Use of novel serum markers in clinical follow-up of Sertoli-Leydig cell turnours

Background: Sertoli-Leyclig cell tumours of the ovary account for only 0.2% of malignant ovarian tumours. Two-thirds of all patients become apparent due to the tumour's hormone production. Methods: A 41-year-old patient (gravida 4, para 4) presented with dyspnoea, enlarged abdominal girth and melaena. Diagnostic imaging was suspicious for an ovarian cancer. The standard tumour marker for ovarian cancer (CA 125) was elevated to 984 U/mL. Results: Surgical exploration of the abdomen revealed a mouldering tumour of both adnexes extending to the level of the navel. Frozen sections showed an undifferentiated carcinoma of unknown origin. Radical surgery was performed. The final histological report described a malignant sex-cord stroma tumour, a Sertoli-Leydig cell tumour, emanating from both ovaries. Analysis of preoperative blood serum showed elevated levels of CYFRA 21-1 (10.4 ng/mL), neuron-specific enolase (36.2 ng/mL), oestradiol (485 pg/mL) and CA-125 (984 U/mL). Adjuvant chemotherapy and regional hyperthermia were performed due to the malignant potential and incomplete resection of the tumour. Conclusions: Undifferentiated Sertoli-Leyclig cell tumours show a poor clinical course. As only two-thirds of patients with this rare disease present with elevated hormone levels, new markers deserve further investigation to offer more specific, individualised tumour monitoring

Phase II trial of tamoxifen and goserelin in recurrent epithelial ovarian cancer

Endocrine therapy is a recognised option in the treatment of chemo-resistant ovarian cancer. We conducted a nonrandomised phase II evaluation of combination endocrine therapy with tamoxifen and goserelin in patients with advanced ovarian cancer that had recurred following chemotherapy. In total, 26 patients entered the study, of which 17 had platinum-resistant disease. The median age was 63 years and enrolled patients had received a median of three chemotherapy regimens prior to trial entry. Patients were given oral tamoxifen 20 mg twice daily on a continuous basis and subcutaneous goserelin 3.6 mg once a month until disease progression. Using the definition of endocrine response that included patients with stable disease (SD) of 6 months or greater, the overall response rate (clinical benefit rate) was 50%. This included one complete response (CR) (3.8%), two partial responses (PR) (7.7%) and 10 patients with SD (38.5%). The median progression-free interval (PFI) was 4 months (95% CI 2.4–9.6) while the median overall survival (OS) was 13.6 months (95% CI 5.5–30.6). Four patients received treatment for more than 2 years (range 1–31) and one of them is still on treatment. In none of the four patients was there any evidence of recurrent or cumulative treatment related toxicity. Treatment-limiting toxicity was not seen in any of the study population. Endocrine data demonstrated a marked suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) to less than 4% of baseline values. No consistent correlation could be established between LH/FSH suppression and tumour response. Likewise no relationship was observed between Inhibin A/B and pro-alpha C levels and tumour response. Inhibin is unlikely to be a useful surrogate marker for response in locally advanced or metastatic ovarian cancer. Combination endocrine therapy with tamoxifen and goserelin is an active regimen in platinum-resistant ovarian cancer patients. Hormonal therapy is advantageous in its relative lack of toxicity, ease of administration and tolerability, thus making it suitable for patients with heavily pretreated disease, compromised bone marrow function and other comorbid conditions that contraindicate cytotoxic therapy as well as in patients with indolent disease

Fish Allergy:Fishing for Novel Diagnostic and Therapeutic Options

Fish allergy is one of the most common food allergies. The currently recommended treatment commonly consists of avoiding all fish species. Recent literature suggests that these recommendations are overprotective for the majority of fish-allergic patients. This review summarizes recent findings and provides practical information regarding management of fish allergy in the individual patient. After precise history taking supported by additional specific IgE measurements and/or skin prick tests, fish-allergic patients can generally be categorized into the following clinical clusters: (A) poly-sensitized patients reacting to all fish species due to their sensitization to the panallergen β-parvalbumin, (B) mono-sensitized patients with selective reactions to individual fish species only, and (C) oligo-sensitized patients reacting to several specific fish. A number of allergens including parvalbumin, enolase, and aldolase can be involved. Depending on the specific cluster the patient belongs to, oral food challenges for one or more fish species can be performed with the aim to provide safe alternatives for consumption. This way, several alternative fish species can be identified for mono- and oligo-sensitized patients that can safely be consumed. Notably, even poly-sensitized patients generally tolerate fish species low in β-parvalbumin such as tuna and mackerel, particularly when processed. Taken together, allergological evaluation of patients with a documented fish allergy should be strongly considered, as it will allow the majority of patients to safely reintroduce one or more fish species

