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Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.
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Continuidad de la Atención al Paciente/tendencias , Infecciones por Coronavirus/epidemiología , Utilización de Instalaciones y Servicios/tendencias , Salud Global/tendencias , Neumonía Viral/epidemiología , Tuberculosis/terapia , Betacoronavirus , COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Tuberculosis/epidemiologíaRESUMEN
Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.
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Infecciones del Sistema Respiratorio/epidemiología , Tuberculosis/epidemiología , Virosis/epidemiología , Vacuna BCG/uso terapéutico , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Epidemias , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Humanos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/diagnóstico , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Gripe Humana/inmunología , Pulmón/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Salud Pública , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/inmunología , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/inmunología , Tuberculosis/diagnóstico , Tuberculosis/inmunología , Tuberculosis/prevención & control , Virosis/diagnóstico , Virosis/tratamiento farmacológico , Virosis/inmunologíaRESUMEN
SUMMARY: Because of the demographic shift and the increased proportion of patients surviving acute critical illnesses, the number of people living with severely disabling chronic diseases and, consequently, the demand for rehabilitation are expected to increase sharply overtime. As underscored by theWorld Health Organization (WHO), there is substantial evidence that the provision of inpatient rehabilitation in specialized rehabilitation units to people with complex needs is effective in fostering functional recovery, improving health-related quality of life, increasing independence, reducing institutionalization rate, and improving prognosis. Recent studies in the real-world setting reinforce the evidence that patients with ischemic heart disease or stroke benefit from rehabilitation in terms of improved prognosis. In addition, there is evidence of the effectiveness of rehabilitation for the prevention of functional deterioration in patients with complex and/or severe chronic diseases. Given this evidence of effectiveness, rehabilitation should be regarded as an essential part of the continuum of care (transitional care). Nonetheless, rehabilitation still is underdeveloped and underused. A new model based on ICD and ICF WHO disease and disfunctioning classification respectively and on pre-set clinical pathways is described. The aim of this model is to optimize clinical care in times of shortage of resources and huge increase in older chronic multi morbid patients.
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Atención a la Salud/organización & administración , Modelos Organizacionales , Rehabilitación/organización & administración , Vías Clínicas , Hospitalización , Humanos , Clasificación Internacional de Enfermedades , Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud , Calidad de VidaRESUMEN
BACKGROUND & AIMS: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. METHODS: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. RESULTS: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. CONCLUSIONS: These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Trasplante de Hígado , Sofosbuvir/uso terapéutico , Listas de Espera , Adulto , Anciano , Carcinoma Hepatocelular/tratamiento farmacológico , Ensayos de Uso Compasivo , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Humanos , Italia , Estimación de Kaplan-Meier , Cirrosis Hepática/cirugía , Cirrosis Hepática/virología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ribavirina/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Advances in direct-acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked-to-care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030. METHODS: Using a modelling approach grounded in Italian real-life data of diagnosed and treated patients, different linkage-to-care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals. RESULTS: Under the 40% linked-to-care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948-1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0-F3 cases. Under the 60% linked-to-care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958-1978 birth cohorts could capture 55% of F0-F3 individuals. Under the 80% linked-to-care scenario, screening limited in 1968-1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals. CONCLUSION: In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required.
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Causas de Muerte , Erradicación de la Enfermedad/tendencias , Hepatitis C/epidemiología , Mortalidad/tendencias , Viremia/epidemiología , Antivirales/uso terapéutico , Carcinoma Hepatocelular/mortalidad , Costo de Enfermedad , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Humanos , Italia/epidemiología , Cirrosis Hepática/mortalidad , Neoplasias Hepáticas/mortalidad , Cadenas de Markov , Respuesta Virológica Sostenida , Viremia/diagnóstico , Viremia/tratamiento farmacológico , Organización Mundial de la SaludRESUMEN
PURPOSE: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. METHODS: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12). RESULTS: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5 g/dL (OR 2.04: 95% CI 1.0-4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3-9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2 mg/dL (OR 4.9: 95% CI 1.17-20.71, p = 0.029) as the only variable independently associated with SVR12. CONCLUSION: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.
