4-week Break Research Articles

The influence of whole-body cryotherapy or winter swimming on the lipid profile and selected adipokines

PurposeThe aim of this study was to investigate the effect of a series of 20 whole-body cryotherapy (WBC) sessions and 20 winter swimming sessions on the lipid profile and selected adipokines.Materials/methodsThe experimental group consisted of 30 people who underwent a series of WBC treatments and 30 people who underwent a winter swimming. The control group consisted of 30 people - without intervention. Study 1: on the day of the commencement of whole-body cryotherapy / at the beginning of the winter swimming season; and Study 2: after a series of 20 cryotherapy sessions / at the end of the winter swimming season. The control group was also tested twice (4-week break). There were 20 WBC treatments − 5 times a week (4 weeks) and 20 cold water baths - once a week (20 weeks).ResultsA statistically significant increase in the concentration of adiponectin, resistin and leptin in women and resistin and leptin in men was observed after the winter swimming season. Differences were also found in the second study between the groups of women using WBC and the control group, as well as the groups of women swimming and the control group. In men, however, these differences were observed in WBC and the control group. The significance level of α = 0.05 was adopted in the analyzes.ConclusionsThe use of WBC may changes in the lipid profile and selected adipokines in men. Regular winter swimming may changes of selected adipokines in both women and men.

Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas

High-grade gliomas (HGGs) constitute the most common and aggressive primary brain tumor, with 5-year survival rates of 30.9% for grade 3 gliomas and 6.6% for grade 4 gliomas. The add-on efficacy of interferon alfa is unclear for the treatment of HGG. To compare the therapeutic efficacy and toxic effects of the combination of temozolomide and interferon alfa and temozolomide alone in patients with newly diagnosed HGG. This multicenter, randomized, phase 3 clinical trial enrolled 199 patients with newly diagnosed HGG from May 1, 2012, to March 30, 2016, at 15 Chinese medical centers. Follow-up was completed July 31, 2021, and data were analyzed from September 13 to November 24, 2021. Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed HGG and had received no prior chemotherapy, radiotherapy, or immunotherapy for their HGG. All patients received standard radiotherapy concurrent with temozolomide. After a 4-week break, patients in the temozolomide with interferon alfa group received standard temozolomide combined with interferon alfa every 28 days. Patients in the temozolomide group received standard temozolomide. The primary end point was 2-year overall survival (OS). Secondary end points were 2-year progression-free survival (PFS) and treatment tolerability. A total of 199 patients with HGG were enrolled, with a median follow-up time of 66.0 (95% CI, 59.1-72.9) months. Seventy-nine patients (39.7%) were women and 120 (60.3%) were men, with ages ranging from 18 to 75 years and a median age of 46.9 (95% CI, 45.3-48.7) years. The median OS of patients in the temozolomide plus interferon alfa group (26.7 [95% CI, 21.6-31.7] months) was significantly longer than that in the standard group (18.8 [95% CI, 16.9-20.7] months; hazard ratio [HR], 0.64 [95% CI, 0.47-0.88]; P = .005). Temozolomide plus interferon alfa also significantly improved median OS in patients with O6-methylguanine-DNA methyltransferase (MGMT) unmethylation (24.7 [95% CI, 20.5-28.8] months) compared with temozolomide (17.4 [95% CI, 14.1-20.7] months; HR, 0.57 [95% CI, 0.37-0.87]; P = .008). Seizure and influenzalike symptoms were more common in the temozolomide plus interferon alfa group, with 2 of 100 (2.0%) and 5 of 100 (5.0%) patients with grades 1 and 2 toxic effects, respectively (P = .02). Finally, results suggested that methylation level at the IFNAR1/2 promoter was a marker of sensitivity to temozolomide plus interferon alfa. Compared with the standard regimen, temozolomide plus interferon alfa treatment could prolong the survival time of patients with HGG, especially the MGMT promoter unmethylation variant, and the toxic effects remained tolerable. ClinicalTrials.gov Identifier: NCT01765088.

CTNI-33. CSNO2012001 STUDY: A PHASE III TRIAL ON ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY WITH OR WITHOUT INTERFERON-ALPHA IN NEWLY DIAGNOSED HIGH-GRADE GLIOMAS

