Combination therapy with lansoprazole and cholecalciferol is associated with a slower decline in residual beta-cell function and lower insulin requirements in children with recent onset type 1 diabetes: results of a pilot study

Abstract Objective To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type 1 diabetes. Methods Children aged 6-12 years with type 1 diabetes were allocated to receive cholecalciferol and lansoprazole (Group 1) or no treatment (Group 2). Children were maintained on their respective insulin regimens and kept records of blood sugar and insulin doses taken. Children were followed at three-month intervals for six months. Changes in mean fasting C-peptide and HbA1c levels, daily insulin doses, fasting blood glucose and mean blood glucose levels from baseline to end of the study were analyzed. Results Twenty-eight children (14 per group) met the eligibility criteria. Fasting C-peptide levels decreased significantly from baseline to study end in both groups (mean decrease -0.19±0.09ng/mL and -0.28±0.08ng/mL, p=0.04 and p=0.001; Group 1 and Group 2 respectively). However, fasting C-peptide level drop was significantly smaller in Group 1 compared to Group 2 (30.6% and 47.5% respectively; p=0.001). Likewise, daily insulin doses decreased significantly in both groups (-0.59±0.14units/kg and -0.37±0.24units/kg respectively; p=0.001). All patients recruited completed the study. No adverse events were reported. Conclusion Combined therapy with cholecalciferol and lansoprazole for six months was associated with smaller decline in residual β-cell function and lower insulin requirements in children with new-onset type 1 diabetes. Preliminary findings of this small-scale study need to be confirmed by larger studies. Registry of Clinical Trials (www.ctri.nic.in) under number REF/2021/03/041415 N.

Características e monitoramento do tapering no triathlon: uma revisão sistemática / Characteristics and monitoring of tapering in triathlon: a systematic review

O tapering é o momento da periodização em que a carga de treino é reduzida visando à minimização do estresse fisiológico, biomecânico e psicológico, acarretando a otimização da performance. O objetivo foi apresentar e discutir as características e monitoramento do tapering no triathlon. A partir dos critérios de seleção estabelecidos, foram encontrados 7 artigos. As evidências apontam que no tapering para triatletas treinados deve ocorrer redução do volume de treinamento na natação em torno de 41% a 60%, no ciclismo e corrida de 21% a 60%. Deve-se manter a intensidade durante o tapering com a utilização do tipo exponencial de queda rápida, durando de 8 a 14 dias no ciclismo e corrida, bem como, 21 dias na natação. O período pré tapering determina a magnitude dos efeitos do tapering, com expectativa do aumento de performance de 3% na competição...(AU)

Tapering is the time of periodization when training load is reduced in order to lower the physiological, biomechanical and psychological stress thus leading to an improved performance. This paper aims to present and discuss the characteristics and monitoring of taper in triathlon. According to the established search criteria, 7 papers were found. Current evidence show that volume training should be lowered in 41% to 60% for swimming and 21% to 60% for cycling and running in the tapering for trained triathletes. Training intensity must be maintained during rapid exponential fall mode taper. It should last from 8 to 14 days for running and cycling and 21 days for swimming. The pre tapering period determines the magnitude of tapering results, and a 3% performance increase is expected in the competition...(AU)

Efficacy of prolonged interval of tumor necrosis factor-α inhibitor treatment in patients with spondyloarthritis: a pilot study / 中华风湿病学杂志