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Antivirales/uso terapéutico , Quimioterapia Combinada , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Cirrosis Hepática/etiología , 2-Naftilamina , Anciano , Anciano de 80 o más Años , Anilidas/administración & dosificación , Antivirales/administración & dosificación , Antivirales/efectos adversos , Biomarcadores , Carbamatos/administración & dosificación , Ciclopropanos , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Humanos , Lactamas Macrocíclicas , Cirrosis Hepática/diagnóstico , Compuestos Macrocíclicos/administración & dosificación , Masculino , Prolina/análogos & derivados , Ribavirina/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/análogos & derivados , ValinaRESUMEN
AIMS: To re-analyse data from a previous retrospective study on 127 555 patients, in which we showed that dipeptidyl peptidase-4 (DPP-4) inhibitor therapy was associated with a lower risk of hospitalization for HF (HHF) than sulphonylurea (SU) therapy, in order to evaluate intraclass differences among DPP-4 inhibitors and SUs. METHODS: We included patients with type 2 diabetes (T2D) initiating DPP-4 inhibitor or SU therapy, alone or in combination with metformin. Patients undergoing intraclass switch, those with a previous HHF, those receiving insulin treatment, and those with <6 months observation were excluded. We calculated the incidence of first and total HHF events/1000 person-years. Cox proportional hazard and Poisson multiple regression models, as well as propensity-score matching, were used to account for baseline confounders. RESULTS: The analysis included 17 615 DPP-4 inhibitor users (60.1% sitagliptin; 27.0% vildagliptin; 12.9% saxagliptin) and 86 734 SU users (37.5% glibenclamide; 34.6% glimepiride; 27.9% gliclazide). No intraclass difference in the incidence rate of first and total HHF events was noted among the 3 DPP-4 inhibitors or among the 3 SUs. Multivariable adjustments for baseline confounders or propensity-score matching did not change the results. In addition, no intraclass difference in HHF risk was observed in patients at high compared with low cardiovascular risk. CONCLUSIONS: In a cohort of patients with T2D taken from approximately one-third of the Italian population, no intraclass difference was noted for DPP-4 inhibitor and SU therapy with regard to HHF risk.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/terapia , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Insuficiencia Cardíaca/terapia , Hospitalización , Compuestos de Sulfonilurea/efectos adversos , Adulto , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores de la Dipeptidil-Peptidasa IV/clasificación , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Compuestos de Sulfonilurea/clasificaciónRESUMEN
Direct antivirals are available for treating recurrent hepatitis C (RHC). This study reported outcomes of 424 patients with METAVIR F3-F4 RHC who were treated for 24 weeks with sofosbuvir/ribavirin and followed for 12 weeks within the Italian sofosbuvir compassionate use program. In 55 patients, daclatasvir or simeprevir were added. Child-Pugh class and model of end stage liver disease (MELD) scores were evaluated at baseline and 36 weeks after the start of therapy. The sustained viral response (SVR) was 86.7% (316/365) in patients who received sofosbuvir/ribavirin and 98.3% (58/59) in patients who received a second antiviral (P < 0.01). In patients treated with sofosbuvir/ribavirin, a significant difference in SVR was observed between patients diagnosed with METAVIR F4 (211/250; 84.4%), METAVIR F3 (95/105; 90.5%) and fibrosing cholestatic hepatitis (10/10; 100%) (P = 0.049). A significant association was found between patients who worsened from Child-Pugh class A and who experienced viral relapse (4/26 vs. 8/189, P = 0.02). In patients with a baseline MELD score <15, a significant association was found between maintaining a final MELD score <15 and the achievement of SVR (187/219 vs. 6/10, P = 0.031). This real-world study indicates that sofosbuvir/ribavirin treatment for 24 weeks was effective, and the achievement of SVR was associated with a reduced probability of developing worsening liver function.
