Chronic Maintenance Research Articles

Macrophage inflammarafts in atherosclerosis.

Advances in single cell techniques revealed a remarkable diversity in macrophage gene expression profiles in atherosclerosis. However, the diversity of functional processes at the macrophage plasma membrane remains less studied. This review summarizes recent advances in characterization of lipid rafts, where inflammatory receptors assemble, in macrophages that undergo reprogramming in atherosclerotic lesions and in vitro under conditions relevant to the development of atherosclerosis. The term inflammarafts refers to enlarged lipid rafts with increased cholesterol content, hosting components of inflammatory receptor complexes assembled in close proximity, including TLR4-TLR4, TLR2-TLR1 and TLR2-CD36 dimers. Macrophages decorated with inflammarafts maintain chronic inflammatory gene expression and are primed to an augmented response to additional inflammatory stimuli. In mouse atherosclerotic lesions, inflammarafts are expressed primarily in nonfoamy macrophages and less in lipid-laden foam cells. This agrees with the reported suppression of inflammatory programs in foam cells. In contrast, nonfoamy macrophages expressing inflammarafts are the major inflammatory population in atherosclerotic lesions. Discussed are emerging reports that help understand formation and persistence of inflammarafts and the potential of inflammarafts as a novel therapeutic target. Chronic maintenance of inflammarafts in nonfoamy macrophages serves as an effector mechanism of inflammatory macrophage reprogramming in atherosclerosis.

Hidden consequences: Uncovering belimumab's role in the development of Pneumocystis jirovecii pneumonia in a lupus patient.

Pneumocystis jirovecii is an opportunistic fungal organism that can cause fatal pneumonia in immunocompromised individuals. It is a disease associated with CD4+ T cell depletion or high-dose steroids. However, there is increasing evidence that B cell dysfunction may also play a role in this illness. A 33-year-old female with SLE, who was maintained on belimumab and low-dose prednisone (2.5mg daily), presented with progressive cough and shortness of breath. She had been on monthly belimumab and prednisone 2.5mg daily for 19months, and her CD4 count was >200/uL, but her CD19+ B cell was <1% due to the belimumab. She developed a persistent cough and progressive dyspnea that did not respond to empiric antibiotic therapy for pneumonia. She went to the hospital for acute worsening of her dyspnea and cough. An extensive workup was performed, including a VATS procedure and surgical biopsy, which gave a definitive diagnosis of PJP. The patient was treated and discharged on trimethoprim-sulfamethoxazole. She made a complete recovery. Our report demonstrates the first confirmed case of pneumocystis jirovecii pneumonia in a patient with B cell depletion due to chronic maintenance therapy with belimumab. Our patient's diagnosis of PJP was unexpected, given her normal CD4+ count and the use of such a low dose of prednisone. We attribute her susceptibility to PJP infection to her profound B cell depletion in response to her belimumab therapy, supporting previous research indicating the importance of CD4+ T cells and B cells in the protective immune response against PJP. This case may help shape future clinical guidelines concerning PJP prophylaxis, particularly in SLE patients with deficient B lymphocytic activity and B cell depletion.

Outcome of COVID-19 and tolerance of Remdesivir in patients with renal failure: a single center experience from Pakistan

Introduction: Coronavirus disease-19 (COVID-19) is known to cause severe disease in chronic kidney disease and maintenance dialysis patients. We aim to report the outcome of COVID-19 and the adverse effects of Remdesivir (RDV) in patients with renal failure. Methodology: A retrospective observational study included all admitted patients with COVID-19 who received Remdesivir. Clinical characteristics and outcomes were compared in patients with renal failure (RF) and non-renal failure (NRF). We also evaluated RDV-associated nephrotoxicity and observed renal functions during antiviral treatment. Results: A total of 142 patients received RDV, 38 (26.76%) in RF and 104 (73.23%) in the non-RF group. The median absolute lymphocyte count was low while C-reactive protein, ferritin, and D-dimer were significantly high on admission in the RF group. A significant number of patients in the RF group required ICU admission (58% vs. 35% p = 0.01) and expired (29% vs. 12.5 p = 0.02). Among survivors and non-survivors in the RF group, raised inflammatory markers and low platelet count on presentation were significantly associated with high mortality. Median serum creatinine (mg/dL) was 0.88 on admission, remained at 0.85 in the NRF group, and improved from 4.59 to 3.87 (mg/dL) after receiving five days of RDV in the RF group. Conclusions: COVID-19 in renal failure has a high risk for ICU admissions leading to increased mortality. Multiple comorbidities and raised inflammatory markers are predictors of poor outcomes. We observed no significant drug-related adverse effects, and none of our patients required discontinuation of RDV due to worsening renal function.

