Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain.

OBJECTIVES: To determine the proportion of patients with rheumatoid arthritis (RA) with severe persisting pain and to identify predictive factors despite treatment-controlled disease activity. METHODS: This prospective multicentre study included outpatients with RA scheduled for escalation of anti-inflammatory treatment due to active disease and severe pain (Disease Activity Score 28 (DAS28)>3.2 and Visual Analogue Scale (VAS)>50). At week 24, patients were stratified into reference group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score<50), non-responders (DAS28 improvement≤1.2 and DAS28>3.2, regardless of VAS pain score) and persisting pain group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score≥50). The former two subgroups ended the study at week 24. The latter continued until week 48. Demographic data, DAS28-C reactive protein, VAS for pain, painDETECT Questionnaire (PD-Q) to identify neuropathic pain (NeP) and the Pain Catastrophising Scale were assessed and tested for relation to persisting pain. RESULTS: Of 567 patients, 337 (59.4%) were classified as reference group, 102 (18.0%) as non-responders and 128 (22.6%) as patients with persisting pain. 21 (8.8%) responders, 28 (35.0%) non-responders and 27 (26.5%) persisting pain patients tested positive for NeP at week 24. Pain catastrophising (p=0.002) and number of tender joints (p=0.004) were positively associated with persisting pain at week 24. Baseline PD-Q was not related to subsequent persisting pain. CONCLUSIONS: Persisting and non-nociceptive pain occur frequently in RA. Besides the potential involvement of NeP, pain catastrophising and a higher number of tender joints coincide with persisting pain.

Symptoms of older orthopedic and rheumatic patients : A telephone survey about symptoms, symptom communication, treatment and further support after hospital discharge.

BACKGROUND: In older multimorbid orthopedic and rheumatic patients, data on symptoms besides pain or reduced mobility are rarely published. OBJECTIVE: We investigated patients' perspectives on their symptoms after hospital discharge. MATERIAL AND METHODS: Orthopedic and rheumatic patients aged over 70 years were asked via telephone interviews about (i) their symptoms, (ii) communication, (iii) treatment, and (iv) support. RESULTS: (i) The 60 participants (35 women and 25 men) reported a median of 6 (min-max: 1-14) different symptoms, of which 86% (356 of 415) had existed before hospitalization, (ii) patients did not communicate 28% (117) of symptoms to either healthcare professionals, family or friends and (iii) 52 (87%) patients desired improvement. Of the 280 most impairing symptoms, 19% (52) were not treated at all. (iv) Almost all patients (59; 98%) considered it easy to obtain support. CONCLUSION: Remarkably, many symptoms were not communicated or treated despite the patients having been hospitalized.

[Number of teeth as indicator for individual risk for delirium]. / Zahnzahl als Indikator für individuelles Delirrisiko.

BACKGROUND: Recent research claims some interdependence between oral health and dementia; however, no empirical data could be found regarding the role of oral hygiene in delirium. This study investigated potential risk indicators related to oral hygiene in relation to development of delirium in the care of older patients. METHODS: A dental examination was performed in 120 patients in the context of a case-control study. The ratio of diseased patients with risk factors to diseased patients without risk factors describes the correlation between risk factors and the risk of disease. A binary logistic regression was performed to determine the correlation of the number of teeth to delirium. RESULTS: Every lost tooth enhances the delirium risk by 4.6%. Edentulous patients had a 2.66-fold higher risk to suffer from delirium. Caries experience and periodontitis has no significant impact on delirium prevalence. DISCUSSION: Both edentulousness and the number of lost teeth could be considered as risk indicators for delirium. Periodontitis or caries experience did not have a direct significant impact. The present study examined the merits of edentulousness and tooth loss as a screening parameter.

[Fibromyalgia as a Rheumatic Pain Syndrome]. / Das Fibromyalgiesyndrom als Schmerzsyndrom in der Rheumatologie.

