Therapy In Management Of Patients Research Articles

Perioperative Management of Antithrombotic Therapy in Patients Undergoing Plastic and Reconstructive Surgery: A Practical Tool Based on Current Guidelines

Introduction: Given the aging population, plastic surgeons are increasingly faced with the challenge of balancing procedural bleeding risk with thromboembolic risk in patients receiving antithrombotic therapies undergoing elective procedures. Guideline recommendations remain unclear in this population, which contributes to heterogeneity in clinical practices. We present a practical approach that summarizes guideline recommendations to facilitate the perioperative management of patients requiring surgery who are already on antithrombotic agents. Methods: Due to the scarcity of plastic surgery-specific guidelines, recommendations were primarily adapted from the 2022 American College of Chest Physicians guidelines on perioperative management of antithrombotic therapy as they are recognized as authoritative and widely used in clinical practice. Results: A clinical practice conceptual framework was adapted based on preexisting guidelines, dividing decision-making into 3 steps: (1) assessing the procedural bleeding risk; (2) assessing the patients’ thromboembolic risk; and (3) determining appropriate management according to antithrombotic agent type. Specific indications are provided for continuing, stopping, and bridging anticoagulants and antiplatelet agents, as well as for consultation with a cardiologist or hematologist. Conclusion: The present framework can be implemented in plastic surgeons’ clinical practice to guide the management of patients on antithrombotic therapies, while minimizing nonessential referrals to the thrombosis service. The lack of plastic surgery-specific guidelines on this topic highlights a need for further research to “bootstrap” the risk categorization of plastic surgical procedures and their appropriate perioperative management.

Management of edoxaban therapy in patients undergoing emergency/urgent procedures: a subanalysis of the global, prospective, observational, multinational EMIT-AF/VTE programme

Abstract Background Physicians are often unable to follow recommendations for preprocedural oral anticoagulant interruption before emergency/urgent (unplanned) procedures, which may lead to a higher incidence of adverse outcomes in these patients compared with those who undergo planned procedures. The Global EMIT-AF/VTE programme found low bleeding and thromboembolic event rates for patients receiving edoxaban who underwent diagnostic or therapeutic procedures. However, edoxaban management and clinical outcomes may differ among the subgroup of patients with emergency/urgent procedures. Purpose To describe periprocedural edoxaban management and clinical outcomes for patients in the EMIT-AF/VTE programme who underwent emergency/urgent procedures. Methods In this subanalysis, only physician-reported unplanned (emergency/urgent) procedures were included, of which dental and dermatological procedures were excluded. Only a patient’s first emergency procedure was included, with the exception of 3 patients having 2 procedures on the same day (in these cases the 2 procedures were combined). Procedure bleeding risk was classified according to EHRA criteria, and baseline characteristics and edoxaban interruption data were collected. Clinical event and procedure dates were compared to determine whether they were related. Results Among 156 patients undergoing emergency/urgent procedures, the mean ± standard deviation age at baseline was 74.5 ± 8.7 years, and the CHA2DS2-VASc score was 3.8 ± 1.6. Medical histories of hypertension and dyslipidaemia were reported in 84.0% and 40.4% of patients, respectively; approximately one-quarter of patients had diabetes mellitus (26.9%) or creatinine clearance ≤50 mL/min (24.4%). The most common procedure types were vascular access and transcatheter diagnostics/interventions (34.6%) and gastroenterological procedures (27.6%). Procedures were more often EHRA-classified as minor (35.9%) or low (35.3%) vs high risk (20.5%). Preprocedure edoxaban interruption rates ranged from 39.3%–50.9% across risk groups, with more than half of the procedures being performed with edoxaban interruption (53%–66%; Figure). By 20 days postprocedure, edoxaban therapy was resumed in approximately 86% and 88% of patients with minor- or low-risk procedures vs 70% with high-risk procedures. Overall, 33 clinical events were recorded, of which 18 (54.5%) preceded a procedure (Table). Five bleeding events and one thrombotic event occurred after and were caused by the procedure. Conclusions Edoxaban resumption was protracted after high- vs minor- or low-risk procedures. Bleeding and thrombotic events resulting from a procedure occurred in <4% of patients, indicating that postprocedure edoxaban therapy can be effectively tailored to optimise clinical outcomes.FigureTable

A Practical Review of Encorafenib and Binimetinib Therapy Management in Patients with BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer.