Abstract Purpose The therapeutic efficacy and toxicity of the combination of temozolomide (TMZ) with interferon-alpha (IFN-α) and TMZ alone were compared in newly diagnosed high-grade glioma (HGG) patients.Patients and Methods Following surgery, patients with newly diagnosed HGG (World Health Organization [WHO] grade 3 or 4)were eligible and randomized into two groups. All the patients were received standard radiotherapy concurrent with TMZ. After a 4-week break,patients in group A received standard TMZ (200mg/m2 for 5 days) combined with interferon-α (3mIU, subcutaneous, d1, d3, and d5) every 28 days. Patients in group B were received standard TMZ.Results A total of 199 HGG patients were enrolled, with a median follow-up time of 77.9 months. The median overall survival (OS) of patients in the TMZ+IFN group was significantly longer than that in the standard group, although the progression-free survival (PFS) of both groups was similar . In grade 3 gliomas, the median OS was 39.57 months in the TMZ+IFN group versus 29.40 months in TMZ alone. The median PFS was also longer in the TMZ+IFN group (24.33 months) than that in the TMZ group (14.13 months) . In grade 4 gliomas, the difference in PFS survival between TMZ+IFN and TMZ group showed no significant difference . However, the TMZ+IFN group had a longer OS than that of the TMZ alone group. TMZ+IFN also significantly improved the OS in O6-methylguanine-DNA methyltransferase (MGMT) unmethylation patients. The incidence of toxic effects such as neutropenia, thrombocytopenia, anemia, increased transaminase, skin reactions, fatigue, nausea, or vomiting, and skin reactions were similar in both groups. However, seizure and influenza-like symptoms were more common in the combination group but can be easily controllable.Conclusions Compared with the standard regimen, TMZ+IFN combination treatment could prolong the survival time of HGG patients, especially MGMT promoter unmethylated patients, and the toxicity remained tolerable.

SYST-10 CSNO2012001 STUDY: A PHASE III TRIAL ON ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY WITH OR WITHOUT INTERFERON-ALPHA IN NEWLY DIAGNOSED HIGH-GRADE GLIOMAS

PURPOSEThe therapeutic efficacy and toxicity of the combination of temozolomide (TMZ) with interferon-alpha (IFN-α) and TMZ alone were compared in newly diagnosed high-grade glioma (HGG) patients. PATIENTS AND METHODSFollowing surgery, patients with newly diagnosed HGG were eligible and randomized into two groups. All the patients received standard radiotherapy concurrent with TMZ. After a 4-week break, patients in group A received standard TMZ (200mg/m2 for 5 days) combined with interferon-α (3mIU, subcutaneous, d1, d3, and d5) every 28 days. Patients in group B received standard TMZ. RESULTSA total of 199 HGG patients were enrolled, with a median follow-up time of 77.9 months. The median overall survival (OS) of patients in the TMZ+IFN group was significantly longer than that in the standard group (TMZ+IFN: 26.67 months, TMZ: 18.83 months, P=0.005), although the progression-free survival (PFS) of both groups was similar (TMZ+IFN:14.83 months, TMZ:12.90months, P=0.114). In grade 3 gliomas, the median OS was 39.57 months in the TMZ+IFN group versus 29.40 months in TMZ alone (P=0.043). The median PFS was also longer in the TMZ+IFN group (24.33 months) than that in the TMZ group (14.13 months) (P=0.046). In grade 4 gliomas, the difference in PFS survival between TMZ+IFN and TMZ group showed no significant difference (TMZ+IFN:12.00 months, TMZ:12.83 months, P=0.582). However, the TMZ+IFN group had a longer OS than that of the TMZ alone group (TMZ+IFN:20.53 months, TMZ:17.70 months, P=0.044). TMZ+IFN also significantly improved the OS in O6-methylguanine-DNA methyltransferase (MGMT) unmethylation patients. The incidence of toxic effects such as neutropenia, thrombocytopenia, anemia, increased transaminase, skin reactions, fatigue, nausea, or vomiting, and skin reactions were similar in both groups. CONCLUSIONSCompared with the standard regimen, TMZ+IFN combination treatment could prolong the survival time of HGG patients, especially MGMT promoter unmethylated patients, and the toxicity remained tolerable.

Effect of Smartphone App–Based Education on Clinician Prescribing Habits in a Learning Health Care System

