A clinical model to predict successful renal replacement therapy (RRT) discontinuation in patients with Acute Kidney Injury (AKI)

Abstract Introduction Ideal timing of Renal Replacement Therapy (RRT) discontinuation in Acute Kidney Injury (AKI) is still unknown. We aimed to study the role of creatinine-related variables in predicting RRT successful discontinuation and to propose a clinical predictive score. Methods In this single-centre retrospective study, we evaluated all AKI patients in whom RRT was interrupted for at least 48 hours. Patients who were still RRT-independent 7 days after initial RRT cessation were included in the "Success" group and opposed to the "Failure" group. We evaluated baseline characteristics and variables collected at the time of RRT interruption, as well as the Kinetic estimated Glomerular Filtration Rate (KeGFR), the simple variation in serum Creatinine (ΔsCr), and the incremental creatinine ratio on the first three days after RRT interruption. Multivariable analysis was performed to evaluate prediction of success. Internal validation using a simple binomial generalized regression model with Lasso estimation and 5-fold cross validation method was performed. Results We included 124 patients, 49 in the "Failure" group and 75 in the "Success" group. All creatinine-related variables predicted success in simple and multiple logistic regression models. The best model generated a clinical score based on the odds ratio obtained for each variable and included urine output, non-renal SOFA score, fluid balance, serum urea, serum potassium, blood pH, and the variation in sCr values after RRT discontinuation. The score presented an area under the ROC of 0.86 (95% CI 0.76‒1.00). Conclusion Creatinine variation between the first 2 consecutive days after RRT discontinuation might predict success in RRT discontinuation. The developed clinical score based on these variables might be a useful clinical decision tool to guide hemodialysis catheter safe removal.

Prevalência, padrões e fatores associados à contracepção no Brasil e meta-análise da descontinuidade contraceptiva no cenário mundial / Prevalence, patterns and factors associated with contraception in Brazil and meta-analysis of contraceptive discontinuation on the global stage

Introdução: O Brasil tem uma elevada prevalência de uso de contraceptivos entre mulheres em idade reprodutiva. No entanto, observa-se que persistem desigualdades, tanto no acesso quanto em relação ao tipo de método usado, o que pode contribuir para as altas taxas de gestações não planejadas e abortos induzidos no país. Outro fator que contribui para esses desfechos é a descontinuidade contraceptiva, porém este indicador não é monitorado no país desde 1996, dificultando dimensionar a magnitude do problema. Objetivos: Estimar fatores individuais e contextuais associados ao uso de contraceptivos de acordo com a paridade das mulheres brasileiras em idade reprodutiva; estimar os fatores associados ao tipo de método contraceptivo usado pelas brasileiras; e estimar a magnitude da descontinuidade contraceptiva na literatura mundial a partir de uma meta-análise. Métodos: Foram utilizados dados da Pesquisa Nacional de Saúde de 2013 e 2019 para responder aos dois primeiros objetivos da tese. Os desfechos principais foram o uso de métodos contraceptivos (MC) e o tipo de método classificado quanto ao tempo de ação: contraceptivos reversíveis de curta duração (SARCs) e contraceptivos reversíveis de longa duração (LARCs), e MC permanentes. Os fatores individuais foram características da história reprodutiva, do acesso aos serviços de saúde e sociodemográficas; e os contextuais: Índice de Desenvolvimento Humano (IDH), Índice Sociodemográfico (SDI), Rendimento Mensal Médio e Cobertura da Atenção Primária (APS). Primeiramente, utilizou-se modelos de regressão logística multinível para estimar os fatores individuais e contextuais associados ao uso de MC, estratificados por paridade. Em seguida, para estimar os fatores associados ao tipo de MC usado pelas mulheres foram utilizados modelos de regressão logística multinomial, cuja categoria de referência foram as usuárias de SARC. Por último, foi conduzida uma revisão sistemática com meta-análise para estimar a magnitude da descontinuidade contraceptiva (abandono e troca) na literatura mundial, que também considerou a classificação dos métodos em SARCs e LARCs. Resultados: A prevalência do uso de MC foi superior a 80% em 2013 e 2019, e menor entre nulíparas. Entre 2013 e 2019, observou-se uma redução da variabilidade da chance de usar MC entre as Unidades Federativas (UFs) para nulíparas. Mesmo assim, nulíparas que residiam em UFs com melhores indicadores socioeconômicos, tais como maior IDH e SDI, tinham mais chance de uso de MC. Por outro lado, a cobertura da APS foi a única variável que permaneceu associada a maior probabilidade de uso de MC em 2019 entre primíparas/multíparas. Quanto ao tipo de MC, mais de 70% das mulheres usavam SARCs. Mulheres com melhores condições socioeconômicas tinham mais chance de usar LARCs e menos chance de usar métodos permanentes quando comparados aos SARCs. Por outro lado, mulheres com maior idade, paridade e que viviam com companheiro tinham maior chance de usar métodos permanentes em relação aos SARCs. Ao realizar a meta-análise dos dados identificou-se que a taxa de descontinuidade de SARCs foi de 56,8%, enquanto para LARCs foi de 17,8%. Para as usuárias de SARCs, a chance de abandono foi quase 7 vezes maior que a de troca. Das mulheres que descontinuaram, a maioria abandonou o uso de MC devido a efeitos colaterais. Conclusão: Existem desigualdades individuais e contextuais em relação ao acesso à contracepção no país, segundo a paridade das mulheres. Além disso, mulheres com melhores condições socioeconômicas têm mais acesso aos MC mais eficazes, como os LARCs. Destaca-se ainda as elevadas taxas de descontinuidade encontradas na meta-análise, principalmente para os SARCs, MC mais usados pelas brasileiras. Nossos achados indicam a necessidade de retomar a discussão da contracepção no país com políticas e programas voltados ao enfrentamento das iniquidades, à qualificação do acesso, à promoção da equidade, tendo em vista grupos mais alijados, bem como retomar o monitoramento da descontinuidade contraceptiva em âmbito nacional, além de incluir aspectos assistenciais que deem conta de manejar melhor esse fenômeno.