According to current guidelines, targeted therapy with a combination of BRAF plus MEK inhibitors is the preferred first-line treatment for patients with BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC). In the open-label, single-arm, phase2 PHAROS trial (NCT03915951), the combination of encorafenib, a potent BRAF inhibitor, and binimetinib, a potent MEK inhibitor, demonstrated durable antitumor activity with a manageable safety profile in this patient population. On the basis of the results of this study, the combination of encorafenib plus binimetinib was approved by the US Food and Drug Administration on October 11, 2023, for patients with BRAF V600E-mutant metastatic NSCLC. In this review, we summarize the efficacy and safety of encorafenib plus binimetinib from the PHAROS study. In addition, we discuss strategies to manage adverse reactions with this combination therapy with the intent of minimizing unnecessary treatment discontinuations in these patients.

The effect of intra-articular ozone injection combined with home-based exercise on pain and function in daily living activities of patients with mild to moderate knee osteoarthritis, a randomized double-blinded controlled clinical trial

BackgroundKnee osteoarthritis is the most common arthritis. Various treatments such as analgesics, exercise therapy, and surgery in high-grade OA have been shown to reduce pain and improve patients' function; however, determining the optimal treatment remains a challenge. Ozone therapy is one of the injection techniques used for symptom relief in these patients. Therefore, this study aimed to evaluate the effect of ozone injection in mild to moderate knee osteoarthritis. MethodsThirty-three patients with grade II-III knee osteoarthritis based on the Kellgren-Lawrence classification were involved in the study, by block randomisation. Totally 42 knees were included. All patients received exercise therapy, 500 mg of acetaminophen tablets (up to 2 g per day as needed), and healthy nutrition. In a double-blinded method, the intervention group received Ozone injections, but the control group received placebo injections. Functional tests, including timed-up-and-go and 6-min walk tests, were assessed at baseline and immediately after the 6-week intervention. In addition, the pain was measured by VAS score, and stiffness and activity of daily living (ADL) were evaluated by KOOS questionnaire before and after a 6-week intervention and then one and six months afterwards. FindingsImprovements in pain and KOOS scores were seen in both groups in the 6th week of injections (p < 0.05), with significant differences between groups. However, the effects on pain and KOOS scores disappeared in the 1st and 6th months of follow-ups in the control group. Nevertheless, the effects persisted in the intervention group compared to the baseline and control group, which means that in the mentioned time points intervention group showed significant improvement compared to the control group (p < 0.05). In addition, functional tests showed significant differences between the two groups in the 6th week of injections (p < 0.001). InterpretationOzone injection is a non-surgical treatment for mild to moderate knee osteoarthritis that could decrease pain and improve function and ADL of patients in the short to mid-term (3–6 months), so it seems that adding Ozone injection to the routine exercise therapy in management of patients with knee OA could improve outcomes.

Antithrombotic therapy in patients with acute coronary syndrome: similarities and differences between a European expert consensus document and the 2023 European Society of Cardiology guidelines.

Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients.

Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus

BackgroundDespite research, there are still controversial areas in the management of Crohn’s disease (CD).ObjectiveTo establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.MethodsClinical controversies...