Effective methods for engaging clinicians in continuing education for learning-based practice improvement remain unknown. To determine whether a smartphone-based app using spaced education with retrieval practice is an effective method to increase evidence-based practice. A prospective, unblinded, single-center, crossover randomized clinical trial was conducted at a single academic medical center from January 6 to April 24, 2020. Vanderbilt University Medical Center clinicians prescribing intravenous fluids were invited to participate in this study. All clinicians received two 4-week education modules: 1 on prescribing intravenous fluids and 1 on prescribing opioid and nonopioid medications (counterbalancing measure), over a 12-week period. The order of delivery was randomized 1:1 such that 1 group received the fluid management module first, followed by the pain management module after a 4-week break, and the other group received the pain management module first, followed by the fluid management module after a 4-week break. The primary outcome was evidence-based clinician prescribing behavior concerning intravenous fluids in the inpatient setting and pain medication prescribing on discharge from the hospital. A total of 354 participants were enrolled and randomized, with 177 in group 1 (fluid then pain management education) and 177 in group 2 (pain management then fluid education). During the overall study period, 16 868 questions were sent to 349 learners, with 11 783 (70.0%) being opened: 10 885 (92.4%) of those opened were answered and 7175 (65.9%) of those answered were answered correctly. The differences between groups changed significantly over time, indicated by the significant interaction between educational intervention and time (P = .002). Briefly, at baseline evidence-concordant IV fluid ordered 7.2% less frequently in group 1 than group 2 (95% CI, -19.2% to 4.9%). This was reversed after training at 4% higher (95% CI, -8.2% to 16.0%) in group 1 than group 2, a more than doubling in the odds of evidence-concordant ordering (OR, 2.56, 95% CI, 0.80-8.21). Postintervention, all gains had been reversed with less frequent ordering in group 1 than group 2 (-9.5%, 95% CI, -21.6% to 2.7%). There was no measurable change in opioid prescribing behaviors at any time point. In this randomized clinical trial, use of smartphone app learning modules resulted in statistically significant short-term improvement in some prescribing behaviors. However, this effect was not sustained over the long-term. Additional research is needed to understand how to sustain improvements in care delivery as a result of continuous professional development at the institutional level. ClinicalTrials.gov Identifier: NCT03771482.

Development of a Web-Based, Guided Self-help, Acceptance and Commitment Therapy-Based Intervention for Weight Loss Maintenance: Evidence-, Theory-, and Person-Based Approach.

BackgroundThe long-term impact and cost-effectiveness of weight management programs depend on posttreatment weight maintenance. There is growing evidence that interventions based on third-wave cognitive behavioral therapy, particularly acceptance and commitment therapy (ACT), could improve long-term weight management; however, these interventions are typically delivered face-to-face by psychologists, which limits the scalability of these types of intervention.ObjectiveThe aim of this study is to use an evidence-, theory-, and person-based approach to develop an ACT-based intervention for weight loss maintenance that uses digital technology and nonspecialist guidance to minimize the resources needed for delivery at scale.MethodsIntervention development was guided by the Medical Research Council framework for the development of complex interventions in health care, Intervention Mapping Protocol, and a person-based approach for enhancing the acceptability and feasibility of interventions. Work was conducted in two phases: phase 1 consisted of collating and analyzing existing and new primary evidence and phase 2 consisted of theoretical modeling and intervention development. Phase 1 included a synthesis of existing evidence on weight loss maintenance from previous research, a systematic review and network meta-analysis of third-wave cognitive behavioral therapy interventions for weight management, a qualitative interview study of experiences of weight loss maintenance, and the modeling of a justifiable cost for a weight loss maintenance program. Phase 2 included the iterative development of guiding principles, a logic model, and the intervention design and content. Target user and stakeholder panels were established to inform each phase of development, and user testing of successive iterations of the prototype intervention was conducted.ResultsThis process resulted in a guided self-help ACT-based intervention called SWiM (Supporting Weight Management). SWiM is a 4-month program consisting of weekly web-based sessions for 13 consecutive weeks followed by a 4-week break for participants to reflect and practice their new skills and a final session at week 18. Each session consists of psychoeducational content, reflective exercises, and behavioral experiments. SWiM includes specific sessions on key determinants of weight loss maintenance, including developing skills to manage high-risk situations for lapses, creating new helpful habits, breaking old unhelpful habits, and learning to manage interpersonal relationships and their impact on weight management. A trained, nonspecialist coach provides guidance for the participants through the program with 4 scheduled 30-minute telephone calls and 3 further optional calls.ConclusionsThis comprehensive approach facilitated the development of an intervention that is based on scientific theory and evidence for supporting people with weight loss maintenance and is grounded in the experiences of the target users and the context in which it is intended to be delivered. The intervention will be refined based on the findings of a planned pilot randomized controlled trial.

CTIM-25. A RANDOMIZED PHASE 3 STUDY OF NIVOLUMAB OR PLACEBO COMBINED WITH RADIOTHERAPY PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA WITH METHYLATED MGMT PROMOTER: CHECKMATE 548