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Antivirales/uso terapéutico , Ensayos de Uso Compasivo , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/prevención & control , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Análisis de Varianza , Estudios de Cohortes , Intervalos de Confianza , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/epidemiología , Humanos , Italia , Cirrosis Hepática/virología , Pruebas de Función Hepática , Modelos Logísticos , Masculino , Análisis Multivariante , Pronóstico , Recurrencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
On November 10, 2014, the representatives of all six certified Good Manufacturing Practices (GMP) cell factories operating in the Lombardy Region of Italy convened a 1-day workshop in Milan titled "Management Models for the Development And Sustainability of Cell Factories: Public-Private Partnership?" The speakers and panelists addressed not only the many scientific, technological and cultural challenges faced by Lombardy Cell Factories, but also the potential impact of advanced therapy medicinal products (ATMPs) on public health and the role played by translational research in this process. Future perspectives for research and development (R&D) and manufacturing processes in the field of regenerative medicine were discussed as well. This report summarizes the most important issues raised by the workshop participants with particular emphasis on strengths and limitations of the R&D and manufacturing processes for innovative therapeutics in Lombardy and what can be improved in this context while maintaining GMP standards. The participants highlighted several strategies to translate patient-specific advanced therapeutics into scaled manufacturing products for clinical application. These included (i) the development of a synergistic interaction between public and private institutions, (ii) better integration with Italian regulatory agencies and (iii) the creation of a network among Lombardy cell factories and other Italian and European institutions.
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Técnicas de Cultivo de Célula , Ingeniería Celular , Laboratorios/organización & administración , Modelos Organizacionales , Terapias en Investigación , Investigación Biomédica/métodos , Investigación Biomédica/organización & administración , Investigación Biomédica/normas , Biotecnología/organización & administración , Biotecnología/normas , Técnicas de Cultivo de Célula/métodos , Técnicas de Cultivo de Célula/normas , Ingeniería Celular/métodos , Ingeniería Celular/normas , Humanos , Italia , Evaluación de Programas y Proyectos de Salud/normas , Mejoramiento de la Calidad , Terapias en Investigación/métodos , Terapias en Investigación/normasRESUMEN
Drug repurposing is considered a valid approach to accelerate therapeutic solutions for rare diseases. However, it is not as widely applied as it could be, due to several barriers that discourage both industry and academic institutions from pursuing this path. Herein we present the case of an academic multicentre study that considered the repurposing of the old drug guanabenz as a therapeutic strategy in amyotrophic lateral sclerosis. The difficulties encountered are discussed as an example of the barriers that academics involved in this type of study may face. Although further development of the drug for this target population was hampered for several reasons, the study was successful in many ways. Firstly, because the hypothesis tested was confirmed in a sub-population, leading to alternative innovative solutions that are now under clinical investigation. In addition, the study was informative and provided new insights into the disease, which are now giving new impetus to laboratory research. The message from this example is that even a repurposing study with an old product has the potential to generate innovation and interest from industry partners, provided it is based on a sound rationale, the study design is adequate to ensure meaningful results, and the investigators keep the full clinical development picture in mind.
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Charities investing on rare disease research greatly contribute to generate ground-breaking knowledge with the clear goal of finding a cure for their condition of interest. Although the amount of their investments may be relatively small compared to major funders, the advocacy groups' clear mission promotes innovative research and aggregates highly motivated and mission-oriented scientists. Here, we illustrate the case of Fondazione italiana di ricerca per la Sclerosi Laterale Amiotrofica (AriSLA), the main Italian funding agency entirely dedicated to amyotrophic lateral sclerosis research. An international benchmark analysis of publications derived from AriSLA-funded projects indicated that their mean relative citation ratio values (iCite dashboard, National Institutes of Health, U.S.) were very high, suggesting a strong influence on the referring international scientific community. An interesting trend of research toward translation based on the "triangle of biomedicine" and paper citations (iCite) was also observed. Qualitative analysis on researchers' accomplishments was convergent with the bibliometric data, indicating a high level of performance of several working groups, lines of research that speak of progression toward clinical translation, and one study that has progressed from the investigation of cellular mechanisms to a Phase 2 international clinical trial. The key elements of the success of the AriSLA investment lie in: (i) the clear definition of the objectives (research with potential impact on patients, no matter how far), (ii) a rigorous peer-review process entrusted to an international panel of experts, (iii) diversification of the portfolio with ad hoc selection criteria, which also contributed to bringing new experts and younger scientists to the field, and (iv) a close interaction of AriSLA stakeholders with scientists, who developed a strong sense of belonging. Periodic review of the portfolio of investments is a vital practice for funding agencies. Sharing information between funding agencies about their own policies and research assessment methods and outcomes help guide the international debate on funding strategies and research directions to be undertaken, particularly in the field of rare diseases, where synergy is a relevant enabling factor.