Systematic Review and Meta-analysis of Randomized Controlled Trials on Manual Therapy for the Treatment of Gastroesophageal Reflux Disease

Abstract Objective The objective of our study was to systematically evaluate the clinical efficacy and safety of manual therapy in the treatment of gastroesophageal reflux disease (GERD), providing a reference value for clinical decision-making. Method Studies of randomized controlled trials (RCTs) evaluating the efficacy of manual therapy in patients with GERD were searched through Chinese National Knowledge Infrastructure, Wanfang, VIP China Science and Technology Journal Database, China Biology Medicine Database, PubMed, The Cochrane Library, OVID Medline, and Embase. Two researchers independently reviewed the literature, extracted data, and performed a risk of bias analysis using the Cochrane risk of bias assessment tool, and conducted meta-analysis analysis and publication bias evaluation, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool 26 was used to rate the caliber of the data in this meta-analysis. Results This study included 11 RCTs. Meta-analysis showed that the manual therapy group had a higher total effective rate (odds ratio [OR] = 4.63, 95% confidence interval [CI; 3.01, 7.14], p &lt; 0.00001) and better Reflux Disease Questionnaire scores {weighted mean difference (WMD) = −1.59, 95% CI [−2.85, −0.33], p = 0.01} than the control group. The subgroup analysis showed significant differences in improving the total effective rate in manual therapy versus Western medicine, manual therapy versus Chinese medicine decoction, manual therapy + Western medicine versus Western medicine, and manual therapy + conventional treatment versus conventional treatment groups. Among the 11 trials, 5 reported adverse events, and all RCTs had the possibility of publication bias. Subgroup analysis shows that the differences in age could significantly influence heterogeneity; The GRADE analysis revealed that the overall quality of evidence for all outcome indicators was low and did not support our recommendation for the outcome. Conclusion Manual therapy is more effective than medication therapy alone in relieving GERD symptoms. Furthermore, conventional therapy combined with manual therapy was found to be even more effective. Hence, it is crucial to consider these findings when applying manual therapy to GERD patients to enhance treatment outcomes. Future studies must address issues such as study quality, treatment duration, and generalizability.

Heel Pain - Plantar Fasciitis: Revision 2023.

The Orthopaedic Section of the American Physical Therapy Association (APTA) has an ongoing effort to create evidence-based practice guidelines for orthopaedic physical therapy management of patients with musculoskeletal impairments described in the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). The purpose of these revised clinical practice guidelines is to review recent peer-reviewed literature and make recommendations related to nonarthritic heel pain. J Orthop Sports Phys Ther 2023;53(12):CPG1-CPG39. doi:10.2519/jospt.2023.0303.

Retracted: Study on Management of Blood Transfusion Therapy in Patients with Hereditary Spherocytosis

Retracted: Study on Management of Blood Transfusion Therapy in Patients with Hereditary Spherocytosis

What did we learn about tocilizumab use against COVID-19? A single-center observational study from an intensive care unit in Serbia.

