Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults.

BACKGROUND: Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. RESEARCH QUESTION: How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? STUDY DESIGN AND METHODS: This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1 month, 3 months, and 6 months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. RESULTS: Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV1 increased initially and then remained stable. BMI also increased significantly from T0 to 6 months (P < .01). Depression improved from T0 to 1 month (P < .001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10% to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). INTERPRETATION: This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator.

Evolução de crianças asmáticas com tratamento homeopático / Evolution in asthmatic children through homeopatic treatment

Estudando 43 crianças asmáticas, atendidas no ambulatório de asma da Associação Paulista de Homeopatia, pudemos observar boa evolução na intensidade e no número de crises com o tratamento, bem como constatar a importância dos fatores físicos e climáticos na etiologia asmática e na busca do remédio adequado. (AU)

The aim of the present paper is to describe the results of a study on the progression of 43 cases of asthmatic children subjected to homeopathic treatment at the asthma outpatient clinic, São Paulo Homeopathic Medical Association, from march to December 1985. Improvement in the intensity and frequency of attacks was observed. The results further demonstrate, based on the preset statistical criteria, the relevance of investigating mental, physical and climate-related factors. (AU)

Which indicators for measuring the daily physical activity? An overview on the challenges and technology limits for Telehealth applications.

BACKGROUND: Obesity is one of the biggest drivers of preventable chronic diseases and healthcare costs in Worldwide. Different prevention activities are suggested. By monitoring daily energy expenditure (EE) could be possible make personalized diets and programming physical activity. In this, physical inactivity is one of the most important public health problems. Some studies refer the effort of the international community in promoting physical activities. Physical activity can be promoted only by increasing citizens' empowerment on taking care of their health, and it passes from the improving of individual information. Technology can offer solutions and metrics for monitoring and measuring daily activity by interacting with individuals, sharing information and feedbacks. OBJECTIVE: In this study we review indicators of total energy expenditure and weaknesses of available devices in assessing these parameters. METHODS: Literature review and technology testing EuNetHta core model. RESULTS: For the clinical aspects, it is fundamental to take into account all the factor that can influence the personal energy expenditure as: heart rate, blood pressure and thermoregulation (influenced by the body temperature). DISCUSSION: In this study we focused the attention on the importance of tools to encourage the physical activity. We made an analysis of the factor that can influence the right analysis of energy expenditure and at the same time the energy regime. A punctual monitoring of the exercise regime could be helpful in Telemedicine application as Telemonitorig. More study are needed to value the impact of physical activity tracker in Telemonitorig protocols. CONCLUSION: On the assessment of the energy expenditure, critical issues are related to the physiological data acquisition. Sensors connected with mobile devices could be important tools for disease prevention and interventions affecting health behaviors. New devices applications are potential useful for telemedicine assistance, but security of data and the related communication protocol limits should be taking into account.

Telemonitoring in Cystic Fibrosis: A 4-year Assessment and Simulation for the Next 6 Years.

BACKGROUND: Innovative technologies and informatics offer a wide range of services to health districts, doctors, nurses, and patients, and is changing the traditional concept of health care. In the last few years, the availability of portable devices, their easiness to transport and use, and the capability to collect and transmit various clinical data have resulted in the fast development of telemedicine. However, despite its potential impact in improving patient conditions, and its cost effectiveness reported in literature, telemedicine is not in daily practice. OBJECTIVE: The aim of this study is to provide evidence of the positive impact of telemonitoring proving the sustainability of an application by sending spirometry outcomes from patients' homes to the hospital doctors via the Internet, and from doctors to patients by an additional phone call solution. METHODS: We examined collected data related to clinical improvement of patients with cystic fibrosis (CF). The patients were followed-up at home using telemonitoring for a period of 10 years, with the aims to prove the sustainability of the methodology (transmissions of spirometry from the patients' home to the doctors and feedback from the doctors to the patients by phone call from the hospital). We stored and analyzed all spirometry transmissions received, and tested the possible presence to decrease the costs between the standard clinical trial (only ambulatory visits) and standard clinical trial with telemonitoring for the follow-up of patients with CF (telemedicine). This was done through an economic analysis of the costs for patients followed at home by telemonitoring. We assessed four years of observation and a simulation of total long-term costs between 2010 and 2020. RESULTS: We discovered a potential saving of €40,397.00 per patient for 10 years, actualized at €36,802.97 for the follow-up of all patients enrolled. CONCLUSIONS: The results from the study suggest that telemedicine can improve the health of patients with CF. It is a relatively cheap and potentially sustainable solution, compared to standard clinical trials. However, to establish and prove the long-term effectiveness and cost-effectiveness, more controlled psychological and behavioral studies are needed.