Objective To investigate whether prolonged the interval of tumor necrosis factor (TNF)-α inhibitors (TNF-i) injection could continuously improve inflammatory biomarkers and imaging changes of sacroiliac joint and spine in spondyloarthritis (SpA).Methods A total of 154 SpA patients were included and 95 of them received TNF-α inhibitor therapy.TNF-i used in this study included etanercept,infliximab and adalimumab.The dose of etanercept was gradually reduced from 50 mg per week to every two weeks,every three weeks and then per month.The infusion of Infliximab was reduced from 4 mg/kg at 0,2,6 week to every 8 weeks,every 12 weeks and then every 16 weeks.The interval of Adalimumub injection was changed from 40 mg every two weeks to 3 weeks to 4 weeks and then to two months.The levels of inflammatory parameters,bath ankylosing spondylitis disease activity index (BASDAI),bath ankylosing spondylitis functional index (BASFI),ankylosing spondylitis disease activity score (ASDAS),spondyloarthritis research consortium of canada (SPARCC) scores of sacroiliac joint and fat metaplasia,bone erosion,sclerosis and ankylosis changes on magnetic resonance imaging (MRI) were investigated every 3 to 6 months.Radiograhs of spine were assessed by modified stoke ankylosing spondylitis spinal score (mSASSS) scores at baseline and 2 years.Analyses were performed by Paired t-test,Wilcoxon test,Mann-Whitney U test,Kruskal-Wallis and Chi-square test.Results After 3 months of treatment,erythrocyte sedimentation rate (ESR),c reactive protein (CRP),immunoglobulin A (IgA),BASDAI,BASFI,ASDAS and SPARCC scores were significantly lower than those of the baseline [13.00(6.00,31.00) mm/1 h vs 3.00 (2.00,6.00) mm/1 h,Z=-5.61;7.39(2.52,17.90) mg/L vs 1.88(1.21,3.75) mg/L,Z=-5.57;2.89(2.52,17.90) g/L vs 2.27(1.60,2.85) g/L,Z=-4.69;(2.57±1.43) vs (1.17±0.92),t=9.81;17.50(5.00,27.00) vs 4.00(0,11.00),Z=-6.69;2.62(2.02,3.52) vs 1.22(0.92,1.59),Z=-6.96;25.00(10.00,37.00) vs 12.00 (6.00,20.25),Z=-6.68;all P＜0.05].Compared to 3-6 months,SPARCC scores were significantly reduced during 2-3 years in the TNF-i group [12.00 (6.00,20.25) vs 7.00 (3.25,14.75),P=0.02].There were no significant progresses in fat metaplaisa,bone erosions,sclerosis or ankylosis during the follow-up period (61％,57％,x2=0.07,P=1.00;53％,43％,x2=0.40,P=0.75;31％,57％,x2=3.02,P=0.11;14％,7％,x2=0.43,P=0.66).The mSASSS scores were not different between TNF-i group and TNF-i group after 2 years of treatment [2.50 (0,8.00) vs 3.00 (0,8.00),Z=-0.30,P=0.76].Conclusion Prolonged the interval of TNF-i treatment could continuously improve bone marrow edema in SPA,whereas structural damages of sacroiliac joints and spine are not deteriorated.

Evolution of tree stem taper in Pinus taeda stands / Evolução do afilamento do tronco em povoamentos de Pinus taeda

ABSTRACT: This study aimed to evaluate the evolution of stem taper of trees in Pinus taedastands using stem analysis data from 126 and 120 trees sampled from established stands in Paraná and Santa Catarina States, respectively. The integer and fractional power polynomial was fitted to estimate diameters inside bark along the stem and was used to construct taper curves by age class. The model identity test was applied to verify the change in stem form of trees. The evolution of natural and artificial form factors in the trees was also analyzed. The curves constructed from the fitted taper functions and form factors showed that the stems become more cylindrical with increasing age; the identity test indicated that, in general, the taper curves statistically differ between themselves. This showed that stratifying the data into age classes for fitting in taper functions can produce more accurate assortment estimates.

RESUMO: O objetivo desta pesquisa foi avaliar a evolução do afilamento dos fustes de árvores em povoamentos de Pinus taeda, utilizando dados de análise de tronco de 126 e 120 árvores amostradas, respectivamente, em plantios estabelecidos nos estados do Paraná e de Santa Catarina. O polinômio de potências inteiras e fracionárias foi ajustado para estimativa dos diâmetros sem casca ao longo do tronco e usado para construção de curvas de afilamento por classe de idade. O teste de identidade de modelos foi aplicado para verificar a mudança na forma do tronco das árvores. Foi analisada também, a evolução do fator de forma natural e artificial das árvores. As curvas construídas a partir das funções de afilamento ajustadas e os fatores de forma mostram que os troncos se tornam mais cilíndricos com o aumento da idade. O teste de identidade indicou que, em geral, as curvas de afilamento diferem estatisticamente entre si. Isso evidencia que a estratificação dos dados em classes de idades nos ajustes de funções de afilamento pode produzir estimativas mais acuradas do sortimento.