Selection of effective and safe therapy for management of patients with coronavirus disease is challenging. Tocilizumab (TZB) has emerged as a potential treatment option for COVID-19. Several aspects regarding Tocilizumab treatment remain uncertain, such as the optimal timing for its administration and the safety profile, including the potential risk of infections. The aim of the study is to present the clinical characteristics of patients with COVID-19 following the application of Tocilizumab. This is a retrospective analysis of 121 patients with severe forms of COVID-19 previously treated with Tocilizumab was conducted. All patients were admitted to intensive care units (ICUs). Of 121 patients, the majority were men 72 (59.5%) with a median age at presentation of 65 ± 13 years. Only 9 (7.43%) patients were without comorbidities, while the other 112 (92.55%) had two or more comorbidities. Almost all of the 120 patients (99.2%) needed oxygen therapy, such as nasal cannulas in 110 (90.9%) patients, high flow nasal catheter (HFNC) in 4 (3.3%) patients, and continuous positive airway pressure (CPAP) in 5 (4.1%) patients while 1 patient was intubated at the time of hospital admission. The average time from Tocilizumab application to admission to the ICU was 3 days. During clinical deterioration, almost half 57 (47.1%) of the patients were intubated, and 52 (82.5%) of these intubated patients (p < 0.001) had lethal outcomes. The most significant predictors for a lethal outcome according to multivariate analysis were diabetes mellitus (p < 0.001) followed by a subsequent elevation in C-reactive protein levels (CRP; p < 0.002) and ferritin (p < 0.013) after Tocilizumab application. Bloodstream infections were found in 20 (16.5%) patients, most frequently with Gram-negative pathogens like Acinetobacter spp. as in 12 (18.6%) patients, Klebsiella spp. in 6 (8%) patients, and Pseudomonas spp. in 2 (3.2%) patients. Urine culture isolates were found in 9 (7.43%) patients, with Candida spp. being most frequently isolated in 7 (5.8%) patients, followed by Klebsiella spp. and Pseudomonas spp. in 1 patient each (0.8%). Significantly lower survival was seen in patients with proven infection. The benefit of tocilizumab was not found in our study. The high mortality rate among intubated patients after Tocilizumab use suggests appropriate patient selection and monitoring and emphasizes the risk of superinfections. Diabetes mellitus, increased levels of CRP, and ferritin were identified as the most significant predictors of poor outcomes in contrast to increased levels of IL-6.

Rational peri-operative management of antithrombotic therapy in patients undergoing radical cystectomy: A 30-day morbidity analysis based on the updated European Association of Urology guidelines for standardized complication reporting

BackgroundRadical cystectomy (RC) in bladder cancer patients with cardiovascular comorbidity poses challenges due to the need for antithrombotic therapy and high perioperative risk. We aimed to assess 30-day complications after RC in patients receiving antithrombotic therapy. Patients and methodsRetrospective study of 416 bladder cancer patients (2009–2017) undergoing open RC with pelvic lymph node dissection, with or without antithrombotic therapy. Antithrombotic therapy and complication reporting followed European guidelines. Procedure-specific 30-day complications were cataloged, graded (Clavien-Dindo), and quantified using the 30-day Comprehensive Complication Index. Multivariable regressions evaluated antithrombotic therapy's independent effect on key morbidity outcomes. ResultsMedian age was 70 years, 78% were male. Patients on antithrombotic therapy were mostly male, had higher comorbidity burden, worse kidney function, more frequent incontinent diversion, and shorter operative time (all p ≤ 0.027). Bleeding complications occurred in 135 patients (32%; 95%CI = 28–37%), more prevalent with antithrombotic therapy (46% vs. 29%; p = 0.004). Thromboembolic complications occurred in 18 patients (4.3%; 95%CI = 2.6–6.8%), no difference between patients with and without antithrombotic therapy (8.4% vs. 3.3%; p = 0.063). Prevalence of myocardial infarction, new-onset hypertension, acute congestive heart failure, and angina pectoris showed no difference (all p ≥ 0.3). Multivariable analyses indicated no association between antithrombotic therapy and cardiac complications, 30-day major complications, or cumulative morbidity (all p ≥ 0.2). Antithrombotic therapy was associated with bleeding complications (OR = 1.92; 95%CI = 1.07–3.45; p = 0.028), predominantly transfusion-related (75% of 152 bleeding complications). Limitations include retrospective data assessment with biases. ConclusionsRC in patients on antithrombotic therapy exhibits a higher incidence of adverse events due to underlying comorbidities. Adherence to thromboprophylaxis guidelines enables safe RC in patients with significant comorbidities, without substantial increase in major bleeding or severe thromboembolic events.

