Restored speech comprehension linked to activity in left inferior prefrontal and right temporal cortices in postlingual deafness

The left inferior prefrontal cortex (LIPC) is involved in speech comprehension by people who hear normally. In contrast, functional brain mapping has not revealed incremental activity in this region when users of cochlear implants comprehend speech without silent repetition. Functional brain maps identify significant changes of activity by comparing an active brain state with a presumed baseline condition. It is possible that cochlear implant users recruited alternative neuronal resources to the task in previous studies, but, in principle, it is also possible that an aberrant baseline condition masked the functional increase. To distinguish between the two possibilities, we tested the hypothesis that activity in the LIPC characterizes high speech comprehension in postlingually deaf CI users. We measured cerebral blood flow changes with positron emission tomography (PET) in CI users who listened passively to a range of speech and non-speech stimuli. The pattern of activation varied with the stimulus in users with high speech comprehension, unlike users with low speech comprehension. The high-comprehension group increased the activity in prefrontal and temporal regions of the cerebral cortex and in the right cerebellum. In these subjects, single words and speech raised activity in the LIPC, as well as in left and right temporal regions, both anterior and posterior, known to be activated in speech recognition and complex phoneme analysis in normal hearing. In subjects with low speech comprehension, sites of increased activity were observed only in the temporal lobes. We conclude that increased activity in areas of the LIPC and right temporal lobe is involved in speech comprehension after cochlear implantation.     

Diffusion-Weighted MRI in Patients with Testicular Tumors—Intra- and Interobserver Variability

In general, magnetic resonance (MR) diffusion-weighted imaging (DWI) has shown potential in clinical settings. In testicles parenchyma, the DW imaging helps differentiate and characterize benign from malignant lesions. Placement and size of the region of interest (ROI) may affect the ADC value. Therefore, the aim of this study was to investigate the intra- and interobserver variability in testicular tumors when measuring ADC using various types of regions of interest (ROI). Two observers performed the ADC measurements in testicular lesions based on three ROI methods: (1) whole volume, (2) round, and (3) small sample groups. Intra- and interobserver variability was analyzed for all ROI methods using intraclass correlation coefficients (ICC) and bland-altman plots. The two observers performed the measurements twice, three months apart. A total of 26 malignant testicle tumors were included. Interobserver agreement was excellent in tumor length (ICC = 0.98) and tumor width (ICC = 0.98). In addition, intraobserver agreement was excellent in tumor length (ICC = 0.98) and tumor width (ICC = 0.99). The whole volume interobserver agreement in the first reading was excellent (ICC = 0.93). Round ADC had an excellent (ICC = 0.93) and fair (ICC = 0.58) interobserver agreement, in the first and second reading, respectively. Interobserver agreement in ADC small ROIs was good (ICC = 0.87), and good (ICC = 0.78), in the first and second reading, respectively. Intraobserver agreement varied from fair, good to excellent agreement. The ROI method showed varying inter- and intraobserver agreement in ADC measurement. Using multiple small ROI conceded the highest interobserver variability, and, thus, the whole volume or round seem to be the preferable methods.     

Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR_1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR_1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR_1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR_1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR_1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR_1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR_1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.     

Binge drinking in pregnancy and risk of fetal death

OBJECTIVE: To examine whether the frequency and timing of binge drinking episodes (intake of five or more drinks on one occasion) during the first 16 weeks of pregnancy increase the risk of fetal death. METHODS: The study is based upon data from 89,201 women who were enrolled in the Danish National Birth Cohort from 1996 to 2002 and participated in an interview that took place in midpregnancy (n=86,752) or after a fetal loss (n=2,449). In total, 3,714 pregnancies resulted in fetal death. Data were analyzed by means of Cox regression models. RESULTS: Neither the frequency nor the timing of binge episodes was related to the risk of early (at or before 12 completed weeks) or late (13-21 completed weeks) spontaneous abortion. However, three or more binge episodes showed an adjusted hazard ratio of 1.56 (95% confidence interval 1.01-2.40) for stillbirth (22 or more completed weeks) relative to nonbinge drinkers. Women with an average intake of three or more drinks per week and two or more binge drinking episodes had a hazard ratio of 2.20 (95% confidence interval 1.73-2.80) compared with women with no average intake and no binge drinking. CONCLUSION: Binge drinking three or more times during pregnancy is associated with an increased risk of stillbirth, but neither frequency nor timing of binge drinking was associated with an increased risk of spontaneous abortion in clinically recognized pregnancies.     

Cluster headache polygenetic risk and known functional variants of CYP3A4 are not associated with treatment response

Background and purpose

The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first-line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil. Further, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine.