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate.

BACKGROUND: Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fibrosis. METHODS: We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fibrosis and low bone mineral density, from ten cystic fibrosis regional centres in Italy. The first phase was an open-label, 12-month observational study of the effect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the efficacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01812551. FINDINGS: We screened 540 patients and enrolled 171 (mean age 13·8 years, SD 5·9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16·3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0·0010). 19 of 57 young people (33·3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational phase, five patients had moderate episodes of hypercalciuria, which resolved after short interruption of calcifediol treatment. During the randomised phase, one patient taking alendronate had mild fever versus none in the placebo group; treatment groups did not differ significantly for other adverse events. INTERPRETATION: Correct calcium intake plus calcifediol can improve bone mineral density in some young patients with cystic fibrosis. In those who do not respond to calcium and calcifediol alone, alendronate can safely and effectively increase bone mineral density. FUNDING: Telethon Foundation (Italy).

Severe reaction in a child with asymptomatic codfish allergy: food challenge reactivating recurrent pancreatitis.

An 8-year-old child during the first year of life manifested severe atopic dermatitis and chronic diarrhea with mucorrhea and rectal bleeding; a fish-free diet was started based on weakly positive skin-prick tests to codfish extract. At the age of 4 years the child began to suffer of recurrent pancreatitis. When he came to our attention for the evaluation of his fish allergy, he was asymptomatic; a weak reactivity to codfish was observed (SPTs: cod, 4 mm, sIgE ImmunoCAP: cod, 1.30 kU/l). The food challenge test with cod was negative. When the child ate cod again, within 5 minutes, developed anaphylactic reaction and complained of abdominal pain compatible with pancreatitis (enzyme serum levels risen and parenchymal oedema at ultrasonography), that resolved within 7 days after specific therapy. This case raises two issues: the elimination diet in asymptomatic food allergy on the basis only of SPT and the ethicality of food challenge in gastrointestinal chronic disease.

Clinical hallmarks and genetic polymorphisms in the CFTR gene contribute to the disclosure of the A1006E mutation.

Since the identification of the Cystic Fibrosis transmembrane conductance regulator (CFTR) gene in 1989, many genetic mutations have been found in cystic fibrosis (CF) patients. Dysfunctions of the CFTR gene are responsible for the highly variable clinical presentation ranging from severe CF, disseminated bronchiectasis, idiopathic chronic pancreatitis and congenital bilateral absence of vas deferens (CBAVD). Linkage disequilibrium studies have shown that some mutations are stringently coupled with polymorphisms in a genetic complex called haplotype. From a familial study of a patient with CBAVD, carrier of the A1006E mutation, we have observed its strict association with the polymorphism 5T-TG11. In order to speed up the genetic diagnosis and to correlate the clinical setting to this genetic feature, we have directly investigated the exon 17a, where the A1006E mutation is located, of five cystic fibrosis patients belonging to two unrelated families. All patients had the 5T-TG11 tract, F508del and one unknown mutation. One more family with two affected individuals carrying the Q220X/A1006E mutations was investigated for the poly-T polymorphism. All the members were found to have the A1006E mutation and the 5T-TG11 in the same DNA strand, demonstrating that this strategy is a reliable and inexpensive method for genotyping the CFTR gene. A detailed description of the clinical presentation and follow-up are provided in order to highlight common phenotypic features useful to improve the management of cystic fibrosis patients.

Evaluation of a home telemonitoring service for adult patients with cystic fibrosis: a pilot study.

We have conducted a pilot trial of a home telemonitoring system involving 60 adult patients with cystic fibrosis (CF) enrolled at four Italian CF centres. Thirty randomly selected patients received a home device to perform spirometry and to measure oxygen saturation. The data were transferred to a data centre which forwarded them to the patient's CF clinic. The telemonitoring system was evaluated using questionnaires completed by patients and their doctors. The doctors reported that telemonitoring was useful in monitoring their patients' health status and in decreasing the CF centre workload. The data transfer procedure posed no particular problems for the patients. The major difficulties reported by the patients were night-time saturimetry measurements, and in the first week of the study, data transmission to the data centre. The pilot trial was positive and therefore merits a larger study.

