Prevalence of Dysphagia and Risk of Malnutrition in Elderly Living in Nursing Homes.

Swallowing difficulties commonly co-occur with malnutrition in the elderly. However, there is no consensus on which assessment tools to use, and thus reported prevalence varies. The aim of this study was to survey the prevalence of dysphagia and risk of malnutrition in elderly people in nursing homes, evaluate the possible associations between swallowing function and malnutrition and survey whether there were associations between self-perceived function and the results of a screening of dysphagia. A total of 35 residents (aged 67-100 years old) without serious cognitive impairment in the general wards of two nursing homes in Gothenburg were investigated. Swallowing ability was assessed with the Gugging Swallowing Screen (GUSS) test, self-rated swallowing ability with the 4QT and the Swedish Eating Assessment Tool-10 (S-EAT-10) and risk of malnutrition with the Minimal Eating Observation and Nutrition Form-Version 2 (MEONF-II). Eleven participants (31.4%) exhibited dysphagia according to the GUSS and 10 participants (29.4%) showed moderate or high risk of malnutrition. In total 16 (46%) participants reported abnormal swallowing on 4QT and 14 (40%) participants reported abnormal swallowing on S-EAT-10. However, less than half of these had dysphagia according to the GUSS. No association was found between swallowing ability measured by the GUSS and risk of malnutrition, although a tendency towards a weak association was noted, or self-rated swallowing ability measured by the 4QT and S-EAT-10. The study found that approximately one-third of the tested participants presented with signs of dysphagia as measured with the screening instrument GUSS, even though only a few were known to have any difficulties prior to testing. This highlights that dysphagia is probably more prevalent than patients themselves and caregivers are aware of, thus, screening is of importance, to enable safer nutritional intake.

Work-Focused Versus Generic Internet-Based Interventions for Employees With Stress-Related Disorders: Randomized Controlled Trial.

BACKGROUND: In recent decades, stress-related disorders have received more attention, with an increasing prevalence, especially within the working population. The internet provides new options for broad dissemination, and a growing body of evidence suggests that web-based interventions for stress might be effective. However, few studies have examined the efficacy of interventions in clinical samples and work-related outcomes. OBJECTIVE: The aim of this study was to evaluate the efficacy of an internet-based cognitive behavioral intervention for stress-related disorders integrating work-related aspects (work-focused and internet-based cognitive behavioral therapy [W-iCBT]), compared with a generic internet-based cognitive behavioral therapy (iCBT) group and a waitlist control (WLC) group. METHODS: In this trial, 182 employees, mainly employed in the health care, IT, or educational sector, who fulfilled the criteria for a stress-related disorder, were randomized to a 10-week W-iCBT (n=61, 33.5%), generic iCBT (n=61, 33.5%), or WLC (n=60, 33%). Self-rated questionnaires on perceived stress, burnout, exhaustion, and other mental health- and work-related outcomes were administered before and after the treatment and at 6- and 12-month follow-ups. RESULTS: Compared with the WLC group, participants of the W-iCBT and iCBT groups showed an equal and significant reduction in the primary outcome (Shirom-Melamed Burnout Questionnaire [SMBQ]) from pretreatment to posttreatment assessment (Cohen d=1.00 and 0.83, respectively) and at the 6-month follow-up (Cohen d=0.74 and 0.74, respectively). Significant moderate-to-large effect sizes were also found in the secondary health- and work-related outcomes. The W-iCBT was the only group that exhibited significant effects on work ability and short-term sickness absence. Short-term sickness absence was 445 days lower than the WLC group and 324 days lower than the iCBT intervention group. However, no significant differences were found in terms of work experience or long-term sick leave. CONCLUSIONS: The work-focused and generic iCBT interventions proved to be superior compared with the control condition in reducing chronic stress and several other mental health-related symptoms. Interestingly, effects on work ability and short-term sickness absence were only seen between the W-iCBT intervention and the WLC groups. These preliminary results are promising, indicating that treatments that include work aspects may have the potential to accelerate recovery and reduce short-term sickness absence because of stress-related disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT05240495; https://clinicaltrials.gov/ct2/show/NCT05240495 (retrospectively registered).

