Age-related Differences in Recall of Information and Handling of Chemotherapy-related Side Effects in Cancer Patients: The ReCap Study.

BACKGROUND: To prevent severe toxicity and hospital admissions, adequate management and recall of information about side effects are crucial and health literacy plays an important role. If age-related factors impact recall of given information and handling of side effects, revised ways to give information are required. PATIENTS AND METHODS: We undertook a questionnaire-based survey among 188 newly diagnosed patients with pancreatic cancer or colorectal cancer and chemo-naive patients with prostate cancer treated with adjuvant or first-line palliative chemotherapy comprising satisfaction with given information, recall of potential side effects, and handling of hypothetical side effect scenarios. We evaluated the association between baseline characteristics, ie, age, frailty (G8 score), comorbidity (Charlson Comorbidity Index), cognitive function (Mini-Cog), satisfaction, recall of information, and handling of side effects. RESULTS: Reduced ability to recall information about several side effects (eg, chest pain) was associated with older age (odds ratio adjusted for cancer [aOR] 0.94 [95% CI, 0.88-0.98]) and poor cognitive screening (aOR 0.56 [95% CI, 0.33-0.91]). Insufficient or dangerous handling of side effects was associated with older age (aOR 0.96 (95% CI, 0.92-0.99)) and cognitive impairment (aOR 0.70 [95% CI, 0.50-0.95]). CONCLUSION: Older age and poor cognitive screening may impact patients' ability to understand and adequately handle chemotherapy-related side effects. Cognitive screening and focus on individual ways to give information including assessment of recall and handling are needed.

Effect of pre-operative oral paracetamol on gastric residual volume and pH in young children in the context of a 1-hour clear fluid fast: a randomised controlled trial.

High gastric residual volume and low pH are associated with increased mortality following pulmonary aspiration in animal studies. The use of pre-operative oral paracetamol has not been investigated in younger children and infants in the context of a prescriptive 1-h clear fluid fast aimed at reducing the risk of pulmonary aspiration while improving patient experience. Children aged 1 month up to a weight of 25 kg and scheduled for elective surgery were randomly allocated to receive a prescribed 3.6 ml.kg-1 drink of water alone (water group) or 3 ml.kg-1 water and oral Infant Calpol® syrup (24 mg.ml-1 concentration, equivalent volume 0.6 ml.kg-1 , paracetamol group) 1 h before the induction of anaesthesia. Following induction, a nasogastric tube was used to aspirate gastric contents and the volume and pH were recorded. Ninety-seven children, median (IQR [range]) age 24 (12-45 [1-96]) months and weight 12.4 (9.7-16.0 [2.9-27.0]) kg, were analysed. Median time from drink to induction was 54 (45-60 [21-113]) min. There was no significant difference in gastric residual volume (p = 1) or pH (p = 0.99) between the water and the paracetamol groups. Sub-group analysis revealed no significant difference in gastric residual volume or pH for 29 children who weighed < 10 kg compared with > 10 kg. Using a prescriptive fluid regime of 3 ml.kg-1 of water, the addition of oral paracetamol syrup did not significantly alter gastric residual volume or pH in the context of a 1-h fast in infants and young children.

Genomic landscape of treatment refractory metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) is a complex and heterogeneous disease with few standard and targeted treatment options. Next-generation sequencing of tumor tissue was performed to identify cancer driver mutations to discover possible personalized treatment options, as targeted treatment possibilities are limited for this patient population. Results of genomic sequencing in patients with treatment-refractory mCRC are described in this retrospective analysis. MATERIAL AND METHODS: Clinico-pathological characteristics and genomic sequence results of consecutive patients with refractory mCRC, referred to the Experimental Cancer Therapy Unit (ECTU) at Department of Oncology, Herlev & Gentofte Hospital in the period from 1 October 2015 to 14 December 2018 were reviewed in this retrospective analysis. Tumor tissue from the patients was analyzed by next-generation sequencing using the Oncomine Comprehensive primer panel to detect actionable variants of cancer driver mutations and microsatellite instability status. From August 2018 tumor mutational burden was also analyzed. RESULTS: A total of 80 patients with treatment-refractory mCRC and in a fairly good performance were referred to the ECTU during this period. Genomic sequencing of tumor tissue was performed for all 80 patients and a cancer driver mutation was identified in 90% (n = 72) of the patients. A total of 31.3% (n = 25) of the patients received therapy either as targetable therapy outside an available trial (n = 2), FDA approved therapy (n = 2), or treatment in phase 1 or 2 trials, independent of the genomic signature 26.3% (n = 21). CONCLUSION: Most mCRC patients refractory to standard anti-neoplastic therapies, presented with a cancer driver mutation, however, only a few of these mutations gave rise to matched therapies as only 2.5% of the patients from this period received targeted therapy.