THU617 Prolonged Exposure To Target Mitotane Concentrations Is Associated With Better Recurrence-free Survival In Patients With Adrenocortical Carcinoma On Adjuvant Treatment

Abstract Disclosure: S. Puglisi: None. A. Calabrese: None. V. Basile: None. O. Kimpel: Speaker; Self; HRA Pharmaceuticals. B. Altieri: None. A. Angelousi: None. G. Kaltsas: None. U. Ambroziak: None. M.L. Appetecchia: None. M. Arosio: None. A. Berruti: Advisory Board Member; Self; HRA Pharmaceuticals. D. Cosentini: None. L. Canu: None. F. Ceccato: None. G. Di Dalmazi: None. L. Bouys: None. R. Libè: None. K. Nowak: None. L. Papierska: None. J. Pittaway: None. T. Kienitz: None. M. Quinkler: None. Y. Elhassan: None. C. Ronchi: None. L. Saiegh: None. A. Stigliano: None. T. Dusek: None. D. Kastelan: None. M. Fassnacht: None. M. Terzolo: Advisory Board Member; Self; HRA Pharmaceuticals. Grant Recipient; Self; HRA Pharmaceuticals. Background: The management of adjuvant mitotane therapy in patients with adrenocortical carcinoma (ACC) is challenging. Plasma mitotane concentrations &amp;gt;14 mg/L have been associated with efficacy in the treatment of advanced ACC; however, data in the adjuvant setting are mixed. Moreover, there is no consensus on how to assess the optimal exposure to mitotane and all the proposed methods have inherent limitations. We have recently proposed a new method analogous to what is established for the anticoagulant warfarin, the time in target range (TTR). We aimed to evaluate whether the TTR is a factor influencing recurrence-free survival (RFS) in patients with ACC on adjuvant mitotane. Methods: This is an international, retrospective, cohort study undertaken in 18 centers in 8 countries, under the auspices of the European Network for the Study of Adrenal Tumors (ENSAT), including adult patients with ACC treated with adjuvant mitotane for at least 1 year following tumor resection, with the availability of at least 3 mitotane measurements per year. TTR was calculated with the Rosendaal method and expressed as the number of months with plasma mitotane concentration &amp;gt;14 mg/L. The following potential predictive factors for RFS have been investigated: patient sex and age, ENSAT stage, hormone secretion, resection status, Weiss score, Ki67 index, and TTR. Data are expressed as median and interquartile range. Results: From a total of 254 patients, 157 fulfilled inclusion criteria and were analyzed (F/M 94/63; age 49, 41-58 years), with a follow-up of 49 (33-92) months. The key baseline features were: 7.0% stage I, 69.4% II, 22.3% III, 1.3% IV; 51.6% secreting tumors; 87.2% R0, 2.6% R1, 10.2% RX; Weiss score 5 (4-7); Ki67 index 11 (5-20). All patients were treated with mitotane for 25 (22-36) months, with a TTR of 14 (6-21) months. At multivariate analysis, Ki67 index (HR 1.07, 95%CI, 1.02-1.12; p&amp;lt;0.01) and Weiss score (HR 1.7, 95%CI, 1.16-2.47; p&amp;lt;0.01) were associated with an increased risk of recurrence, while female sex (HR 0.14, 95%CI, 0.04-0.58; p&amp;lt;0.01) and TTR (HR 0.80, 95%CI, 0.70-0.90; p&amp;lt;0.001) were associated with a reduced risk. Conclusions The present findings show that the patients who are exposed to plasma mitotane &amp;gt;14 mg/L for longer periods have better RFS. These findings provide indirect evidence of the value of adjuvant therapy with mitotane and support the importance of drug monitoring to guide dose adjustment in clinical practice and improve patient outcome. Presentation: Thursday, June 15, 2023

Knowledge, attitude, and readiness of pharmacists toward medication therapy management for patients with attention deficit hyperactivity disorder: a cross-sectional quantitative study.