Epidemiology and pathophysiology: Fibromyalgia is significantly more common in people with rheumatic diseases than in the general population. Nevertheless, it can occur independent of other diseases. Physical and psychosocial factors are responsible for the genesis for fibromyalgia making it a multifactorial disease. Most importantly, central pain processing seems to be abnormal. The relevance of a small fibre neuropathy is yet to be determined. For the very first time, a study was able to demonstrate that fibromyalgia might be passively transferred from one organism to another in an experimental setting.Diagnosis: Fibromyalgia is a clinical diagnose. Besides generalized pain, sleep disturbances and fatigue are common features. Furthermore, there can be an association with depressive disorders. Determining the Widespread Pain Index (WPI) and the Symptom Severity Score (SSS) can help in diagnosing Fibromyalgia and to determine severity of the disease.Therapy: Cornerstones of the treatment are patient education, physical exercise, physical therapy, and cognitive behavioural therapy. In therapy-resistant cases, a multimodal approach might be considered. Analgesic drugs, particularly opioids, should basically be avoided or only be used for a short period of time. Naltrexone, an opioid antagonist, is a promising treatment candidate. Another possible approach might be the use of TENS. While there are positive observational studies on the therapeutic use of cannabinoids, evidence from controlled trials is still missing.

Management, vaccination status and COVID-19 morbidity of patients with Gaucher disease in Germany during the COVID-19 pandemic.

BACKGROUND: Continuation of standard management of Gaucher disease (GD) has been challenging during the COVID-19 pandemic, resulting in infrequent/missed infusions and follow-up appointments. Little data are available on the consequences of these changes and on the SARS-CoV-2 vaccinations in German GD patients. METHODS: A survey with 22 questions about GD management during the pandemic was sent to 19 German Gaucher centres. It was answered by 11/19 centres caring for 257 GD patients (almost ¾ of the German GD population); 245 patients had type 1 and 12 had type 3 GD; 240 were ≥ 18 years old. RESULTS: Monitoring intervals were prolonged in 8/11 centres from a median of 9 to 12 months. Enzyme replacement therapy (ERT) was changed to home ERT in 4 patients and substituted by oral substrate reduction therapy (SRT) in 6 patients. From March 2020 to October 2021, no serious complications of GD were documented. Only 4 SARS-CoV-2 infections were reported (1.6%). Two infections were asymptomatic and two mild; all occurred in adult type 1, non-splenectomized patients on ERT. Vaccination rate in adult GD was 79.5% (95.3% mRNA vaccines). Serious vaccination complications were not reported. CONCLUSIONS: The COVID-19 pandemic has lowered the threshold for switching from practice- or hospital-based ERT to home therapy or to SRT. No major GD complication was documented during the pandemic. Infection rate with SARS-CoV-2 in GD may rather be lower than expected, and its severity is mild. Vaccination rates are high in GD patients and vaccination was well tolerated.

Association between the Ile164 ß2 Adrenergic Receptor Polymorphism and Fatigue in Patients with Rheumatoid Arthritis.

INTRODUCTION: In the present work, the frequency of inherited polymorphisms of the beta 2 adrenergic receptor (ß2AR) gene and their association with fatigue in patients with rheumatoid arthritis (RA) was examined. METHODS: An allele-specific polymerase chain reaction was used to determine the common variants of the ß2AR at position 16, 27, and 164 in 92 German RA outpatients. Health Assessment Questionnaire (HAQ-DI), Beck Depression Inventory (BDI), Perceived Stress Questionnaire (PSQ-30), Multidimensional Fatigue Inventory (MFI-20) were utilized. RESULTS: 34.7% of German RA patients were diagnosed with associated fatigue. Fatigued patients were more likely to carry the Ile allele at position 164 (OR 7.33, 95% CI 1.09-59.8, p = 0.049). Comparing these risk factors' contribution to different fatigue dimensions revealed that Ile164 carriers only had significantly higher MFI-20 mean values for general fatigue (p = 0.014) while the clinical difference among other MFI subscales was the largest for mental fatigue (carrier: 8.23, SD: 4.22, noncarrier: 5.67, SD: 1.56, p = 0.089, Cohen's d = 0.629). Disease activity, perceived stress, and depression were also associated with fatigue with higher mean values for DAS28CRP (p = 0.038), PSQ (p < 0.001), and BDI-II (p < 0.001) in fatigued patients. Physical fatigue was correlated with disease activity (p = 0.009) and depression (p = 0.001) while mental fatigue showed associations with depression (p = 0.001) and perceived stress (p = 0.028). CONCLUSION: The discovery study indicates that the Ile164 polymorphism might in contrast to other ß2AR polymorphisms affect fatigue levels in RA patients. This association was observed especially with mental fatigue. Further replication studies are warranted to determine further role of ß2AR polymorphisms in RA patients.