Pre-clinical evaluation of the effect of co-medication with antibiotics and oral steroids in Göttingen Minipigs on the biological activity of the probiotic medicinal product TSO (Trichuris suis ova).

The probiotic medicinal product TSO (Trichuris suis ova) is administered to patients with active ulcerative colitis in an ongoing clinical phase IIb trial where the typical co-medications are steroids (prednisolone or budesonide) and antibiotics (e.g., phenoxymethylpenicillin). The present pre-clinical study evaluates the effects of these co-medications on the biological activity of TSO in Göttingen Minipigs. This translationally relevant pre-clinical model allows administration of TSO with and without oral steroids or antibiotics in a manner similar to the administration to patients, followed by quantification of the biological activity of TSO. The biological activity of TSO was not affected by oral steroids but was reduced by oral antibiotics. Fecal calprotectin, the common marker of intestinal inflammation in patients with UC, did not differ between groups.

PD-L1 diagnostics in the neoadjuvant setting: implications of intratumoral heterogeneity of PD-L1 expression in triple negative breast cancer for assessment in small biopsies.

PURPOSE: PD-L1 expression is a predictive biomarker for anti-PD-L1 immunotherapy in triple negative breast cancer (TNBC). In the neoadjuvant setting, immunohistochemical (IHC) evaluation of PD-L1 expression can only be performed on small tissue biopsies. In our study we investigated heterogeneity of PD-L1 expression in TNBC, and how reliably PD-L1 expression in small tissue samples reflects PD-L1 expression in larger tumor sections in TNBC. METHODS: Tissue microarrays (TMAs) were constructed from surgical specimens of 110 patients with TNBC. TMAs contained 4 cores (1 mm in diameter) per patient. To evaluate PD-L1 expression, TMAs were stained with PD-L1 IHC 22C3 PharmDx. Single-core PD-L1 expression was compared to overall PD-L1 expression of each patient's tumor, to ascertain how often small samples of tumor tissue show the same PD-L1 expression as larger tumor samples. RESULTS: Our study found substantial heterogeneity of PD-L1 expression between different TMA cores from the same patient. Heterogeneity was greater in immune cells (ICs) than in tumor cells, in large part due to the uneven distribution of ICs in the tumor. For IC PD-L1 expression, we found that sensitivity can be as low as 0.81 for detecting PD-L1 expression at the 1% threshold most commonly used in breast cancer. Negative predictive value for ICs was 0.7. CONCLUSIONS: There is substantial heterogeneity of PD-L1 expression between small tissue samples from the same TNBC tumor, especially for IC expression. This poses challenges for evaluation of PD-L1 expression in the neoadjuvant setting. Negative biopsies should prompt further investigation, and multiple biopsies might be necessary.

The influence of socioeconomic position on adjuvant treatment of stage III colon cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with colon cancer (CC) with low socioeconomic position (SEP) have a worse survival than patients with high SEP. We investigated the association between different socioeconomic indicators and the steps in the treatment trajectory leading to initiation of adjuvant chemotherapy (ACT) for patients with stage III CC. MATERIALS AND METHODS: A systematic review and meta-analyses were conducted in accordance with the MOOSE checklist. MEDLINE and EMBASE were searched for eligible studies. Meta-analyses were performed on the separate socioeconomic indicators with the random-effects model. The heterogeneity across studies was assessed by the Q and the I 2 statistic. RESULTS: In total, 27 observational studies were included. SEP was measured by insurance, income, poverty, employment, education, or an index on an area or individual level. SEP, regardless of indicator, was negatively associated with the steps in the treatment trajectory leading to initiation of ACT among patients with resected stage III CC. The meta-analyses showed that patients with low SEP had a significantly lower odds of receiving ACT and increased odds of delayed treatment start, whereas SEP had no impact on the choice of therapy: combination or single-agent therapy. CONCLUSION: SEP was associated with less initiation of and higher risk for delayed initiation of ACT. Our findings suggest there is a social disparity in receipt of ACT in patients with stage III CC.