Good clinical practice guide for opioids in pain management: the three Ts - titration (trial), tweaking (tailoring), transition (tapering) / Orientação para boa prática clínica para opioides no tratamento da dor: os três "Ts" - titulação (teste), ajustes (individualização), transição (redução gradual)

ABSTRACT BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial) during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation). Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring). Finally, for those patients for whom transition (tapering) from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. CONCLUSION: We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's): titration (or trial), tweaking (or tailoring), and transition (or tapering). Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non-pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: Uma boa prática clínica com o uso de opioides como parte de um regime abrangente de tratamento da dor pode enfrentar desafios significativos. Apesar das diretrizes provenientes de sociedades/organizações não governamentais para o manejo da dor, ainda existem obstáculos significativos. A revisão de alguns princípios básicos da analgesia com opioide com base na experiência e no conhecimento das publicações atuais sobre esse cuidado importante da saúde é justificável. CONTEÚDO: De acordo com as diretrizes, a literatura apoia o uso da dose total mais baixa de opioides que forneça o controle adequado da dor com menos efeitos adversos. A titulação (teste), ao iniciar a administração de um opioide, é uma maneira de começar com uma concentração baixa e ir devagar (avaliar a adequação da fórmula específica de um opioide). O ajuste (individualização) é reconhecer que vários fatores contribuem para a experiência pessoal da dor de um indivíduo, tais como fatores físicos, psicológicos, sociais, culturais, espirituais, farmacogenômicos e comportamentais. Finalmente, para aqueles pacientes nos quais a transição (redução gradual) do opioide é desejada, fazer essa transição muito rapidamente pode ter consequências negativas e é possível minimizar os problemas durante essa etapa por meio de uma redução gradual. CONCLUSÃO: Uma abordagem simultânea, agressiva, porém conservadora, é defendida na literatura em que a terapia com opioides é dividida em três etapas principais (os 3 Ts - em inglês: titration, tailoring, tapering): titulação (teste), ajuste (individualização) e transição (redução gradual). Estabelecer os três Ts, juntamente com a aplicação de outra boa prática médica e experiência/julgamento clínico, incluindo abordagens não farmacológicas, pode ajudar os profissionais de saúde no esforço para alcançar o tratamento ideal da dor.

Maintenance of the therapeutic efficacy of etanercept in active ankylosing spondylitis patients ahen taper-ing its dosage / 实用医学杂志

Objective To evaluate the efficacy of etanercept in active ankylosing spondylitis (AS) pa-tient for 48 weeks by tapering the dosage of etanercept every 12 weeks. Methods 52 patients with active AS were enrolled in this study , and 47 patients finished 48 Weeks of observation. 50 mg etanercept was applied subcutaneously once a week for 12 weeks , and was tapered to 50 mg every two weeks for another 12 weeks , and then 25 mg every two weeks for another 24 weeks. BASDAI, BASFI, BASMI, ASDAS, as well as Serum levels of CRP and ESR were doaunented at week 0, 12, 24 and 48, respectively. Result Among the 47 active AS patients, 40 (85.1%) were male, with mean disease duration of 4.1 ± 3.8 years. After 12 -week treatment with 50 mg etanercept weekly, the scores of BASDAI, BASFI, BASMI, ASDAS, as well as levels of ESR and CRP, declined significantly compared to the baseline (P < 0.05, respectively). Despite of tapering the dosage of etan-ercept gradually, most of the patients (87.2%, 41/47) kept in ASAS 40 response during the following 36 weeks. No severe adverse events were observed during the treatment period. Conclusion This study demonstrat-ed the clinical efficacy of etanercept in patients with active AS. A dosage reduction strategy could maintain the clinical efficacy of etanercept during 48 weeks , which indicates that gradually tapering etanercept might be a po-tential effective, economic and safe way for active AS patients.