Two years of pegvaliase in Germany: Experiences and best practice recommendations.

BACKGROUND: In 2019, pegvaliase was approved in Europe for the treatment of phenylketonuria (PKU) in patients aged 16 years and older with blood phenylalanine (Phe) concentrations above 600 µmol/L despite prior management with available treatment options. Since its European approval, German metabolic centres have gained valuable experience, which may be of benefit to other treatment centres managing patients on pegvaliase. METHODS: After a virtual meeting that was attended by nine German physicians, three German dietitians and one American physician, a follow-up discussion was held via an online platform to develop a set of recommendations on the use of pegvaliase in Germany. Eight German physicians contributed to the follow-up discussion and subsequent consensus voting, using a modified Delphi technique. The recommendations were supported by literature and retrospectively collected patient data. RESULTS: Consensus (≥75% agreement) was achieved on 25 recommendations, covering seven topics deemed relevant by the expert panel when considering pegvaliase an option for the treatment of patients with PKU. In addition to the recommendations, a retrospective chart review was conducted in seven of the centres and included 71 patients who initiated treatment with pegvaliase. Twenty-seven patients had been treated for at least 24 months and 23 (85.2%) had achieved blood Phe ≤600 µmol/L with some degree of diet normalisation. Of these patients, 14 had physiological blood Phe on a normalised diet. CONCLUSION: The practical consensus recommendations provide guidance on the different steps along the pegvaliase journey from clinical site requirements to treatment goals and outcomes. The recommendations are intended to support less experienced European metabolic centres with the implementation of pegvaliase, emphasising that a core treatment team consisting of at least a dietitian and metabolic physician is sufficient to initiate pegvaliase and support patients during their treatment journey.

[Trial of the GeriNOT screening tool : Identification of geriatric risk potentials on admission to hospital care from the age of 70 years]. / Prüfung des Screening-Tools GeriNOT : Identifikation geriatrischer Risikopotenziale bei Aufnahme ab 70-Jähriger in die Krankenhausversorgung.

BACKGROUND: Geriatric-specific characteristics influence patient-relevant outcomes of inpatient hospital care in patients aged 70 years and older: prolonged length of stay, complications, increase in utilization of required services as well as mortality rates. OBJECTIVE: The screening tool GeriNOT, identification of geriatric risk potential with 7 items, of which mobility and cognition are double-weighted, score 9 points, was tested for its predictive content and diagnostic quality. MATERIAL AND METHODS: Diagnostic study from a retrospective, bicentric complete survey in all types of admission from 70 years with 2541 patient cases. Regression analyses in linked samples of the 7 items in GeriNOT and as noncombined end points: prolonged length of stay, complications, increase in need-based service at discharge and death. RESULTS: Mean age ± SD: 77.0 ± 6.4 years. ROC analyses report at a cut-off value calculated using the Youden index of ≥ 4 points in 2541 cases: increase in need-based service at discharge (AUC = 0.693, 95% CI = 0.663-0.723, sensitivity 75.2%, specificity 59.7%), complications (AUC = 0.662, 95% CI = 0.636-0.688, sensitivity 64.2%, specificity 61.6%) and death (AUC = 0.734, 95% CI = 0.682-0.786, sensitivity 76.4%, specificity 57.5%). Possibly suitable for use as screening to identify geriatric risk potentials at a cut-off of ≥ 4 points. DISCUSSION: Provide an initial filter screening with regard to mobility. Such identification could provide the involved persons with the opportunity for an improved treatment outcome by adapting the inpatient process. Prospective validation of GeriNOT needed.