Effectiveness of maternal immunization with trivalent inactivated influenza vaccine in pregnant women and their infants.

BACKGROUND: In randomized trials, it has been found that maternal influenza vaccination reduces influenza infections in both women and their infants. However, these trials have been performed in low-resource settings, and evidence from high-resource settings is limited. METHODS: Nested within a register-based cohort of all women giving birth in Denmark between 2010 and 2016 (n = 357 810 births), we conducted two case-control studies using a test-negative design of all pregnant women and their infants, respectively, tested for influenza virus with reverse transcriptase-polymerase chain reaction. Influenza virus-positive cases were matched (1:1) with influenza virus-negative controls for calendar time and (gestational or infant) age at testing. The effectiveness of maternal immunization with trivalent inactivated influenza vaccine was estimated from the odds ratios of vaccination among cases versus controls using logistic regression with adjustment for potential confounders. RESULTS: Among 313 pregnant women positive for influenza virus, 16 (5.1%) were vaccinated; by comparison, 34 (10.9%) pregnant women were vaccinated among 313 matched influenza virus-negative controls. The effectiveness of vaccination against laboratory-confirmed influenza infection in pregnant women was 63.9% [95% confidence interval (CI), 29.1 to 81.6]. Among 460 infants positive for influenza virus, 23 (5.0%) were offspring of women vaccinated during pregnancy; by comparison, 52 (11.3%) infants were the offspring of women vaccinated during pregnancy among 460 matched influenza virus-negative controls. The effectiveness of maternal vaccination against laboratory-confirmed influenza infection in infants younger than 6 months of age was 56.8% (95% CI, 25.0 to 75.1). CONCLUSIONS: Seasonal trivalent inactivated influenza vaccination in pregnancy was associated with a statistically significant reduced risk of laboratory-confirmed influenza infections in pregnant women and their infants in a high-resource setting.

Circulating cell-free DNA as predictor of treatment failure after neoadjuvant chemo-radiotherapy before surgery in patients with locally advanced rectal cancer.

Background: Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery. Patients and methods: In total, 123 patients with LARC were included in 2 biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy with capecitabine + oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after induction chemotherapy, and after CRT. Serial samples 5 years after surgery were collected in 51 patients (41%). Results: Median follow-up was 55 months. Distant or local recurrence was seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared with patients with plasma cfDNA below the 75th percentile (HR = 2.48, 95% CI: 1.3-4.8, P = 0.007). The same applied to disease-free survival (DFS) (HR = 2.43, 95% CI: 1.27-4.7, P = 0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis. Conclusion: We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC.

Quality of life in childhood, adolescence and adult food allergy: Patient and parent perspectives.

BACKGROUND: Studies of children with food allergy typically only include the mother and have not investigated the relationship between the amount of allergen needed to elicit a clinical reaction (threshold) and health-related quality of life (HRQL). Our aims were (i) to compare self-reported and parent-reported HRQL in different age groups, (ii) to evaluate the impact of severity of allergic reaction and threshold on HRQL, and (iii) to investigate factors associated with patient-reported and parent-reported HRQL. METHODS: Age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQ) were completed by 73 children, 49 adolescents and 29 adults with peanut, hazelnut or egg allergy. Parents (197 mothers, 120 fathers) assessed their child's HRQL using the FAQLQ-Parent form. Clinical data and threshold values were obtained from a hospital database. Significant factors for HRQL were investigated using univariate and multivariate regression. RESULTS: Female patients reported greater impact of food allergy on HRQL than males did. Egg and hazelnut thresholds did not affect HRQL, but lower peanut threshold was associated with worse HRQL. Both parents scored their child's HRQL better than the child's own assessment, but whereas mother-reported HRQL was significantly affected by limitations in the child's social life, father-reported HRQL was affected by limitations in the family's social life. Severity of allergic reaction did not contribute significantly to HRQL. CONCLUSION: The risk of accidental allergen ingestion and limitations in social life are associated with worse HRQL. Fathers provide a unique perspective and should have a greater opportunity to contribute to food allergy research.