Communicative participation in goal-setting meetings for patients with aphasia after stroke. A study using patients' and healthcare professionals' self-ratings.

PURPOSE: Communicative participation poses a challenge in meetings between healthcare professionals (HCPs) and people with aphasia (PwA). How communication is affected by aphasia in group meetings, where several healthcare professionals participate together with the patient, is largely unexplored. The aim of this study was to investigate self-rated communicative participation during goal-setting meetings among PwA compared to patients without aphasia and to investigate whether communicative participation among PwA was associated with self-rated knowledge about aphasia among HCPs. A further aim was to investigate if there was a difference in the use of communication strategies among HCPs in the respective situations. METHODS: Nine PwA and nine control patients without aphasia rated their experience of communication during a goal-setting meeting. Thirty-eight HCPs rated their knowledge about aphasia and communication, and their use of communication strategies during goal-setting meetings. RESULTS: The PwA reported being listened to by the HCPs as well as being able to comprehend the meeting. PwA with more severe language impairment did not report a lower level of communicative participation compared to PwA with milder impairment. Half of the patients from both groups indicated some difficulty asking questions during the meeting. Patients' ratings of communication were not correlated to HCPs' knowledge of communication strategies. There was a significant difference in self-rated use of communication strategies among HCPs for the two conditions, although the individual variation was large. CONCLUSION: Results from both PwA and controls imply that patients may need more support to be able to ask questions in meetings with HCPs. Although self-ratings increase the ecological validity of the study of participation, further studies could benefit from using video observations in combination with self-reported experience, since awareness might influence results. WHAT THIS PAPER ADS: What is already known on this subject Aphasia is an acquired language disorder that affects patient-provider communication. In stroke rehabilitation, person-centred goal setting is a key component. If healthcare professionals (HCPs) are not able to use adequate communication strategies, a lack of accessible communication can become a barrier to person-centredness. There are evidence-based communication strategies which can be used to overcome this barrier. What this paper adds to existing knowledge This study aimed to investigate communicative participation during goal-setting meetings from the perspective of patients with aphasia and HCPs. To our knowledge, this is the first study where persons with aphasia are asked to rate communicative participation in goal-setting meetings. To broaden the perspective on communication and goal setting, ratings of patients with aphasia are compared to ratings by patients with stroke but no aphasia. The results of this study indicate that there is room for improvement regarding communication during goal-setting meetings. However, asking direct questions on communicative participation to persons with severe aphasia may not be feasible. What are the potential or actual clinical implications of this work? The results of this study imply that both patients with and without aphasia may need more support to be able to express themselves during goal-setting meetings. There also seems to be a need for further education on aphasia and communication strategies among rehabilitation professionals.

Effects of inorganic nitrate on ischaemia-reperfusion injury after coronary artery bypass surgery: a randomised controlled trial.

BACKGROUND: Nitric oxide (NO) is an important signalling molecule in the cardiovascular system with protective properties in ischaemia-reperfusion injury. Inorganic nitrate, an oxidation product of endogenous NO production and a constituent in our diet, can be recycled back to bioactive NO. We investigated if preoperative administration of inorganic nitrate could reduce troponin T release and other plasma markers of injury to the heart, liver, kidney, and brain in patients undergoing cardiac surgery. METHODS: This single-centre, randomised, double-blind, placebo-controlled trial included 82 patients undergoing coronary artery bypass surgery with cardiopulmonary bypass. Oral sodium nitrate (700 mg×2) or placebo (NaCl) were administered before surgery. Biomarkers of ischaemia-reperfusion injury and plasma nitrate and nitrite were collected before and up to 72 h after surgery. Troponin T release was our predefined primary endpoint and biomarkers of renal, liver, and brain injury were secondary endpoints. RESULTS: Plasma concentrations of nitrate and nitrite were elevated in nitrate-treated patients compared with placebo. The 72-h release of troponin T did not differ between groups. Other plasma biomarkers of organ injury were also similar between groups. Blood loss was not a predefined outcome parameter, but perioperative bleeding was 18% less in nitrate-treated patients compared with controls. CONCLUSION: Preoperative administration of inorganic nitrate did not influence troponin T release or other plasma biomarkers of organ injury in cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT01348971.