Brazil has a high prevalence of contraceptive use among women of reproductive age. However, it is observed that inequalities persist, both in access and in relation to the type of method used, which may contribute to the high rates of unplanned pregnancies and induced abortions in the country. Another factor that contributes to these outcomes is contraceptive discontinuity, but this indicator has not been monitored in the country since 1996, making it difficult to measure the magnitude of the problem. Objectives: To estimate individual and contextual factors associated with the use of contraceptives according to the parity of Brazilian women of reproductive age; to estimate the factors associated with the type of contraceptive method used by Brazilian women; and to estimate the magnitude of contraceptive discontinuity in the world literature based on a meta-analysis. Methods: Data from the National Health Survey of 2013 and 2019 were used to answer the first two objectives of the thesis. The main outcomes were the use of contraceptive methods (CM) and the type of method classified according to the time of action: short-acting reversible contraceptives (SARCs) and long-acting reversible contraceptives (LARCs), and permanent CM. Individual factors were reproductive history, access to health services and sociodemographic characteristics; and the contextual ones: Human Development Index (HDI), Sociodemographic Index (SDI), Average Monthly Income and Primary Care Coverage (PHC). First, multilevel logistic regression models were used to estimate the individual and contextual factors associated with CM use, stratified by parity. Then, to estimate the factors associated with the type of CM used by women, multinomial logistic regression models were used, whose reference category was users of SARCs. Finally, a systematic review was conducted with meta-analysis to estimate the magnitude of contraceptive discontinuity (abandonment and switch) in the world literature, which also considered the classification of methods in SARCs and LARCs. Results: The prevalence of MC use was greater than 80% in 2013 and 2019, being lower among nulliparous women. Between 2013 and 2019, there was a reduction in the variability of the chance of using CM between the Federative Units (FUs) for nulliparous women. Even so, nulliparous women residing in FUs with better socioeconomic indicators, such as higher HDI and SDI, were more likely to use MC. On the other hand, PHC coverage was the only variable that remained associated with a greater chance of CM use in 2019 among primiparous/multiparous women. As for the type of CM, more than 70% of the women used SARCs. Women with better socioeconomic conditions were more likely to use LARCs and less likely to use permanent methods when compared to SARCs. On the other hand, women of greater age, parity and who lived with a partner were more likely to use permanent methods in relation to SARCs. When performing a meta-analysis of the data, it was identified that the discontinuity rate for SARCs was 56.8%, while for LARCs it was 17.8%. For users of SARCs, the chance of dropping out was almost 7 times greater than switching. Of the women who discontinued, most discontinued MC use due to side effects. Conclusion: There are individual and contextual inequalities regarding access to contraception in the country, according to women's parity. In addition, women with better socioeconomic conditions have more access to the most effective CM, such as LARCs. Also noteworthy are the high rates of discontinuity found in the meta-analysis, especially for SARCs, the MC most used by Brazilian women. Our findings indicate the need to resume the discussion of contraception in the country with policies and programs aimed at confronting inequities, qualifying access, promoting equity, with a view to more marginalized groups, as well as resuming the monitoring of contraceptive discontinuity in nationwide, in addition to including assistance aspects that manage this phenomenon better.