Green, Yellow, and Red risk perception in everyday life - a communication tool.

BACKGROUND: Adolescents have the highest risk for food allergy-related fatalities. Our main aim was to investigate the level of risk in everyday social situations as perceived by adolescents/young adults with peanut allergy, their families, and their friends. METHODS: The web-based 'Colours Of Risks' (COR) questionnaire was completed by 70 patients (aged 12-23 years), 103 mothers and fathers, 31 siblings (aged 12-26 years), and 42 friends (aged 12-24 years). COR deals with six main contexts (home, school/university, work, visiting/social activities, special occasions/parties, and vacations), each with 1-12 items. Response categories are green (I feel safe), yellow (I feel uncertain), or red (I feel everything is risky). RESULTS: There was a high level of agreement between participants in defining situations as safe, uncertain, or risky, but female patients and mothers rated fewer situations as safe compared to male patients and fathers. Being with close friends and family, and attending planned parties without alcohol were perceived as situations of low risk. While 94% of patients took an epinephrine auto-injector (EAI) into risky situations, only 65% took it into safe situations. In contrast to the close family, 31% of the friends did not know the patient had an EAI, and fewer knew how to administer the EAI. CONCLUSION: Young adults with peanut allergy face challenges when moving from the safe home with ready assistance if needed, to independence with unpredictable surroundings and less certain help. Perceived 'safe' situations may in fact be the riskiest, as patients often do not take the EAI with them.

The effect of geriatric intervention in frail elderly patients receiving chemotherapy for colorectal cancer: a randomized trial (GERICO).

BACKGROUND: Better surgical techniques, chemotherapy and biological therapy have improved survival in patients with colorectal cancer (CRC), most markedly in younger patients. About half of patients over 70 years receive dose reductions or early treatment discontinuation of the planned adjuvant or first-line treatment due to side effects. The Comprehensive Geriatric Assessment (CGA) is a multidisciplinary evaluation of an elderly individual's health status. This assessment in older patients with cancer can predict survival, chemotherapy toxicity and morbidity. METHODS: This randomized phase II trial (GERICO) is designed to investigate whether comprehensive geriatric assessment and intervention before and during treatment with chemotherapy in frail elderly patients with stages II-IV CRC will increase the number of patients completing chemotherapy. All patients ≥70 years in whom chemotherapy for CRC is planned to start at Herlev and Gentofte Hospital are screened for frailty using the G8 questionnaire at the first visit to the outpatient clinic. The G8 questionnaire is a multi-domain screening tool to identify frail or vulnerable patients at risk of increased toxicity and morbidity. Frail patients are offered inclusion and are then randomized to two groups (the intervention group and the control group). Patients in the intervention group receive a full geriatric assessment of comorbidity, medication, psycho-cognitive function, physical, functional and nutrition status, and interventions are undertaken on identified health issues. Simultaneously, they are treated for their cancer according to international guidelines. Patients in the control group receive the same chemotherapy regimens and standard of care. Primary outcome is number of patients completing scheduled chemotherapy at starting dose. Secondary outcomes are dose reductions, treatment delays, toxicity, time to recurrence, survival, cancer-related mortality and quality of life. DISCUSSION: This ongoing trial is one of the first to evaluate the effect of geriatric intervention in frail elderly patients with CRC. The trial will provide new and valuable knowledge about whether it is beneficial for the elderly patient undergoing chemotherapy to be treated simultaneously by a geriatrician. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02748811 . The trial was registered retrospectively; registration date 04/28/2016.

Radiological and pathological evaluation of the level of arterial division after colon cancer surgery.

