Elexacaftor/tezacaftor/ivacaftor, a game-changer in cystic fibrosis: The Portuguese experience.

BACKGROUND: Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population. METHODS: Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year. RESULTS: 132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the F508del variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV1 was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV1 was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m2 (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was -44.5 mmol/L (95 % CI: -49.8, -39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = -0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common. CONCLUSIONS: ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.

Amlodipine in pediatric patient with uncontrolled multifactorial hypertension. Formulation of amlodipine oral suspension.

OBJECTIVE: To describe the case of treatment with amlodipine in a poorly controlled hypertension in a pediatric patient diagnosed with tricodistrofia. CASE SUMMARY: Girl 5 years old, diagnosed of tricodistrofia included within the Tay-Sachs syndrome. As a consequence of a cardiac arrest suffered in the context of a respiratory distress syndrome associated with infection by influenza A, she developed hypertension initially treated with nifedipine and captopril. After several months of treatment and a poor control of the hypertension, a change of treatment was decided, substituting nifedipine by amlodipine (2.5 mg/24 hours orally) and captopril by enalapril (2.5 mg/24 hours orally). Pharmacy service is request to get a amlodipine syrup that allows a dose adjustment to the needs of the patient. After the change of treatment the patient begins to maintain diastolic blood pressure levels within the normal range, suspending the administration of enalapril, maintaining good control of blood pressure with amlodipine 2 mg/24 hours. DISCUSSION: Most of antihypertensive drugs used in adults do not have clinical trials to evaluate its effects in the pediatric population. Furthermore, the lack of familiarity with the pharmacokinetic characteristics of the child, raises problems to adjust the dose to the changing reality of a child. In this situation, clinical experience supports the use of some of these drugs in children with optimal results. With the addition to the pediatric field of calcium antagonists and ACE-inhibitors or ARB-II, they allow as to have greater potential therapeutic alternatives.

Mandibular implant-supported removable partial denture with distal extension: a systematic review.

The aim of this article is to investigate patient satisfaction, survival rate of implants, and prosthetic complications or maintenance for rehabilitation with removable partial dentures associated with implants in mandibular Kennedy class I and II cases. A systematic literature review was conducted by three independent reviewers including articles published from January 1981 through September 2011. Medline and Cochrane Library electronic databases were used in addition to hand searching to assess clinical outcomes for mandibular implant-supported removable partial denture with distal extension. This review yielded 1751 records that were narrowed down to 5. The studies revealed implant survival rates ranging from 95% to 100% with one failure reported of 98 implants. The removable partial dentures associated with implant in mandibular free-end arches showed some complications and need of repair for relining, pitting of the healing abutment, replacement of resilient component of the attachment, damage in framework, screw loosening and damage in acrylic denture base. Patient satisfaction was evaluated through a five-point questionnaire, and results ranged between 4.12 and 5.0, considering 1 as the least favourable situation. The literature review showed increase in patient satisfaction and high survival rates of implants associated with mandibular removable partial dentures with distal extensions. However, some complications and need of prosthetic repair were reported. Although this treatment approach could represent a low-cost and beneficial rehabilitation for free-end mandibular ridges, the lack of controlled and randomised well-designed clinical trials suggests further studies with more representative samples to validate the outcomes of this treatment modality.

Dynamic functional impression technique for severely resorbed alveolar ridges.

The process of bone resorption can reduce the volume of the alveolar crest, which makes may make difficult impression taking of the alveolar tissue and the subsequent fit of a new denture. This clinical report describes a fast and simple technique for impressions of edentulous ridges to replace complete dentures, using a temporary tissue conditioner material on the denture base. The existing denture must cover the whole supporting area and should be in harmony with the adjacent oral structures. This technique reduces the number of steps involved and minimizes treatment time and expenses.

A clinical follow-up study of the periodontal conditions of RPD abutment and non-abutment teeth.

The purpose of this study was to evaluate the periodontal conditions of removable partial denture (RPD) wearers, comparing direct and indirect abutment teeth, and the teeth not involved in the denture design before denture placement and 1 year later. Fifty patients (32 women and 18 men), average age 45, were assessed by the same examiner at the moment of denture insertion and 3, 6, 9 and 12 months later. The following items were verified in each assessment: probing depth (PD), plaque index (PI) and gingival index (GI). PD and PI data were evaluated by anova test for linear trend followed by Tukey-Kramer post-test, while GI data were analysed by Friedman's test. Results showed that the teeth not involved in the denture design were the least affected for all variables studied. It was also verified that PD and GI mean values increased from the initial assessment to 1 year of RPD wearing in every group, but that only PI showed a significant increase. This study indicated that direct and indirect retainer elements tend to undergo more damaging periodontal effects associated with RPD wearing when compared with non-abutment elements. Plaque index values were significantly higher after 1 year of denture use.