Medication Therapy Management (MTM) is a patient-centered service that optimizes drug therapy, improves clinical outcomes, and enhances quality of life. Pharmacists play a critical role in MTM services and provide comprehensive medication management for patients with attention deficit hyperactivity disorder (ADHD). The aim of this study was to assess the knowledge, attitude, and readiness of Iraqi community pharmacists regarding MTM services for ADHD patients. A cross-sectional study was conducted among 480 Iraqi pharmacists working in community pharmacies in Baghdad. Data were collected using a pre-validated, self-administered questionnaire with 34 items. Results showed that only 127 (26.5%) pharmacists had good knowledge, 146 (30.4%) had good attitude, and 148 (30.8%) had high readiness regarding MTM services in ADHD patients. Multivariate analyses showed that a higher number of hours worked per week in the hospital was significantly associated with a lower likelihood of high attitude, whereas practicing MTM services, high knowledge, and high attitude were significantly associated with a higher likelihood of high readiness. The findings of this study indicate that knowledge, attitudes, and readiness for MTM services for ADHD patients are inadequate. Therefore, there is an urgent need for effective educational strategies to better prepare pharmacists for their potential role in the community, particularly for providing MTM services to ADHD patients.

The effect of patient-led goal setting approach combined with pain neuroscience education or manual therapy in patients with chronic low back pain: protocol for a parallel-group randomized controlled trial

BackgroundLow back pain (LBP) is a multifactorial disorder associated with a high range of physical and psychological burden on the society. Patient-led goal-setting approach has shown potential effects for improving chronic LBP. However, there are few studies investigating its benefits when combined with a supplementary intervention. This paper, therefore, presents a protocol for a randomized control trial (RCT) to study the effect of a patient-led goal-setting approach combined with pain neuroscience education (PNE) or manual therapy (MT) among patients with chronic LBP.MethodsA total of 105 patients suffering from chronic LBP will be recruited via flyers displayed in hospitals and universities, and those meeting the study’s criteria will randomly be allocated into a patient-led goal-setting approach with the PNE group, and/or with the MT program group, and/or a control group. The primary outcomes will be the pain intensity and disability. Secondary outcomes include quality of life, depression, anxiety and stress, fear avoidance beliefs, kinesophobia, pain self-efficacy, catastrophic pain, neurophysiology of pain, and central sensitivity. All the outcomes will be recorded at 2 months after receiving the treatment as post-test sessions and after 4 and 12 months as follow-up sessions. The Ethics Committee in Research at Sport Sciences Research Institute of Iran approved the protocol of this trial (IR.SSRC.REC.1400.084). Written, informed consent to participate will be obtained from all participants. All methods will be conducted in accordance with the ethical standards of the Declaration of Helsinki and in accordance with relevant guidelines and regulations. We will disseminate the findings through peer-reviewed publications and conference presentations and send them to the participants.DiscussionThis trial will demonstrate which supplementary intervention can better improve the impact of a patient-led goal-setting approach to treat LBP. If successful, the results will potentially have implications for athletic trainers, physiotherapists, and health care practitioners.Trial registrationIRCT Iranian Registry of Clinical Trials IRCT20210927052616N1. Registered on November 03, 2021.

Perioperative management of the antiplatelet therapy in patients with ischemic heart disease undergoing noncardiac surgery

Perioperative management of the antiplatelet therapy in patients with ischemic heart disease undergoing noncardiac surgery

Narrative Review: Terapi Kortikosteroid Pada Pasien COVID-19 dengan Komorbiditas Diabetes Melitus

COVID-19 is a respiratory disease caused by SARS-CoV-2, a corona virus that was discovered at the end of 2019. Diabetes mellitus (DM) is the second highest comorbidities in Indonesia of COVID-19 patients. One of the treatments for COVID-19 patients is corticosteroids. Commonly used corticosteroids are dexamethasone, methylprednisolone, and hydrocortisone. This study aims to determine the effect of corticosteroid therapy in COVID-19 patients with DM comorbidities so that it can be a source of information and a reference in the management of therapy in patients. This research is a narrative review using literature from the science databases Cochrane, PubMed and Science Direct. Literature search used the keywords COVID-19, diabetes, and corticosteroids. The results of the literature screening obtained 16 study articles that met the inclusion criteria. The conclusion of this narrative review study is that the recommended corticosteroid therapy for COVID-19 patients is dexamethasone. Administering corticosteroids to COVID-19 patients with comorbid DM can increase the incidence of hyperglycemia, especially at high doses and in the long term, thereby worsening the patient's prognosis, causing new onset diabetes, and increasing the need for insulin doses.

