Eosinophils Are an Endogenous Source of Interleukin-4 during Filarial Infections and Contribute to the Development of an Optimal T Helper 2 Response.

INTRODUCTION: Interleukin-4 (IL-4) is a central regulator of type 2 immunity, crucial for the defense against multicellular parasites like helminths. This study focuses on its roles and cellular sources during Litomosoides sigmodontis infection, a model for human filarial infections. METHODS: Utilizing an IL-4 secretion assay, investigation into the sources of IL-4 during the progression of L. sigmodontis infection was conducted. The impact of eosinophils on the Th2 response was investigated through experiments involving dblGATA mice, which lack eosinophils and, consequently, eosinophil-derived IL-4. RESULTS: The absence of eosinophils notably influenced Th2 polarization, leading to impaired production of type 2 cytokines. Interestingly, despite this eosinophil deficiency, macrophage polarization, proliferation, and antibody production remained unaffected. CONCLUSION: Our research uncovers eosinophils as a major source of IL-4, especially during the early phase of filarial infection. Consequently, these findings shed new light on IL-4 dynamics and eosinophil effector functions in filarial infections.

Interdisciplinary Physician-Pharmacist Medication Review for Outpatients With Heart Failure: A Subanalysis of the PHARM-CHF Randomized Controlled Trial.

Aims: Patients with chronic heart failure (CHF) require polypharmacy and are at increased risk for drug-related problems. Interdisciplinary physician-pharmacist medication review may improve drug treatment. Our goal was to analyze the changes from the physician-documented medication plan (MP) and patient-stated medication to an interdisciplinary consolidated MP (CMP). Methods: This pre-specified subanalysis of the PHARM-CHF randomized controlled trial analyzed the medication review of CHF patients in the pharmacy care group. Community pharmacists compared the MP with the drug regimen stated by the patient and consulted with physicians on identified discrepancies and other medication-related problems resulting in a CMP. Results: We analyzed 93 patients (mean 74.0 ± 6.6 years, 37.6% female), taking a median of ten (IQR 8-13) drugs. 80.6% of patients had at least one change from MP to CMP. We identified changes in 32.7% (303/926) of drugs. The most common correction was the addition of a drug not documented in the MP to the CMP (43.2%). We also determined frequent modifications in the dosing regimens (37.6%). The omission of a drug documented in the MP but left out of the CMP accounted for 19.1%. Comparing patient-stated medication to CMP, the current drug regimen of patients was changed in 22.4% of drugs. Conclusion: The medication review resulted in changes of medication between MP and CMP in most of the patients and affected one-third of drugs. Structured physician-pharmacist interdisciplinary care is able to harmonize and optimize the drug treatment of CHF patients.

The evidence for pharmacist care in outpatients with heart failure: a systematic review and meta-analysis.

AIMS: Patients with heart failure (HF) have poor outcomes, including poor quality of life, and high morbidity and mortality. In addition, they have a high medication burden due to the multiple drug therapies now recommended by guidelines. Previous reviews, including studies in hospital settings, provided evidence that pharmacist care improves outcomes in patients with HF. Because most HF is managed outside of hospitals, we aimed to synthesize the evidence for pharmacist care in outpatients with HF. METHODS AND RESULTS: We conducted a systematic literature search in PubMed of randomized controlled trials (RCTs) and integrated the evidence on patient outcomes in a meta-analysis. We found 24 RCTs performed in 10 countries, including 8029 patients. The data revealed consistent improvements in medication adherence (independent of the measuring instrument) and knowledge, physical function, and disease and medication management. Sixteen RCTs were included in meta-analyses. Differences in all-cause mortality (odds ratio (OR) = 0.97 [95% CI, 0.84-1.12], Q-statistic, P = 0.49, I2  = 0%), all-cause hospitalizations (OR = 0.86 [0.73-1.03], Q-statistic, P = 0.01, I2  = 45.5%), and HF hospitalizations (OR = 0.89 [0.77-1.02], Q-statistic, P = 0.11, I2  = 0%) were not statistically significant. We also observed an improvement in the standardized mean difference for generic quality of life of 0.75 ([0.49-1.01], P < 0.01), with no indication of heterogeneity (Q-statistic, P = 0.64; I2  = 0%). CONCLUSIONS: Results indicate that pharmacist care improves medication adherence and knowledge, symptom control, and some measures of quality of life in outpatients with HF. Given the increasing complexity of guideline-directed medical therapy, pharmacists' unique focus on medication management, titration, adherence, and patient teaching should be considered part of the management strategy for these vulnerable patients.