Organ uptake and release of inorganic nitrate and nitrite in the pig.

Numerous studies have shown beneficial cardiovascular and metabolic effects of dietary nitrate but the release or uptake of these anions on an organ level is still poorly elucidated. Here we administered sodium nitrate in the pig and measured acute changes in release/uptake of nitrate and nitrite across several organs as well as cardiovascular and metabolic functions. In 17 anesthetized pigs multiple venous catheters and arterial ultrasonic blood flow probes were positioned. After pretreatment with the NO synthase (NOS) inhibitor l-NAME to minimize involvement of NOS-dependent nitrate/nitrite generation, the animals received bolus injections of either sodium nitrate or sodium chloride. Organ blood flows and release/uptake of nitrate and nitrite were measured in the pulmonary, splanchnic, hepatic and renal circulations for up to two hours. In addition, small intestinal luminal NO, gut secretion of nitrate, as well as hepatic and renal NADPH oxidase activity were measured. At baseline there was a significant uptake of nitrite in the liver and kidneys together with a release of nitrite from the lungs. In the control pigs, arterial plasma nitrite progressively declined during the observation period (-54%) but was stable in the nitrate group, indicating conversion of nitrate to nitrite. Sodium nitrate led to a marked accumulation of nitrate in the small intestinal lumen with a parallel increase in luminal nitrite. This was coupled with release of nitrite in the portal vein and a concomitant uptake of this anion in the liver. There was a trend towards reduced NADPH oxidase-dependent superoxide generation in the liver but an increase in the kidney. Nitrate had no acute effects on cardiovascular parameters or regional and systemic oxygen consumption. In conclusion, we found a notable difference in release and uptake of nitrate and nitrite between the organs investigated. Our findings indicate an acute conversion of nitrate to nitrite, most likely independent of oral bacteria but by a mammalian nitrate reductase and/or gut bacteria.

Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain: a single group, clinical trial in patients with chronic intractable phantom limb pain.

BACKGROUND: Phantom limb pain is a debilitating condition for which no effective treatment has been found. We hypothesised that re-engagement of central and peripheral circuitry involved in motor execution could reduce phantom limb pain via competitive plasticity and reversal of cortical reorganisation. METHODS: Patients with upper limb amputation and known chronic intractable phantom limb pain were recruited at three clinics in Sweden and one in Slovenia. Patients received 12 sessions of phantom motor execution using machine learning, augmented and virtual reality, and serious gaming. Changes in intensity, frequency, duration, quality, and intrusion of phantom limb pain were assessed by the use of the numeric rating scale, the pain rating index, the weighted pain distribution scale, and a study-specific frequency scale before each session and at follow-up interviews 1, 3, and 6 months after the last session. Changes in medication and prostheses were also monitored. Results are reported using descriptive statistics and analysed by non-parametric tests. The trial is registered at ClinicalTrials.gov, number NCT02281539. FINDINGS: Between Sept 15, 2014, and April 10, 2015, 14 patients with intractable chronic phantom limb pain, for whom conventional treatments failed, were enrolled. After 12 sessions, patients showed statistically and clinically significant improvements in all metrics of phantom limb pain. Phantom limb pain decreased from pre-treatment to the last treatment session by 47% (SD 39; absolute mean change 1·0 [0·8]; p=0·001) for weighted pain distribution, 32% (38; absolute mean change 1·6 [1·8]; p=0·007) for the numeric rating scale, and 51% (33; absolute mean change 9·6 [8·1]; p=0·0001) for the pain rating index. The numeric rating scale score for intrusion of phantom limb pain in activities of daily living and sleep was reduced by 43% (SD 37; absolute mean change 2·4 [2·3]; p=0·004) and 61% (39; absolute mean change 2·3 [1·8]; p=0·001), respectively. Two of four patients who were on medication reduced their intake by 81% (absolute reduction 1300 mg, gabapentin) and 33% (absolute reduction 75 mg, pregabalin). Improvements remained 6 months after the last treatment. INTERPRETATION: Our findings suggest potential value in motor execution of the phantom limb as a treatment for phantom limb pain. Promotion of phantom motor execution aided by machine learning, augmented and virtual reality, and gaming is a non-invasive, non-pharmacological, and engaging treatment with no identified side-effects at present. FUNDING: Promobilia Foundation, VINNOVA, Jimmy Dahlstens Fond, PicoSolve, and Innovationskontor Väst.