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Clinical experience has shown an increase of behavioural and mood symptoms, especially in the areas of aggressiveness, sexuality and obsessiveness, during the late stages of ALS. The lack of conclusive data concerning these symptoms prompted us to assess the psychological aspects of ALS patients in advanced stages of the disease. Moreover, we evaluated the personality of their caregivers in order to analyse the relationship between the pair. For these purposes, we studied 10 patients with ALS in late stages (tracheostomized for 36 months) and their caregivers using a questionnaire specifically elaborated for patients' communication limits. To assess the state of anxiety and depression of both patients and caregivers, we used the Hospital Anxiety and Depression Scale (HADS). To investigate caregivers' personality, we administered the Big Five Questionnaire (BFQ). Data showed a trend of aggression and high level of obsessiveness in ALS patients, associated with several clinical characteristics. High levels of anxiety emerged in both patients and caregivers. Regarding BFQ, caregivers obtained higher scores in the dimension of Conscientiousness and very low scores in Extraversion and Emotional Stability. In conclusion, the study showed a potential and considerable effect of the long duration of ALS on patients' personality and caregivers' distress.
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Agresión/psicología , Esclerosis Amiotrófica Lateral/psicología , Cuidadores/psicología , Sexualidad/psicología , Estrés Psicológico/psicología , Anciano , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To verify the safety and potential effect on ALS progression of a low-intensity immunosuppressive regimen followed by autologous hematopoietic stem cell transplantation (aHSCT) in amyotrophic lateral sclerosis (ALS) patients. METHODS: ALS eligible patients underwent a set of clinical and laboratory evaluations at T-4 (screening), T-1 (pre-treatment visit), and for the 12 consecutive months after treatment (T3, T6, T9, T12). We evaluated the tolerability of the procedure, its efficacy on clinical course and quality of life (QoL). RESULTS: Eight of the 11 ALS patients enrolled received the established immunoablative protocol. The procedure was well tolerated and side effects were those expected. One patient died 4 months after the conditioning regimen and another patient underwent tracheotomy just before T3 for a sudden respiratory failure, but he is still alive 4 years after the procedure without being ventilated any more. A third patient died 10 months after conditioning. In the other cases, there was no statistical difference in all functional measures and QoL pre- and post-treatment; however, a transitory slopes' reduction of ALSFRS-R and seated SVC% after the conditioning procedures was reported. Moreover, although not statistically significant, trends of reduction of CD4 + and increment of CD8 + were found. CONCLUSIONS: aHSCT was overall well tolerated, but it was not followed by any significant modification in disease progression. Considering the negative results of this small trial, further studies aimed to evaluate the possible efficacy of the aHSCT using a higher-intensity regimen should be carefully and with caution evaluated.
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Esclerosis Amiotrófica Lateral , Trasplante de Células Madre Hematopoyéticas , Esclerosis Amiotrófica Lateral/cirugía , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Calidad de Vida , Acondicionamiento Pretrasplante/métodos , Trasplante AutólogoRESUMEN
Granulocyte colony-stimulating factor (G-CSF) induces a transient mobilization of hematopoietic progenitor cells from bone marrow to peripheral blood. Our aim was to evaluate safety of repeated courses of G-CSF in patients with amyotrophic lateral sclerosis (ALS), assessing disease progression and changes in chemokine and cytokine levels in serum and cerebrospinal fluid (CSF). Twenty-four ALS patients entered an open-label, multicenter trial in which four courses of G-CSF and mannitol were administered at 3-month intervals. Levels of G-CSF were increased after treatment in the serum and CSF. Few and transitory adverse events were observed. No significant reduction of the mean monthly decrease in ALSFRS-R score and forced vital capacity was observed. A significant reduction in CSF levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-17 (IL-17) was observed. G-CSF treatment was safe and feasible in a multicenter series of ALS patients. A decrease in the CSF levels of proinflammatory cytokines MCP-1 and IL-17 was found, indicating a G-CSF-induced central anti-inflammatory response.
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Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Adulto , Anciano , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/sangre , Factor Estimulante de Colonias de Granulocitos/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
We report an Italian male with juvenile onset familial disease characterized by progressive weakness and wasting of four limbs and prolonged survival. Diagnostic work-up revealed the diffuse involvement of central and peripheral motor neurons. Genetic analysis revealed a L389S mutation in the senataxin (SETX) gene.