Patterns of treatment discontinuation in patients receiving anti-vascular endothelial growth factor for neovascular age-related macular degeneration

Purpose: To report the reasons for treatment discontinuation within 5 years in patients receiving intravitreal anti?vascular endothelial growth factor (anti?VEGF) therapy for neovascular age?related macular degeneration (nAMD). Methods: A retrospective case?notes review of patients commenced on anti?VEGF for nAMD who failed to complete 5 years of follow?up was undertaken. The reasons for treatment discontinuation, baseline age, baseline visual acuity (VA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the VA change at the last follow?up were recorded. Age?specific all?cause mortality was calculated for deceased patients. Results: Of the 1177 patients, 551 patients (46.8%) failed to complete the 5?year follow?up. The reasons for treatment discontinuation were death (251), early discharge due to stable disease (110), further treatment deemed futile (100), failure to attend (15), ill health (14), patient choice (7), and transfer of care (1). In 53 patients, no reason was documented. The mean baseline age of those who completed the 5?year follow?up (77.4 ± 7.8 years, 95% confidence interval (CI): 76.8–77.9) was significantly lower than those who discontinued the treatment for any reason (82 ± 7.7 years, 95% CI: 81.4–82.6) (P < 0.0001). Survival analysis showed that baseline VA was not a factor in treatment discontinuation; however, visual stability (±5 letters from baseline) was associated with treatment continuation. The age?specific all?cause mortality in deceased patients was lower than that in the general population. Conclusion: At 5 years, only 53% of patients remained in active care, and death was the most common reason for treatment discontinuation. Lower baseline age and VA stability during therapy were associated with treatment continuation.

Analysis of adverse drug reactions and reasons for drug discontinuation during acitretin therapy in 171 patients with psoriasis vulgaris / 中华皮肤科杂志

Objective:To analyze adverse drug reactions (ADR) and reasons for drug discontinuation during acitretin therapy in patients with psoriasis vulgaris.Methods:A total of 292 patients with psoriasis vulgaris treated with acitretin were collected from the First Affiliated Hospital of Guangxi Medical University from 2014 to 2019. According to the inclusion and exclusion criteria, 193 patients who received periodic follow-up were included in this study, clinical data were collected from these patients and retrospectively analyzed. ADRs occurring during the acitretin treatment and reasons for drug discontinuation were analyzed.Results:Totally, 519 cases of ADRs occurred in 171 of the 193 patients, with the incidence rate being 88.6%. Of these cases, 174 (33.5%) involved the epithelial tissues, 126 (24.3%) the endocrine system, 1 (0.2%) the reproductive system, 29 (5.6%) the motor system, 77 (14.8%) the circulatory system, 3 (0.6%) the nervous system, 71 (13.7%) the digestive system, and 38 (7.3%) involved the urinary system. Relatively common ADRs included dryness of skin and mucous membranes, as well as musculoskeletal pain, and common biochemical changes included dyslipidemia, elevated platelets, and abnormal aminotransferase levels. Most ADRs (81.6%) were reported within 1 month after the start of acitretin therapy. Rare ADRs included alopecia, tinnitus, paronychia, myasthenia, sensory abnormalities, headache, menstrual disorders and hyperbilirubinemia, which were mainly (70.6%) reported within 1 to 6 months after the start of therapy. Of the 519 cases of ADRs, 324 could be alleviated or subsided without drug intervention, 195 were alleviated or subsided after drug withdrawal and/or drug intervention, and there were no cases of serious illness or death. Among the 193 patients, 186 had discontinued acitretin therapy, of whom 116 (62.4%) discontinued due to improvement in disease condition, 35 (18.8%) discontinued due to ADR-induced poor medication compliance, 27 (14.5%) discontinued under the guidance of clinicians due to ADRs, and 8 (4.3%) discontinued due to poor disease control.Conclusion:The incidence of adverse reactions to acitretin is high in the treatment of psoriasis vulgaris, but most of them have a good prognosis.