On the diverse outcome of communication partner training of significant others of people with aphasia: an experimental study of six cases.

BACKGROUND: Communication partner training (CPT) has been shown to improve the communicative environment of people with aphasia. Interaction-focused training is one type of training that provides an individualized intervention to participants. Although shown to be effective, outcomes have mostly been evaluated in non-experimental case studies. AIMS: The aim of the controlled experimental intervention study was to evaluate an individualized approach in a CPT programme directed to significant others of people with aphasia. Specifically the effects on conversation partners' ability to support the person with aphasia in conversation and on the individuals with aphasias' perception of their functional communication were explored. METHODS & PROCEDURES: Six dyads consisting of a person with aphasia and a significant other were included in a replicated single-subject design with multiple baselines across individuals. The intervention followed the interaction-focused communication training programme included in Supporting Partners of People with Aphasia in Relationships and Conversation (SPARRC). The main elements of the training consisted of supervised viewing of the couples' own video-recorded natural interaction and the formulation of individual goals for the adaptation of particular communicative strategies. Outcome was measured via blinded ratings of filmed conversational interaction obtained once a week throughout the different phases of baseline, intervention and follow-up. A rating scale to assess overall quality of conversation was used, taking into account both transfer of information and social aspects of conversation. Measures of perceived functional communication in the persons with aphasia were also collected from the individuals with aphasia and their conversation partners. OUTCOMES & RESULTS: The results were mixed, with two of the six participants showing small improvements in ability to support their partner with aphasia in conversation. Half the participants with aphasia and half the significant others reported improvements on perceived functional communication in the person with aphasia after intervention, but no changes were statistically significant. CONCLUSIONS & IMPLICATIONS: This study adds to the growing body of research concerning CPT by pinpointing the importance of careful consideration regarding set-up of training, suitability of participants and evaluation of outcome.

Effects of hyperbaric oxygen on nitric oxide generation in humans.

BACKGROUND: Hyperbaric oxygen (HBO2) has been suggested to affect nitric oxide (NO) generation in humans. Specific NO synthases (NOSs) use L-arginine and molecular oxygen to produce NO but this signaling radical may also be formed by serial reduction of the inorganic anions nitrate and nitrite. Interestingly, commensal facultative anaerobic bacteria in the oral cavity are necessary for the first step to reduce nitrate to nitrite. The nitrate-nitrite-NO pathway is greatly potentiated by hypoxia and low pH in contrast to classical NOS-dependent NO generation. We investigated the effects of HBO2 on NO generation in healthy subjects including orally and nasally exhaled NO, plasma and salivary nitrate and nitrite as well as plasma cGMP and plasma citrulline/arginine ratio. In addition, we also conducted in-vitro experiments in order to investigate the effects of hyperoxia on nitrate/nitrite metabolism and NO generation by oral bacteria. METHODS: Two separate HBO2 experiments were performed. In a cross-over experiment (EXP1) subjects breathed air at 130 kPa (control) or oxygen at 250 kPa for 100 minutes and parameters were measured before and after exposure. In experiment 2 (EXP 2) measurements were performed also during HBO2 at 250 kPa for 110 minutes. RESULTS: HBO2 acutely reduced orally and nasally exhaled NO by 30% and 16%, respectively. There was a marked decrease in salivary nitrite/nitrate ratio during and after HBO2, indicating a reduced bacterial conversion of nitrate to nitrite and NO. This was supported by in vitro experiments with oral bacteria showing that hyperoxia inhibited bacterial nitrate and nitrite reduction leading to reduced NO generation. Plasma nitrate was unaffected by HBO2 while plasma nitrite was reduced during HBO2 treatment. In contrast, plasma cGMP increased during HBO2 as did citrulline/arginine ratio after treatment and control. CONCLUSION: HBO2-exposure in humans affects NO generation in the airways and systemically differently. These data suggest that the individual NOSs as well as the nitrate-nitrite-NO pathway do not respond in a similar way to HBO2.

