to instability, many of which are ageing-related: visual spatial deficit, strength reduction, weight imbalance with COP lateralization sometimes favoured by LLD (leg length discrepancy). It seems useful to detect an heterometry which could be corrected, if present. The aim of our work is to assess the responses of individuals with heterometry diagnosis to the wedge positioning, using the balance board Lizard 3.0®. In the period between January 2013 and September 2013, 52 patients were recruited with clinical heterometry >5 mm among those that were treated in the Recovery and Rehabilitation Agency's postural clinic of the Careggi Hospital Orthopedic Trauma Centre in Florence. Our measurements have revealed that there is a statistically significant correlation (p<0.5) between clinical limb shortening expressed in mm and location of the weight imbalance at the stabilometric examination at T0; our data shows that the majority of patients with clinical heterometry shows a weight imbalance on the longer limb. After heterometry correction, 21 patients showed a statistically significant reduction (p<0,01) in weight imbalance expressed in kg between T0 and T1 and have been assigned to group 1, the remaining 31 worsened and have been assigned to group 2. From the results of our study, it is clear that the correction of lower limbs heterometry shouldn't be based only on clinical measuring of the limbs length discrepancy, even if very accurate.

Conservative treatment of carpal tunnel syndrome: comparison between laser therapy and Fascial Manipulation(®).

The etiopathogenesis of Carpal Tunnel Syndrome (CTS) is multifactorial and most cases are classified as idiopathic (Thurston 2013). A randomized controlled trial was performed to compare the effectiveness of Fascial Manipulation(®) (FM) and Low-Level Laser Therapy (LLLT) for CTS. This prospective trial included 42 patients (70 hands with symptoms) with clinical and electroneuromyographic diagnosis of CTS. The patients were randomly assigned to receive multiple sessions of FM or multiple session of LLLT. The Visual Analogic Scale (VAS) and Boston Carpal Tunnel Questionnaire (BCTQ) were performed at baseline, end of treatment and after three months. The group that received FM showed a significant reduction in subjective pain perception and an increased function assessed by BCTQ at the end of the treatment and follow-up. The group that received LLLT showed an improvement in the BCTQ at the end of the treatment but the improvement level was not sustained at the three month follow-up. FM is a valid alternative treatment for CTS.

Infiltrative treatment with Platelet Rich Plasma (PRP) in gonarthrosis.

The aim of the study is to evaluate and to quantify the effects on the quality of life and the decrease of pain in short and middle term in patients affected of gonarthrosis and treated with a series of 3 injections of Platelet Rich Plasma (PRP). Gonarthrosis is one of the most frequent causes of disability on old ages and leads to difficulties in social, relational and daily activities (1). The most common therapeutic approach depends on the stage of the disease, it can be conservative (FKT), palliative (HA injections, chondro - protector) or reconstructive (TKR). Between October 2010 and January 2013, 72 patients referring to the outpatient clinic of the Rehabilitation Department of the Trauma Center, University Hospital of Careggi, Florence, have been enrolled if a primary gonarthrosis was diagnosed. The patients, after a hematology visit in Immune-Hematology Department of Careggi, have been evaluated with the WOMAC scale for the knee, VAS at rest and VAS in movement before a series of 3 injections with PRP (T0), after 1 months (T1), after 3 months (T2) after 6 year (T3) and after 1 year (T4) from the last injection. PRP injections can be considered a valid method in the control of pain, stiffness and joint function (24, 25) but it have to be considered as a second approach to the treatment of knee OA, due to the high cost and complexity of the procedure. Most of our patients shown good clinical results after one year, were satisfied of the treatment and returned to their previous daily activities.

Pathogenesis and treatment of falls in elderly.

Falls in the elderly are a public health problem. Consequences of falls are increased risk of hospitalization, which results in an increase in health care costs. It is estimated that 33% of individuals older than 65 years undergoes falls. Causes of falls can be distinguished in intrinsic and extrinsic predisposing conditions. The intrinsic causes can be divided into age-related physiological changes and pathological predisposing conditions. The age-related physiological changes are sight disorders, hearing disorders, alterations in the Central Nervous System, balance deficits, musculoskeletal alterations. The pathological conditions can be Neurological, Cardiovascular, Endocrine, Psychiatric, Iatrogenic. Extrinsic causes of falling are environmental factors such as obstacles, inadequate footwear. The treatment of falls must be multidimensional and multidisciplinary. The best instrument in evaluating elderly at risk is Comprehensive Geriatric Assessment (CGA). CGA allows better management resulting in reduced costs. The treatment should be primarily preventive acting on extrinsic causes; then treatment of chronic and acute diseases. Rehabilitation is fundamental, in order to improve residual capacity, motor skills, postural control, recovery of strength. There are two main types of exercises: aerobic and muscular strength training. Education of patient is a key-point, in particular through the Back School. In conclusion falls in the elderly are presented as a "geriatric syndrome"; through a multidimensional assessment, an integrated treatment and a rehabilitation program is possible to improve quality of life in elderly.