Progress of chronic myeloid leukemia / 白血病·淋巴瘤

In the tyrosine kinase inhibitor (TKI) therapy era, patients with chronic myeloid leukemia (CML) have embarked on the trend of "chronic disease management". With the advent of 4 generations TKI drugs, there remain unmet needs for optimal CML treatment, such as treatment-free remission and disease recurrence after discontinuation. This article reviews the research progress of CML at the 63rd American Society of Hematology annual meeting.

Attitudes of patients with a rheumatic disease on drug use in the COVID-19 pandemic

Abstract Background: Anti-rheumatic drugs can increase the predisposition to infection, and patients may be unaware of continuing their treatment during the COVID-19 pandemic. Objective: This study aimed to assess whether patients maintain their treatment for rheumatic conditions during the pandemic period and determine the factors responsible for discontinuation. Methods: Patients were randomly selected from the prospectively collected database of our tertiary referral center. The patients were interviewed by telephone through a standardized closed-ended questionnaire, which is targeting the continuity of the treatment plan and the considerations related to the individual choice. The patients were asked whether they hesitated to visit the hospital for follow-up or intravenous drug administration. Results: A total of 278 patients completed the questionnaire. While 62 of the patients (22.3%) had reduced or interrupted the treatment, only 11 patients (3.9%) stopped the treatment completely. A significant difference was observed between the duration of illness and the discontinuation of treatment. (p = 0.023) There was a significant difference in disease activity between the group that stopped treatment and continued treatment. (p = 0.001) There was no statistically significant difference in other demographic characteristics. One hundred thirty-five patients (48.6%) made the treatment decision by themselves, and 80% continued the treatment. Reasons for stopping the treatment were anxiety (48.4%), not being able to go to the hospital for intravenous treatment (45.1%), and not being able to find the drug (6.5%). Conclusion: Since patients with long-term illnesses were found to be significantly more likely to stop their treatment, this group of patients should be monitored.

Current Challenges in Osteoporosis Treatment Discontinuation

@#Osteoporosis is a chronic disease that may require lifelong therapy. Therefore, evidence-based approach regarding the efficacy and safety of long‐term osteoporosis therapy and therapy discontinuation is important. The most important goals for osteoporosis and fragility fracture patients are the recovery of pre-fracture functional level and reduction of fracture risk. There has been increasing consensus that a treat-to-target (T2T) strategy is applicable to osteoporosis and that bone mineral density (BMD) is currently the most clinically appropriate target. However, there is no clear consensus with regard to the definition of a specific BMD treatment target and timeframes applicable to T2T in osteoporosis, and these would need to be individually determined. Treatment with bisphosphonates may be interrupted after 3-5 years, only in patients in whom fracture risk is low or lowered because of the treatment itself. It is recommended never to discontinue treatment in patients with one or more prevalent osteoporotic fractures or in whom the BMD values are still below -2.5 (T score). Recent reports imply that denosumab discontinuation may lead to an increased risk of multiple vertebral fractures. Patients considered at high fracture risk should either continue denosumab therapy for up to ten years or be switched to an alternative treatment. For patients at low-risk, a decision to discontinue denosumab could be made after five years, but bisphosphonate therapy should be considered to reduce or prevent the rebound increase in bone turnover.

Factores involucrados en la adherencia a la inmunoterapia sublingual y subcutánea en pacientes del Servicio de Alergología de una institución de salud en Medellín-Colombia / Factors involved in adherence to sublingual and subcutaneous immunotherapy in patients from the Allergy Service at a health institution in Medellin-Colombia

Introducción. Las enfermedades alérgicas en el mundo han aumentado en el último siglo, requiriendo a su vez nuevos tratamientos que permitan mejorar la calidad de vida de los pacientes; como respuesta, la inmunoterapia ha surgido como una opción terapéutica. El objetivo de este estudio fue identificar aspectos de la adherencia a la inmunoterapia sublingual (ITSL) y subcutánea (ITSC), y los motivos de abandono. Materiales y métodos. Estudio descriptivo retrospectivo de pacientes con enfermedades alérgicas (rinitis, asma o dermatitis atópica) que iniciaron inmunoterapia, por vía subcutánea o sublingual, en el Servicio de Alergología de una institución de salud de la ciudad de Medellín, Colombia. Para el análisis estadístico se utilizaron distribuciones absolutas, relativas, medidas de resumen y la prueba Chi cuadrado de independencia. Resultados. Se incluyeron 144 pacientes (ITSC=84,7%; ITSL=15,3%). El 38,9% de los pacientes fueron considerados adherentes; no se hallaron diferencias significativas en la adherencia según la vía de administración (p=0,833). La razón más importante para la selección de la vía de la inmunoterapia en ambos grupos fue la recomendación médica. De los pacientes no adherentes, el 95,5% (n=84) abandonaron el tratamiento. Las características sociodemográficas de los dos grupos de inmunoterapia fueron relativamente similares, sin diferencias significativas. Se encontró una diferencia significativa entre el servicio prestado por la institución en salud y el abandono al tratamiento, siendo mayor para el grupo tratado con ITSL (38,5%; p=0,007). Conclusión. La principal causa de abandono de la terapia fue la no autorización del tratamiento por parte de las Entidades Promotoras de Salud (53,6%).