The ancient Britons: groundwater fauna survived extreme climate change over tens of millions of years across NW Europe.

Global climate changes during the Cenozoic (65.5-0 Ma) caused major biological range shifts and extinctions. In northern Europe, for example, a pattern of few endemics and the dominance of wide-ranging species is thought to have been determined by the Pleistocene (2.59-0.01 Ma) glaciations. This study, in contrast, reveals an ancient subsurface fauna endemic to Britain and Ireland. Using a Bayesian phylogenetic approach, we found that two species of stygobitic invertebrates (genus Niphargus) have not only survived the entire Pleistocene in refugia but have persisted for at least 19.5 million years. Other Niphargus species form distinct cryptic taxa that diverged from their nearest continental relative between 5.6 and 1.0 Ma. The study also reveals an unusual biogeographical pattern in the Niphargus genus. It originated in north-west Europe approximately 87 Ma and underwent a gradual range expansion. Phylogenetic diversity and species age are highest in north-west Europe, suggesting resilience to extreme climate change and strongly contrasting the patterns seen in surface fauna. However, species diversity is highest in south-east Europe, indicating that once the genus spread to these areas (approximately 25 Ma), geomorphological and climatic conditions enabled much higher diversification. Our study highlights that groundwater ecosystems provide an important contribution to biodiversity and offers insight into the interactions between biological and climatic processes.

Markers of imminent myocardial infarction.

Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case-cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.

Clinical Outcomes in Patients With Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants Across Varying Body Mass Index.

Background There are conflicting data on outcomes in patients with atrial fibrillation treated with non-vitamin K oral anticoagulants across varying body mass index (BMI). We investigated cardiovascular and bleeding risk in patients with atrial fibrillation with varying BMI. Methods and Results Observational cohort study from the Swedish oral anticoagulation registry between August 2, 2011, and December 31, 2018. Primary outcomes were mortality, ischemic stroke/systemic embolism, and major bleeding. Baseline BMI (kg/m2) was analyzed continuously and categorized: underweight (<18.5 kg/m2), normal weight (18.5 to <25 kg/m2), preobesity (25 to <30 kg/m2), and obesity class I to III (30 to <35, 35 to <40, and ≥40 kg/m2). Adjusted Cox models and nonlinear relationships of BMI were modeled using restricted cubic splines. Non-vitamin K oral anticoagulant-treated patients with atrial fibrillation were included (n=26 047). At baseline, 602 (2.3%) were underweight, 9101 (34.9%) were normal weight, 9970 (38.3%) were preobese, 4280 (16.4%) were obese class I, 1486 (5.7%) were obese class II, and 608 (2.3%) were obese class III. Underweight and obesity class III were in adjusted continuous analysis associated with increased mortality and major bleeding, with lowest risk observed among preobese patients with BMI 28.2 and 26.2 kg/m2, respectively. In adjusted categorical analysis, underweight was associated with increased mortality (hazard ratio [HR], 1.77 [95% CI, 1.57-1.99]) and nonsignificant higher risk of major bleeding (HR, 1.23 [95% CI, 0.95-1.58]). Similarly, obesity class III was associated with increased mortality (HR, 1.67 [95% CI, 1.40-1.99]) and major bleeding (HR, 1.68 [95% CI, 1.29-2.17]). No significant association was observed between higher BMI and ischemic stroke/systemic embolism. Conclusions In non-vitamin K oral anticoagulant-treated patients with atrial fibrillation, there appears to be a U-shaped relationship between BMI and mortality and major bleeding.

Dysphagia terminology for texture modified fluid and food: a national survey of speech-language pathologists' practice.

PURPOSE: To investigate: (a) Swedish Speech-Language Pathologists (SLPs) dysphagia management with TMC, including terminology, inter-professional collaboration, and knowledge of standard TMC guides; and (b) the current TMC terminology/guides used within university hospitals, in Sweden. METHOD: Part One surveyed SLPs from 19/21 regions. Recruitment occurred via regional SLP/department managers, the national SLP association and email lists. Non-parametric statistics were employed. Part Two explored TMC guides within the seven university hospitals. RESULT: The initial survey identified 78 Swedish TMC terms. Overlap of both TMC terms and descriptions occurred. Different terms to describe same/similar textures were used by 70% of the SLPs. Knowledge of established guides was high (>90%), though TMC was often (60%) based on locally developed documents. Collaboration with other professions was reported by 97% of SLPs, however almost half perceived collaboration to be inadequate, citing difficulties with transfer of TMC recommendations. Variance in TMC terms/guides within/across the university hospitals occurred. CONCLUSION: Variable TMC terminology is used in Sweden, impacting optimal dysphagia management. Future research should focus upon implementation of standardised TMC terminology.