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Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/fisiopatología , Progresión de la Enfermedad , Mutación Missense , ARN Helicasas/genética , Edad de Inicio , Esclerosis Amiotrófica Lateral/diagnóstico , ADN Helicasas , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Enzimas Multifuncionales , Linaje , Adulto JovenRESUMEN
BACKGROUND AND AIMS: The aim of this study was to evaluate and characterize the feasibility and safety of bone marrow-derived cell (BMC) mobilization following repeated courses of granulocyte-colony stimulating factor (G-CSF) in patients with amyotrophic lateral sclerosis (ALS). METHODS: Between January 2006 and March 2007, 26 ALS patients entered a multicenter trial that included four courses of BMC mobilization at 3-month intervals. In each course, G-CSF (5 microg/kg b.i.d.) was administered for four consecutive days; 18% mannitol was also given. Mobilization was monitored by flow cytometry analysis of circulating CD34(+) cells and by in vitro colony assay for clonogenic progenitors. Co-expression by CD34(+) cells of CD133, CD90, CD184, CD117 and CD31 was also assessed. RESULTS: Twenty patients completed the four-course schedule. One patient died and one refused to continue the program before starting the mobilization courses; four discontinued the study protocol because of disease progression. Overall, 89 G-CSF courses were delivered. There were two severe adverse events: one prolactinoma and one deep vein thrombosis. There were no discontinuations as a result of toxic complications. Circulating CD34(+) cells were monitored during 85 G-CSF courses and were always markedly increased; the range of median peak values was 41-57/microL, with no significant differences among the four G-CSF courses. Circulating clonogenic progenitor levels paralleled CD34(+) cell levels. Most mobilized CD34(+) cells co-expressed stem cell markers, with a significant increase in CD133 co-expression. CONCLUSIONS: It is feasible to deliver repeated courses of G-CSF to mobilize a substantial number of CD34(+) cells in patients with ALS; mobilized BMC include immature cells with potential clinical usefulness.
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Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Células de la Médula Ósea/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas/efectos de los fármacos , Adulto , Esclerosis Amiotrófica Lateral/fisiopatología , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Células de la Médula Ósea/fisiología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Linaje de la Célula/efectos de los fármacos , Linaje de la Célula/fisiología , Movimiento Celular/fisiología , Ensayo de Unidades Formadoras de Colonias , Esquema de Medicación , Femenino , Células Madre Hematopoyéticas/fisiología , Humanos , Masculino , Persona de Mediana Edad , Regeneración Nerviosa/efectos de los fármacos , Regeneración Nerviosa/fisiología , Neuroglía/citología , Neuroglía/fisiología , Neuronas/citología , Neuronas/fisiología , Estudios Prospectivos , Células Madre/efectos de los fármacos , Células Madre/fisiología , Resultado del TratamientoRESUMEN
Italy was used as a case study to investigate the determinants of the difference between the price proposal for medicines submitted by the industry and the final negotiated price (∆P). Data was gathered through the information system used by Italian Medicines Agency (AIFA) and the time-frame for this analysis is 2013-2017. Factors influencing the delta price were analyzed through a regression analysis. Forty four orphan drugs and 89 new other molecular entities obtained reimbursement in the period considered. Following the negotiation process, prices proposed by Marketing Authorization Holders (MAH) were lowered during the negotiation process by 25.1% and 28.6% on average for orphan drugs and other molecules respectively. The price reduction was higher for innovative drugs (-32.2%). Statistically significant determinants associated to higher price reduction were: i) the implementation of a product specific monitoring registry, ii) the negotiation of a financial-based (FB) Managed Entry Agreement, iii) a target population larger than 20,000 patients, iv) an expected National Health Service expenditure larger than 200 million. The impact of some variables on the delta price was predictable (e.g. for drugs with an expected higher budget impact and a larger target population), others were more surprising (e.g. a significant price reduction for "innovative" drugs). The implementation of FB agreements, which often rely on confidential arrangements, was one of the determinants with higher impact on price reduction.