Abstract BACKGROUND Novel therapies are needed in newly diagnosed glioblastoma as nearly all patients experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ), including patients with tumors with methylated MGMT promoter, a positive prognostic factor and predictor of benefit with TMZ. Here, we report the final analysis of progression-free survival (PFS), overall survival (OS), and safety from an international randomized, single-blind phase-3 study of nivolumab (NIVO)+RT+TMZ in patients with newly diagnosed glioblastoma with methylated/indeterminate MGMT promoter (CheckMate 548; NCT02667587). METHODS Patients (N=716) aged ≥ 18y were randomized 1:1 regardless of tumor PD-L1 expression to NIVO (240 mg Q2W×8, then 480 mg Q4W) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 QD during RT, then 4-week break, then 150–200 mg/m2 QD on days 1–5 of every 28-day cycle for 6 cycles) or placebo (PBO)+RT+TMZ. The dual-primary endpoints were PFS by blinded independent central review and OS, both overall and without baseline corticosteroids. RESULTS As of December 22, 2020, median PFS was 10.6 months (95% CI, 8.9–11.8) with NIVO+RT+TMZ and 10.3 months (95% CI, 9.7–12.5) with PBO+RT+TMZ (HR, 1.06 [95% CI, 0.90–1.25]). Median OS was 28.9 months (95% CI, 24.4–31.6) with NIVO+RT+TMZ and 32.1 months (95% CI, 29.4–33.8) with PBO+RT+TMZ (HR, 1.10 [95% CI, 0.91–1.33]). Among patients without baseline corticosteroids, median OS was 31.3 months (95% CI, 28.6–34.8) with NIVO+RT+TMZ and 33.0 months (95% CI, 31.0–35.1) with PBO+RT+TMZ (HR, 1.12 [95% CI, 0.87–1.43]). Grade 3–4 treatment-related adverse events were 52.4% and 33.6% with NIVO+RT+TMZ and PBO+RT+TMZ, respectively. CONCLUSIONS NIVO added to RT+TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated/indeterminate MGMT promoter. No new safety signals were observed with NIVO. The role of immunotherapy in this treatment landscape remains an area for further investigation.

Follicular extension of atypical keratinocytes predicts the resistance of actinic keratosis to topical imiquimod treatment: A single-center retrospective analysis.

Topical imiquimod therapy has been widely used for actinic keratosis (AK). However, some cases are refractory to treatment. Therefore, an indicator that can predict its efficacy is desired. Herein, we retrospectively analyzed 52 AK lesions treated with imiquimod to investigate the characteristics of refractory lesions. Imiquimod was applied in a cycle of three times weekly for 4weeks, followed by a 4-week break. This treatment cycle was repeated up to three times and treatment responses were evaluated. As a result, a complete response (CR) was observed in 78.8% (41/52) of lesions. Next, treatment response of lesions was correlated with clinicopathological characteristics including clinical morphology and thickness, pathological morphology and thickness, and presence of follicular extension (FE). Of these, lesions with FE were significantly less responsive to imiquimod treatment; while 92.6% of AK lesions without FE achieved a CR, only 64.0% of AK lesions with FE achieved a CR (p=0.029). Logistic regression analysis revealed that FE was the sole significant predictor of its efficacy (p=0.019). These results suggest that preliminary histological evaluation of FE may be useful to predict the efficacy of imiquimod for AK.

P2 3-year observation study of Plerixafor use in New Zealand

IntroductionPlerixafor, a novel CXCR4 pathway antagonist, is used to mobilise CD34-positive stem cells for autologous stem cell transplantation to treat haematological malignancy. Data regarding the rates of failure to mobilise and frequency of use of Plerixafor vary widely.MethodsThis retrospective study reviewed 203 consecutive patients with myeloma (n = 122) or lymphoma (n = 81) undergoing peripheral blood stem cell mobilisation between 1/1/2016 and 5/8/2019 at a New Zealand hospital using data from an institution transplant database and the electronic medical record.Patients with myeloma were mobilised using cyclophosphamide and G-CSF after induction chemotherapy with cyclophosphamide, bortezomib and dexamethasone. Patients with lymphoma were mobilised with G-CSF after induction or salvage chemotherapy according to disease type.Patients failing to mobilise sufficient stem cells either received “pre-emptive” Plerixafor added to G-CSF +/- chemotherapy during the 1st attempt or were re-mobilised after a 4-week break with Plerixafor and G-CSF alone.ResultsThe success rate of mobilisation for lymphoma and myeloma patients at first attempt was 79% and 87% respectively. Plerixafor allowed successful harvest for 5 of 7 lymphoma patients and 8 of 9 myeloma patients who failed to harvest at first attempt, resulting in 88% and 94% of all patients having a successful harvest on either first or second attempt, respectively. Age greater than 60 years was a risk factor for failed mobilisation in lymphoma patients.ConclusionThis study shows that an approach using pre-emptive and rescue Plerixafor is effective and allows haematopoietic stem cell mobilisation for ≥88% of patients. Further research is required to establish the optimal strategy for its use.