The certification of anti-myeloperoxidase immunoglobulin G in human serum ERM® - DA476/IFCC

This report describes the production and certification of ERM-DA476/IFCC, a new serum protein reference material intended for the standardisation of measurements of anti-myeloperoxidase immunoglobulin G (anti-MPO IgG) antibodies. The material was produced according to ISO Guide 34:2009. The raw material used to prepare ERM-DA476/IFCC was a plasmapheresis material containing a high concentration of anti-MPO IgG. After a thorough commutability study lyophilised serum was selected as the format for the candidate reference material. Serum processing was performed based on the procedure used for the reference material ERM-DA470k/IFCC. The plasma was converted into serum which was then delipidated. After the addition of preservatives the processed serum was diluted with plasmapheresis solution containing albumin, prior to the transfer of 1 mL aliquots to glass vials. The serum was then lyophilised and the vials closed with rubber stoppers and screw caps under nitrogen atmosphere prior to storage at -70 °C. The between unit-homogeneity was quantified and stability during dispatch and storage were assessed in accordance with ISO Guide 35:2006. The material was characterised by an inter-laboratory comparison exercise performed by laboratories of demonstrated competence and with adherence to ISO/IEC 17025 , using a purified anti-MPO IgG preparation as calibrant. This was achieved using a value transfer protocol previously used in the characterisation of ERM-DA470k/IFCC. Technically invalid results were removed. However no other outliers were eliminated on statistical grounds only. Uncertainties of the certified values were calculated in accordance to the Guide to the Expression of Uncertainty in Measurement (GUM) and include uncertainties relating to possible lack of homogeneity, instability and characterisation. The material is intended for the calibration of methods and quality control. As any reference material, it can also be used for control charts or validation studies. The CRM is available in glass vials containing the lyophilised residue of 1 g serum. The minimum amount of reconstituted sample to be used is 10 μL. The CRM was accepted as European Reference Material (ERM®) after peer evaluation by the partners of the European Reference Materials consortium

Incentive Compatible Reimbursement Schemes for Physicians

We consider physicians with fixed capacity levels. If a physician’s capacity exceeds demand, she may have an incentive to overtreat, i.e., she may provide unnecessary treatments to use up idle capacity. By contrast, with excess demand she may undertreat, i.e., she may not provide necessary treatments since other activities are financially more attractive. We first show that simple fee-for-service reimbursement schemes do not provide proper incentives. If insurers use, however, fee-for-service schemes with quantity restrictions, they solve the fraudulent physician problem

The assessment and impact of careless responding in routine outcome monitoring within mental health care

Careless responding by mental health patients on self-report assessments is rarely investigated in routine care despite the potential for serious consequences such as faulty clinical decisions. We investigated validity indices most appropriate for detecting careless responding in routine outcome monitoring (ROM) in mental health-care. First, we reviewed indices proposed in previous research for their suitability in ROM. Next, we evaluated six selected indices using data of the Brief Symptom Inventory and the Mood and Anxiety Symptom Questionnaire from 3,483 outpatients. Simulations showed that for typical ROM scales the L max  Lmax index, Mahalanobis distance, and inter-item standard deviation may be too strongly confounded with the latent trait value to compare careless responding across patients with different symptom severity. Application of two different classification methods to the validity indices did not converge in similar prevalence estimates of careless responding. Finally, results suggest that careless responding does not have a substantial biasing effect on scale-score statistics. We recommend the l p z  lzp person-fit index to screen for random careless responding in large ROM data sets. However, additional research should further investigate methods for detecting repetitive responding in typical ROM data and assess whether there are specific circumstances in which simpler validity statistics or direct screening methods perform similarly as the l p z  lzp index.Stress and Psychopatholog

Effects of two behavioral cardiac rehabilitation interventions on physical activity:A randomized controlled trial

Background: Standard cardiac rehabilitation (CR) is insufficient to help patients achieve an active lifestyle. The effects of two advanced and extended behavioral CR interventions on physical activity (PA) and sedentary behavior (SB) were assessed.Methods: In total, 731 patients with ACS were randomized to 1) 3 months of standard CR (CR-only); 2) 3 months of standard CR with three pedometer-based, face-to-face PA group counseling sessions followed by 9 months of after care with three general lifestyle, face-to-face group counseling sessions (CR+F); or 3) 3 months of standard CR, followed by 9 months of aftercare with five to six general lifestyle, telephonic counseling sessions (CR + T). An accelerometer recorded PA and SB at randomization, 3 months, 12 months, and 18 months.Results: The CR+ F group did not improve their moderate-to-vigorous intensity PA (MVPA) or SB time compared to CR-only (between-group difference= 0.24% MVPA, P= 0.349; and 0.39% SB, P= 0.529). However, step count (between-group difference = 513 steps/day, P = 0.021) and time in prolonged MVPA (OR = 2.14, P= 0.054) improved at 3 months as compared to CR-only. The improvement in prolonged MVPA was maintained at 18 months (OR = 1.91, P = 0.033). The CR + T group did not improve PA or SB compared to CR-only.Conclusions: Adding three pedometer-based, face-to-face group PA counseling sessions to standard CR increased daily step count and time in prolonged MVPA. The latter persisted at 18 months. A telephonic after-care program did not improve PA or SB. Although after-care should be optimized to improve long-term adherence, face-to-face group counseling with objective PA feedback should be added to standard CR. (C) 2017 Elsevier B.V. All rights reserved