Determination of Half-lives of Circulating FSH and LH Glycoforms in Women During GnRH Receptor Blockade.

CONTEXT: Both FSH and LH circulate as 2 glycoforms, differing in number of glycans: low-N-glycosylated glycoforms, FSHtri and LHdi, and fully N-glycosylated glycoforms, FSHtetra and LHtri. OBJECTIVES: To determine the half-lives of endogenous circulating gonadotropin glycoforms in women during GnRH receptor blockade. DESIGN/PARTICIPANTS: Serum samples were collected in 8 healthy women before and up to 20 hours after administration of the NAL-GLU GnRH antagonist. Three women were in early follicular phase, 2 at mid-cycle phase, and 3 were postmenopausal. MAIN OUTCOME MEASURES: The half-life of each glycoform was estimated by monoexponential decay for FSH (n = 8) and LH (n = 5). Data were analyzed using paired t tests. RESULTS: Half-lives in the circulation of low-N-glycosylated glycoforms of both FSH and LH were shorter than those of the fully N-glycosylated glycoforms (mean; range, FSHtri 343; 116-686 minutes vs FSHtetra 757; 436-1038, minutes, P = 0.0003; LHdi 125, 84-198 minutes vs LHtri 164, 107-235 minutes, P = 0.004). The half-lives of low-and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH glycoforms, P = 0.0008. CONCLUSIONS: For both FSH and LH, low-N-glycosylated glycoforms disappeared from the circulation faster than the fully N-glycosylated. The half-lives of low and fully N-glycosylated forms of LH were shorter than the corresponding half-lives of FSH. The estimated values for half-life in the circulation of total FSH and total LH will depend on the relative amounts of the 2 glycoforms of each hormone and their individual disappearance rates in circulation.

'They get the opportunity to say what is important for them': exploring staff's early perceptions of the implementation of a new communicative approach to patients with aphasia.

PURPOSE: This study explored the perceptions of staff members regarding the implementation of a new communicative approach at a multidisciplinary neurorehabilitation centre in Denmark. Communication partner training according to Supported Conversation for Adults with Aphasia (SCATM) was combined with augmentative strategies from the KomHIT programme to increase the influence of patients with aphasia on their own rehabilitation process. METHODS: A qualitative approach was used involving two semi-structured group interviews with multidisciplinary staff in two wards. Three staff members from each ward participated. The recorded interviews were transcribed, and a thematic analysis of the data was conducted. RESULTS: Three main themes emerged from the analysis. Participants reported increased influence of patients with aphasia on their own rehabilitation process, as well as an increased focus on communication with patients with aphasia. Challenges included time restrictions and dilemmas in goal setting. CONCLUSIONS: Increasing staff knowledge of communication support and augmentative strategies seemed to improve the influence of patients with aphasia on their own rehabilitation process. Because the results were based on interviews with a small number of staff, they cannot be generalized and require further investigation that should also include interviews with the patients themselves and their families.IMPLICATIONS FOR REHABILITATIONThe combination of partner training with augmentative strategies may increase staff understanding of all individuals' rights to have their communicative needs met.The combination of partner training with augmentative strategies may support the influence of persons with aphasia on their own rehabilitation.Goal setting discrepancies between staff and patients with aphasia can be brought to light by more successful communication.The implementation of a new communicative approach can be challenged by a number of factors, e.g., time restrictions.The implementation process needs to be supported by actions on a higher organisational level.

Thyrotropin N-glycosylation and Glycan Composition in Severe Primary Hypothyroidism.