Systemic Corticosteroids for Treating Respiratory Diseases: Less Is Better, but… When and How Is It Possible in Real Life?

Systemic corticosteroids (CSs), a keystone in pulmonology, are drugs with strong antiinflammatory activity. They are cheap, easily available, and accessible, but with common and serious side effects. Moreover, the use of exogenous CSs may suppress the hypothalamic-pituitary-adrenal (HPA) axis, predisposing to adrenal insufficiency. Safe CS treatment is a challenge of pharmacological research. This narrative review examined the indications of CSs in some respiratory diseases, analyzing what types, dosages, and length of treatment are required as the dosage and duration of CS treatments need to be minimized. Chronic maintenance treatments with CSs are associated with poor prognosis, but they are still prescribed in patients with severe asthma, Chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. When CS discontinuation is not possible, all efforts should be made to achieve clinically meaningful reductions. Guidelines suggest the use of methylprednisolone at a dose of 20-40mg/day or equivalent for up to 10days in subjects with COVID-19 pneumonia (but not other respiratory viral diseases) and respiratory failure, exacerbations of asthma, and COPD. Some guidelines suggest that CS treatment shorter than 10-14days can be abruptly stopped, strictly monitoring subjects with unexplained symptoms after CS withdrawal, who should promptly be tested for adrenal insufficiency (AI) and eventually treated. CSs are often used in severe community-acquired pneumonia associated with markedly increased serum inflammation markers, in acute respiratory distress syndrome (ARDS), in septic shock unresponsive to hydro-saline replenishment and vasopressors, and acute exacerbations of interstitial lung diseases. As these cases often require higher doses and longer duration of CS treatment, CS tapering should be gradual and, when useful, supported by an evaluation of HPA axis function.

The establishment, maintenance, and adaptation of high- and low-impact chronic pain: a framework for biopsychosocial pain research.

The establishment, maintenance, and adaptation of high- and low-impact chronic pain: a framework for biopsychosocial pain research.

#3161 CLINICAL EFFICACY AND OPTIMAL REGIMEN OF BNT162B2 VACCINE IN CHRONIC DIALYSIS PATIENTS

Abstract Background and Aims Highly effective vaccines against severe acute respiratory syndrome virus 2 (SARS-CoV-2) have been developed and administered worldwide. Protection from coronavirus disease 2019 (COVID-19), however, is not absolute, and optimal vaccination regimens need to be established. Concerns regarding breakthrough COVID-19 disease in vaccinated patients are increasing, as vaccine efficacy appears to gradually decline in the months following vaccination. The emergence of highly infective variants, escalates these issues. This study assessed the clinical efficacy of the BNT162b2 vaccine and all-cause mortality among dialysis patients receiving varying numbers of vaccine doses. Method This study was conducted using the electronic database of Clalit Health Services in Israel. Patients receiving chronic hemodialysis or peritoneal dialysis during COVID-19 pandemic were included in the analysis. The control group consisted of age-and sex-matched individuals, in a 4:1 ratio to the dialysis group. The study included the pre- and post-vaccination periods. Results A total of 14,230 people were included; 2,846 on chronic dialysis and 11,384 controls. Mean age was 66.2±14.3 years (range 18-97). Before the vaccine was available in Israel, 223 dialysis patients were infected with SARS-CoV2. Their mortality rate was 18.4% compared to 10.8% among uninfected, unvaccinated patients in the same period (p = 0.001). On post-vaccination period, we compared the clinical efficacy of a fourth dose to patients who received only 3 doses of BNT162b2 vaccine. SARS-CoV-2 infection rates, hospitalizations due to severe COVID-19, COVID-19–related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after adjusting for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, an additional booster dose was associated with reduced COVID-19–related mortality (1.7% vs. 3.8%, p = 0.04, HR 0.44 (95% CI 0.2–0.98) in patients who received 4 doses compared to 3 doses. Conclusion As seen in the general population, and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19 hospitalization and mortality among chronic dialysis patients. This study strengthens the recommendation to administer a fourth booster dose of vaccine to dialysis patients. Further studies are needed to establish the exact dose and schedule of the COVID-19 vaccine in the vulnerable population patients on chronic maintenance dialysis.