Unraveling the interplay between daily life fatigue and physical activity after subarachnoid hemorrhage: an ecological momentary assessment and accelerometry study

Background Fatigue is one of the most commonly reported symptoms after subarachnoid hemorrhage (SAH) and is indirectly associated with physical activity (PA). Associations between fatigue and PA are primarily examined based on conventional measures (i.e. a single fatigue score or average PA levels), thereby assuming that fatigue and PA do not fluctuate over time. However, levels of fatigue and PA may not be stable and may interrelate dynamically in daily life. Insight in direct relationships between fatigue and PA in daily life, could add to the development of personalized rehabilitation strategies. Therefore we aimed to examine bidirectional relationships between momentary fatigue and PA in people with SAH. Methods People (n = 38) with SAH who suffer from chronic fatigue were included in an observational study using Ecological Momentary Assessment (EMA) and accelerometry. Momentary fatigue was assessed on a scale from 1 to 7 (no to extreme fatigue), assessed with 10–11 prompts per day for 7 consecutive days using EMA with a mobile phone. PA was continuously measured during this 7-day period with a thigh-worn Activ8 accelerometer and expressed as total minutes of standing, walking, running and cycling in a period of 45 min before and after a momentary fatigue prompt. Multilevel mixed model analyses including random effects were conducted. Results Mean age was 53.2 years (SD = 13.4), 58% female, and mean time post SAH onset was 9.5 months (SD = 2.1). Multilevel analyses with only time effects to predict fatigue and PA revealed that fatigue significantly (p < 0.001) increased over the day and PA significantly (p < 0.001) decreased. In addition, more PA was significantly associated with higher subsequent fatigue (β = 0.004, p < 0.05) and higher fatigue was significantly associated with less subsequent PA (β=-0.736, p < 0.05). Moreover, these associations significantly differed between participants (p < 0.001). Conclusions By combining EMA measures of fatigue with accelerometer-based PA we found that fatigue and PA are bidirectionally associated. In addition, these associations differ among participants. Given these different bidirectional associations, rehabilitation aimed at reducing fatigue should comprise personalized strategies to improve both fatigue and PA simultaneously, for example by combining exercise therapy with cognitive behavioral and/or energy management therapy

Physical Activity and Sedentary Behavior From Discharge to 1 Year After Inpatient Rehabilitation in Ambulatory People With Spinal Cord Injury:A Longitudinal Cohort Study

Objective: To evaluate changes in duration of physical activity (PA) and sedentary behavior (SB) from discharge to 1 year after inpatient rehabilitation in ambulatory people with spinal cord injury (SCI). Design: Longitudinal cohort study with objective measurements of physical behavior at discharge and at 6 and 12 months post discharge. Setting: Three rehabilitation centers and the participant's home environment. Participants: Participants (N= 47) with ambulatory function were consecutively recruited from the self-management and self-efficacy in patients with SCI cohort (age 18 years or older, recent SCI, expected inpatient stay >4wk). Mean age was 54.5 +/- 12.9 years, all had incomplete lesions, 53% were men, 49% had tetraplegia, and 51% were community ambulators at discharge. Interventions: Not applicable. Main Outcome Measures: Duration (min) of PA (summed duration of walking, cycling, running, and wheeling) and SB (sitting/lying). Results: Mean duration of PA increased by 21 min/d (95% confidence interval, 7-35) and SB decreased by 64 min/d (95% confidence interval, -94 to -35) from discharge to 6 months after inpatient rehabilitation. No changes were found in the second half-year. One year after discharge mean PA was 116 +/- 59 min/d and mean SB was 665 +/- 121 min/d. The increase in PA was the result of an almost doubling of time spent walking. Variability in physical behavior and its change was large. Older age and lower ambulation level were associated with lower PA, lower ambulation level with higher SB, and tetraplegia was associated with a reduced increase in PA. Conclusions: At group level, duration of PA and SB improved following inpatient rehabilitation in ambulatory people with SCI. However, there were large differences between individuals. Levels 1 year after discharge were still unfavorable, particularly regarding SB. (C) 2020 by the American Congress of Rehabilitation Medicin