Introduction. Allergic diseases in the world have increased in the last century, requiring novel treatments to improve the quality of life of patients. As a result, immunotherapy has emerged as a therapeutic option. The aim of this study was to identify aspects of adherence to sublingual (SLIT) and subcutaneous (SCIT) immunotherapy and reasons for non-adherence. Materials and methods. We present a retrospective study of patients with allergic diseases (rhinitis, asthma or atopic dermatitis) who initiated SCIT or SLIT at the allergology clinic in a health institution in Medellin, Colombia. Absolute and relative distributions, descriptive statistics and Chi square test were used for statistical analysis. Results. A total of 144 patients were selected (SCIT=84.7%; SLIT=15.3%). From the total of patients, 38.9% were considered adherent; no significant differences were found in adherence according to the route of administration (p=0.833). The most important reason for selecting the type of immunotherapy was medical recommendation. Of the non-adherent patients, 95.5% (n=84) discontinued the treatment. Sociodemographic characteristics of the two immunotherapy groups were relatively similar, with no significant differences. A significant difference was found between the service provided by the health institution and discontinuation of treatment, being greater for the group treated with SLIT (38.5%; p=0.007). Conclusion. The main cause of discontinuation of immunotherapy was the lack of approval for funding by the Health Promoting Agencies (53.6%).

Analysis of premature ticagrelor discontinuation in patients with acute coronary syndrome during dual antiplatelet therapy / 第二军医大学学报

Objective To explore the incidence, causes and influencing factors of premature ticagrelor discontinuation (PTD) in patients with acute coronary syndrome (ACS). Methods A total of 400 hospitalized ACS patients who were treated with aspirin and ticagrelor in the Department of Cardiovasology, Changhai Hospital, Naval Medical University (Second Military Medical University) from Jan. to Oct. 2018 were retrospectively enrolled. Baseline data were collected and patients were followed up to analyze the incidence, causes and influencing factors of PTD in ACS patients. Results At 12 months after discharge, PTD occurred in 49 patients (12.2%), and was free in 351 patients (87.8%). The proportions of patients with age>75 years, heart failure history or previous percutaneous coronary intervention (PCI) and the levels of serum potassium and urea in PTD group were significantly higher than those in non-PTD group (P=0.004, 0.031, 0.028, 0.037, 0.001). The proportion of patients using β-blocker and the severity of vascular stenosis in PTD group were significantly lower than those in non-PTD group (P=0.041, 0.018). Dyspnea (22.4%, 11/49), drug unavailability (18.4%, 9/49) and bleeding (12.2%, 6/49) were the three most common causes of PTD. PTD occurred in all dyspnea patients with modified British Medical Research Council (mMRC) being grade 2 or higher (two cases with grade 1, six cases with grade 2, two cases with grade 3, and one case with grade 4). Kaplan-Meier curve analysis showed that 67.3% (33/49) of patients with PTD occurred within 90 days after discharge. Multivariate logistic regression analysis showed that age>75 years old (odds ratio [OR]=2.58, 95% confidence interval[ CI] 1.26-5.26, P=0.009) and elevated urea (OR=1.17, 95% CI 1.04-1.30, P=0.007) were independent predictors of PTD in ACS patients, while severity of vascular stenosis (OR=0.95, 95% CI 0.92-0.98, P=0.001) was the related factor of adherence to ticagrelor. Conclusion The incidence of PTD in ACS patients during dual antiplatelet therapy is 12.2%. For dyspnea patients with mMRC score of grade 2 or higher, P2Y12 receptor antagonist should be replaced in time. Age> 75 years old is an independent predictor of PTD in ACS patients and more attention is needed for elderly patients taking ticagrelor whether they have dyspnea or PTD.