CTNI-43. ANLOTINIB COMBINED WITH STUPP REGIMEN IN TREATING PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME: A PHASE II PILOT STUDY

Abstract PURPOSE Anlotinib, an orally multi-target tyrosine kinase inhibitor, inhibits tumor angiogenic and proliferative signal pathways. We performed a phase II trial of anlotinib in combination with the STUPP regimen in patients with newly diagnosed glioblastoma multiforme（GBM）to determine whether the combination therapy would safely improve outcomes in this group of patients. An initial pilot study assessed interim safety and tolerability. METHODS AND MATERIALS Ten newly diagnosed GBM patients were included in this study. All patients received standard radiation of 60 Gy in 30 fractions starting within 4–6 weeks after surgery with concurrent TMZ (daily, 75 mg/m2) and anlotinib (8mg per day, from day 1 to 14, every 3 weeks). After a 4-week break, adjuvant therapy including 6 cycles of TMZ (150–200 mg/m², from day 1 to 5, every 4 weeks) and 8 cycles of anlotinib (8mg per day, from day 1 to 14, every 3 weeks) was given. For patients completing adjuvant therapy, anlotinib alone (8mg per day, from day 1 to 14, every 3 weeks) was administrated until disease progression. RESULTS All patients completed concurrent chemo-radiotherapy without interruption. One patient developed grade 3 weight loss at 56th week and grade 3 presumed radiation-induced cognitive disturbance at 60th week. Fatigue and hypertension were frequently observed during treatment, which potentially be related to the treatment. No severe toxicity was observed in other patients. Up to this writing, none of these patients developed disease progression. CONCLUSION Anlotinib combined with the STUPP regimen is a potential choice for newly diagnosed GBM patients. It is well tolerated and the toxicity is manageable. It’s acceptable to continue enrolling of this Phase II study.

CTIM-20. PHASE I STUDY OF IBRUTINIB WITH RADIATION AND TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma is a devastating disease that is notoriously resistant to current therapies, leading to dismal patient outcomes and a median survival of just 14.6 months. A major problem in glioblastoma treatment is the inability to effectively target the cell population that gives rise to recurrence. These cells, known as glioma stem cells (GSCs) or tumor propagating cells are endowed with a large capacity for self-renewal to propagate the tumor. GSCs are resistant to radiation. Ibrutinib is a first-in-class, potent, orally administered, covalently binding Inhibitor of Bruton’s Tyrosine Kinase (BTK). Ibrutinib is a small-molecule tyrosine kinase. It also inhibits BMX. Bone marrow X-linked (BMX) nonreceptor tyrosine kinase activates STAT3 signaling to maintain self-renewal and tumorigenic potential of GSCs. Hence a combination of ibrutinib with radiation and or temozolomide in patients with newly diagnosed Glioblastoma is warranted. METHODS This is a two arm study. Arm 1 is for patients with unmethylated MGMT Glioblastoma. Every patient gets ibrutinib and 60 Gy radiation over 6 weeks. Patients will undergo a 4-week break and Ibrutinib treatment will then continue until disease progression, intolerable toxicity or death. Arm 2 is for patients with MGMT methylated glioblastoma. Every patient will receive Ibrutinib and 60 Gy radiation and daily Temozolomide at 75 mg/m2 for 6 weeks. Patients will undergo a 4-week break then receive daily ibrutinib and adjuvant Temozolomide. The temozolomide will continue until disease progression, intolerable toxicity or death or maximum of 6 cycles. Ibrutinib treatment will continue until disease progression, intolerable toxicity or death. RESULTS The maximum tolerated dose (MTD) of Ibrutinib with radiation (2 Gy x 30) in patients in each arm will be reported. The safety of Ibrutinib with radiation and with radiation and temozolomide will be reported. The Progression free survival and overall survival in each arm will be reported. CONCLUSION This is an ongoing clinical trial. Results will be reported once study is complete.

Performance Enhancing And Pro Regenerative Effects Of Alpha Lipoic Acid Supplementation After Acute And Chronic Resistance And Endurance Training.

PURPOSE: Oxidative stress is an important key player in the initiation of training induced adaptations but also a risk factor with respect to over training and lack of regeneration. Alpha lipoic acid (ALA) has been described to be a powerful antioxidant. Therefore it was the aim of this study to investigate the effects of acute and chronic ALA supplementation on the regeneration and performance of athletes after intensive exercise. METHODS: In this double-blinded, randomised, controlled trial in cross-over design, 17 male resistance and endurance-experienced athletes successfully participated. The subjects were divided into two groups (ALA and Placebo) and underwent a standardized acute (3sets back squats of 12 reps each and 3 sets of low jumps with 15 reps each) and chronic training protocol (6 days of intensive resistance and endurance training). Between the acute and chronic training experiments was a 4-week break. At certain time points before and after exercise (T0, T1 (+24h) and T2 (+7d)) blood samples were taken and the concentrations of muscle damage (creatine kinase, myoglobin), inflammation (interleukin 6 and 10) and oxidative stress (ox LDL) markers were investigated. In addition, the maximum performance in the back squat was measured at all timepoints. RESULTS: In the 6 day chronic training intervention a clear inhibition of muscle damage and inflammation could be observed in individuals under chronic supplementation of ALA compared to the control group. Whereas performance in the back squat was significantly reduced after 6 day of chronic training in the placebo group no significant loss of performance could be detected in the ALA group. In contrast after an acute training a single application of ALA did not result in significant differences between the placebo and ALA groups with respect to all before mentioned markers and back squat performance CONCLUSIONS: Based on these data we conclude that that ALA supplementation has only limited effects if given acute and directly after exercise but results in remarkably and significant pro-regenerative and performance enhancing effects after chronic supplementation. Mechanistically these effects seem to be mediated via a modulation of the immune response and less by antioxidative effects, which needs to be investigated in more detail in future investigations.