Acetylcholine-induced whealing in cholinergic urticaria - What does it tell us?

BACKGROUND: Cholinergic urticaria (CholU) is characterized by the occurrence of itchy wheals induced by sweating. Intradermal injections of acetylcholine (ACh) have been proposed to help with diagnosing CholU and subgrouping of patients, but controlled studies are largely missing. OBJECTIVE: To compare the rates of positive ACh test results in well characterized CholU patients and controls and to identify clinical features of CholU linked to ACh reactivity. METHODS: Acetylcholine was injected intradermally into 38 CholU patients and 73 matched healthy controls. Wheal and flare skin responses were assessed after 15 and 30 min and correlated with clinical features of CholU. RESULTS: At 15 min after intradermal injections of ACh, wheal and flare responses were significantly more frequent in CholU patients than healthy controls, wheals: 34 % vs.15% (P = 0.028); flares: 50 % vs.18 % (P <0.001). Also, wheals were 37 % and flares 172 % larger and of longer duration in CholU patients than in healthy controls (both P < 0.01). CholU patients with ACh-induced wheals (ACh+) had larger flare but not wheal responses in response to histamine than those without (ACh-; P = 0.011). Also, ACh-induced wheal responses were significantly correlated with sweating (r = 0.54, P = 0.046) in CholU patients. Finally, wheal responses lasted longer in ACh+ than in ACh- patients (P = 0.03). CONCLUSION: Intradermal ACh testing does not allow for the identification of CholU patients due to its low sensitivity. ACh-induced wheals, in patients with CholU, is linked to sweating and longer lasting symptoms. Intradermal ACh testing is an interesting tool for mechanistic studies in CholU.

Development and implementation of blood pressure screening and referral guidelines for German community pharmacists.

Involvement of community pharmacists in the detection and control of hypertension improves patient care. However, current European or North-American guidelines do not provide specific guidance how to implement collaboration between pharmacists and physicians, especially when and how to refer patients with undetected or uncontrolled hypertension to a physician. The German Society of Cardiology and the ABDA - Federal Union of German Associations of Pharmacists developed and tested referral recommendations for community pharmacists, embedded in two guideline worksheets. The project included a guideline-directed blood pressure (BP) measurement and recommendations when patients should be referred to their physician. A "red flag" referral within 4 weeks was recommended when SBP was >140 mm Hg or DBP >90 mm Hg (for subjects <80 years), and >160 mm Hg or >90 mm Hg (≥80 years) in undetected individuals, or >130 mm Hg or >80 mm Hg (<65 years) and >140 mm Hg or >80 mm Hg (≥65 years) in treated patients. BP was measured in 187 individuals (86 with known hypertension, mean [±SD] age 62 ± 15 years, 64% female, and 101 without known hypertension, 47 ± 16 years, 75% female) from 17 community pharmacies. In patients with hypertension, poorly controlled BP was detected in 55% (n = 47) and were referred. A total of 16/101 subjects without a history of hypertension were referred to their physician because of uncontrolled BP. Structured BP testing in pharmacies identified a significant number of subjects with undetected/undiagnosed hypertension and patients with poorly controlled BP. Community pharmacists could play a significant role in collaboration with physicians to improve the management of hypertension.

The impact of pharmacist/physician care on quality of life in elderly heart failure patients: results of the PHARM-CHF randomized controlled trial.

