The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study.

BACKGROUND: Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. METHODS: We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. RESULTS: A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI - 0.09, - 0.05; p ≤ 0.001) and early mobilisation (adjusted OR 0.83; 95% CI 0.76, 0.90; p ≤ 0.001), while a higher norepinephrine dose corresponded to a lower chance to be mobilised out-of-bed (adjusted OR 0.01; 95% CI 0.00, 0.04; p ≤ 0.001). Mobilisation with norepinephrine did not significantly affect mortality (p > 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 µg/kg/min norepinephrine for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation. CONCLUSIONS: Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 µg/kg/min for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0-1) mobilisation.

[Acute rehabilitation after COVID-19 infection : A selected case series]. / Akutrehabilitation nach COVID­19­Infektion : Eine ausgewählte Fallserie.

BACKGROUND: While the first wave of the coronavirus disease 2019 (COVID-19) pandemic mainly affected the old, currently younger patients also become infected and hospitalized. After severe and critical COVID-19 infections and also after surviving acute phase symptoms, these patients often show symptoms (e.g. exertional dyspnea), organ damage (e.g. of the lungs, the cardiovascular system) as well as psychological impairments. OBJECTIVE: The severe courses after critical cases of COVID-19 represent challenges for rehabilitation and require more than ever rehabilitative treatment approaches even in acute hospitals. METHODS: This article presents a selected case series of patients with a typical constellation of pre-existing conditions due to immunosuppression plus critical course of COVID-19 and indications for acute rehabilitation. RESULTS: This case series depicts the long duration of hospitalization with high numbers of hours on ventilation in the intensive care unit. At the time of transfer to acute rehabilitation these patients are immobile and have severe limitations in all activities of daily life, so that an inpatient rehabilitation in an acute hospital is indicated and the usual means of continuation of rehabilitation were not feasible. The sequelae of lying prone and complications, such as exertional desaturation in the early stage of convalescence are detected in the acute phase of early rehabilitation. CONCLUSION: After severe COVID-19 infections new challenges for rehabilitation are to be expected, so that rehabilitative treatment approaches with an interdisciplinary early rehabilitation in an acute hospital are urgently needed. Finally, acute rehabilitation not only enables a seamless treatment chain for these patients but also the flow of patients from the intensive care unit to ensure the functioning of local infrastructures.

[Interdisciplinary Acute Medical Rehabilitation after Sepsis - A Retrospective Analysis]. / Fachübergreifende Frührehabilitation nach Sepsis ­ Eine retrospektive Analyse .

BACKGROUND: Surviving sepsis may have consequences of high impact for the patients' further life regarding functioning in mobility and activities of daily living, among other fields. Patients consecutively have a great need of rehabilitation interventions beginning with early mobilization in the Intensive Care Unit ICU. Acute medical rehabilitation is a concept of early rehabilitation still in the acute care hospital, normally beginning after a direct transferal from the ICU. Its aim is to improve the patients' functioning in mobility and activities of daily living (ADL) to enable further post-acute rehabilitation interventions. METHODS: In this retrospective analysis a sample of patients who received acute medical rehabilitation after surviving a sepsis or severe sepsis was followed. The study targeted the question if basic functions of mobility and ADL could be improved by acute medical rehabilitation. Furthermore, the need for aid supply was evaluated, as well as the type of discharge or transferal after acute care. RESULTS: The increase of mobility and ADL capability before and after acute medical rehabilitation was highly significant (p<0.001 each) and showed very large effect sizes (d=1.3, 1.4 respectively). Aid supply was organized for 92% of patients. A majority of patients could receive consecutive post-acute rehabilitation after re-gaining function. DISCUSSION: The data shows the enormous gain in functioning that can be reached with an acute medical rehabilitation intervention after ICU treatment of sepsis.

[Why and How Should I Assess Frailty? A Guide for the Preoperative Anesthesia Clinic]. / Warum und wie sollte ich Frailty erfassen? ­ ein Ansatz für die Anästhesieambulanz.