Personality, plasticity and predictability in sticklebacks: bold fish are less plastic and more predictable than shy fish

It is well established that animals often differ consistently from one another in their behaviour. Most work has focused on consistent differences in average behaviour, generally referred to as ‘animal personality’. However, individuals may also differ consistently from one another in how they change their behaviour over time or across environments, that is, plasticity, as well as in the predictability of their behaviour. How these three sources of behavioural variation are linked is rarely explored. Here we tested 80 wild-caught three-spined sticklebacks, Gasterosteus aculeatus, repeatedly over a 10-week period for their tendency to explore an open arena from the safety of cover, generally termed ‘boldness’. Using a mixed-modelling approach, we detected consistent individual differences in boldness, as well as in the extent to which fish changed this behaviour over time, that is, temporal plasticity. Boldness and plasticity were negatively correlated, with shy fish spending increasing amounts of time out of cover while bold fish changed little over time. After accounting for variation in personality and plasticity, we still detected individual differences in intraindividual behavioural variation (‘IIV’), that is, individual predictability. This residual variation was linked to fish’ boldness score, with shy fish having higher IIV and thus being less predictable in their behaviour than bold fish. After a 4-week break from testing, individuals on average decreased their time out of cover again to baseline levels. However, shyer, more plastic fish showed the largest changes in behaviour. Statistical simulations show that our experimental data set has sufficient statistical power to provide accurate and precise variance parameter estimates. Together, our results provide strong evidence that individual variation in boldness is linked with behavioural plasticity and predictability. Establishing the evolutionary causes as well as fitness consequences of these links in behavioural variation is an exciting challenge for future research.

The Effects of a Nurse-Led Education and Counseling Program on Dyspnea, Health Status, and Care Dependency in Patients With Chronic Obstructive Pulmonary Disease: A Feasibility Study

The aim of this feasibility study was to determine the effects of a nurse-led education and counseling program for chronic obstructive pulmonary disease (COPD-ECP) on dyspnea, health status, and care dependency in patients. A quasi-experimental, pre-posttest research design without a control group was performed on 30 COPD patients. The patients received an 8-week COPD-ECP via home visits during the first 4 weeks and via phone interviews in the subsequent 4 weeks. After completion of COPD-ECP and a 4-week break, a final follow-up was conducted at the end of 12th week. The Dyspnea-12, COPD Assessment Test (CAT), and Care Dependency Scale (CDS) scores were calculated during the first interview, and on the 4th, 8th, and 12th week of the study. The patients completed all sessions of COPD-ECP without side effects. There was a significant decrease in the total Dyspnea-12 scores at the end of the study period. Compared to the baseline assessment, CAT total scores significantly decreased in the 4th, 8th, and 12th week ( p < 0.05), and CDS scores showed a significant reduction at the 12th week ( p < 0.05). In conclusion, COPD-ECP is feasible in regular clinical practice and well accepted by patients, and it seems to improve health status and decrease dyspnea, and care dependency. Future randomized controlled studies are warranted to explore the effects of COPD-ECP on fatigue, cough and sleep problems, and the best innovative strategies to improve the efficiency of COPD-ECP.

Four-Week Unstructured Break Improved Athletic Performance in Collegiate Rugby Players.

Jensen, CD, Gleason, D, and VanNess, JM. Four-week unstructured break improved athletic performance in collegiate rugby players. J Strength Cond Res 32(6): 1671-1677, 2018-This study analyzed the changes in athletic performance and anthropometric characteristics in collegiate male club rugby athletes (n = 14) after a 4-week winter break. All measurements were collected before and after the break. Body composition was assessed by body mass index and hydrostatic weighing. Performance measurements were as follows: V[Combining Dot Above]O2max, vertical jump, 10-yard sprint, squat max, and bench press max. Before testing, each subject was acclimated to the protocols to reduce learning effects. During the 4-week break, no workouts were provided for the athletes; it was unsupervised and unstructured. Participants were required to maintain and submit self-reported nutritional and activity logs during this period. After the break, the athletes demonstrated a 5.0% improvement in V[Combining Dot Above]O2max (absolute increase of 2.25 ml·kg·min), 6.8% improvement in vertical jump (1.50 inches), and a 14.3% increase in squat max (38.64 lb). Although increases in body mass (1.0%) were not significant, the body fat percentage exhibited a relative increase of 19.3% (absolute change from 13.35 to 15.93%). A significant discriminate function analysis indicated statistical differences between groups based on these variables. Self-reported behavior logs confirmed participation in >3 days of moderate to intense physical activity per week but somewhat poor dietary habits. These results indicate that collegiate rugby athletes may not need prescribed exercise routines during seasonal breaks in the athletic schedule. However, it may be beneficial to provide structured nutritional advice during unsupervised periods.

