Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease

<b><i>Background:</i></b> Erythropoietin-stimulating agent (ESA) hyporesponsiveness is commonly observed in patients with anemia secondary to chronic kidney disease (CKD). Because of its complexity, a global consensus on how we should define ESA hyporesponsiveness remains unavailable. The reported prevalence and demographic information on ESA hyporesponsiveness within the CKD population are variable with no consensus definition. <b><i>Summary:</i></b> ESA hyporesponsiveness is defined as having no increase in hemoglobin concentration from baseline after the first month of treatment on appropriate weight-based dosing. The important factors associated with ESA hyporesponsiveness include absolute or functional iron deficiency, inflammation, and uremia. Hepcidin has been demonstrated to play an important role in this process. Mineral bone disease secondary to CKD and non-iron malnutrition among other factors are also associated with ESA hyporesponsiveness. There is continued debate toward determining a gold-standard treatment pathway to manage ESA hyporesponsiveness. The development of hypoxia-inducing factor-stabilizers brings new insights and opportunities in the management of ESA hyporesponsiveness. <b><i>Key Message:</i></b> Management of ESA hyporesponsiveness involves a comprehensive multidisciplinary team approach to address its risk factors. The progression of basic and clinical research on identifying risk factors and management of ESA hyporesponsiveness brings greater hope on finding solutions to eventually tackling one of the most difficult problems in the topic of anemia in CKD.

A 10-year follow-up service evaluation of the treatment pathway outcomes for patients in nine in-patient psychiatric rehabilitation services

Aims and method This study examines the treatment pathway outcomes over a 10-year period for patients in nine rehabilitation wards at the beginning of this time period. Results Data were obtained on 85 patients, of whom 59 were discharged during the 10-year period; 29 were readmitted, of whom 15 had further in-patient rehabilitation admissions. Nineteen patients remained in hospital throughout the period. Only nine patients were living independently at the time of follow-up or death, and 34 were in longer-term in-patient settings. Eighteen patients had died during the 10-year period. Clinical implications New planning of rehabilitation services needs to ensure an integrated whole-systems approach, across in-patient and community settings, with specialist mental health rehabilitation teams to support people moving from hospital to the community, and for the small number remaining in hospital for very long periods, development of sufficient high-quality, local in-patient provision.

How to evaluate and treat the spectrum of TMA syndromes in pregnancy

Thrombotic microangiopathy (TMA) is the broad definition for thrombocytopenia, microangiopathic hemolytic anemia, and end-organ damage. Two important categories are thrombotic thrombocytopenic purpura (TTP) and complement-mediated hemolytic-uremic syndrome (CM-HUS). Pregnancy and the immediate postpartum period are associated with TMAs specific to pregnancy in rare situations. These include pregnancy-induced hypertension, preeclampsia, and hemolysis, elevated liver enzymes, and low platelets. TTP and CM-HUS may present in pregnancy. However, the diagnosis may not be immediately obvious as they share characteristics of pregnancy-related TMAs. Within this review, we discuss investigations, differential diagnosis of TMAs in pregnancy, and management. The importance is a risk of maternal mortality but also poor fetal outcomes in relation to TTP and CM-HUS. Treatment of these disorders at presentation in pregnancy is discussed to achieve remission and prolong fetal viability if possible. In subsequent pregnancies, a treatment pathway is presented that has been associated with successful maternal and fetal outcomes. Critical to this is a multidisciplinary approach involving obstetricians, the fetal medicine unit, and neonatologists.

Long-term treatment outcomes from the perspective of a patient with unilateral cleft lip and palate

The management of patients with orofacial cleft (OFC) often extends from diagnosis or birth well into adulthood and requires many different specialists within multidisciplinary teams (MDT). The aims of treatment are to restore form and function relating to hearing, speech, occlusion and facial aesthetics. People with OFCs that include the lip, alveolus and palate (cleft lip and palate (CLP)) require several different staged and coordinated surgical and non-surgical interventions, and the treatment pathway is associated with a heavy burden of care. Due to the extensive nature of the interaction with these patients, MDT members have opportunities to provide enhanced patient-centred care and support. This case report provides an overview of the current knowledge of the aetiology of OFC and the management of these patients. It provides a unique perspective from one of the coauthors who has a unilateral CLP (UCLP) and reports on his treatment experiences and long-term treatment outcomes. By having a better understanding of the impact of UCLP and treatment provided, MDT members can not only provide improved clinical treatment but also offer improved patient experiences for those with craniofacial anomalies, in particular, an increased awareness of the psychosocial challenges, they endure throughout their treatment pathway and beyond.