Introduction: Frailty is a condition of decreased physiological reserves seen in approx. one third of elderly anesthesiological patients, and affecting many aspects of treatment as well as outcome. Although there are over 60 measurement instruments, frailty assessment is still poorly implemented. Understanding why and how to assess frailty is key to its implementation in preoperative anesthesia clinics. Method: After presenting the impact of perioperative frailty and the benefits of an early diagnosis on health related quality of life, we present an overview of the most important tools that can be used in the preoperative frailty assessment. Results: Early diagnosis offer several optimization opportunities for the perioperative period. The most efficient frailty assessment tools are presented and discussed, including physical, cognitive, and psychosocial aspects. Conclusion: Frailty assessments vary immensely in terms of required time, equipment, and expertise. We recommend at least one test for each domain of frailty, so as to obtain a more holistic view of the patient's physiological reserve. The implementation of an adequate and consistent preoperative frailty assessment has the potential to improve patient safety as well as short and long term outcomes.

A prospective pilot study to evaluate an animated home-based physical exercise program as a treatment option for patients with rheumatoid arthritis.

BACKGROUND: Physical exercises and physiotherapy are of great importance for maintenance of joint function in patients with rheumatoid arthritis (RA). However, many RA patients complain about problems to receive prescriptions or have a lack of access to physiotherapy. Recent reports have shown positive effects of the Wii game console on physical and psychosocial conditions of patients with other underlying diseases. The primary objectives of this prospective controlled pilot study were to investigate feasibility and patients' assessment using an animated home-based exercise program. METHOD: This pilot study was conducted as a single-center, cross-over trial with two treatment arms over 24 weeks. Eligibility criteria included patients with RA reaching low disease activity under therapy with a biological disease modifying anti-rheumatic drug (bDMARD). After detailed instruction, 15 patients started with a conventional home-based physical exercise program and 15 patients began with a predefined animated exercise program by using the Wii game console for 12 weeks. Afterwards, patients were crossed-over to the other treatment arm for another period of 12 weeks. Multi-methodical assessments were performed by qualitative analysis of the interview-data as well as statistical analysis of functional tests and patient reported outcomes (PRO's). RESULTS: Evaluation of the interviews indicated feasibility and usefulness of the chosen animated home-based exercise program. Forefoot disabilities were identified as a main limiting factor for performing some of the animated exercises. After 12 weeks, both treatment arms showed improvement of functional tests without significant differences between groups: Overall muscle strength improved for a mean value of 10 Newton (+12 %) and the mean 6-min walk test (6-MWT) distance increased for 28 meters (+5 %). CONCLUSION: This study showed that an animated home-based exercise program by using a Wii game console was feasible and beneficial for RA patients. Compared to standard physical home exercises, similar effects were observed indicating that such an animated program might be an alternative supportive option for RA patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02658370 (19-Jan-2016).

Children with dry skin and atopic predisposition: daily use of emollients in a participant-blinded, randomized, prospective trial.

BACKGROUND: Dry skin reflects a skin barrier defect which can lead to atopic dermatitis. Little is known about the distinct effects of emollient use in children with dry skin and atopic predisposition. OBJECTIVES: We investigated the effects of daily application of pressed ice plant juice (PIPJ)-based emollients and petrolatum-based emollients. METHODS: Children aged 2-6 years with dry skin and atopic predisposition were randomized into 2 groups: group 1 received emollients containing PIPJ and natural lipids, while group 2 received petrolatum-based emollients. Skin condition and biophysical properties of the skin barrier were assessed at inclusion and weeks 4, 12 and 16. RESULTS: Skin condition improved significantly in all children. Comparing the groups, children treated with emollients containing PIPJ showed significantly higher stratum corneum hydration values and significantly lower transepidermal water loss values at week 16 on the forearm and forehead. A significant decrease in skin pH was noted in group 2 on the forearm and forehead; group 1 showed a stable course. CONCLUSION: Early intervention with emollients in children with dry skin condition and atopic predisposition may improve their skin condition during daily emollient application. PIPJ-based formulations may be helpful to maintain skin barrier integrity.

Long-term complications of prone position ventilation with relevance for acute and postacute rehabilitation: a systematic review of the literature.