The effect of bisphosphonate discontinuation on the incidence of postoperative medication-related osteonecrosis of the jaw after tooth extraction

OBJECTIVES: The discontinuation of bisphosphonate (BP) treatment before tooth extraction may induce medication-related osteonecrosis of the jaw (MRONJ). Whether the long-term discontinuation of BP treatment before tooth extraction affects the risk of developing MRONJ after tooth extraction or whether extended drug holidays induce systemic side effects remains unclear. The present study assessed the incidence of MRONJ among patients who underwent tooth extraction and did not discontinue BP therapy prior to the procedure.MATERIALS AND METHODS: Patients were classified according to whether or not they discontinued BP therapy before tooth extraction. Differences in the incidence of MRONJ after tooth extraction were compared between the two groups using the chi-squared test.RESULTS: The BP-continuation (BPC) and BP-discontinuation (BPDC) groups included 179 and 286 patients, respectively. One patient in the BPC group and no patients in the BPDC group developed MRONJ (P=0.385). The patients in the BPDC group stopped receiving BP therapy at a mean of 39.0±35.5 months prior to tooth extraction.CONCLUSION: The possibility of pre-existing MRONJ in the extraction area must be considered during the extraction procedure. Routine discontinuation of BP medications for several months before the extraction procedure should be carefully considered, as evidence of its efficacy in reducing the development of post-extraction MRONJ is limited.

Diagnosis and treatment progress of chronic myeloid leukemia / 白血病·淋巴瘤

Chronic myeloid leukemia (CML) has made a milestone progress due to the development of the first generation tyrosine kinase inhibitor(TKI). Nowadays, most clinical trials in CML focus on discontinuation, even the second discontinuation, and the third generation TKI against T315I mutation. The conventional treatments are more focused on decreasing BCR-ABL transcripts rapidly. At the same time, the treatment management of some special patients has been valued.

Vasopressor Discontinuation Order in the Recovery Phase of Septic Shock: A Systematic Review and Meta-Analysis

@#BACKGROUND: Septic shock causes life threatening organ dysfunction needing vasopressor despite adequate fluid resuscitation. Numerous studies and meta-analysis have proven norepinephrine as the initial vasopressor of choice in septic shock with vasopressin as add-on. Although guidelines have established the goal monitoring response in septic shock, optimal approach in discontinuation of the vasopressors in the recovery phase of septic shock remains limited. METHODS: A systematic review and meta-analysis was performed on randomized controlled trials (RCTs) and nonrandomized studies comparing incidence of hypotension within 24 hours of discontinuing norepinephrine first versus vasopressin. Three reviewers independently selected studies, assessed their quality, and extracted the following data: the number and characteristics of patients enrolled, inclusion and exclusion criteria for each study, the description of interventions (discontinuing norepinephrine first versus discontinuing vasopressin first) and outcomes (incidence of hypotension within 24 hours). RESULTS: Seven retrospective cohort studies and one prospective randomized control trial were included. Compared with norepinephrine, risk of hypotension is higher when vasopressin is discontinued first among patients in the recovery phase of septic shock (RR 2.06; 95% CI [1.11,3.82]; I 2 91%). Results were consistent in the subgroup analysis after excluding abstract-only and poor-quality studies (RR 1.73; 95% CI [0.74, 4.03]; I 2 93%). There is no difference in ICU (RR 0.97; 95% CI [0.71, 1.32]; I 2 38%) and in-hospital mortality (RR 0.88; 95% CI [0.66, 1.16]; I 2 41%) between the two vasopressor weaning strategies. Finally ICU length of stay was reported on 5 studies with no significant difference between the two strategies. CONCLUSION: Based on the results, there is increased risk of hypotension when vasopressin is discontinued first versus norepinephrine.

Uptake of hormonal implants contraceptives compared to other forms of contraceptives in Abuja, Nigeria