Impact of pregnancy planning and preconceptual dietary training on metabolic control and offspring's outcome in phenylketonuria.

To prevent maternal phenylketonuria (PKU) syndrome low phenylalanine concentrations (target range, 120-360 µmol/L) during pregnancy are recommended for women with PKU. We evaluated the feasibility and effectiveness of current recommendations and identified factors influencing maternal metabolic control and children's outcome. Retrospective study of first successfully completed pregnancies of 85 women with PKU from 12 German centers using historical data and interviews with the women. Children's outcome was evaluated by standardized IQ tests and parental rating of child behavior. Seventy-four percent (63/85) of women started treatment before conception, 64% (54/85) reached the phenylalanine target range before conception. Pregnancy planning resulted in earlier achievement of the phenylalanine target (18 weeks before conception planned vs. 11 weeks of gestation unplanned, p < 0.001) and lower plasma phenylalanine concentrations during pregnancy, particularly in the first trimester (0-7 weeks of gestation: 247 µmol/L planned vs. 467 µmol/L unplanned, p < 0.0001; 8-12 weeks of gestation: 235 µmol/L planned vs. 414 µmol/L unplanned, p < 0.001). Preconceptual dietary training increased the success rate of achieving the phenylalanine target before conception compared to women without training (19 weeks before conception vs. 9 weeks of gestation, p < 0.001). The majority (93%) of children had normal IQ (mean 103, median age 7.3 years); however, IQ decreased with increasing phenylalanine concentration during pregnancy. Good metabolic control during pregnancy is the prerequisite to prevent maternal PKU syndrome in the offspring. This can be achieved by timely provision of detailed information, preconceptual dietary training, and careful planning of pregnancy.

IL-10 Induced by mTNF Crosslinking-Mediated Reverse Signaling in a Whole Blood Assay Is Predictive of Response to TNFi Therapy in Rheumatoid Arthritis.

(1) Background: To date, the response of patients with rheumatoid arthritis (RA) to the various biologic DMARD available cannot be predicted due to a lack of reliable biomarkers. Based on our preliminary work on tmTNF reverse signaling, we developed a whole-blood assay measuring tmTNF crosslinking-induced IL-10 production to predict the response to TNF inhibitor (TNFi) therapy. (2) Methods: This prospective study included patients with active RA. Depending on the clinical judgment of the attending rheumatologist, either therapy with a TNF or JAK inhibitor was initiated. Clinical parameters and blood samples were obtained at baseline and after 8 weeks of therapy. The blood samples were collected using a newly developed whole-blood assay based on the principle of tmTNF reverse signalling. Subsequently, IL-10 was measured via enzyme-linked immunosorbent assay (ELISA) technique. (3) Results: 63 patients with RA were enrolled. In fifteen patients, TNFi therapy was initiated, while eight patients started a JAKi treatment. The cross-sectional analysis of all patients showed a positive correlation between tmTNF crosslinking-induced IL-10 and parameters of disease activity (CRP [r = 0.4091, p = 0.0009], DAS28 [r = 0.3303, p = 0.0082]) at baseline. In the TNFi treatment study, IL-10 was found to be significantly higher in EULAR responders than in non-responders (p = 0.0033). After initiation of JAKi treatment, in contrast, IL-10 induction was not linked to response. Longitudinal analysis of the TNFi-treated patients revealed IL-10 to decrease in responders (p = 0.04), but not in non-responders after 8 weeks of therapy. Of importance, the IL-10 production at baseline correlated inversely with TNFi response determined by ΔDAS28 in patients with TNFi treatment (r = -0.5299, p = 0.0422) while no such link was observed under JAKi therapy (p = 0.22). Receiver operation characteristics (ROC) analysis demonstrated a high performance of tmTNF/crosslinking-induced IL-10 in predicting a TNFi therapy response according to the EULAR criteria (AUC = 0.9286, 95% Confidence interval 0.7825-1.000, p = 0.0055). (4) Conclusions: In this pilot investigation, we demonstrated the feasibility of a whole-blood assay measuring tmTNF-induced IL-10 to predict clinical response to TNF inhibitor treatment. This approach might support rheumatologists in their decision for an individually tailored RA therapy.