Bone and body composition analyzed by Dual-energy X-ray Absorptiometry (DXA) in clinical and nutritional evaluation of young patients with Cystic Fibrosis: a cross-sectional study.

BACKGROUND: the improved general therapy has led to reduced morbidity and mortality from Cystic Fibrosis (CF), and bone status may have a potentially greater clinical impact.We investigated the correlation between the severity of the clinical condition, bone status and body composition parameters, in a group of children and young adults with CF. METHODS: we measured lumbar spine bone density and total body composition by dual energy x-ray absorptiometry (DXA) in 82 consecutive CF patients (42 males; median age: 13 years - range: 5-30). Eighty-two healthy subjects, matched for age, gender, height and pubertal stage were recruited as a control group. RESULTS: 37 patients (45.1%) had a normal bone mineral density (BMD). A BMD reduction were observed in 45 (54.8%) patients. Lumbar spine Z score was positively related to Body Mass Index (BMI) and a higher Shwachman-Kulczycki score, and negatively related to Crispin-Norman score. A positive and significant correlation was also observed between lumbar spine Z score and total body composition. CONCLUSION: a significant BMD reduction can be present early in CF children and adolescents. A careful follow up of bone status is required starting in childhood.

Exhaled 8-isoprostane and prostaglandin E(2) in patients with stable and unstable cystic fibrosis.

We measured 8-isoprostane, a biomarker of oxidative stress, and prostaglandin (PG) E(2) in exhaled breath condensate in 36 stable and 14 unstable cystic fibrosis (CF) patients, and in 15 healthy age-matched controls. We studied the relationships of these eicosanoids with clinical, radiological, and systemic inflammatory parameters. Compared with controls [15.5 (11.5-17.0) pg/ml] exhaled 8-isoprostane was increased in stable CF patients [30.5 (25.3-36.0) pg/ml, P<0.001]. Unstable CF patients had higher exhaled 8-isoprostane levels [47.5 (44.0-50.0) pg/ml, P<0.001] than stable CF patients. Unlike PGE(2), exhaled 8-isoprostane was negatively correlated with FEV(1) (r=-0.67; P<0.0001; r=-0.63; P<0.02) and Shwachman score (r=-0.43, P=0.012; r=-0.58, P=0.031) and positively correlated with Chrispin-Norman score (r=0.51, P<0.002; r=0.56, P=0.039) in stable and unstable CF patients, respectively. No correlation was observed with C-reactive protein. Compared with controls [41.0 (29.0-50.0) pg/ml], exhaled PGE(2) was also elevated in stable [72.0 (64.3-81.8) pg/ml, P<0.001) and, to a greater extent, in unstable CF patients [83.0 (74.3-91.3) pg/ml, P<0.001). In patients with CF, exhaled 8-isoprostane and PGE(2) could be a useful marker of disease severity.

Low doses of dexamethasone constantly delivered by autologous erythrocytes slow the progression of lung disease in cystic fibrosis patients.

OBJECTIVE: To evaluate the safety and efficacy of the administration of low doses of glucocorticoids in patients with cystic fibrosis (CF) by using autologous erythrocytes loaded with dexamethasone 21-phosphate. STUDY DESIGN: Nine consecutive CF patients (patients nos. 1-9) received autologous erythrocytes loaded with increasing amounts of dexamethasone 21-phosphate to obtain a slow delivery of dexamethasone in circulation. The appearance of possible adverse effects, the reproducibility of the procedure, and the dexamethasone pharmacokinetics were evaluated. Subsequently, patient no. 9 and eight additional patients (patient nos. 10-17) received dexamethasone 21-phosphate-loaded erythrocytes at 1-month intervals to evaluate the efficacy of continuous release in circulation of low doses of dexamethasone. RESULTS: Erythrocytes from CF patients can be processed to be loaded with increasing dexamethasone 21-P concentrations. Once reinfused in respective donors, a slow and prolonged delivery of dexamethasone in the blood stream was measured up to 28 days. Repeated administrations of drug-loaded erythrocytes at 4-week intervals for 15 months showed that very low doses of glucocorticoids provide significant improvement in FEV1 values and significant reduction of infective relapses due to Pseudomonas aeruginosa without adverse effects. CONCLUSIONS: The administration of very low doses of glucocorticoids using autologous erythrocytes is possible, with benefits for patients and without side effects. This method is likely to be extended to other chronic diseases.