Background: Subdermal implants are a long-term, efficacious, and easily reversible contraceptive with few adverse effects that pose no risk to the health of the users. It is increasingly accepted as a method of contraception in sub-Sahara Africa like ours. Despite this, its uptake in Nigeria has not reached optimum level. This study is aimed at evaluating the socio-demographic characteristics of subdermal implants users in Abuja, Nigeria, its acceptance rate, efficacy, and discontinuation rate.Methods: The case notes of all the women from the family planning unit were studied. Data on socio-demographic characteristics, uptake rate, side effects profile and the discontinuation rates between January 2013 and December 2017 were retrieved and analyzed using SPSS software and results expressed in numbers and percentagesResults: Out of a total of 1,716 clients that were for contraception during the period under review, 786 accepted Jadelle/Implanon accounting for 45.8% of the implants acceptance rate. Of the 786 acceptors, 485(28.3%) chose Implanon, whereas 301(17.5%) preferred Jadelle. Discontinuation rate for both implants was 20.7%; the main reasons cited by the women were desire to have more children; 51(31.35%) and irregular vaginal bleeding; 30(18.4%). The Pearl Index for the implants in the study was zero. The peak parity for implant users was para 3. Approximately 72.1% the users of all forms of contraception were Christians, while 25.4% were Muslims. About 74.0% of the users had tertiary education.Conclusions: Jadelle/Implanon uptake was relatively high compared to other forms of contraception.

Postpartum Implanon/Nexplanon continuation rates and associated factors among women who ever used Implanon/Nexplanon in a tertiary hospital in Accra, Ghana

Background: Postpartum Implanon use serves as an important conduit to bridge the wide gap of unmet need for contraception. The study sought to determine the continuation rates of postpartum Implanon/Nexplanon use and factors associated with it.Methods: A retrospective review of electronic data of 391 women who had received postpartum Implanon/Nexplanon insertions from January 2012 to December 2015 was conducted at a family planning hospital in Accra, Ghana. Continuation rates and factors associated with discontinuation at 6 months, one year and two years post-partum were determined. Data were analysed using IBM Statistical Package for Social Science (SPSS) version 20.Results: A total of 391 postpartum Implanon/Nexplanon insertions were done during study period. Their mean age was 28.51±5.29 years and median parity was 2.0. Continuation rates of postpartum Implanon/Nexplanon at 6 months, 1 year and 2 years post uptake were 94.9%, 92.8% and 86.4% respectively. Women with tertiary level education were 64% less likely to continue Implanon/Nexplanon use at one-year post uptake (OR=0.36, CI=0.16-0.85). Women with education up to Senior High School were 62% less likely to continue postpartum Implanon/Nexplanon use at 2 years after uptake (OR=0.38, CI=0.18-0.81). Women between ages 20 and 29 years were 53% less likely to continue postpartum Implanon/Nexplanon use at 2 years (OR=0.47, CI=0.26-0.86). Reasons for discontinuation of postpartum Implanon/Nexplanon use were wishes to get pregnant and side effects of the method.Conclusions: Post -partum Implanon/Nexplanon continuation rates are high and remain as a viable choice for reduction of unplanned pregnancies post- delivery.

Fracturas vertebrales múltiples postsuspensión de denosumab: revisión del tema a partir de dos casos clínicos / Discontinuation of denosumab and multiple vertebral fractures: report of two cases and review of the literature

Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)

The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)

Changes and Relationship Analysis of Ocular Parameters After Short-term Discontinuation of Orthokeratology / 中山大学学报(医学科学版)

@#【Objective】To observe and assess the changes of refraction error，axial length，anterior chamber depth， intraocular pressure，and corneal topography parameters 1 month after discontinuation of orthokeratology，and analyse the related factors of refraction error growth. 【Methods】 This was a retrospective self-control clinical study ． A total of 66 children（66 eyes）with a history of wearing orthokeratology lens and voluntary discontinuation，aged 8 to 15 years，were enrolled in this study. They had worn orthokeratology lens for about 1 year，averaged 13（S = 3）months，with about 1 month of discontinuation ，averaged 29（S = 4）days. Observation of refraction error ，axial length ，anterior chamber depth ， intraocular pressure，and corneal topography parameters were taken before wearing orthokeratology lens and 1 month after discontinuation，and the changes and correlation were analyzed by paired t test and linear regression analyses.【Results】 Compared with the values at baseline，spherical equivalent refraction error and cylindrical degree increased［-0.13（-0.50~0.00）］D and［0.00（-0.25~0.00）］D，（P = 0.113）after 1 month of discontinuation，respectively. The value of steep Keratometry，and that of flat K，Em and Es both decreased 了 0.10（- 0.10~0.30）D，0.20（0.00~0.48）D，- 0.10（- 0.30~0.20）D，（P1 = 0.001，P2 < 0.001，P3 = 0.015）. Significantly，change of refraction error was only strongly correlated with axial elongation（X），and we built a predictive model for growth of refraction error（Y）：＾y = -1.294X+0.095（P < 0.001）.【Conclusion】 Refractive error exceed to baseline values completely ，and corneal power rebounded to baseline values basically after 1 month of discontinuation in children who wore orthokeratology lens for about 1 year.