Biomechanical analysis and rehabilitation in athletes.

Posture is defined as the position of the body at a given point in time. Incorrect relationship among different parts of body produces an higher tension on retaining structure that causes postural problems. Posturology is fundamental to recognize the relationship between postural attitude and some pathological conditions otherwise difficult to recognize. We can use force platform, baropodometric or dynamometric platform to analyze tonic postural system and to evaluate sensitive receptors. The main injuries in athletes are caused by cumulative trauma. Rehabilitation process is divided in three phases: an acute phase, a post-acute phase and a "return to play" phase. The goal of prevention and rehabilitation is to find and remove stress and pathologic agent, to reduce the limitation of the range of motion, control pain and come back to sport.

Radial extracorporeal shock-wave therapy in rotator cuff calcific tendinosis.

The objective of the study is to evaluate the effectiveness of Radial Extracorporeal Shock-wave Therapy (RESWT) compared with High Power LASER Therapy (HPLT) for the treatment of patients with Rotator Cuff Calcific Tendinosis (RCCT). RCCT is widely diffused, it is painful and invalidating. It is an important public health problem with social and economic implications. The most common therapeutic approach is a physiotherapic one. Both HPLT and RESWT give positive results. There is a debate on which is to be preferred. Therefore there is need to obtain scientific evidence to support either case. An observational study was carried out in the period between October 2008 and September 2009 in our outpatient clinic with 62 patients, divided into 3 groups: group A 36 patients treated only with RESWT, group B 26 patients treated only with HPLT and group C 16 patients with only short term improvement with HPLT retreated with RESWT. Patients were evaluated with Constant-Murley scale before and after treatment (immediately, 1 month and 3 months) for mean constant score, pain and range of movement. Data were examined statistically with SPSS. Criteria for inclusion and exclusion were defined. Patients treated with HPLT have shown good clinical results but have returned to original syndrome 1 month after treatment. RESWT has given improvement after treatment extended in time (3 months) in terms of pain and recover of functionality with a limited number of applications. The evidence collected indicates that RESWT is the method of choice.

Evaluation with stabilometric platform of balance disorders in osteoporosis patients. A proposal for a diagnostic protocol.

Osteoporosis is a systemic disease with reduced bone mass and qualitative alterations of the bone, associated to increased risk of fracture. Pathogenesis of osteoporosis fractures is multifactorial. Main risk factor is falls (except for vertebral fragility fractures which occurs often in absence of trauma). Aging by itself produces physiological changes: muscular hypotrophy with asthenia, deficit of visus and hearing together with associated pathologies and multi-drug therapies. In osteoporosis patients with vertebral fractures posture change occurs which reduces balance. After clinical postural evaluation it is possible to carry out instrumental evaluation of posture with computerized methods such as stabilometry, baropodometry, dynanometry and gait analysis. Examination carried out with use of stabilometric computerized platform allows stabilometric (body sway assessment) as well as posturometric examination (center of pressure assessment during quiet standing). Fundamental parameters obtained are: position of the body center of gravity, area and shape of sway density curve and velocity variables. Protocol of evaluation includes assessment of examination in standard condition and in condition of temporary sensorial deprivation (to investigate the influence of various afferent systems on the maintenance of posture and balance). Accurate evaluation of postural control in osteoporosis patients constitutes a fundamental tool in fracture risk evaluation due to fall and in identification and correction of modifiable factors responsible for balance defect. This approach, together with adequate drug therapy, may lead to significant reduction of fractures in osteoporosis patients with subsequent reduction of hospitalization and residual consequent disabilities.

Rehabilitation in osteoporotic vertebral fractures.

Vertebral fractures occur particularly in osteoporotic patients due to an increased bone fragility. Vertebral fractures influence the quality of life, mobility and mortality. Preventive training exercises and proprioception reeducation can be utilised for improving posture, balance and level of daily function and for decreasing pain. Quality of life is improved even beyond the active training period. This mini review provides information based on the literature for the rehabilitation of osteoporotic vertebral fractures after conservative or surgical treatment.

Rehabilitation in peripheral non femoral fractures: a review.

This paper is a short review of the available information on peripheral non femoral fractures (PNFF) which are strictly related to osteoporosis. Particular attention is focused on wrist fractures in view of their frequent occurrence as indicated by world wide statistics. Of special interest is the definition of risk groups (old age), risk areas (developed countries) and risk factors. Reference is made to 2008 WHO guidelines for fracture risk assessment. PNFF are a serious concern to health authorities because their high incidence in constant growth, causes a serious burden on the health budget. The pathway of patient care is described, from initial evaluation (including bone fragility, multi-morbidity and risk factors) to specific diagnosis and treatment. The multiplicity of etiological factors involved requires multidisciplinary approach. This aspect justifies the importance given to rehabilitation, which is the longest part of patient care and is strictly connected to preventive measures. There is ample reference to falls, to exercises, to appropriate sports, to complications and to active and passive mobilization. The paper suggests research in areas related to PNFF, to health economics, epidemiology, prevention, health education, training and multidisciplinary coordination.