Cost-Effectiveness of Second-Line Therapies in Adult Patients with Chronic Immune Thrombocytopenia

Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by accelerated platelet clearance and impaired platelet production. Up to 75% of cases in adults assume a chronic course. Standard second-line treatment options include rituximab, thrombopoietin receptor agonists (TPO-RAs), and splenectomy. The 2019 American Society of Hematology (ASH) guidelines provide three dichomotous evaluations of these treatments with conditional recommendations for 1) splenectomy or TPO-RA, 2) rituximab over splenectomy, and 3) TPO-RA over rituximab. The guideline panel noted that there were no studies available to evaluate the cost-effectiveness of these therapies. We sought to address this knowledge gap by conducting the first cost-effectiveness analysis of second-line therapies for chronic ITP. Methods: We built a Markov model comparing the cost-effectiveness of all six treatment pathways utilizing rituximab, TPO-RA (romiplostim or eltrombopag), and splenectomy. We assumed a median age of 50 at diagnosis and a 20-year time-horizon. Costs were assessed from the health system perspective. Effectiveness was calculated in quality-adjusted life-years (QALYs). The costs of splenectomy treatment included the cost of surgery, postoperative care, accessory spleen imaging and repeat splenectomy, treatment for post-splenectomy sepsis and thromboembolism. The annual risks of post-splenectomy sepsis and thromboembolism were assumed to be the highest reported, every post-splenectomy infectious complication was assumed to be severe septic shock, and patients with thromboembolism accrued the costs of indefinite anticoagulation. To minimize bias against TPO-RAs, TPO-RA therapy was assumed to have no adverse events, a constant high overall response without any loss of effectiveness, and the highest reported rate of successful TPO-RA therapy discontinuation after two years, which we assumed to be permanent. Rituximab treatment was assumed to have no adverse events and overall response rates as previously reported. Cost-effectiveness of each treatment pathway was calculated as the incremental cost-effectiveness ratio (ICER), calculated as ratio of costs to QALYs. The ICER was compared against a 2019 US willingness-to-pay (WTP) threshold of $195,300. We then performed one-way deterministic sensitivity analyses varying all parameters including the costs of splenectomy, TPO-RA, rituximab, splenectomy complications, splenectomy complete response rates, TPO-RA and rituximab overall response rates, utilities of the well and diseases states, annual post-splenectomy septic shock mortality and perioperative splenectomy mortality. We concluded with a probabilistic sensitivity analysis running 10,000 Monte Carlo simulations. Results: The most cost-effective treatment pathway was #5 (splenectomy-&gt;rituximab-&gt;TPO-RA; Figure). The next most cost-effective pathway was #4 (rituximab followed by splenectomy and then TPO-RA therapy), with an ICER of $369,289. All four remaining treatment pathways (#1-3, 6) utilizing TPO-RA therapy early (first or second) had an ICER above $1 million, far above the US WTP of $195,300, and/or were dominated. Of these, pathways #1 and #3 were externally dominated and #2 was absolutely dominated. No parameter change in one-way deterministic sensitivity analysis in any of the 4 pathways featuring TPO-RA early brought down the ICER to under $1 million. In the probabilistic sensitivity analysis, pathway #5 was favored in 100% of 10,000 Monte Carlo simulations. The cost of TPO-RA would have to be decreased to under $20,000 annually (e.g., &gt;80% reduction in the cost of eltrombopag or romiplostim) before it could become cost-effective in any TPO-early treatment pathway. Conclusion: Four treatment pathways (#1-#4) are consistent and two pathways (#5-#6) are at variance with the ASH guidelines. Although it does not align with the ASH guidelines, pathway #5 (splenectomy-&gt;rituximab-&gt;TPO-RA) was most cost-effective. Over a 20-year time-horizon, all pathways featuring early use of a TPO-RA exceeded an ICER &gt;$1 million or were dominated. Because our model was designed to maximize the cost-effectiveness of TPO-RA, it is likely that the actual ICER of pathways featuring early use of TPO-RA are higher than what we report here. Preferred second-line treatment strategies in adults with chronic ITP may be worth considering in light of our findings. Figure 1 Figure 1. Disclosures Cuker: Synergy: Consultancy; Novo Nordisk: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Novartis: Research Funding; Bayer: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; Spark Therapeutics: Research Funding.