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Costos de los Medicamentos , Industria Farmacéutica/economía , Producción de Medicamentos sin Interés Comercial/economía , Preparaciones Farmacéuticas/economía , Humanos , Italia , Mecanismo de Reembolso , Medicina EstatalRESUMEN
Because of the demographic shift and the increased proportion of patients surviving acute critical illnesses, the number of people living with severely disabling chronic diseases and, consequently, the demand for rehabilitation are expected to increase sharply over time. As underscored by the World Health Organization, there is substantial evidence that the provision of inpatient rehabilitation in specialized rehabilitation units to people with complex needs is effective in fostering functional recovery, improving health-related quality of life, increasing independence, reducing institutionalization rate, and improving prognosis. Recent studies in the real world setting reinforce the evidence that patients with ischemic heart disease or stroke benefit from rehabilitation in terms of improved prognosis. In addition, there is evidence of the effectiveness of rehabilitation for the prevention of functional deterioration in patients with complex and/or severe chronic diseases. Given this evidence of effectiveness, rehabilitation should be regarded as an essential part of the continuum of care. Nonetheless, rehabilitation still is underdeveloped and underused. Efforts should be devoted to foster healthcare professional awareness of the benefits of rehabilitation and to increase referral and participation.
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Isquemia Miocárdica/rehabilitación , Medicina Física y Rehabilitación/tendencias , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Rehabilitación de Accidente Cerebrovascular/normas , Enfermedad Crítica/rehabilitación , Personas con Discapacidad , Humanos , Guías de Práctica Clínica como Asunto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la FunciónRESUMEN
OBJECTIVES: The aim of this paper is to investigate the determinants of the difference between the price proposal submitted by the industry and the final negotiated price. We used Italy as a case-study. METHODS: Data were gathered through the information system used by Italian Medicines Agency. The time-frame for this analysis is 2013-2017. Factors influencing the delta price were analyzed through a regression analysis. RESULTS: 44 orphan drugs and 89 new other molecular entities obtained reimbursement in the last five years. Following the negotiation process, prices were lowered by 25.1% and 28.6% on average for orphan drugs and other molecules respectively. The price reduction was higher for innovative drugs (-32.2%). Statistically significant determinants associated to higher price reduction were: i) the implementation of a product specific monitoring registry, ii) the negotiation of a financial-based Managed Entry Agreement, iii) a target population larger than 20,000 patients, iv) an expected National Health Service expenditure larger than 200 million. DISCUSSION: The impact of some variables on the delta price was predictable (e.g. for drugs with an expected higher budget impact and a larger population target), others were more surprising (e.g. a significant price reduction for "innovative" drugs). The implementation of financial-based agreements, which often rely on confidential arrangements, was one of the determinants with higher impact on price reduction.
Asunto(s)
Costos de los Medicamentos/estadística & datos numéricos , Negociación , Costos y Análisis de Costo , Costos de los Medicamentos/legislación & jurisprudencia , Humanos , Italia , Producción de Medicamentos sin Interés Comercial/economía , Evaluación de la Tecnología BiomédicaRESUMEN
The objective of our study was to perform a randomized controlled trial (RCT) aimed to evaluate the effects of three strictly monitored exercise programs(SMEP) compared to "usual care" (UCP) in a cohort of ALS patients. We included patients with definite and probable ALS and disease duration ≤24 months. Patients were randomized to receive a SMEPs or a UCP. SMEPs included three subgroups of treatment: active exercises associated with cycloergometer activity (1A), only active (1B) and passive (1C) exercises, respectively. Moreover, SMEP patients and their caregivers were trained to a daily home-based passive exercise program. The UCP group was treated with passive and stretching exercises twice weekly. The treatment period for both groups was 6 months (T180), and patients were assessed by revised ALS Functional Rating Scale (ALSFRS-R), % Forced Vital Capacity (FVC %), and McGill Quality of Life (MGQoL) questionnaire. ALSFRS-R score was also evaluated at 6 months after the treatment period (T360). Sixty ALS patients were randomly assigned to one of two arms: SMEP Group included 30 patients, ten subjects for each subgroup (1A, 1B, and 1C); 30 patients were included in the UCP Group.At T180 and T360, SMEPs group had significantly higher ALSFRS-R score compared to the UCP group (32.8 ± 6.5 vs 28.7 ± 7.5, p = 0.0298; 27.5 ± 7.6 vs 23.3 ± 7.6, p = 0.0338, respectively). No effects of SMEPs on survival, respiratory decline and MGQol were found. In conclusion, although no effect on survival was demonstrated,our data suggest that a strictly monitored exercise program may significantly reduce motor deterioration in ALS patients.