AIM: In aiming to cure patients with colorectal cancer surgery, the surgeon must carefully dissect the mesocolon and mesorectum and divide the vascular pedicle near to its origin so as to include all local lymph nodes. This has been termed complete mesocolic excision. The distance from the distal vascular tie to the bowel wall in the fixed specimen is an indication as to the quality of surgery but this does not assess the length of the residual vascular pedicle and, by implication, residual lymph nodes. The aim of this study was to establish if our surgeons were carrying out complete mesocolic excision by assessing the length of the proximal arterial pedicle and relating this to arterial length in the fixed specimen. METHOD: This was a single centre prospective study of patients undergoing elective surgery for locally advanced colorectal cancer. An abdominal and pelvic CT scan was performed 2 days postoperatively and a radiologist blinded to the operative procedure measured the length of the residual arterial stump. Similarly, the length of the vessel in the fixed resected specimen and lymph node yield were also recorded. RESULTS: Fifty-two patients were recruited. The mean length of the residual arterial stump was 38 mm (95% CI: 33-43), which was significantly longer than the < 10 mm recommended in guidelines (P < 0.0001). The mean length was 31 mm (95% CI: 25-37) and 49 mm (95% CI: 40-57) for left and right sided resections respectively. There was no correlation between the residual arterial stump and the pathology. CONCLUSIONS: The residual arterial length was greater than suggested by guidelines and may indicate that our surgery is less radical than we planned. Caution should be taken when using pathological measurements of vascular ligation as it may not reflect the height of the pedicle division.

Reflections on two years after establishing an orthogeriatric unit: a focus group study of healthcare professionals' expectations and experiences.

BACKGROUND: For decades hospitals have been "vertically" organized, with the risk that specialization leads to fragmented and one-sided views of patient care and treatment that may cause poor communication and coordination of care and treatment. Two years after the introduction of an orthogeriatric unit for elderly patients admitted with fragility fractures, we studied the involved healthcare professionals' perspectives and experiences with working in an interprofessional organization. METHODS: We performed four focus groups interviews with 19 healthcare workers representing different professions. The interviews were analysed using systematic text condensation (STC). RESULTS: Three themes were identified: 1) A patient-centred approach, 2) An opportunity for professional growth and 3) The benefits of interprofessional collaboration. The interviewees emphasized in particular the systematic and frequent face-to-face communication enabled by the interprofessional team meetings as essential to their feeling of enhanced collegial solidarity. All groups expressed their respect for other groups' competences and their vital contributions to good orthogeriatric care. However, collaboration was challenged by the groups' divergent views of the patients and of the relevance of the information given in the weekly meetings. Heavy workloads were also mentioned. The opportunity for professional growth was also felt to be imperilled by some professionals. CONCLUSIONS: All participants indicated their view that the orthogeriatric organization had improved the quality of care and treatment. Furthermore, good communication, mutual respect for other professional competences and shared goals were found to have enhanced interprofessional collaboration and improved the sense of having a shared mission. However, differences in approaches and expectations continued to challenge the orthogeriatric model after 2 years. Neither did all professionals find orthogeriatric care professionally challenging.

TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition.

TL1A is a proinflammatory cytokine, which is prevalent in the gut. High TL1A concentrations are present in patients with inflammatory bowel disease (IBD) and in IBD mouse models. However, the role of TL1A during steady-state conditions is relatively unknown. Here, we used TL1A knockout (KO) mice to analyse the impact of TL1A on the intestinal immune system and gut microbiota. The TL1A KO mice showed reduced amounts of small intestinal intraepithelial TCRγδ(+) and CD8(+) T cells, and reduced expression of the activating receptor NKG2D. Moreover, the TL1A KO mice had significantly reduced body weight and visceral adipose tissue deposits, as well as lower levels of leptin and CXCL1, compared with wild-type mice. Analysis of the gut microbial composition of TL1A KO mice revealed a reduction of caecal Clostridial cluster IV, a change in the Firmicutes/Bacteroidetes ratio in caecum and less Lactobacillus spp. in the mucosal ileum. Our results show that TL1A deficiency impacts on the gut microbial composition and the mucosal immune system, especially the intraepithelial TCRγδ(+) T-cell subset, and that TL1A is involved in the establishment of adipose tissue. This research contributes to a broader understanding of TL1A inhibition, which is increasingly considered for treatment of IBD.

The half-life and exposure of cefuroxime varied in newborn infants after a Caesarean section.