INTRODUCTION: Prone positioning ventilation (PPV) is an effective treatment for patients with moderate to severe acute respiratory distress syndrome (ARDS). Despite the benefits of PPV, different kinds of short and long-term consequences have been noted. This review summarizes long-term complications of PPV that impact treatment strategies and outcomes in acute and postacute rehabilitation. EVIDENCE ACQUISITION: PubMed/Medline, Cochrane Library, Cochrane COVID-19 Study Register databases and the Google Scholar search engine were systematically searched for studies investigating long-term complications of PPV. The final search date for all sources/databases was January 31, 2022. For our methodological appraisal, we conducted a systematic review of articles without any restrictions on types of articles or publication dates. Only articles published in English and available as full texts were eligible for inclusion. After the screening process, data of interest were extracted from eligible sources: PPV sequelae and conclusions (i.e. possible effects on the course of rehabilitation and therapy strategies). EVIDENCE SYNTHESIS: A total of 59 studies are included in this review. Long-term consequences are mainly pressure ulcers and nerve lesions that exist after discharge from the Intensive Care Unit (ICU). Publications rarely recommend treatment strategies for long-term complications after PPV. Due to the quality of the included studies, no robust conclusions as to effective strategies can be drawn. CONCLUSIONS: Further high-quality research is required, considering the different long-term complications after PPV and their impact on rehabilitation in order to draw conclusions about viable physical therapies. Crucially, however, prone positioning (PP) sequelae pose new challenges to physicians and therapists in acute and postacute rehabilitation medicine as well as follow-up care.

Mobilisation practices during the SARS-CoV-2 pandemic: A retrospective analysis (MobiCOVID).

BACKGROUND: Corona Virus Disease 2019 (COVID-19) patients display risk factors for intensive care unit acquired weakness (ICUAW). The pandemic increased existing barriers to mobilisation. This study aimed to compare mobilisation practices in COVID-19 and non-COVID-19 patients. METHODS: This retrospective cohort study was conducted at Charité-Universitätsmedizin Berlin, Germany, including adult patients admitted to one of 16 ICUs between March 2018, and November 2021. The effect of COVID-19 on mobilisation level and frequency, early mobilisation (EM) and time to active sitting position (ASP) was analysed. Subgroup analysis on COVID-19 patients and the ICU type influencing mobilisation practices was performed. Mobilisation entries were converted into the ICU mobility scale (IMS) using supervised machine learning. The groups were matched using 1:1 propensity score matching. RESULTS: A total of 12,462 patients were included, receiving 59,415 mobilisations. After matching 611 COVID-19 and non-COVID-19 patients were analysed. They displayed no significant difference in mobilisation frequency (0.4 vs. 0.3, p = 0.7), maximum IMS (3 vs. 3; p = 0.17), EM (43.2% vs. 37.8%; p = 0.06) or time to ASP (HR 0.95; 95% CI: 0.82, 1.09; p = 0.44). Subgroup analysis showed that patients in surge ICUs, i.e., temporarily created ICUs for COVID-19 patients during the pandemic, more commonly received EM (53.9% vs. 39.8%; p = 0.03) and reached higher maximum IMS (4 vs. 3; p = 0.03) without difference in mobilisation frequency (0.5 vs. 0.3; p = 0.32) or time to ASP (HR 1.15; 95% CI: 0.85, 1.56; p = 0.36). CONCLUSION: COVID-19 did not hinder mobilisation. Those treated in surge ICUs were more likely to receive EM and reached higher mobilisation levels.

Effect of biofeedback and deep oscillation on Raynaud's phenomenon secondary to systemic sclerosis: results of a controlled prospective randomized clinical trial.

Our aim was to evaluate the effect of deep oscillation and biofeedback on Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). A prospective randomized study was performed in SSc patients receiving either deep oscillation (n = 10) or biofeedback (n = 8) thrice a week for 4 weeks, or patients were randomized into the waiting group untreated for vasculopathy (n = 10) in time of running the study interventions. Biofeedback resulted in an improvement of RP as determined by score reduction of visual analogue scale compared with patients of the control group (P < 0.05), whereas deep oscillation revealed a tendency for improvement (P = 0.055). The study underlines the beneficial role of physiotherapy for the treatment of SSc-related RP.

Depression, mood, stress, and Th1/Th2 immune balance in primary breast cancer patients undergoing classical massage therapy.