Indexacao bibliografica computadorizada em homeopatia: uma revolucao no estudo e na pesquisa / Computerized bibliographical indexation: a study and research revolution

Os autores apresentam uma base de dados que pretende revolucionar o estudo e a pesquisa na Homeopatia Seguindo os padroes internacionais para bases de dados medicos, oferece aos profissionais possibilidade de acessar de qualquer localidade uma Biblioteca computadorizada aonde estao arquivados todos os conhecimentos homeopaticos ja publicados Atraves de um vocabulario de descritores especialmente desenvolvido, o homeopata pode em poucos minutos realizar uma pesquisa de seu local de trabalho e ter as maos todos os documentos publicados sobre o assunto de seu interesse

Indexacao bibliografica computadorizada em homeopatia: uma revolucao no estudo e na pesquisa / Computerized bibliographical indexation: a study and research revolution

Os autores apresentam uma base de dados que pretende revolucionar o estudo e a pesquisa na Homeopatia. Seguindo os padroes internacionais para bases de dados medicos, oferece aos profissionais possibilidade de acessar de qualquer localidade uma Biblioteca computadorizada aonde estao arquivados todos os conhecimentos homeopaticos ja publicados. Atraves de um vocabulario de descritores especialmente desenvolvido, o homeopata pode em poucos minutos realizar uma pesquisa de seu local de trabalho e ter as maos todos os documentos publicados sobre o assunto de seu interesse

Avaliacao da terapeutica homeopatica em individuos portadores do virus HIV / Homeopathic treatment evaluation in HVI virus carriers persons

No presente trabalho e feita uma avaliacao da terapeutica homeopatica em individuos aideticos em todas as fases de apresentacao clinicadurante o periodo de um ano e oito meses. Com o tratamento homeopatico foram observadas alteracoes para melhor clinica, fasica, laboratorial e subjetivas. Entretanto, enfermos enquadrados na fase AIDS plenamente manifesta, ate o presente sao irreversiveis, incuraveis e terminais. A principio, a intencao, atraves do tratamento homeopatico, e a de permitir uma maior sobrevida do enfermo ou uma melhoria em sua sobrevida

Avaliacao da terapeutica homeopatica no aidetico / Homeopathic treatment evaluation in the AIDS patient

Neste trabalho sao feitas criticas ao trabalho anteriorvisto que nao houve mudancas de fase retroativa, como imaginou-se ja que uma vezatingida a fase nao ha volta, mas sim, manutencao do mesmo quadro sem grandes comprometimentos e uma evolucao mais amena do quadro. Tambem a valorizacao dos exames laboratoriais como parametro para evolucao e prognostico e bem aquem do desejado. Os nosodios das doencas oportunistas obtiveram resultados favoraveis

Avaliacao da terapeutica homeopatica em individuos portadores do virus HIV / Homeopathic treatment valuation in HVI virus carriers persons

No presente trabalho e feita uma avaliacao da terapeutica homeopatica em individuos aideticos em todas as fases de apresentacao clinicadurante o periodo de um ano e oito meses. Com o tratamento homeopatico foram observadas alteracoes para melhor clinica, fasica, laboratorial e subjetivas. Entretanto, enfermos enquadrados na fase AIDS plenamente manifesta, ate o presente sao irreversiveis, incuraveis e terminais. A principio, a intencao, atraves do tratamento homeopatico, e a de permitir uma maior sobrevida do enfermo ou uma melhoria em sua sobrevida

Avaliacao da terapeutica homeopatica no aidetico / Homeopathic treatment valuation in the AIDS patient

Neste trabalho sao feitas criticas ao trabalho anteriorvisto que nao houve mudancas de fase retroativa, como imaginou-se ja que uma vezatingida a fase nao ha volta, mas sim, manutencao do mesmo quadro sem grandes comprometimentos e uma evolucao mais amena do quadro. Tambem a valorizacao dos exames laboratoriais como parametro para evolucao e prognostico e bem aquem do desejado. Os nosodios das doencas oportunistas obtiveram resultados favoraveis

Evoluçäo de crianças asmáticas com tratamento homeopático / Evolution in asthmatic children through homeopathic treatment

Estudando 43 crianças asmáticas atendidas nos ambulatórios de asma da Associaçäo Paulista de Homeopatia pudemos observar a boa evoluçäo na intensidade e no número de crises com o tratamento, bem como constatar a importância dos fatores físicos e climáticos na etiologia asmática e na busca do remédio adequado