Modeling the impact of players' workload on the injury-burden of English Premier League football clubs.

The loss of players through injury is known to affect team performance in many sports; it is important, therefore, for professional teams to be able to quantify the likely injury-burden that will be encountered throughout a season. A kinetic model, based on the rates at which match and training injuries are sustained and resolved, a team's squad size and the 2017/2018 season fixture schedule for teams competing in the English Premier League, is used to produce daily forecasts of injury-burden experienced by a typical team. The incidences and median severities of match (incidence: 26.9 injuries/1000 player-match hours, 95% CI: 21.5-33.7; severity: 17.5days, 95% CI: 13.0-28.0) and training (incidence: 4.3 injuries/1000 player-training hours, 95% CI: 3.4-5.5; severity: 14.0days, 95% CI: 11.0-22.0) injuries were determined using data collected from four English Premier League football clubs during the 2016/2017 season. Time-to-recovery curves for the match and training injuries sustained in the Premier League closely matched the time-to-recovery curves predicted by the kinetic model used in this study. The kinetic model predicted higher match and lower training injury burdens and a higher overall injury burden for successful teams competing in both national and European club competitions compared to teams competing only in national competitions. The model also showed that, in terms of injury-burden, there were no benefits in adopting a 4-week mid-season break during the season: reducing the number of clubs competing in the Premier League would, however, reduce the overall injury burden during a season.

Multiple bone metastases from glioblastoma multiforme without local brain relapse: a case report and review of the literature.

Extracranial metastases from glioblastoma multiforme (GBM) are a very rare event, even if an increasing incidence has been documented. We report the case of a young woman with primary GBM who developed bone metastases without local brain relapse. Because of persistent headache and visual disturbances, in March 2011 the patient underwent magnetic resonance imaging (MRI) evidencing a temporoparietal mass, which was surgically resected. Histology revealed GBM. She was given concomitant chemoradiotherapy according to the Stupp regimen. After a 4-week break, the patient received 6 cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. In December 2011 she complained of progressive low back pain, and MRI showed multiple bone metastases from primary GBM, confirmed by histology. Cases of metastatic GBM in concurrence with a primary brain tumor or local relapse are more common in the literature; only a few cases have been reported where extracranial metastases from GBM occurred without any relapse in the brain. Here we report our experience.

Combined Cognitive-Behavioural and Physiotherapeutic Therapy for Patients with Chronic Pelvic Pain Syndrome (COMBI-CPPS): study protocol for a controlled feasibility trial

BackgroundChronic pelvic pain syndrome (CPPS) is a pain condition perceived in the pelvic area for at least 6 months. While evidence of the aetiology and maintenance of CPPS is still unclear and therapy options are rare, there is preliminary evidence for the efficacy of cognitive behavioural therapy and physiotherapy. However, an integrated treatment has not yet been studied. The primary aim of this study is therefore to test the feasibility of combined psychotherapy and physiotherapy for female and male patients with CPPS. The secondary aim is to explore changes in patient-relevant and economic outcomes compared to a control group.MethodsA feasibility study with a crossover design based on the principles of a ‘cohort multiple randomized controlled trial’ will be conducted to test a combined therapy for patients with CPPS. The study will consist of two consecutive treatment modules (cognitive behavioural group psychotherapy and physiotherapy as individual and group sessions), which will be applied in varying order. The modules will consist of nine weekly sessions with a 4-week break between the modules. The control group will undergo treatment as usual. Study subjects will be recruited from the interdisciplinary outpatient clinic for CPPS at the University Medical Center Hamburg-Eppendorf. Thirty-six patients will be assigned to the intervention, and 18 patients will be assigned to the control group. The treatment groups will be gender homogeneous. Feasibility as the primary outcome will be analysed in terms of the demand, acceptability, and practicality. Secondary study outcomes will be measured using validated self-rating-scales and physical examinations.DiscussionTo the best of our knowledge, this study is the first to investigate the feasibility of combined psychotherapy and physiotherapy for patients with CPPS. In addition to testing feasibility, the results can be used for the preliminary estimation of therapeutic effects. The results from this study will be used to generate an enhanced therapeutic approach, which might be subject to further testing in a larger study.Trial registrationGerman Clinical Trials Register, DRKS00009976. Registered on 15 March 2016.ISRCTN, ISRCTN43221600. Registered on 10 May 2016.