The Added Benefit of Opicapone When Used Early in Parkinson's Disease Patients With Levodopa-Induced Motor Fluctuations: A Post-hoc Analysis of BIPARK-I and -II

Introduction: Opicapone (OPC) was efficacious in reducing OFF-time in two pivotal trials in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (BIPARK-I and -II). Post-hoc analyses of these trials evaluated the efficacy of OPC following pre-defined segmentation of the wide spectrum of motor fluctuations in PD.Methods: Data from matching treatment arms in BIPARK-I and -II were combined for the placebo (PLC) and OPC 50-mg groups, and exploratory post-hoc analyses were performed to investigate the efficacy of OPC 50 mg vs. PLC in subgroups of patients who were in “earlier” vs. “later” stages of both their disease course (e.g., duration of PD &lt;6 years vs. ≥6 years) and levodopa treatment pathway (e.g., number of daily levodopa intakes &lt;4 vs. ≥4). Efficacy variables included changes from baseline in absolute OFF-time and total ON-time.Results: The Full Analysis Set included 517 patients (PLC, n = 255; OPC 50 mg, n = 262). OPC 50 mg was significantly more effective than PLC in reducing OFF-time and increasing ON-time in the majority of subgroup analyses (p &lt; 0.05). Moreover, patients in “earlier” stages of both their disease course and levodopa treatment pathway experienced numerically greater efficacy when using OPC 50 mg, in comparison with those in “later” stages.Conclusion: OPC 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in PD patients. There was also a signal for enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway.

Clinical management of complex motor stereotypies

This paper will review complex motor stereotypies and provide a summary of the current proposed treatment pathway.

The Effectiveness of Telemedical Monitoring Program DiabCare Tirol for Patients with Gestational Diabetes Mellitus

The aim of this paper was to evaluate the effect of telemedical care of gestational diabetes mellitus (GDM) patients with the digital treatment pathway model DiabCare Tirol. Methods: 27 courses of patients with GDM, who were telemonitored through the integrated care program DiabCare Tirol in a diabetes outpatient clinic in Tyrol, Austria during the COVID-19 pandemic in 2020, were analyzed. In addition, randomized controlled trials (RCTs) on telemedicine interventions for GDM were researched, and their results were used for comparison with this disease management method. The patient outcome analysis was used to examine the effects of the integrated care program involving telemonitoring support and compared them to the results of RCTs in which participants were randomly assigned to one of two groups, either mobile monitored or standard treatment group. Results: The feasibility of the digital treatment pathway model was confirmed in practice, as the trend analysis of the 27 GDM patients involved showed significantly improved glycaemic control. Results of RCT studies tend to support the findings of DiabCare Tirol. Conclusion: Benefits of telemonitoring with integrated care to support conventional therapy cannot be dismissed, especially in times of the pandemic. Continuous outcome research with larger patient numbers will be necessary to confirm the effectiveness of telemonitoring in a regular care setting.

Advances in the curative management of oesophageal cancer

The incidence of oesophageal cancer, in particular adenocarcinoma, has markedly increased over the last four decades with adenocarcinoma becoming the dominant subtype in the West, and mortality rates are high. Nevertheless, overall survival of patients with oesophageal cancer has doubled in the past 20 years, with earlier diagnosis and improved treatments benefiting those patients who can be treated with curative intent. Advances in endotherapy, surgical approaches, and multimodal and other combination therapies have been reported. New vistas have emerged in targeted therapies and immunotherapy, informed by new knowledge in genomics and molecular biology, which present opportunities for personalised cancer therapy and novel clinical trials. This review focuses exclusively on the curative intent treatment pathway, and highlights emerging advances.