AIMS: Patients with heart failure (HF) have impaired quality of life (QoL). The randomized controlled trial PHARM-CHF investigated whether an interdisciplinary intervention consisting of regular contacts with the community pharmacy and weekly dosing aids improves medication adherence in patients with HF. It is unknown how an intervention involving frequent structured pharmacy visits affects QoL. Our aim was to explore adherence to the intervention and effects on QoL. METHODS AND RESULTS: Among 237 patients, n = 110 were randomized to pharmacy care and n = 127 to usual care. The pharmacy care group received a medication review followed by (bi-)weekly dose dispensing and counselling. The median follow-up was 2.0 years [inter-quartile range (IQR) 1.2-2.7]. Median interval between pharmacy visits was 8.4 days (IQR 8.0-10.3) and the visits lasted in median 14 min (IQR 10-15). Median adherence to the intervention was 96% (IQR 84-100). QoL at 365 days was predefined as a main secondary and at 730 days as another secondary endpoint in PHARM-CHF. QoL was measured by the Minnesota Living with Heart Failure Questionnaire; and for 111 patients (n = 47 in the pharmacy care group and n = 64 in the usual care group), data were available at baseline, and after 365 and 730 days (mean age 74 years; 41% female). Improvement in QoL was numerically higher in the pharmacy care group after 365 days and was significantly better after 730 days (difference in total scores -7.7 points [-14.5 to -1.0]; P = 0.026) compared to the usual care group. In all subgroups examined, this treatment effect was preserved. Improvements in the physical and emotional dimensions were numerically higher in the pharmacy care group after 365 days and were significantly better after 730 days: -4.0 points [-6.9 to -1.2]; P = 0.006, and -1.9 points [-3.7 to -0.1]; P = 0.039, respectively. CONCLUSIONS: A pharmacy-based interdisciplinary intervention was well received by the patients and suggests clinically important improvements in QoL.

Sensitization against skin resident fungi is associated with atopy in cholinergic urticaria patients.

BACKGROUND: Cholinergic urticaria (CholU) is a common type of chronic inducible urticaria, characterized by small itchy wheals that appear upon physical exercise or passive warming. Malassezia globosa, a skin resident fungus, has been identified as an antigen that induces mast cell/basophil degranulation and wheal formation through specific IgE, in Japanese patients with atopic dermatitis and CholU. In this study we aimed in assessing the rate of IgE sensitizations against skin resident fungi in European CholU patients. METHODS: We assessed serum IgE levels to Malassezia furfur, Candida albicans and Trichophyton mentagrophytes using routine lab testing and Malassezia globosa using a newly established ELISA. We correlated the results to wheal formation and other clinical features. RESULTS: Four patients (of 30 tested) had elevated levels of IgE against Malassezia furfur and Candida albicans and two had elevated levels of IgE against Trichophyton mentagrophytes. Four sera (of 25 tested) had elevated levels of IgE to the Malassezia globosa antigen supMGL_1304. Sensitization to one skin fungus was highly correlated with sensitization to the other tested fungi. We saw highly significant correlations of sensitization to supMGL_1304 with wheal size in the autologous sweat skin test (rs = 0.7, P = 0.002, n = 19), the Erlangen atopy score (rs = 0.5, P = 0.03, n = 19), total IgE serum levels (rs = 0.5, P = 0.04, n = 19) and a positive screen for IgE against common airborne/inhalant allergens s (sx1; rs = 0.54, P = 0.02, n = 19). CONCLUSIONS: Sensitization to skin resident fungi including Malassezia globosa is uncommon in European CholU patients, but is associated with atopy and pronounced wheal formation upon dermal contact with their own sweat.Trial registration German Clinical Trials Registry DRKS-ID: DRKS00004277.

Pharmacy-based interdisciplinary intervention for patients with chronic heart failure: results of the PHARM-CHF randomized controlled trial.