[Osteoarthritis: what's new?] / Arthrose ­ neue therapeutische Ansätze.

Osteoarthritis (OA) is a very common disease. As a consequence of the ageing society, osteoarthritis prevalence will further increase. Age itself, trauma, unequal load distribution and overweight are risk factors. Cellular senescence and overweight have been in the focus of scientific interest for the last few years. Both risk factors are able to facilitate joint inflammation, independent of a mechanical approach. Senescent chondrocytes as well as adipocytes can produce increased amounts of inflammatory cytokines. Cornerstones of the therapy are patient education including information on the character/course of the disease and intentional weight loss. Although NSAIDs can be recommended as analgesics, their contraindications limit the widespread use. Alternatively, acetaminophen or low-potency opioids such as tramadol might be considered. Topical NSAIDs and intraarticular glucocorticoid injections can be helpful in pain reduction particularly in knee osteoarthritis. There is still no general recommendation for nutritional supplements including chondroitin or glycosaminoglycan, but they might be considered as an accompanying therapy. With the current non-approval of the nerve growth factor (NGF)-antibody tanezumab, a new therapeutical option for OA suffered a setback. Unfortunately, the results of the phase 2 study on the Wnt inhibitor lorecivivint are barely encouraging. However, the results of the according phase 3 study are eagerly awaited.

COVID-19 Vaccination Coverage in Patients with Rheumatic Diseases in a German Outpatient Clinic: An Observational Study.

BACKGROUND: In the second year of the COVID-19 pandemic, highly effective and safe vaccines became available. Since patients with rheumatic diseases show increased susceptibility to infections and typical medications raise the risk of severe COVID-19, high vaccination coverage is of significant importance to these patients. METHODS: Consecutive patients with different rheumatic diseases were asked for their vaccination status regarding COVID-19, influenza and Streptococcus pneumoniae during their routine consultations. Any reported vaccination was validated with their personal vaccination card and/or by reviewing the CovPass smartphone app. Reasons for not having a COVID-19 vaccination were documented. RESULTS: A total of 201 patients (mean age 62.3 ± 14.1 years) were included, the majority of them (44.3%) with rheumatoid arthritis, followed by spondyloarthritis (27.4%) and connective tissue diseases (21.4%). Vaccination coverage for SARS-CoV-2 was 80.1%; 85.6% got at least the first vaccination shot. Both valid influenza and pneumococcus coverage were associated with a higher probability of SARS-CoV-2 vaccination (odds ratio (OR) 6.243, 95% confidence interval (CI) 2.637-14.783, p < 0.0001 and OR 6.372, 95% CI 2.105-19.282, p = 0.0003, respectively). The main reason for a missing SARS-CoV-2 vaccination (70%) was being sceptical about the vaccine itself (i.e., the subjective impression that the vaccine was not properly tested and fear of unwanted side effects). CONCLUSIONS: Vaccination coverage against SARS-CoV-2 is high in patients with rheumatic diseases. Nevertheless, there are unmet needs regarding vaccination education to further increase vaccination rates.

Humoral and cellular response to COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases under real-life conditions.

OBJECTIVES: Successful vaccination is key to overcoming the COVID-19 pandemic. Immunosuppressive medication is known to potentially compromise vaccination responses, and expansion of our knowledge on vaccination efficacy in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is therefore of utmost importance. METHODS: We conducted a single-centre observational study and evaluated the efficacy of approved COVID-19 vaccines in 303 adult AIIRD patients. Serum levels of IgG antibodies against the S1 subunit of SARS-CoV-2 spike proteins (anti-S IgG) were measured at least two weeks after vaccination. In a subgroup of patients without humoral response, T-cell responses were determined using an interferon-γ gamma release assay. RESULTS: Overall seropositivity rate was 78.5% and was significantly lower in patients under immunosuppressive therapy (75.7 vs 93.2%, P = 0.009). No difference regarding the vaccination type was observed. Glucocorticoids, mycophenolate-mofetil, TNF inhibitors, tocilizumab, abatacept and rituximab were all associated with non-response after proper vaccination. The risk was highest under RTX therapy (OR 0.004, 95% CI 0.001, 0.023, P < 0.0001). A strong negative correlation was observed between time since vaccination with an mRNA vaccine and anti-S antibody levels (r=-0.6149, P < 0.0001). In patients without humoral response, a T-cell response was found in 50%. CONCLUSIONS: COVID-19 vaccination in patients with AIIRD is effective using any approved vaccine. Humoral response might be impaired depending on the individual immunosuppressive medication. The risk of non-response is highest under rituximab therapy. Anti-S IgG antibody levels wane over time after mRNA vaccination. Importantly, 50% of humoral non-responders showed a T-cellular response, suggesting T-cell-mediated protection to a certain extent.