PURPOSE: Cancer patients frequently suffer from psychological comorbidities such as depression and elevated stress. Previous studies could demonstrate that cancer patients benefit from massage therapy on the physical and psychological level. This pilot study investigates the effects of massage on depression, mood, perceived stress, and the Th1/Th2 ratio in breast cancer patients. METHODS: Thirty-four breast cancer patients were randomly assigned to a massage group (n=17) and a control group (n=17). Patients of the massage group received two 30-min classical massages per week for 5 weeks. At baseline, at the end of the intervention period, and 6 weeks after the end of intervention, patients of both groups completed the Perceived Stress Questionnaire (PSQ), the Patient Health Questionnaire (PHQ), and the Berlin Mood Questionnaire (BFS) and blood was withdrawn for determining cytokine concentrations and the Th1/Th2 ratio. RESULTS: Twenty-nine patients were included in the statistical analysis. Depression (PHQ) and anxious depression (BSF) were significantly reduced immediately after massage compared to the control group. Stress (PSQ) and elevated mood (BSF) did not show significant alterations after massage therapy. Changes of cytokine concentrations and Th1/Th2 ratio were insignificant as well, although there was a slight shift towards Th1 in the massage group over time. CONCLUSIONS: Massage therapy is an efficient treatment for reducing depression in breast cancer patients. Insignificant results concerning immunological parameters, stress, and mood indicate that further research is needed to determine psychological and immunological changes under massage therapy.

Effect of baby swimming and baby lotion on the skin barrier of infants aged 3-6 months.

BACKGROUND: Skin care is important especially in infancy as the skin barrier matures during the first year of life. We studied the effects of baby swimming and baby lotion on the skin barrier function of infants. SUBJECTS AND METHODS: 44 infants aged 3-6 months were included in this mono-center prospective study. The healthy infants swam four times and were randomized to group(L) : baby lotion was applied after swimming all over the body and to group(WL) : no lotion was used. Transepidermal water loss, stratum corneum hydration, skin-pH and sebum were measured on four body regions using non-invasive methods. RESULTS: In group(L), sebum and pH remained stable. In group(WL), significant decrease in sebum was noted on forehead and thigh, and for pH on thigh and buttock. Group(L) had fewer infants with at least one adverse event compared to group(WL). Location-dependent gender differences in skin barrier function were observed. CONCLUSIONS: Reaction of skin barrier function to baby swimming and skin care regimens showed typical regional variability between body areas. Influence of baby lotion on skin barrier and gender differences in skin functional parameters were demonstrated for the first time in healthy infants participating in baby swimming.

Factors Predicting Limb Volume Reduction Using Compression Bandaging Within Decongestive Lymphatic Therapy in Lymphedema: A Multicountry Prospective Study.

Objectives: To identify predictive factors associated with limb volume reduction using different decongestive lymphatic therapy (DLT) systems in patients with lymphoedema, over a period of up to 28 days. Methods: A multicountry (Canada, France, Germany, the United Kingdom) prospective cohort study using (DLT): skin care, exercise, compression bandaging, and manual lymphatic drainage for up to 4 weeks. Reduction in limb volume comparing DLT with (1) standard multilayer bandaging with inelastic material, and with (2) multilayer bandaging with Coban2, together with the identification of factors associated with limb volume changes. Results: Out of 264 patients with upper or lower limb lymphedema, 133 used Coban2 and 131 used standard care. Following DLT, mean limb volume reduction was 941 mL using Coban2 compared with 814 mL using standard care. A difference of 127 mL was found (95% confidence interval -275 to 529 mL, p = 0.53). Of the 176 patients with leg swelling, 166 (94.3%) had a limb volume measurement after 28 days and were included in the risk factor analysis. Of these, 132 (79.5%) were female, with overall mean age of 60.1 years (standard deviation = 14.7), with secondary lymphedema in 102/163 (62.6%). Duration of lymphedema was >10 years in 75/161 (46.6%) and 99/166 (59.7%) were International Society of Lymphology late-stage II/III, indicating longstanding and/or a high frequency of patients with advanced stages of lymphedema. Ninety-one (54.8%) received Coban2 and 75 (45.2%) had standard care. Multivariable factors for a greater leg volume reduction were large initial leg volume (p < 0.001), DLT treatment duration of 4 weeks compared with 2 weeks (p = 0.01), and peripheral arterial disease (p = 0.015). Conclusion: Limb volume changes were found to be similar between groups. Lack of standardization of DLT makes interpretation of effectiveness problematic. There is an urgent need for randomized-controlled trials. Despite this, severe lymphedema with a large limb volume responded well to DLT in this study.