The evaluation by pulmonary wedge angiography of children with pulmonary artery hypertension ;associated with congenital heart disease / 中国介入心脏病学杂志

Objective To study pulmonary wedge angiography ( PWA ) with hemodynamic the evaluation of children with congenital heart disease and pulmonary artery hypertension ( PAH) . Methods Hemodynamic measurement and pulmonary wedge angiography were performed in 50 children with congenital heart disease. Comparison and analysis were made from the data obtained from PWA and catheterization. Results After PWA, the patients were categorized into 3 groups according to the measured hemodynamics parameters:group A [ n=15, patients with normal mean pulmonary artery pressure ( mPAP≤25 mmHg) and normal pulmonary vessel resistance (PVR﹤300 dyne?s?cm5)], group B [n=24, patients with PAH (mPAP﹥25 mmHg) but normal PVR] and group C (n=11, patients with PAH and elevated PVR (PVR≥300 dyne?s?cm5). Rote of tapering (ROT) was significant lower in group C than in group A and B (F=42. 559,P﹤0. 05). Pulmonary circulation time (PCT) was higher in group C than in group A and B (F=6. 037,P﹤0. 05). ROT correlated negatively with PVR (r = -0. 606, P ﹤0. 05). PCT index correlated positively with PVR (r=0. 783,P=0. 01). There was no significant correlation between PCT and mean pulmonary artery hypertension (mPAP). Conclusions PWA may help to make quantitative analysis of the pulmonary vascular status in patients with congenital heart disease.

Relapse in psoriasis with two different tapering regimens of methotrexate: A randomized open-label controlled study.

Background: Systemic therapy with methotrexate is a very useful modality in psoriasis, but relapses can occur soon after stopping it. Aim: To compare the relapse rates in psoriasis with two different tapering regimens of methotrexate after control is achieved. Methods: This was a randomized open-label controlled study, and patients of chronic plaque psoriasis with psoriasis area and severity index (PASI) >10 were included. Methotrexate 0.3 mg/kg weekly was given and the PASI calculated every 2 weeks. After achieving a 75% reduction in the PASI (PASI-75), patients were assigned randomly in to one of three groups. In the half-dose group, the dose of methotrexate was reduced to half and given weekly; in the 2-weekly group, the same dose was given at 2-week intervals; in the control group, methotrexate was stopped. Patients were followed up for 12 weeks. Results: Out of 141 registered patients, 81 were included: 27 in the half-dose group, 28 in the 2-weekly group, and 26 in the control group. After further exclusions due to adverse effects and loss to follow-up, the results were analysed for 16, 17 and 19 patients respectively in the 3 groups. There was statistically a highly signifi cant difference in relapse rates between the half-dose and control groups (P < 0.001), and a signifi cant difference between the 2-weekly and control groups (P = 0.001). Relapse rates in the half-dose and 2-weekly groups did not show a signifi cant difference (P = 0.680). Limitation: Many (35.8%) patients were excluded and only 52 (64.2%) completed the study. Conclusion: There appears to be no signifi cant difference in the frequency of relapse in psoriasis whether methotrexate is tapered by halving the weekly dose or by doubling the interval between two doses, and both methods led to fewer relapses than abrupt cessation of the drug.

Management of benzodiazepine dependence and toxicity.

The key target of this review is to compare the efficacies of the different adjuncts and methods used in the management of benzodiazepine dependence (tolerance and withdrawal) and poisoning. A systemic review of randomized controlled trials was carried out to determine which method of adjuvant therapy can be best used to overcome the withdrawal symptoms exhibited during benzodiazepine discontinuation. In addition, different tapering methods employed have also been presented in this review. Zolpidem in combination with cognitive behavioural therapy with a parallel gradual taper after conversion to long half-life Benzodiazepine seems to be a promising method among the several analysed. Finally the efficacies of the two available methods to combat benzodiazepine toxicity, namely flumazenil and naloxone have been discussed and compared.