Can a Kidney Failure Patient Survive with One to Two Hemodialysis Sessions per Month for More than 5 Years?

Background: Kidney failure known as renal failure or Stage 5 CKD or End Stage Renal Diseases is a major problem among kidney diseases worldwide, its incidence and prevalence are rising yearly. The management requires renal replacement therapy, hemodialysis, 3 sessions per week or peritoneal dialysis until the time of renal transplantation. The cost is high in low income countries and is not covered by major medical insurances. Few renal patients are able to afford dialysis and renal transplantation. Case Presentation: A 45-year-old man Butcher, living in rural Rwanda presented with renal failure and Hypertension with history of native medication intake. He remained on chronic maintenance hemodialysis since October 2017, at one to two hemodialysis sessions per month. He preserved quality of life and cognitive function. He is reporting to have more than 1000 cc of urine volume per day. Conclusion: This case demonstrates that suboptimal hemodialysis sessions can help the renal patients to survive when they preserve residual renal functions.

Association of Clinical Outcomes With Sex in Patients Receiving Chronic Maintenance Antiplatelet Monotherapy After Percutaneous Coronary Intervention: A Post Hoc Gender Analysis of the HOST-EXAM Study.

Background Clopidogrel monotherapy was more effective in reducing the risk of adverse clinical events than aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES), according to the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it remains unknown whether these effects differ based on sex. Methods and Results This was a prespecified secondary analysis of HOST-EXAM in South Korea. Patients who maintained dual antiplatelet therapy without adverse clinical events for 6 to 18 months after PCI with DES were included. The primary end point was a composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, or Bleeding Academic Research Consortium (BARC) bleeding type ≥3 at 24 months after randomization. The bleeding end point was BARC types 2 to 5. The primary end point was comparable between the sexes (adjusted hazard ratio [HR], 0.79 [95% CI, 0.62-1.02]; P=0.067), and the bleeding end point (adjusted HR, 0.79 [95% CI, 0.54-1.17]; P=0.240) was also similar. Compared with aspirin, clopidogrel was associated with lower risk of primary composite end point (adjusted HR, 0.70 [95% CI, 0.55-0.89]; P=0.004) and bleeding end point (adjusted HR, 0.65 [95% CI, 0.44-0.96]; P=0.031) in men but not in women. Conclusions The primary composite end point and bleeding events were comparable between the sexes during chronic maintenance antiplatelet monotherapy after PCI with DES. Clopidogrel monotherapy, compared with aspirin, significantly reduced the risk of the primary composite end point and bleeding events in men. However, the beneficial effect of clopidogrel on the primary end point and bleeding events was mitigated in women. Registration Information clinicaltrials.gov. Identifier: NCT02044250.

Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Study

BackgroundThe HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Disease–Extended Antiplatelet Monotherapy) trial showed superior efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention (PCI). ObjectivesThe goal of this study was to investigate the cost-effectiveness of clopidogrel monotherapy compared with that of aspirin monotherapy. MethodsA Markov model was developed for patients in the stable phase after PCI. From the perspectives of the South Korean, UK, and U.S. health care systems, the lifetime health care costs and quality-adjusted life-years (QALYs) of each strategy were estimated. Transition probabilities were obtained from the HOST-EXAM trial, and health care costs and health-related utilities were obtained from data and literature for each country. ResultsFrom the perspective of the South Korean health care system, the base-case analysis showed that clopidogrel monotherapy was $3,192 higher in lifetime health care costs and 0.139 lower in QALYs compared with aspirin. This result was greatly influenced by the numerically but insignificantly higher cardiovascular mortality of clopidogrel compared with aspirin. In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient compared with aspirin monotherapy while reducing QALYs by 0.103 and 0.175, respectively. ConclusionsBased on empirical data from the HOST-EXAM trial, clopidogrel monotherapy was projected to lead to reduced QALYs compared with aspirin during the chronic maintenance period after PCI. These results were affected by a numerically higher rate of cardiovascular mortality in clopidogrel monotherapy reported from the HOST-EXAM trial. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis–Extended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250)

Tirzepatide for Weight Loss: Can Medical Therapy "Outweigh" Bariatric Surgery?