Prescribing Pattern of Clozapine and Clinical Factors associated with Discontinuation of Clozapine / 대한정신분열병학회지

OBJECTIVES: Clozapine is the drug of choice in treatment-resistant schizophrenia. However, its use is often delayed and a significant proportion of clozapine treated patients fails to respond and experience potentially dangerous side-effects. The aim of this retrospective study was to describe the clinical characteristics of patients started on clozapine and the rate and reason of discontinuation of clozapine. METHODS: Medical records of 83 patients started on clozapine during the period of 2012–2016 were reviewed. RESULTS: Clozapine started on patients in chronic phase; the mean age of start was 38.1 years old and the mean number of psychiatric admission was 6.5. A majority (80.7%) of the patients had been subjected to antipsychotic polypharmacy prior to clozapine and most (61.5%) of them were being treated with polypharmacy including clozapine. Overall, 39 (47.0%) subjects had continued clozapine whereas 15 (18.1%) discontinued it; 29 (34.9%) were lost to follow-up. The most common reason for discontinuation was side-effects (n=13) including six life-threatening cases, most of which occurred within 6 months of its start. CONCLUSION: This study demonstrated that there is some evidence of delays to clozapine use, high rates of polypharmacy and significant rate of discontinuation during the early phase of clozapine treatment.

Treatment progress of chronic myeloid leukemia / 白血病·淋巴瘤

A great progress has been made in the treatment of chronic myeloid leukemia (CML) owing to the first generation tyrosine kinase inhibitor (TKI). Nowadays, more and more hematologists are eager to understand how to rapidly reduce the BCR-ABL transcripts level, and to get the standard therapeutic reactions, which emerges the second generation TKI. However, the first and second generation TKI have the potential of drug resistance, and thus the third and fourth generation TKI may resolve this problem. Imatinib drug discontinuation trial emphasizes the importance of digital polymerase chain reaction (PCR) and the probability of the second treatment-free remission.

Is It Possible to Discontinue Tumor Necrosis Factor Antagonists after Psoriasis Remission?

Tumor necrosis factor (TNF) antagonists are highly effective treatments for psoriasis. These agents provide the opportunity to improve disease activity and achieve clinical remission. Despite its efficacy, long-term use of biologics is associated with high financial costs and possibly life-threatening adverse events. Recently, there has been an increasing interest in discontinuing TNF antagonists in patients with psoriasis who have achieved a positive clinical response. However, there is a paucity of data and clinical guidelines concerning the cessation TNF antagonists in psoriasis treatment. Several factors, including cost, subsequent treatment efficacy, relative risks, and tolerability, should be considered before the decision is made to discontinue TNF antagonists. Well-designed clinical trials are necessary to identify factors that may trigger disease exacerbation after medication discontinuation in order to recognize the potential disadvantages of discontinuing treatment in patients who are previously successfully managed on TNF antagonists.

Cascada de fracturas vertebrales en paciente osteoporótica al año de suspender Denosumab / Cascade of vertebral fractures in osteoporotic patient one year after Denosumab

Una paciente con osteoporosis había sido tratada por 4 años con ibandronato oral, luego por 1 año con ranelato de estroncio, y finalmente por 4 años con denosumab. En vista de la buena respuesta densitométrica este fármaco fue suspendido a fines de 2015. A los 14 meses la enferma tuvo lumbalgia aguda y se detectó hundimiento del platillo superior de L1, a lo que siguieron en rápida sucesión iguales lesiones en L2 y L3, y acuñamiento de D11 y D12. Se descartaron causas de osteoporosis secundaria. El plan terapéutico incluye corsé ortopédico, analgésicos, y teriparatida. En los dos últimos años se han publicado varios casos de este síndrome.

A patient with osteoporosis had been treated for 4 years with oral ibandronate, then for 1 year with strontium ranelate, and finally for 4 years with denosumab. In view of the good densitometric response to the latter, the drug was discontinued in December 2015. Fourteen months later the patient had acute low back pain; crushing of the upper plate of L1 was detected, followed by similar lesions in L2 and L3, and wedging of D11 and D12. Causes of secondary osteoporosis were ruled out. The therapeutic strategy includes a corset, analgesics, and teriparatide. In the last two years several cases of this syndrome have been reported.