AIMS: Medication non-adherence is frequent and is associated with high morbidity and mortality in patients with chronic heart failure (CHF). We investigated whether an interdisciplinary intervention improves adherence in elderly CHF patients. METHODS AND RESULTS: The study population (mean age 74 years, 62% male, mean left ventricular ejection fraction 47%, 52% in New York Heart Association class III) consisted of 110 patients randomized into the pharmacy care and 127 into the usual care group. The median follow-up was 2.0 years (interquartile range 1.2-2.7). The pharmacy care group received a medication review followed by regular dose dispensing and counselling. Control patients received usual care. The primary endpoint was medication adherence as proportion of days covered (PDC) within 365 days for three classes of heart failure medications (beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and mineralocorticoid receptor antagonists). The main secondary outcome was the proportion of adherent patients (PDC ≥ 80%). The primary safety endpoint was days lost due to unplanned cardiovascular hospitalizations (blindly adjudicated) or death. Pharmacy care compared with usual care resulted in an absolute increase in mean adherence to three heart failure medications for 365 days [adjusted difference 5.7%, 95% confidence interval (CI) 1.6-9.8, P = 0.007]. The proportion of patients classified as adherent increased (odds ratio 2.9, 95% CI 1.4-5.9, P = 0.005). Pharmacy care improved quality of life after 2 years (adjusted difference in Minnesota Living with Heart Failure Questionnaire scores -7.8 points (-14.5 to -1.1; P = 0.02), compared to usual care. Pharmacy care did not affect the safety endpoints of hospitalizations or deaths. CONCLUSION: Pharmacy care safely improved adherence to heart failure medications and quality of life.

Counseling patients on correct drug handling in German community pharmacies: experiences and opinions of pharmaceutical staff.

Background For a safe drug therapy, outpatients have to self-administer their medications correctly. However, these procedures are known as error-prone. In community pharmacies, the pharmaceutical staff has to recognize patients' counseling needs and to use adequate strategies to prevent possible handling errors. Objective Assessing the experiences and opinions of pharmaceutical staff on counseling patients on practical drug handling. Setting Community pharmacies in a German city and surrounding area. Method Descriptively evaluating a self-administered questionnaire to be completed by members of the pharmaceutical staff involved in patient counseling. Main outcome measures Estimated counseling needs of patients, current counseling strategies and limitations of counseling. Results 520 staff members of 119 pharmacies (59.8%, 199 invited) participated. The majority prioritized counseling on dosage over counseling on practical drug handling. Participants saw a particular need when medication was dispensed for the first time compared to repeated use (all medication types, each p < 0.001). The need and counseling strategy depended on the dosage form with a special focus on practical demonstration in bronchopulmonary (83.9%) and oral liquid formulations (54.3%). As one main limitation, they cited the refusal of patients to accept information on drug handling (34.4%). Conclusion Participants considered drug handling an important counseling topic. However, reduced awareness for handling errors made at repeated use and at administration of certain dosage forms may affect the safety and success of medication therapy. Additionally, patients' resistance to information may limit the intent on counseling. Still, it is important to verify patients' abilities to handle their medication as intended.

Optimizing parents' performance in anticonvulsant rescue medication administration.

OBJECTIVE: Parents of children with epilepsy are at risk of committing high-risk handling errors with a high potential to harm the patient when administering anticonvulsant rescue medication. We developed a training concept addressing identified high-risk handling errors and investigated its effects on parents' skills. STUDY DESIGN: In a controlled prospective intervention study, parents of children with epilepsy were asked to demonstrate their administration of rescue medication by using dummy dolls. A clinical pharmacist monitored rectal or buccal administration and addressed errors in the intervention group with training and information sheets. Three to 6weeks later, intervention's sustainability was assessed at a home visit. RESULTS: One hundred sixty-one parents completed full study assessment: 92 in the intervention group and 69 in the control group. The number of processes with at least one handling error was reduced from 96.4% to 56.7% in rectal tube administration and from 66.7% to 13.5% in buccal administration (both p<0.001). CONCLUSION: A one-time intervention for parents significantly and sustainably reduced high-risk handling errors. Dummy dolls and information sheet were adequate for an effective and feasible training to support the correct administration of anticonvulsant rescue medication.

[Interdisciplinary Concepts of Paediatrics and Clinical Pharmacy to Optimise Anticonvulsant Treatment]. / Interdisziplinäre Konzepte von Pädiatrie und Klinischer Pharmazie zur Optimierung der Antikonvulsivatherapie.

