The molecular immunology of human susceptibility to fungal diseases: lessons from single gene defects of immunity

Introduction: Fungal diseases are a threat to human health. Therapies targeting the fungus continue to lead to disappointing results. Strategies targeting the host response represent unexplored opportunities for innovative treatments. To do so rationally requires the identification and neat delineation of critical mechanistic pathways that underpin human antifungal immunity. The study of humans with single-gene defects of the immune system, i.e. inborn errors of immunity (IEIs), provides a foundation for these paradigms.

Areas covered: A systematic literature search in PubMed, Scopus, and abstracts of international congresses was performed to review the history of genetic resistance/susceptibility to fungi and identify IEIs associated with fungal diseases. Immunologic mechanisms from relevant IEIs were integrated with current definitions and understandings of mycoses to establish a framework to map out critical immunobiological pathways of human antifungal immunity.

Expert opinion: Specific immune responses non-redundantly govern susceptibility to their corresponding mycoses. Defining these molecular pathways will guide the development of host-directed immunotherapies that precisely target distinct fungal diseases. These findings will pave the way for novel strategies in the treatment of these devastating infections.     

Diagnostische Bedeutung von Muskelbiopsien bei metabolischen Myopathien

Summary In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.

Mit Unterstützung durch die DFG und die Friedrich Baur Stiftung, München     

Cognitive and behavioural correlates of non‐adherence to HIV anti‐retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology

This cross‐sectional study identified variables associated with protease inhibitor (PI) non‐adherence in 179 patients taking anti‐retroviral therapy. Univariate analyses identified 11 variables associated with PI non‐adherence. Multiple logistic regression modelling identified three predictors of PI non‐adherence: low adherence self‐efficacy and seriousness of non‐adherence and HIV (p < .001), perceived absence of HIV associated illness (p < .01), and use of more than one type of recreational drug (p = .001). The model correctly classified 83.9% of the sample, offers psychologists insight into psychological barriers to treatment adherence to guide interventions for improving adherence, and supports a modified version of the reformulated health belief model.     

Relational continuity of care in community pharmacy: A systematic review

Relational continuity of care (COC) is becoming an important concept related to improving healthcare quality, reducing medical costs and increasing patient satisfaction with primary care. While community pharmacy (CP) has a considerable role in primary care, there are few reports dedicated to the role of relational COC in CP. This study reviewed the existing evidence of relational COC in CP and its effect on patients. PubMed, Embase, CINAHL, Cochrane Library CENTRAL and Google Scholar were used to search for relevant studies from the date of database inception through to January 2021, which were appraised according to eligibility criteria. There were no limitations on the primary outcome or language. Case reports and studies without control groups were excluded. The Newcastle–Ottawa quality assessment scale was used to assess the quality of the studies. Database searches identified 13 records. Relational COC measures in the included studies were grouped in three kinds; pharmacy-visiting pattern, Continuity of Care Index and loyalty. The assessed outcomes were medication adherence behaviour (e.g., the proportion of days covered, medication possession ratio), adverse drug reactions, potentially inappropriate drug prescribing and clinical outcomes. The odds of patients adhering to their medication regimen were about 1.1~2.5 times higher among those who consistently visited a single pharmacy compared to patients visiting multiple pharmacies. Additionally, the care provision with a high level of relational continuity could lower inappropriate drug use by 21~32 per cent and the use of other costly services by 12~29 per cent. This study suggests that a high degree of relational COC in CP could improve safe use of medications among patients. Future research is needed to employ more rigorous methods to reduce heterogeneity and to measure effects on clinical outcomes.     

艾滋病患者渐进性肌肉放松训练配合心理干预的应用效果

目的 探讨渐进性肌肉放松训练配合心理干预对艾滋病患者服药依从性及心理状态的影响。方法 选择2017年8月—2020年8月于本院就诊的68例艾滋病患者,按随机数字表法分为对照组和观察组,每组34例。对照组实施常规护理干预,观察组在此基础上实施渐进性肌肉放松训练配合心理干预,比较两组服药依从性及医院焦虑抑郁量表(HospitalAnxietyand Depresseo Scale,HAD)评分。结果 观察组服药总依从率为97.06%,高于对照组的70.59%,(χ2=8.785,P=0.003);观察组干预2周后焦虑评分为(14.35±1.67)分、抑郁评分为(13.98±1.38)分,均低于对照组的(15.63±1.59)分、(15.08±1.27)分,(t=3.237、3.420,P=0.002、0.001)。结论 渐进性肌肉放松训练配合心理干预应用于艾滋病患者,能够提高患者服药依从性,改善患者心理状态。     

Management of Chronic Pain in Nursing Homes: Navigating Challenges to Improve Person-Centered Care