The worldwide prevalence of obesity has been increasing progressively over the past few decades and is predicted to continue to rise in coming years. Unfortunately, this epidemic is also affecting increasing rates of children and adolescents, posing a serious global health concern. Increased adiposity is associated with various comorbidities and increased mortality risk. Conversely, weight loss and chronic weight management are associated with improvements in overall morbidity and mortality. The pathophysiology of obesity is multifactorial with complex interactions between genetic and environmental factors. The foundation of most weight loss plans is lifestyle modification including dietary change and exercise. However, lifestyle modification alone is often insufficient to achieve clinically meaningful weight loss due to physiological mechanisms that limit weight reduction and promote weight regain. Therefore, research has focused on adjunctive pharmacotherapy to enable patients to achieve greater weight loss and improved chronic weight maintenance compared to lifestyle modification alone. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin hormone analogs that have proven effective for the management of type 2 diabetes mellitus as well as obesity and overweight. Tirzepatide is a novel "twincretin" that functions as a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA. Tirzepatide was recently approved by the Food and Drug Administration for the management of type 2 diabetes. Similar to previously approved GLP-1RAs, weight loss is a common side effect of tirzepatide which prompted research focused on its use as a primary weight loss therapy. Although this drug has not yet been approved as an antiobesity medication, there are several phase 3 clinical trials that have demonstrated superior weight loss efficacy compared with previously approved medications. This review article will discuss the discovery and mechanism of tirzepatide, as well as the completed and ongoing trials that may lead to its approval as an adjunctive pharmacotherapy for weight loss.

English

Health communication campaigns along with the targeted social health indicator such as the at-risk group can make an impactful difference in preventive care and chronic disease health maintenance. The logistic regression technique is employed to examine if Rwanda&rsquo;s health media campaign impacted household health behavior and whether this impact was influenced by literacy aptitude and current sexual health practices.&nbsp; Interactive effects of health campaigns were found on household sexual behavior among at-risk households in Rwanda. Tests on model validity and reliability favor the models and give statistically greater confidence in the results. Key words: HIV, AIDS, health campaign, HIV campaign, AIDS campaign.

Perfil de un paciente con enfermedad obstructiva crónica tratado con la combinación de un agonista β2 adregénico de acción prolongada y un corticoide inhalado en un dispositivo presurizado en la práctica clínica habitual: estudio ARIES

Background and objectiveThe study aimed to describe the profile of patients with stable chronic obstructive pulmonary disease (COPD) and maintenance treatment with a long-acting beta2-adrenergic agonist and an inhaled corticosteroid (LABA/ICS) in a pressurised device (pMDI), and to assess the quality of life (HRQoL). Materials and methodsObservational, multicentre, cross-sectional study in routine clinical practice, conducted in 50 sites in Spain. 390 patients aged ≥ 40 years, treated with LABA/ICS in a pMDI device for at least the previous 3 months before the inclusion, were assessed. Demographic and clinical data were collected from medical records and patient-reported COPD Assessment Test (CAT). ResultsThe patients analysed in the study were mostly male (71.3%); 84.9% in GOLD 2-3 groups; and 32.6% and 38.2% of participants with dyspnoea grade 1 and 2 according to the modified Medical Research Council (mMRC) scale, respectively. The mean CAT questionnaire score (standard deviation [SD]) was 16.3 (8.4). ConclusionsThe profile of the patients treated with LABA/ICS in a pMDI device is mainly male, with no or low comorbidities, moderate-severe functional severity, and mild-moderate dyspnoea. Patients reported a medium impact on their quality of life.