The efficacy of classical massage on stress perception and cortisol following primary treatment of breast cancer.

To investigate the efficacy of classical massage on stress perception and mood disturbances, 34 women diagnosed with primary breast cancer were randomized into an intervention or control group. For a period of 5 weeks, the intervention group (n = 17) received biweekly 30-min classical massages. The control group (n = 17) received no additional treatment to their routine health care. The Perceived Stress Questionnaire (PSQ) and the Berlin Mood Questionnaire (BSF) were used and the patients' blood was collected at baseline (T1), at the end of the intervention period (T2), and 6 weeks after T2 (T3). Compared with control group, women in the intervention group reported significantly lower mood disturbances, especially for anger (p = 0.048), anxious depression (p = 0.03) at T2, and tiredness at T3 (p = 0.01). No group differences were found in PSQ scales, cortisol and serotonin concentrations at T2 and T3. However, perceived stress and cortisol serum levels (p = 0.03) were significantly reduced after massage therapy (T2) compared with baseline in the intervention group. Further research is needed to validate our findings.

Massage therapy reduces physical discomfort and improves mood disturbances in women with breast cancer.

BACKGROUND. A randomized controlled trial was conducted to investigate the efficacy of classical massage treatment in reducing breast cancer-related symptoms and in improving mood disturbances. METHODS. Women diagnosed with primary breast cancer were randomized into an intervention group and a control group. For a period of 5 weeks, the intervention group received bi-weekly 30-min classical massages in the back and head-neck areas. The control group received no additional treatment to their routine healthcare. To evaluate treatment efficacy, the following validated questionnaires were administrated at baseline (T1), at the end of the intervention (T2), and at a followup at 11 weeks (T3): the Short Form-8 Health Survey, the European Organization of Research and Treatment of Cancer quality of life questionnaire breast module (EORTC QLQ-BR23), the Giessen Complaints Inventory (GBB), and the Berlin Mood Questionnaire (BSF). RESULTS. Eighty-six eligible women (mean age: 59 years) were enrolled in the study. A significantly higher reduction of physical discomfort was found in the intervention group compared with the control group at T2 (p=0.001) and at T3 (p=0.038). A decrease in fatigue was also observed. Women in the intervention group reported significantly lower mood disturbances at T2 (p<0.01) but not at T3. The effect of treatment on mood disturbances was significantly higher if a patient was treated continuously by the same masseur. CONCLUSION. Classical massage seems to be an effective adjuvant treatment for reducing physical discomfort and fatigue, and improving mood disturbances in women with early stage breast cancer.

A pilot clinical trial of the effects of coenzyme Q10 on chronic tinnitus aurium.

OBJECTIVE: To determine the short-term effects of coenzyme Q10 (CoQ10) on the antioxidative status and tinnitus expression in patients with chronic tinnitus aurium. STUDY DESIGN: A 16-week prospective nonrandomized clinical trial (n = 20). Tinnitus and Short Form-36 Questionnaires (TQ/SF-36) were evaluated together with the plasma concentrations of CoQ10, malondialdehyde, and the total antioxidant status. RESULTS: The mean plasma CoQ10 concentration rose under external CoQ10 supply and remained elevated after medication stopped without overall effects on the tinnitus score. However, in a subgroup of 7 patients with low initial plasma CoQ10 concentration and significant increase in the plasma CoQ10 level, a clear decrease in the TQ score was observed. CONCLUSION: In patients with a low plasma CoQ10 concentration, CoQ10 supply may decrease the tinnitus expression. SIGNIFICANCE: This is the first study to examine the effect of CoQ10 in chronic tinnitus aurium.

Hair and stress: A pilot study of hair and cytokine balance alteration in healthy young women under major exam stress.