Despite the dynamic demands in the nursing home (NH), a definitive approach to managing chronic pain in older adults has yet to be established. Due to concerns for potential adverse pharmacologic effects, balancing appropriate pain management is a challenge among NH residents. The challenges encompass but are not limited to medical complexities, functional disabilities, and physical frailty. Barriers to the successful implementation of a comprehensive chronic pain management at the NH may include ambiguous directions on specific therapeutic interventions, insufficient guidance on treatment duration, and limited available treatment options. The Centers for Medicare and Medicaid Services’ reporting requirement of adequate pain control among NH residents coupled with widely variable clinician-prescribing habits highlights the difficulties in overcoming the preceding challenges and barriers. The Coronavirus Disease 2019 (COVID-19) pandemic has further complicated pain management due to its negative consequences on well-being of residents of NHs. Associated symptoms of psychosocial stress, anxiety and depression, and chronic pain symptoms can exacerbate during the COVID-19 pandemic, leading to increased requirement for pain medications including but not limited to opioids.Pain is a multidimensional symptom and requires a strategic multimodal approach for its management. Nonpharmacologic modalities are underutilized in the NH setting and are the preferred first steps for mild pain, and nonopioid pharmacological agents can be added as a second step for a synergistic effect for moderate to severe pain. Opioids should be used as a last resort. Short-acting opioids are preferred over extended-release/long-acting opioids for chronic pain. Clinicians are encouraged to engage residents in proactive strategies in managing their pain, and to set realistic expectations toward improving their quality of life, as complete elimination of pain is not feasible in most cases.This review article provides the interdisciplinary team with a contemporary perspective of the multitude of changes and challenges influencing the prescribing as well as deprescribing of various pain medications.     

Antihypertensive Medication Classes and the Risk of Dementia: A Systematic Review and Network Meta-Analysis

ObjectivesTo systematically review and synthesize the evidence on differential associations between antihypertensive medication (AHM) classes and the risk of incident dementia.DesignSystematic review and random effects frequentist network meta-analysis. Embase, MEDLINE, and the Cochrane library were searched from origin to December 2019.Setting and participantsRandomized controlled trials (RCTs) and prospective cohort studies that compared associations of different AHM classes with incident all-cause dementia and/or Alzheimer's disease over at least 1 year of follow-up.MeasuresAll cause dementia and/or Alzheimer's disease.ResultsFifteen observational studies and 7 RCTs were included. Data on AHM classes were available for 649,790 participants and dementia occurred in 19,600 (3.02%). Network meta-analysis showed that in observational studies, treatment with either calcium channel blockers (CCBs) or angiotensin II receptor blockers (ARBs) was associated with lower dementia risks than treatment with other antihypertensives: CCBs vs angiotensin converting enzyme inhibitors (ACE inhibitors) (HR=0.84, 95% CI 0.74-0.95), beta blockers (HR=0.83, 95% CI 0.73-0.95) and diuretics (HR=0.89, 95% CI 0.78-1.01) and ARBs vs ACE inhibitors (HR=0.88, 95% CI 0.81-0.97), beta blockers (HR=0.87, 95% CI 0.77-0.99), and diuretics (HR=0.93, 95% CI 0.83-1.05). There were insufficient RCTs to create a robust network based on randomized data alone.Conclusions and ImplicationsRecommending CCBs or ARBs as preferred first-line antihypertensive treatment may significantly reduce the risk of dementia. If corroborated in a randomized setting, these findings reflect a low-cost and scalable opportunity to reduce dementia incidence worldwide.     

The Effect of Medication Reconciliation via a Patient Portal on Medication Discrepancies: A Randomized Noninferiority Study

BackgroundMedication reconciliation has become standard care to prevent medication transfer errors. However, this process is time-consuming but could be more efficient when patients are engaged in medication reconciliation via a patient portal.ObjectivesTo explore whether medication reconciliation by the patient via a patient portal is noninferior to medication reconciliation by a pharmacy technician.Design (including intervention)Open randomized controlled noninferiority trial. Patients were randomized between medication reconciliation via a patient portal (intervention) or medication reconciliation by a pharmacy technician at the preoperative screening (usual care).Setting and ParticipantsPatients scheduled for elective surgery using at least 1 chronic medication were included.MeasuresThe primary endpoint was the number of medication discrepancies compared to the electronic nationwide medication record system (NMRS). For the secondary endpoint, time investment of the pharmacy technician for the medication reconciliation interview and patient satisfaction were studied. Noninferiority was analyzed with an independent t test, and the margin was set at 20%.ResultsA total of 499 patients were included. The patient portal group contained 241 patients; the usual care group contained 258 patients. The number of medication discrepancies was 2.6 ± 2.5 in the patient portal group and 2.8 ± 2.7 in the usual care group. This was not statistically different and within the predefined noninferiority margin. Patients were satisfied with the use of the patient portal tool. Also, the use of the portal can save on average 6.8 minutes per patient compared with usual care.Conclusions and ImplicationsMedication reconciliation using a patient portal is noninferior to medication reconciliation by a pharmacy technician with respect to medication discrepancies, and saves time in the medication reconciliation process. Future studies should focus on identifying patient characteristics for successful implementation of patient portal medication reconciliation.