Expertise in a variety of fields is required for the diagnostic process of epilepsies in children and adolescents as well as for their treatment with anticonvulsants. Patients benefit in the process from the cooperation of different health care professionals. It is of critical importance for risks to be minimised and for the efficacy shown in controlled clinical trials to be maintained in routine conditions. In the first instance, drug prescription procedures, including the choice of anticonvulsants and combinations of drugs and dosing, have to be considered. The administration of drugs has, of course, also to be taken into account. Only if patients are given their anticonvulsants appropriately, the intended success of the therapy can be accomplished. Strategies aimed at improving drug administration have to be directed not only at nurses but also at parents, children and adolescents themselves, as well as caregivers in schools and children's day-care facilities. By providing theoretical teaching, practical training, and routinely including pharmacists in the therapeutic team, drug-related problems that may result in limited effectiveness and increased risks are prevented. As a result, drug (therapy) safety is not only qualitatively improved, but the degree of participation and quality of life of patients and families is improved as well.

Seizure management by preschool teachers: A training concept focussing on practical skills.

PURPOSE: Prolonged seizures can cause severe harm and even death. For seizures lasting longer than 5min, an administration of rescue medication is therefore recommended. Caregivers such as preschool teachers should be able to administer correctly anticonvulsive rescue medication to children. METHODS: A training concept for preschool teachers on seizure management focussing on practical skills was developed. To assess the success of the training, a structured interview on attitudes relating to rescue medication administration was conducted. The number of committed errors during administration of a rectal/buccal rescue medication to dummy dolls was compared before and after training. RESULTS: 210 teachers from 115 preschools participated while all teachers from 303 preschools had been invited. The self-reported level of confidence in their own skills to administer anticonvulsive rescue medication increased from 5 to 8 on a scale from 1 to 10 (p<0.001). The number of participants who agreed to administer rescue medication rose from 195/210 (92.8%) before training to 209/210 (99.5%, p<0.001) after training for the rectal route, and from 173/210 (82.4%) to 209/210 (99.5%, p<0.001) for the buccal route. For teachers who administered rescue medication before and after training, the number of administrations without any administration errors rose from 1/195 (0.5%) to 117/195 (60.0%, p<0.001) for the rectal route, and from 13/173 (7.5%) to 95/173 (54.9%, p<0.001) for the buccal route. CONCLUSION: A training for preschool teachers boosted the level of self-confidence relating to administration of anticonvulsive rescue medication. Teachers also committed fewer errors when administering rescue medication to dummy dolls.

Administration of anticonvulsive rescue medication in children-discrepancies between parents' self-reports and limited practical performance.

UNLABELLED: Quality of parents' performance in administering anticonvulsive rescue medication to their children suffering from seizures is unknown. After obtaining ethical approval, we used a questionnaire to ask parents of children with seizures, who had been prescribed rescue medications, about their experience in administering those. To assess the frequency of actually committed drug-handling errors, we let them administer rescue medications to dummy dolls. An expert panel rated the clinical risk of handling errors from "1" (lowest) to "6" (highest). Eighty-one parents completed the study. In the questionnaire, 85 % (100 %) of parents that already conducted rectal (buccal) administration reported that they had never experienced problems. The number of rectal administrations with at least one handling error (97 %, 58/60) was higher than in buccal administration (58 %; 14/24; p < 0.001). According to logistic regressions, previous use of rescue medication was not a predictor of the number of committed errors per process (n. s.). All errors were rated with a high clinical risk (class 4-6). CONCLUSION: By observing parents' administration of rescue medication to dummy dolls, we found a high frequency of clinically relevant drug-handling errors. Most parents, however, self-reported to have never experienced problems while administering rescue medications to their children. WHAT IS KNOWN: • For seizures with duration of more than 5 min, the administration of anticonvulsive rescue medication is recommended. • Outside the hospital, the administration of rescue medication to children is performed most frequently by their parents. What is New: • Most of the parents reported that they had never experienced problems in handling anticonvulsive rescue medication. • But in the observed drug-handling performances, identified errors committed by parents were alarmingly frequent and pose a high clinical risk according to an expert panel.