Mouse models show that experimental stress mimicking prolonged life-stress exposure enhances neurogenic inflammation, induces adaptive immunity cytokine-imbalance characterized by a shift to Type 1 T-helper cell cytokines and increases apoptosis of epithelial cells. This affects hair growth in otherwise healthy animals. In this study, we investigate whether a prolonged naturalistic life-stress exposure affects cytokine balance and hair parameters in healthy humans. 33 (18 exam, 15 comparison) female medical students with comparable sociobiological status were analyzed during a stressful final examination period, at three points in time (T) 12 weeks apart. T1 was before start of the learning period, T2 between the three-day written exam and an oral examination, and T3 after a 12 week rest and recovery from the stress of the examination period. Assessments included: self-reported distress and coping strategies (Perceived Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress [TICS]), COPE), cytokines in supernatants of stimulated peripheral blood mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis). Comparison between students participating in the final medical exam at T2 and non-exam students, revealed significantly higher stress perception in exam students. Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and hair parameters changed significantly from T1 to T2 in the exam group, but not the control. However, no group differences were found for cytokine balance or hair parameters at T2. The study concludes that in humans, naturalistic stress, as perceived during participation in a major medical exam, has the potential to shift the immune response to TH1 and transiently hamper hair growth, but these changes stay within a physiological range. Findings are instructive for patients suffering from hair loss in times of high stress. Replication in larger and more diverse sample populations is required, to assess suitability of trichogram analysis as biological outcome for stress studies.

Adjustment to chronic pain in back pain patients classified according to the motivational stages of chronic pain management.

UNLABELLED: According to Prochaska's transtheoretical model, the Freiburg Questionnaire stages of chronic pain management (FQ-STAPM) were used to classify chronic back patients into 4 distinct motivational stages. The FQ-STAMP was completed by 163 chronic back pain patients. Pain chronicity was measured by the Mainz Pain Staging System; pain intensity was measured by the numeric rating scale. Healthcare system expenses were considered as number of consulted physicians, number of stays in hospital, and number of rehabilitation programs. As psychometric tests, the lower pain disability index (PDI), the Hospital Anxiety and Depression Scale (HADS), and a quality of life score (SF36) were used. Patients were in the following motivational stages: precontemplation in 30%, preparation in 19%, action in 30%, maintenance in 21%. The intensity of pain in the precontemplation stage patients was significantly higher compared to patients in the maintenance stage. A lower pain chronicity was related to a significantly higher motivation. Moreover, there was a significant increase in healthcare system expenses by the lesser motivated patients. Patients in the maintenance stage used significantly less opioids than patients in the precontemplation stage. The higher motivated patients had a significantly lower PDI, a significantly lower HADS, and a significantly higher quality of life compared to less motivated patients. PERSPECTIVE: The study indicates that the FQ-STAPM might be a useful tool to classify chronic back pain patients and to work out a strategy together with the patient relevant to the outcome of pain management among chronic back pain patients.

A model of peripherally developing hearing loss and tinnitus based on the role of hypoxia and ischemia.

The incidence of sensorineural hearing loss often caused by direct damage to the cochlear hair cells is by far more frequent and more serious than disorders affecting the external ear or the middle ear. Mechanisms that are discussed to be relevant for the genesis of tinnitus and acquired hearing impairment are hair cell loss, signal transduction disturbances in the region of the outer and inner hair cells and the spiral ganglion, impairment of cochlear blood flow, mechanical disturbance, and hypoxia and ischemia. The present model surveys the possible cellular and molecular biological causes of peripherally developing hearing loss and tinnitus. In particular, the paper discusses the roles of hypoxia and ischemia in the cochlea and in the etiology of the neurosensory types of tinnitus. Peripheral origins of hearing disturbances and tinnitus may be: (a) damage to the stereocilia and the tip links, (b) dysfunction of potassium channels or (c) modification of the glutamate release. Moreover, the hypoxia inducible factor-1 may have an important role to play as a key transcription factor in the cells' adaptation to hypoxia and ischemia. An impairment of the cochlear blood flow may be induced by the expression of target genes like nitrogen monoxide synthase and endothelin-1 resulting in tinnitus. The paper discusses consequences resulting from the present model for the medical treatment of peripherally developing tinnitus and hearing loss.