Effect of Linear Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction-12-Month Follow-Up of a Randomized, Double-Blinded, Sham-Controlled Study.

IntroductionShort-term data on the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on erectile dysfunction (ED) have been inconsistent. The suggested mechanisms of action of Li-ESWT on ED include stimulation of cell proliferation, tissue regeneration, and angiogenesis, which can be processes with a long generation time. Therefore, long-term data on the effect of Li-ESWT on ED are strongly warranted.AimTo assess the outcome at 6 and 12 months of linear Li-ESWT on ED from a previously published randomized, double-blinded, sham-controlled trial.MethodsSubjects with ED (N = 126) who scored lower than 25 points in the erectile function domain of the International Index of Erectile Function (IIEF-EF) were eligible for the study. They were allocated to 1 of 2 groups: 5 weekly sessions of sham treatment (group A) or linear Li-ESWT (group B). After a 4-week break, the 2 groups received active treatment once a week for 5 weeks. At baseline and 6 and 12 months, subjects were evaluated by the IIEF-EF, the Erectile Hardness Scale (EHS), and the Sexual Quality of Life in Men.Main Outcome MeasuresThe primary outcome measure was an increase of at least 5 points in the IIEF-EF (ΔIIEF-EF score). The secondary outcome measure was an increase in the EHS score to at least 3 in men with a score no higher than 2 at baseline. Data were analyzed by linear and logistic regressions.ResultsLinear regression of the ΔIIEF-EF score from baseline to 12 months included 95 patients (dropout rate = 25%). Adjusted for the IIEF-EF score at baseline, the difference between groups B and A was −1.30 (95% CI = −4.37 to 1.77, P = .4). The success rate based on the main outcome parameter (ΔIIEF-EF score ≥ 5) was 54% in group A vs 47% in group B (odds ratio = 0.67, P = .28). Improvement based on changes in the EHS score in groups A and B was 34% and 24%, respectively (odds ratio = 0.47, P = .82).ConclusionExposure to 2 cycles of linear Li-ESWT for ED is not superior to 1 cycle at 6- and 12-month follow-ups.Fojecki GL, Tiessen S, Osther PJS. Effect of Linear Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction—12-Month Follow-Up of a Randomized, Double-Blinded, Sham-Controlled Study. Sex Med 2018;6:1–7.

Effect of Low-Energy Linear Shockwave Therapy on Erectile Dysfunction—A Double-Blinded, Sham-Controlled, Randomized Clinical Trial

IntroductionPrevious studies have shown that focal low-energy extracorporeal shockwave therapy (Li-ESWT) can have a positive effect in men with erectile dysfunction (ED). Linear Li-ESWT (LLi-ESWT) for ED has not been previously assessed in a randomized trial. AimTo evaluate the treatment outcome of LLi-ESWT for ED. MethodsMen with ED (n = 126) and a score lower than 25 points on the International Index of Erectile Function erectile function domain (IIEF-EF) were included. Subjects were allocated to receive LLi-ESWT once a week for 5 weeks or sham treatment once a week for 5 weeks. After a 4-week break, the two groups received active treatment once a week for 5 weeks. Subjects completed the IIEF, Erection Hardness Scale (EHS), Sexual Quality of Life–Men, and the Erectile Dysfunction Inventory of Treatment Satisfaction at baseline, after 9 weeks, and after 18 weeks. Main Outcome MeasuresThe primary outcome measurement was an increase of at least five points on the IIEF-EF score. The secondary outcome measurement was an increased EHS score to at least 3 in men with a score no higher than 2 at baseline. Data were analyzed by linear and logistic regression. ResultsMean IIEF-EF scores were 11.5 at baseline (95% CI = 9.8–13.2), 13.0 after five sessions (95% CI = 11.0–15.0), and 12.6 after 10 sessions (95% CI = 11.0–14.2) in the sham group and correspondingly 10.9 (95% CI = 9.1–12.7), 13.1 (95% CI = 9.3–13.4), and 11.8 (95% CI = 10.1–13.4) in the ESWT group. Success rates based on IIEF-EF score were 38.3% in the sham group and 37.9% in the ESWT group (odds ratio = 0.95, 95% CI = 0.45–2.02, P = .902). Success rates based on EHS score were 6.7% in the sham group and 3.5% in the ESWT group (odds ratio = 0.44, 95% CI = 0.08–2.61, P = .369). A limitation of this study is that device settings (number of shockwaves and penetration depth) were estimated based on an existing trial on focused ESWT. ConclusionNo clinically relevant effect of LLi-ESWT on ED was found.