Sepsis Mortality Is high in Patients With Connective Tissue Diseases Admitted to the Intensive Care Unit (ICU).

OBJECTIVES: Patients with connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE) have an increased risk for infections. This study investigated the outcome and characteristics of CTD patients under intensive care unit (ICU) treatment for sepsis. METHODS: A single-center retrospective analysis was conducted and reviewed all patients with a CTD diagnosis admitted to the ICU of a university hospital for sepsis between 2006 and 2019. Mortality was computed and multivariate logistic regression was used to detect independent risk factors for sepsis mortality. Furthermore, the positive predictive value of ICU scores such as Sequential Organ Failure Assessment (SOFA) score was evaluated. RESULTS: This study included 44 patients with CTD (mean age 59.8 ± 16.1 years, 68.2% females), most of them with a diagnosed SLE (61.4%) followed by systemic sclerosis (15.9%). 56.8% (n = 25) were treated with immunosuppressives and 81.8% (n = 36) received glucocorticoids. Rituximab was used in 3 patients (6.8%). The hospital mortality of septic CTD patients was high with 40.9%. It was highest among systemic sclerosis (SSc) patients (85.7%). SOFA score and diagnosis of SSc were independently associated with mortality in multivariate logistic regression (P = 0.004 and 0.03, respectively). The Simplified Acute Physiology Score II (SAPS II), SOFA and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were good predictors of sepsis mortality in the investigated cohort (SAPS II AUC 0.772, P = 0.002; SOFA AUC 0.756, P = 0.004; APACHE II AUC 0.741, P = 0.007). CONCLUSIONS: In-hospital sepsis mortality is high in CTD patients. SSc diagnoses and SOFA were independently associated with mortality. Additionally, common ICU scores were good predictors for mortality.

A non-interventional observational study to identify and validate clinical outcome assessments for adults with phenylketonuria for use in clinical trials.

INTRODUCTION: Current clinical outcome assessments (COAs) are not effectively capturing the complex array of symptoms of adults with phenylketonuria (PKU). This study aimed to identify concepts of interest relevant to adults with PKU. Based on these concepts, COAs for patient-reported outcomes (PROs), observer-reported outcomes (ObsROs), and clinician-reported outcomes (ClinROs) were selected or developed and content validity was assessed. MATERIALS AND METHODS: Concept-elicitation interviews were conducted with an international cohort of adults with PKU (n = 30), family member observers (n = 14), and clinical experts (n = 8). Observers and clinical experts were included to overcome the risk of lack of self-awareness among adults with PKU. The concepts of interests endorsed by ≥30% of patients, observers, and/or clinical experts were selected, mapped to items in existing COAs, and used to develop global impression items for patients, observers, and clinicians. Next, the content validity of the COAs and global impression items was evaluated by cognitive interviews with patients (n = 22), observers (n = 11), and clinical experts (n = 8). All patients were categorized according to blood phenylalanine (Phe) levels (i.e., <600 µmol/L, 600-1200 µmol/L, and >1200 µmol/L). RESULTS: Concepts of interests were identified across four domains: emotional, cognitive, physical, and behavioral. After mapping, eight existing COAs were selected based on the concept coverage (six PROs, one ObsRO, and one ClinRO). The six PRO measures were considered as potentially fit-for-purpose. The ObsRO measure was not deemed relevant for use in observers of adults with PKU and only a subscale of the ClinRO measure was considered valid for assessing adults with PKU by clinicians. Due to the lack of existing COAs covering all concepts of interests, global impression items for symptom severity and change in symptoms were developed, which were limited to one question covering in total 14 concepts. Upon validation, some of the patient and observer global impression items were excluded as they were subject to lack of insight or could not be reported by observers. Due to the limited interaction time between clinician and patient, use of the clinician global impression items was not supported. CONCLUSION: Existing COAs relevant to adults with PKU were selected and PKU-specific global impression items were developed by mapping the most frequently identified concepts of interests from internationally-conducted in-depth interviews. Future studies should address the appropriateness of the selected COAs and global impression items to assess if these can be used as efficacy endpoints in PKU clinical trials.