Effects of intensified training and taper on immune function

Although resting immune function is not very different in athletes compared with non-athletes periods of intensified training (overreaching) in already well trained athletes can result in a depression of immunity in the resting state. Illness-prone athletes appear to have an altered cytokine response to antigen stimulation and exercise. Having low levels of salivary IgA secretion also makes athletes more susceptible to upper respiratory tract infections. Overtraining is associated with recurrent infections and immunodepression is common, but immune functions do not seem to be reliable markers of impending overtraining. There are several possible causes of the diminution of immune function associated with periods of heavy training. One mechanism may simply be the cumulative effects of repeated bouts of intense exercise (with or without tissue damage) with the consequent elevation of stress hormones, particularly glucocorticoids such as cortisol, causing temporary inhibition of TH-1 cytokines with a relative dampening of the cell-mediated response. When exercise is repeated frequently there may not be sufficient time for the immune system to recover fully. Tapering has been described as a gradual reduction in the training load which allows the recovery of physiological capacities that were impaired by previous intensive training and permits further training-induced adaptations to occur accompanied by competition performance enhancements. The majority of the studies that have examined the recovery of immunoendocrine responses during 1-3 week tapers in trained athletes have mainly reported enhanced performance, often accompanied by increased anabolic activity, reduced physiological stress and restoration of mucosal immunity and immune function.

Quando se compara a função imune, em repouso, de atletas e não atletas, não se verificam grandes diferenças. Porém, períodos de treinamento intensificado ("overreaching") em atletas bem treinados podem induzir supressão da imunidade no estado de repouso. Os atletas com maior propensão para contrair doenças parecem apresentar uma resposta alterada de citocinas, tanto quando estas são estimuladas por antígenos, quanto em resposta ao exercício propriamente dito. Baixos níveis de secreção de IgA salivar também contribuem para tornar os atletas mais susceptíveis à infecções do trato respiratório superior. A síndrome do "overtraining" é associada a infecções recorrentes e a imunossupressão é comum; no entanto, marcadores da função imune não parecem ser suficientemente sensíveis ao "overtraining" eminente. Existem várias possíveis causas para a diminuição da função imune associadas com períodos de treinamento severo. Um possível mecanismo pode ser simplesmente, o efeito acumulativo de atividades e sessões repetidas de exercício intenso (com ou sem dano tecidual), com a consequente elevação dos hormônios de estresse, particularmente os glicocorticóides como o cortisol, causando assim, uma inibição temporária das citocinas de TH-1, com uma relativa atenuação da resposta imune celular. Quando o exercício é repetido frequentemente, pode não haver tempo suficiente para uma total recuperação do sistema imunológico. O "Tapering" tem sido descrito como uma gradual redução na carga de treinamento a qual permite a recuperação das capacidades fisiológicas, que por sua vez, foram afetadas pelo treinamento intensivo anterior, permitindo assim, que adaptações adicionais decorrentes do treinamento ocorram, acompanhadas pelo incremento do desempenho competitivo. A maioria dos estudos que investigaram a recuperação das respostas imuno-endócrinas em atletas durante uma a três semanas de "taper" tem registrado aumento do desempenho, frequentemente...

Experience with Tapering Enteroplasty in Intestinal Atresia

Tapering enteroplasty was first described by Thomas in 1969 as one method of intestinal anastomosis. The advantages of tapering enteroplasty in the intestinal atresia are: First, it makes end-to-end anastomosis possible between the atretic bowel ends with considerable differences in diameters. Second, it promotes the recover of the postoperative bowel function. Third, it prevents the possibility of the short bowel syndrome by eliminating the need of resecting the dilated bowel. A total of 22 patients with intestinal atresia who underwent tapering enteroplasty from January 1988 to December 2005 at our institute were reviewed. In 3 of 22 cases, tapering enteroplasty was the 2nd operation after an initial end-to-oblique anastomosis. We reviewed the following items: age, sex, type and location of intestinal atresia, initial feeding and total enteral feeding start day, the length of hospital stay and complications. The average age of the patients was 7 days. Male to female ratio was 1 to 1.2 (10 cases: 12 cases). We performed the tapering enteroplasty on all types and locations of the intestinal atresia from the duodenum to the colon: type I (n=3), type II (n=4), type IIIA (n=7), type IIIB (n=5), type IIIB and IV (n=1), type IV (n=1) and type C (duodenum) and type IIIB and IV (jejunum). On the average, the oral feeds were started on the postoperative 8.8th day, and full caloric intake via the enteric route was achieved on postoperative 13.3th day. The average length of hospital stay was 19.6 days. There were 1 case (4.5 %) of anastomotic complication and 2 cases (9 %) of adhesive ileus among 22 patients. The tapering enteroplasty on all types of intestinal atresia is a usefull operative method when there are considerable diameter differences between the atretic bowel ends.