Efeitos do propofol administrado por via intracelomática em cágados-de-barbicha (Phrynops geoffroanus) Schweigger, 1812 / Effects of propofol administered by intracelomatic route in Geoffroy's toadhead turtle (Phrynops geoffroanus) Schweigger, 1812

O presente estudo avaliou a influência do regime hídrico sobre efeitos do propofol em Phrynops geoffroanus, bem como a qualidade da contenção farmacológica produzida. Foram utilizados 10 animais, anestesiados em dois momentos com propofol, na dose de 35mg/kg, por via intracelomática, com intervalo de 15 dias. O grupo 1 fora retirado da água 12 horas antes do procedimento e o grupo 2 permaneceu dentro da água até o momento da indução anestésica. Foram mensuradas frequência cardíaca, pressão arterial sistólica, temperatura, frequência respiratória e saturação de oxi-hemoglobina, e avaliados duração do período de latência, período hábil, período de recuperação e qualidade da contenção farmacológica. Houve diferença significativa entre grupos apenas quanto à frequência cardíaca. No grupo 1, as médias dos períodos de latência, hábil anestésico e de recuperação foram de 16,8±8,4, 86,5±79,4 e 1,5±3,8 minutos, respectivamente. Já no grupo 2, as médias foram de 19,9±9,8, 110,9±104,7 e 28,8±58,2 minutos, respectivamente. Concluiu-se que o regime hídrico de 12 horas não influenciou os parâmetros anestésicos e fisiológicos dos animais e que a qualidade da contenção farmacológica foi considerada boa em ambos os grupos.(AU)

The present study evaluated the influence of the water regime on the effects of propofol on Phrynops geoffroanus, as well as the quality of the pharmacological containment produced. Ten animals, anesthetized at two times with propofol at a dose of 35mg / kg, were used intracelomatically with a 15 day interval. Group 1 was withdrawn from the water 12 hours prior to the procedure and Group 2 remained in the water until the time of anesthetic induction. Heart rate, systolic blood pressure, temperature, respiratory rate and oxyhemoglobin saturation were measured and the duration of the latency period, skill period, recovery period and quality of pharmacological containment were measured. There was a significant difference between groups only regarding heart rate. In Group 1, the means of the latency, skillful anesthesia and recovery periods were 16.8±8.4, 86.5±79.4 and 1.5±3.8 minutes, respectively. In Group 2, the mean values were 19.9±9.8, 110.9±104.7 and 28.8±58.2 minutes, respectively. It was concluded that the 12-hour water regime did not influence the anesthetic and physiological parameters of the animals, and the quality of the pharmacological restraint was considered good in both groups.(AU)

[The TPN of newborn infants: the rationalization of the calculations and of the prescription]. / NPT de neonatos: racionalización de los cálculos y de la presecripción.

We try to simplify the calculus of TPN necessities in newborns adjusting the most common bibliography tabulated values to mathematical equations. Values are transformed into factors: Fn (g of N/Kg of weight), Fk (no protein Kcal/g of N), Fg (glucose Kcal/total Kcal) and Fv (volume/total Kcal) that can be correlated with the analytical state of patient, weight and nutrition day. Once the functions were established we automated calculations using a spreadsheet program that simplifies and make easier the TPN elaboration.

Impact of comorbidities in pulmonary rehabilitation outcomes in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) represents an increasing burden worldwide. COPD can no longer be considered a disease which only involves the lungs, its systemic consequences make it an important risk factor for other chronic comorbidities. AIM: To determine the frequency of comorbidities in patients with COPD undergoing a pulmonary rehabilitation program (PRP) and to evaluate the influence of baseline characteristics as well as comorbidities on the outcomes of PRP. METHODS: The present study included all COPD patients that were admitted to a PRP in our unit. The response to PR was measured by the improvement in exercise tolerance (6 minute walk test), dyspnea (Mahler's Dyspnea Index) and health status (St. George's Respiratory Questionnaire). RESULTS: 114 patients with COPD were included. Most patients (96,5%) had at least one comorbidity. Metabolic diseases (71.1%), cardiovascular diseases (67.5%), other respiratory conditions (57.9%) and anxiety/depression (21.1%) were the most prevalent ones. 64.9%, 64.9% and 51.1% of the patients improved in terms of exercise tolerance, quality of life and dyspnea, respectively. The overall results were similar in all levels of the disease and in all comorbid subgroups. Logistic regression analysis showed that respiratory failure and ischemic heart disease negatively influenced improvement in health status and anxiety/depression predicted lower improvement in dyspnea. CONCLUSION: PR was associated with improvements in all comorbid subgroups of patients, underlining the important role of exercise training in rehabilitation of those chronic diseases associated with COPD. On the other hand, the presence of comorbidities in COPD patients, if clinically controlled, should not preclude access to PR.