Methods

In, 508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta-analysis of the latest two genome-wide association studies on cluster headache.

Results

Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found.

Conclusion

The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study.     

Real-world evidence on efmoroctocog alfa in patients with haemophilia A: A systematic literature review of treatment experience in Europe

Introduction

The real-world effectiveness of the efmoroctocog alfa (recombinant FVIII Fc fusion protein, a rFVIIIFc) has been investigated in numerous studies, however, currently, there exists no comprehensive collection of the existing real-world evidence (RWE) on the performance of prophylactic use of rFVIIIFc.

Aim

The aims of this systematic literature study were to identify, review, evaluate and collate the RWE of prophylactic rFVIIIFc for patients with haemophilia A reported in Europe.

Methods

We searched Medline and Embase from 2014 to February 2022 to identify publications reporting the effectiveness of rFVIIIFc in patients with haemophilia A. The outcomes of interest were annualised bleeding rates (ABR, AjBR, AsBR), injection frequency, factor consumption, adherence, development of inhibitors and quality-of-life measures.

Results

46 eligible publications (eight full-text articles) were included. rFVIIIFc showed a low ABR in patients with haemophilia A. Studies assessing treatment switching from a standard half-life (SHL) treatment to rFVIIIFc found that the ABR and consumption were reduced in most patients. Studies assessing rFVIIIFc effectiveness reported a median ABR between 0.0 and 2.0 with median injections per week ranging between 1.8 and 2.4 and median doses between 60 and 105 IU/kg/week. Of the studies assessing inhibitor development, only one study reported an incidence of a low titre inhibitor, and no patients developed clinically significant inhibitors.

Conclusion

rFVIIIFc prophylaxis treatment results in a low ABR across studies in patients with haemophilia A in a European real-world setting, which correlates with findings from clinical trials assessing the efficacy of rFVIIIFc in patients with haemophilia A.     

Health-related quality of life the first year after a prostate cancer diagnosis a systematic review

How do patients, newly diagnosed with prostate cancer, experience their health-related quality of life? There are numerous treatment options, all affecting health-related quality of life in different ways. How each treatment method affects patients is used when guiding these patients in the choice of treatment. However, we are missing knowledge about how the newly diagnosed patient specifically experiences the first year of treatment, supporting the decision making. Therefore, this review aimed to provide evidence on how newly diagnosed prostate cancer patients experience their health-related quality of life during the first year after their diagnosis, regardless of treatment choice. This review was performed in 2021 (renewed in 2022) in medline, cinahl, and embase. Studies showing the results for newly diagnosed patients with PC were included. A total of 12 studies were included. Across treatment types, sexual function was the most negatively affected domain, and emotional function was the domain with the most improvement from baseline to 12 months. Active surveillance seems to have similar to no impact on health-related quality of life, radical proctectomy negatively impacts urinary function, external beam radiotherapy mostly has a negative impact on bowel function, and brachytherapy negatively impacts urinary function. Across treatment types, sexual function was the most negatively affected domain, and emotional function was the domain with the most improvement from baseline to 12 months. This knowledge can be used by urologists and nurses when guiding newly diagnosed patients in how the early part of treatment for prostate cancer is experienced.     

Patients' experiences of completing patient-reported outcomes in clinical trials: An interview study

This study aimed to gain insight into how older men diagnosed with prostate cancer experience responding to ePRO about their quality of life in a clinical trial as well as what motivates and demotivates them in the process. Drop-outs in patient-reported outcome studies are a well-known challenge that influence both the reliability and validity of clinical trials. Furthermore, retaining older people in electronic patient-reported outcome (ePRO) studies has proven difficult. This study was based on qualitative semi-structured interviews with 13 male patients. The interviews were conducted between April and May 2022 and were audio-recorded and transcribed verbatim. We analysed the interview inductively using Braun and Clark's thematic analysis. Resulting in five core themes among participants' responses: (1) the ePRO frame is feasible, (2) it is challenging to rate one's life on a scale, (3) increased disease insight, (4) unmet expectations of emotional support, and (5) from motivation to demotivation. The informants were motivated primarily by the idea of helping with new knowledge, but also because ePRO was seen as easy to use and access from home. They were further motivated by the new knowledge they gained through ePRO about symptoms and the possibility to follow their own progress. However, relating to their own quality of life creates an expectation that nurses and doctors will do the same in their treatment, and when this does not happen, the initial motivation turns into demotivation as ePRO knowledge was not used to tailor their treatment and follow-up. In conclusion, older men can participate in ePRO. They are motivated by helping with new knowledge, the ability to answer ePRO from home, and the insights they gain from the questionnaire. They lose motivation when their responses are not used to tailor their disease management.