Mediating effects of heart rate variability on the association between chronic stress, cardiorespiratory fitness and working memory maintenance

Young adulthood is a demanding developmental stage during which an individual is required to learn to adequately respond to physical and psychosocial stressors (Malter Cohen et al., 2013). High degrees of chronic stress have been shown to have detrimental effects on physical and mental health outcomes in young adults, accompanied by decreases in academic achievement and subjective well-being (Bayram &amp; Bilgel, 2008; Malter Cohen et al., 2013). While effects of acute stress on neurocognitive functioning have been examined, documentation on effects of prolonged stress exposure on working memory is scarce. While chronic stress may impair working memory, empirical evidence supports the assumption that exercise targeting cardiorespiratory fitness has the potential to buffer harmful effects of stress on working memory performance (Loprinzi &amp; Frith, 2019). According to the Neurovisceral Integration Theory, shared neurophysiological areas are involved in cardiac autonomic control as well as the modulation of attentional and emotional regulatory processing (Forte et al., 2019). Therefore, heart rate-variability (HRV) may be a physiological correlate mediating the association between chronic stress, cardiorespiratory fitness and working memory maintenance.&#x0D; The present study investigated the mediating role of resting heart rate-variability on the association between chronic stress, cardiorespiratory fitness and working memory maintenance in young healthy adults.&#x0D; Working memory maintenance was assessed in N = 115 healthy adults (48% female) aged 18 to 35 years (M = 24.1, SD = 3.8) using a modified version of the Sternberg task with low (3 items) and high cognitive load (6 items). Additionally, the Åstrand test was conducted on a bicycle ergometer to estimate maximal oxygen consumption (VO2max). Resting HRV was recorded using electrocardiography. The LF/HF ratio was extracted for mediation analyses.&#x0D; Path analysis revealed a significant association between cardiorespiratory fitness and accuracy on high cognitive load trials, but not on trials with low cognitive load. Levels of perceived chronic stress showed a trend for a positive association with working memory maintenance, independently of cognitive load. The pattern of results remained unchanged after introduction of HRV as a mediator.&#x0D; Results indicate that despite young adulthood being characterized by peak cognitive performance, cardiorespiratory fitness influences working memory maintenance. The lack of mediating effects of HRV, indicates that this association cannot be explained by vagal influences on memory processing driven by the autonomic nervous system. As working memory is crucial for performance in many real-life domains, such as workplace and learning environments in general maintenance and promotion of cardiorespiratory fitness is encouraged.&#x0D; References&#x0D; Bayram, N., &amp; Bilgel, N. (2008). The prevalence and socio-demographic correlations of depression, anxiety and stress among a group of university students. Social Psychiatry and Psychiatric Epidemiology, 43(8), 667-672. https://doi.org/10.1007/s00127-008-0345-x&#x0D; Forte, G., Favieri, F., &amp; Casagrande, M. (2019). Heart rate variability and cognitive function: A systematic review [Mini Review]. Frontiers in Neuroscience, 13, Article 710. https://doi.org/10.3389/fnins.2019.00710&#x0D; Loprinzi, P. D., &amp; Frith, E. (2019). Protective and therapeutic effects of exercise on stress-induced memory impairment. Journal of Physiological Sciences, 69(1), 1-12. https://doi.org/10.1007/s12576-018-0638-0&#x0D; Malter Cohen, M., Tottenham, N., &amp; Casey, B. J. (2013). Translational developmental studies of stress on brain and behavior: Implications for adolescent mental health and illness? Neuroscience, 249, 53-62. https://doi.org/https://doi.org/10.1016/j.neuroscience.2013.01.023

The cytokine milieu of bullous pemphigoid: Current and novel therapeutic targets.

Bullous pemphigoid (BP) is the most common autoimmune bullous disease, characterized by severe pruritus and skin blistering. The loss of tolerance against Collagen XVII, also referred to as BP180, is the main pathogenic event of BP, leading to production of IgG autoantibodies which mainly target the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180. A complex inflammatory network is activated upon autoantibody binding to the basement membrane zone; this inflammatory loop involves the complement cascade and the release of several inflammatory cytokines, chemokines and proteases from keratinocytes, lymphocytes, mast cells and granulocytes. Collectively, these events disrupt the integrity of the dermal-epidermal junction, leading to subepidermal blistering. Recent advances have led to identify novel therapeutic targets for BP, whose management is mainly based on the long-term use of topical and systemic corticosteroids. As an example, targeting type-2 T-helper cell-associated cytokines, such as Interleukin-4 and interleukin-13 has shown meaningful clinical efficacy in case series and studies; targeting IL-17 and IL-23 has also been tried, owing to an important role of these cytokines in the chronic maintenance phase of BP. In this review article, we discuss the complex cytokine milieu that characterized BP inflammation, highlighting molecules, which are currently investigated as present and future therapeutic targets for this life-threatening disease.