Preventing maternal phenylketonuria (PKU) syndrome: important factors to achieve good metabolic control throughout pregnancy.

BACKGROUND: Insufficient metabolic control during pregnancy of mothers with phenylketonuria (PKU) leads to maternal PKU syndrome, a severe embryo-/fetopathy. Since maintaining or reintroducing the strict phenylalanine (Phe) limited diet in adults with PKU is challenging, we evaluated the most important dietary and psychosocial factors to gain and sustain good metabolic control in phenylketonuric women throughout pregnancy by a questionnaire survey with 38 questions concerning therapy feasibility. Among them, the key questions covered 5 essential items of PKU care as follows: General information about maternal PKU, PKU training, diet implementation, individual metabolic care, personal support. In addition, all participating PKU mothers were asked to estimate the quality of their personal metabolic control of the concluded pregnancies. 54 PKU mothers with 81 pregnancies were approached at 12 metabolic centers in Germany and Austria were included. According to metabolic control, pregnancies of PKU women were divided in two groups: group "ideal" (not more than 5% of all blood Phe concentrations during pregnancy > 360 µmol/l; n = 23) and group "suboptimal" (all others; n = 51). RESULTS: The demand for support was equally distributed among groups, concerning both amount and content. Personal support by the direct social environment (partner, family and friends) ("suboptimal" 71% vs "ideal" 78%) as well as individual metabolic care by the specialized metabolic center (both groups around 60%) were rated as most important factors. The groups differed significantly with respect to the estimation of the quality of their metabolic situation (p < 0.001). Group "ideal" presented a 100% realistic self-assessment. In contrast, group "suboptimal" overestimated their metabolic control in 53% of the pregnancies. Offspring of group "suboptimal" showed clinical signs of maternal PKU-syndrome in 27%. CONCLUSION: The development of training programs by specialized metabolic centers for females with PKU in child bearing age is crucial, especially since those mothers at risk of giving birth to a child with maternal PKU syndrome are not aware of their suboptimal metabolic control. Such programs should provide specific awareness training for the own metabolic situation and should include partners and families.

Evaluating the effectiveness of a structured, simulator-assisted, peer-led training on cardiovascular physical examination in third-year medical students: a prospective, randomized, controlled trial.

Background: Previous research suggests that cardiac examination skills in undergraduate medical students frequently need improvement. There are different ways to enhance physical examination (PE) skills such as simulator-based training or peer-assisted learning (PAL). Aim: The aim of this study was to evaluate the effectiveness of a structured, simulator-assisted, peer-led training on cardiovascular PE. Methods: Participants were third-year medical students at Leipzig University Faculty of Medicine. Students were randomly assigned to an intervention group (IG) and a control group (CG). In addition to standard curricular training, IG received a peer-led, simulator-based training in cardiac PE. Participant performance in cardiac PE was assessed using a standardized checklist with a maximum of 25 points. Primary outcome was assessed via checklist point distribution. Results: 89 students were randomised to either CG (n=43) or IG (n=46) with 70 completing the study. Overall, IG students performed significantly better than CG students did (max. points: 25, M±SD in IG was 17±3, in CG 12±4, p<.0001). Simple mistakes such as not using the stethoscope correctly were more frequent in CG students. Prior experience did not lead to a significant difference in performance. Conclusions: Structured, peer-led and simulator-assisted teaching sessions improve cardiac PE skills in this setting compared to control students that did not receive this training.