AIM: No information was available on how fast intravenous cefuroxime administered to pregnant women before a Caesarean section was cleared in newborn infants. This study investigated the drug's half-life and the exposure of healthy newborn infants after their mothers received the drug. METHODS: Healthy mothers received a single dose of cefuroxime 15-60 minutes before skin incision. One blood sample was drawn from the umbilical cord, and two blood samples were drawn from the infant after delivery. Total plasma cefuroxime (µg/mL) was measured using high-pressure liquid chromatography. RESULTS: Cefuroxime was given to 22 mothers, including two who had twins. The concentration of cefuroxime varied significantly among infants (p < 0.001), while the rate of decline did not (p = 0.24). The median cefuroxime half-life was 3.5 hours (range 2.9-5.5), which was approximately three times longer than in normal adults and seemed to clear within 24 hours. The median area under the concentration-time curve was 65.0 hour µg/mL (range 31.7-162.4). CONCLUSION: We found that the cefuroxime half-life after a Caesarean section varied among infants and was longer than in normal adults but cleared within 24 hours. Exposure to cefuroxime in newborn infants may influence the gut microbiota and should be investigated further.

Strategies to increase the stability of intermediate moisture foods towards Zygosaccharomyces rouxii: the effect of temperature, ethanol, pH and water activity, with or without the influence of organic acids.

Intermediate moisture foods (IMF) are in general microbiologically stable products. However, due to health concerns consumer demands are increasingly forcing producers to lower the fat, sugar and preservatives content, which impede the stability of the IMF products. One of the strategies to counteract these problems is the storage of IMF products at lower temperatures. Thorough knowledge on growth/no growth boundaries of Zygosaccharomyces rouxii in IMF products, also at different storage temperatures is an important tool for ensuring microbiologically stability. In this study, growth/no growth models for Z. rouxii, developed by Vermeulen et al. (2012) were further extended by incorporating the factor temperature. Three different data sets were build: (i) without organic acids, (ii) with acetic acid (10,000 ppm on product basis) and (iii) with sorbic acid (1500 ppm on product basis). For each of these data sets three different growth/no growth models were developed after 30, 60 and 90 days. The results show that the influence of temperature is only significant in the lower temperature range (8-15 °C). Also, the effect of pH is negligible (pH 5.0-6.2) unless organic acids are present. More specific, acetic acid had only an additive effect to ethanol and aw at low pH, whereas sorbic acid had also an additive effect at the higher pH values. For incubation periods longer than 30 days the growth/no growth boundary remained stable but enlarged gradually between day 60 and 90, except for the lower temperature range (<12 °C) where the boundary shifts to more stringent environmental conditions.

Shoulder rotational profiles in young healthy elite female and male badminton players.

The aim of the present study was to profile shoulder passive range of motion (ROM) and isometric strength for external (ER) and internal (IR) rotation as part of a preseason screening in adolescent national badminton players. Passive external range of motion (EROM) and internal range of motion (IROM) were examined on the dominant and nondominant shoulder in 31 adolescent national badminton players (12 females and 19 males) with a standard goniometer. Muscle strength was examined with a hand-held dynamometer in ER and IR. Total range of motion (TROM = EROM+IROM) was lower on the dominant side compared with the nondominant side in both groups (P < 0.001). Males were generally stronger than females in all strength measurements except for IR on the dominant side (P < 0.01). In females, IR dominant side strength was greater compared with IR on the nondominant side (P < 0.05). TROM was reduced on the dominant side compared with the nondominant side in young elite badminton players, irrespective of gender. No rotational strength differences existed between the dominant and nondominant side in male players, but in female players a higher IR strength on the dominant side was not balanced by a higher ER strength.

Fatal accidents and injuries among merchant seafarers worldwide.