Hierarchical multiple regression investigating factors associated with depressive symptoms in the middle-aged and elderly undergoing haemodialysis

BackgroundDepressive moods are commonly seen in patients who receive haemodialysis. This can cause a lack of compliance in their treatment procedures and increase the rate of hospitalization. This study aimed to investigate the relationship between social support and degree of depression in middle-aged and elderly patients undergoing haemodialysis and the predictors of depressive symptoms.MethodsA cross-sectional correlational study was designed with a structured questionnaire survey. Patients over 40 years of age were included from five haemodialysis centres. Measures embraced a demographic and clinical characteristics questionnaire, the Centre for Epidemiologic Studies Depression Scale, and the Personal Resource Questionnaire 2000. Statistical analysis was performed using hierarchical multiple regression analysis.ResultsA total of 179 patients over 40 years of age were included from five haemodialysis centres in the analysis. The mean CES-D score was 19.0(12.3); the majority of participants (60.3%) had a CES-D score ≥ 15, indicating likely depressive status. The mean PRQ2000 score was 75.7(15.9). The proportional mean of the PRQ2000 was 72.11%, indicating moderate social support for participants in this study. Data disclosed that marital status, number of comorbidities, exercise behaviour, and social support could significantly predict depressive symptoms; total explanatory variance was 31.3%.ConclusionHealth care professionals should identify those at high risk of depressive symptoms when they provide care to the middle-aged and elderly patients undergoing haemodialysis. These findings may lead to greater insights into the nursing and rehabilitative care of patients treated by chronic maintenance haemodialysis.

The antidepressant agomelatine attenuates morphine-induced reinstatement but not self-administration or precipitated withdrawal

BackgroundExogenous melatonin appears to have anti-addictive properties and was recently shown to improve mental health and metabolic measures in patients receiving chronic opioid maintenance therapy. Agomelatine is a marketed antidepressant which acts as a melatonin agonist. We evaluated its effects using a rat model of morphine-reinforced behavior. MethodsAfter pretreatment with noncontingent morphine, male Wistar rats were trained to self-administer intravenous morphine (1.0 mg/kg-injection) under a progressive-ratio schedule. Rats were pretreated with vehicle or agomelatine during extinction, reinstatement, and reacquisition of morphine-reinforced behavior. ResultsDaily treatment with 10 mg/kg-day of agomelatine decreased the number of ratios completed and prolonged latency during morphine-induced reinstatement. There were no significant effects on cue-induced reinstatement, morphine self-administration, or naloxone-precipitated withdrawal. Treatment with 32 mg/kg-day of agomelatine caused postural changes. That dose prolonged withdrawal-induced loss of body weight and caused delayed reductions in food reinforcement. SummaryIn addition to postural effects, high-dose agomelatine worsened the course of spontaneous withdrawal and produced nonspecific effects on food-reinforced behavior. When administered at a selective dose, agomelatine did not modify morphine self-administration or precipitated withdrawal, but decreased morphine-induced reinstatement. Our findings show potential detrimental effects of high-dose agomelatine, with reductions in opioid-seeking behavior after a lower, more selective dose.

Porphyria cutanea tarda: An uncommon condition in a patient on chronic hemodialysis

Patients with chronic kidney disease can have many dermatological manifestations. One of the very rare conditions is porphyria cutanea tarda (PCT), which manifests with hyperpigmentation of skin and photosensitivity along with painful bullae in sun-exposed areas. It is due to deficiency of uroporphyrinogen III decarboxylase enzyme which takes part in heme synthesis. The deficiency could be genetic or sporadic. Iron therapy and hepatitis C infection are known to precipitate these lesions. We report a case of PCT in a woman undergoing chronic maintenance hemodialysis, review the literature, and discuss the problems with management specific to the dialysis population.

Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most recognized form of autoimmune encephalitis. It is characterized by a constellation of neurologic and psychiatric features along with positive NMDAR antibody, which is more sensitive and specific in CSF than serum. All patients should be screened at least once for neoplasm, with ovarian teratoma being found in most tumor-related cases. In the acute phase, first-line immunotherapy, often a combination of high-dose steroids, immunoglobulins, and/or plasma exchange, is strongly recommended. When first-line therapy fails, escalation to second-line immunotherapy, particularly rituximab, can further improve outcomes and prevent relapses. In refractory cases, additional complementary immunotherapies, such as cyclophosphamide, bortezomib and/or tocilizumab may be considered. Relapses occur in 10-30% of cases, mostly within the first two years from onset. Individuals should be followed up to determine if chronic maintenance therapy is required.

An evaluation of sodium zirconium cyclosilicate: a new treatment option for hyperkalaemia in China

ABSTRACT Introduction Hyperkalemia is a common complication of chronic kidney disease (CKD), diabetes mellitus (DM), and heart failure (HF) that can lead to severe arrhythmias and sudden death and is associated with a higher risk of mortality. Therefore, the prevention and treatment of hyperkalemia is important. Sodium zirconium cyclosilicate (SZC), a new oral potassium-lowering drug, has offered an additional treatment option for Chinese patients with hyperkalemia since its launch in China in late 2019, and some experience has been accumulated regarding its efficacy and safety. Areas covered In this review, the authors summarize the epidemiological features of hyperkalemia in China and review the clinical data regarding the use of sodium zirconium cyclosilicate in Chinese patients. Expert opinion The prevalence of hyperkalemia is particularly high in Chinese patients with chronic kidney disease and heart failure. In China, recent clinical studies have shown that SZC rapidly reduces serum potassium, maintains normal potassium concentration, and is well tolerated and safe. Two Chinese expert consensus statements have recommended the use of SZC for the acute correction and chronic maintenance of potassium concentration.

Multidisciplinary medication therapy management and participant responses to recommendations: Results from the INCREASE trial

AbstractBackgroundMedication use, especially in the context of polypharmacy and inappropriate medications, may be a modifiable risk factor for cognitive impairment and dementia. Medication therapy management (MTM) interventions, which seek to optimize patient‐specific medication regimens, may restore cognitive function and delay onset of cognitive decline. Here, we describe an MTM protocol, delivering patient‐centered recommendations through joint decision‐making among the study participant, pharmacy specialist, and non‐pharmacist clinician (e.g., study physician) directed at delaying the symptomatic onset and progression of AD.MethodCommunity dwelling adults age 65 and older, without dementia, using at least one potentially inappropriate medication (PIM) were enrolled in a clinical trial to evaluate the effect of the MTM on improving medication appropriateness and cognition (INCREASE; NCT08245639). In a three‐step process, study pharmacists first identified potential mediation‐related problems (MRPs) and made initial recommendations for prescribed and over‐the‐counter medications, vitamins, and supplements. Second, study team clinicians and pharmacists reviewed all initial recommendations together with the participants, allowing for revisions to make a final recommendation. Third, participant responses to final recommendations were recorded. Here, we evaluated participant responses in relation to medication class and type of final recommendation.ResultAmong the 90 randomized participants, a mean 6.7±3.6 MRPs per participant were reported. A total of 259 initial MTM recommendations were made for the treatment group participants, with 40% percent undergoing revision in the second step (Table 1). Participants reported willingness to adopt 46% of final recommendations and need for additional primary care input in response to 38% of final recommendations. Willingness to adopt final recommendations was highest when therapeutic switches were offered and/or with anticholinergic medications (Table 1).ConclusionAs integration of healthcare disciplines and specialized services become an increasingly important part of collaborative healthcare practices, this study demonstrated that initial MTM recommendations often change through group discussion, and multidisciplinary decision‐making that incorporated the preferences of patients themselves often led to positive participant responses. Further studies are needed to assess whether participants adhere to MTM recommendations long‐term, and to evaluate the health and economic impact of MTM on chronic disease prevention and maintenance, such as with AD and related dementias.