Podcast to Discuss Therapy Management for Patients with Metastatic Renal Cell Carcinoma Receiving First-Line Axitinib Plus an Immune Checkpoint Inhibitor.

Podcast to Discuss Therapy Management for Patients with Metastatic Renal Cell Carcinoma Receiving First-Line Axitinib Plus an Immune Checkpoint Inhibitor.

Clinical management of second-generation tyrosine kinase inhibitor therapy in patients with newly diagnosed chronic myeloid leukemia in the chronic phase, focusing on age and dose effects.

ABL1-tyrosine kinase inhibitors (TKIs) are an established treatment choice for patients with chronic myeloid leukemia in the chronic phase (CML-CP). However, effects of TKI dose modification have not been well investigated. In this study, we retrospectively analyzed 178 patients with newly diagnosed CML-CP who were treated with dasatinib or nilotinib, focusing on age and dose effects. Efficacy as measured by cumulative major molecular response (MMR) and molecular response 4.5 rates did not differ significantly between the younger group and elderly group. Elderly patients who started nilotinib at a reduced dose had similar or better efficacy outcomes (including cumulative MMR and continuation ratios) than other groups, and elderly patients who started dasatinib at a reduced dose had the lowest MMR ratio and longest MMR duration. Effects of dose modification based on age and TKI selection can be attributed to flexible management of TKI therapy in real-world practice, but further studies are required to validate the findings of this study.

Unusual causes of hyperthyrotropinemia and differential diagnosis of primary hypothyroidism: a revised diagnostic flowchart.

The clinical consequences of primary hypothyroidism include cardiovascular morbidity, increased mortality, and poor quality of life; therefore guidelines endorsed by several Scientific Societies recommend measuring circulating thyroid-stimulating hormone (TSH) in patients at risk. The assessment of serum TSH levels is also deemed to be the most robust and accurate biomarker during the management of replacement therapy in patients with a previous diagnosis of primary hypothyroidism. In line with a reflex TSH laboratory strategy, free thyroxine is measured only if the TSH falls outside specific cutoffs, in order to streamline investigations and save unjustified costs. This serum TSH-based approach to both diagnosis and monitoring has been widely accepted by several national and local health services; nevertheless, false-negative or -positive testing may occur, leading to inappropriate management or treatment. This review aims to describe several infrequent causes of increased circulating TSH, including analytical interferences, resistance to TSH, consumptive hypothyroidism, and refractoriness to levothyroxine replacement treatment. We propose a clinical flowchart to aid correct recognition of these various conditions, which represent important potential pitfalls in the diagnosis and treatment of primary hypothyroidism.

Management of luspatercept therapy in patients with transfusion-dependent β-thalassaemia.

Patients with transfusion-dependent β-thalassaemia require lifelong, regular red blood cell transfusions for survival; however, frequent blood transfusions are associated with an increased risk of iron overload, transfusion-transmitted disease and alloimmunization, as well as reduced quality of life. Luspatercept, an erythroid maturation agent that promotes late-stage erythroid maturation independently of erythropoietin, has demonstrated efficacy in reducing transfusion burden in patients with transfusion-dependent β-thalassaemia. In this review, we discuss treatment initiation, ongoing evaluation, dose adjustment and management of adverse events in transfusion-dependent patients with β-thalassaemia receiving luspatercept, and we provide guidance on how to determine whether patients are deriving clinical benefit.