BACKGROUND: The British merchant fleet has expanded in recent years but it is not known whether this expansion has led to proportionate changes in mortality. AIMS: To investigate mortality from accidents and injuries in British merchant shipping, to determine whether this has increased in recent years, to compare fatal accident rates across British industries and to review fatal accident rates in merchant shipping worldwide over the last 70 years. METHODS: Examinations of marine accident investigation files, death registers and death inquiry files, national mortality statistics, worldwide surveys and review methodology. The main outcome measure was the fatal accident rate per 100 000 worker-years. RESULTS: Of 66 deaths in British shipping from 2003 to 2012, 49 were caused by accidents, which largely affected deck ratings. The fatal accident rate in British shipping increased by 4.7% per annum from 2003, although this was not significant (95% confidence interval: -5.1 to 15.6%). During 2003-12, the fatal accident rate in shipping (14.5 per 100 000) was 21 times that in the general British workforce, 4.7 times that in the construction industry and 13 times that in manufacturing. Of 20 merchant fleets worldwide with population-based fatal accident rates, most have shown large reductions over time. CONCLUSIONS: The expansion of the British merchant fleet in recent years does not appear to have had a major impact on fatal accidents. Further preventive measures should target fatalities during mooring and towing operations. Internationally, most shipping fleets have over time experienced large decreases in fatal accident rates.

Val/Met BDNF as a genetic risk for a false sense of security in post-discharge suicide risk.

BACKGROUND: The time after discharge from psychiatric inpatient care is one of the most dangerous periods in terms of suicide risk. Predicting who is at higher risk could help with resource allocation to assure patients at high risk of suicide attempts are most closely followed. We previously showed that inpatients who improve their suicide ideation levels faster while in inpatient treatment are the ones with highest rates of post-discharge suicide. Here, we studied the possible genetic underpinnings associated with such risk. METHOD: We recorded the slope of suicide ideation recovery of 710 psychiatric inpatients from which we studied two genetic variants likely associated with suicide risk: The serotonin transporter variant 5-HTTLPR, and the BDNF gene variant Val66Met. RESULTS: We found that inpatients carrying the BDNF Met variant (hypothesized as conferring higher suicide risk) improved their suicide ideation scores faster than Val/Val carrying inpatients. No significant association was found for 5-HTTLPR. LIMITATIONS: The present sample was genetically homogenous, and future research should replicate these findings on a more diverse sample. CONCLUSIONS: In conclusion, we found a paradoxical result: Carrying the BDNF Met variant allows inpatients to improve faster, which was shown to confer higher risk at the post-discharge period. This may explain some inconsistencies in the literature in terms of the role of BDNF in suicide ideation and attempts.

Circulating immune-related proteins associated with immune checkpoint inhibitor efficacy in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Most patients with pancreatic ductal adenocarcinoma (PDAC) do not benefit from immune checkpoint inhibitor treatment. However, the phase II study CheckPAC (NCT02866383) showed a clinical benefit (CB) rate of 37% and a response rate of 14% in patients with metastatic PDAC receiving stereotactic radiation therapy and nivolumab with or without ipilimumab. Translational studies were initiated to characterize the patients who would benefit from this treatment. Here, we evaluated the association between treatment outcome and 92 circulating immuno-oncology-related proteins in patients from the CheckPAC trial. MATERIALS AND METHODS: The study included 78 patients with chemoresistant metastatic PDAC treated with nivolumab ± ipilimumab combined with radiotherapy. Proteins were measured in serum samples collected at baseline and on treatment with the use of the Olink Target 96 Immuno-Oncology panel. A cohort of 234 patients with metastatic PDAC treated with first-line chemotherapy were also included. RESULTS: High levels of Fas ligand (FASLG) and galectin 1 (Gal-1) and low levels of C-C motif chemokine 4 were associated with CB. High FASLG and Gal-1 were associated with longer progression-free survival in univariable analysis. In the multivariable Cox regression analysis, the association was significant for Gal-1 (P < 0.001) but not significant for FASLG (P = 0.06). A focused unsupervised hierarchal clustering analysis, including T-cell activation and immune checkpoint-related proteins, identified clusters of patients with higher CB rate and higher tumor expression of leukocyte or T-cell markers (CD3, CD45, granzyme B). Thirty-six proteins increased significantly during immunotherapy. Several proteins (including FASLG, checkpoint proteins, and immune activation markers) increased independently of response during immunotherapy but did not increase in the cohort of patients treated with chemotherapy. CONCLUSIONS: Circulating levels of immune-related proteins like FASLG and Gal-1 might be used to predict the efficacy of checkpoint inhibitors in patients with metastatic PDAC.