CONTEXT: In severe primary hypothyroidism (sPH), the serum thyrotropin (TSH) levels are elevated with an increased degree of sialylation. The circulating TSH comprises 2 different TSH glycoforms: TSHdi with 2 and TSHtri with 3 N-glycans and methods have developed to determine their contents of anionic monosaccharides (AMS), that is, sialic acid (SA) and sulfonated N-acetylglactosamine (SU) residues. OBJECTIVE: Characterize N-glycosylation and glycan composition of circulating TSH molecules and determine the effects during levothyroxine treatment in patients with sPH. METHODS: Serum samples were obtained from 25 patients with sPH, from 159 euthyroid individuals, and from 12 women during treatment with levothyroxine for sPH. Degrees of N-glycosylation and concentrations of TSHdi and TSHtri as well as their contents of AMS, SA, and SU residues were determined. RESULTS: The circulating TSH molecules in sPH patients had lower degrees of N-glycosylation, higher degrees of sialylation, and lower degrees of sulfonation than in euthyroid individuals. Levothyroxin restored sialylation and sulfonation of the glycans already at low free thyroxine (FT4) levels, while degree of N-glycosylation was not restored until the FT4 levels were normal. CONCLUSIONS: The majority of TSH molecules in severe primary hypothyroidism were less N- glycosylated, more sialylated, and less sulfonated compared with euthyroid individuals. This glycan pattern favors a prolonged half-life in the circulation combined with lower in vitro biopotency at the target cells. During levothyroxine treatment of sPH patients, the sialylation and sulfonation of glycans were restored already at low FT4 levels, while N-glycosylation of TSH was not restored until the FT4 levels were normal.

Continuous renal replacement therapy in intensive care patients with COVID-19; survival and renal recovery.

BACKGROUND: Outcome for critically ill patients with COVID-19 treated with continuous renal replacement therapy (CRRT) is largely unknown. We describe mortality and renal outcome in this group. METHODS: This observational study was conducted at a university hospital in Sweden. We studied critically ill adult COVID-19 patients with Acute Kidney injury (AKI) who received CRRT. RESULTS: In 451 patients, AKI incidence was 43.7%. 18.2% received CRRT. Median age of CRRT patients was 60 years (IQR 54-65), 90% were male, median BMI was 29 (IQR 25-32), 23.2% had Diabetes, 37.8% hypertension and 6.1% chronic kidney disease prior to admission. 100% required mechanical ventilation. 8.5% received Extra Corporeal Membrane Oxygenation. Median length of stay was 23 days (IQR 15-26). ICU mortality was 39% and 90-day mortality was 45.1%. Age, baseline creatinine values and body weight change were associated with 60 days mortality. Of the survivors, no patients required dialysis at hospital discharge, 73.8% recovered renal function and a median 10.5% of body weight was lost during admission. CONCLUSIONS: Critically ill COVID-19 patients with AKI who received CRRT had a 90-day mortality of 45.1%. At follow-up, three quarters of survivors had recovered renal function. This information is important in the clinical management of COVID-19.

Low- and Fully N-Glycosylated Gonadotropins Circulating in Women With Polycystic Ovary Syndrome.

CONTEXT: A preponderance of basic luteinizing hormone (LH) molecules having elevated bioactivity was detected in the circulation of women with polycystic ovary syndrome (PCOS). Subsequent studies have shown that LH and follicle-stimulating hormone (FSH) both circulate as glycoforms differing in number of glycans: low-N-glycosylated glycoforms, LHdi and FSHtri, with high in vitro bioactivity, and fully glycosylated glycoforms, LHtri and FSHtetra, with high in vivo bioactivity. OBJECTIVE: This work aims to characterize the glycosylation patterns on circulating gonadotropin glycoforms in women with PCOS. METHODS: Serum samples, collected from 8 women with PCOS were included. The concentration, sulfonation, and sialylation of each glycoform were determined and compared with values of serum samples from healthy women: 22 women at follicular phase, 16 at midcycle, and 15 after menopause. RESULTS: All the women with PCOS had higher LHdi serum levels compared with those in the follicular-phase group. Median LHdi and median LHtri levels were significantly elevated in PCOS women. The percentage of LHdi was increased from 37 to 49 and that of FSHtri was decreased from 41 to 33. The LHdi, LHtri, and FSHtetra glycoforms were more sialylated and both LH glycoforms less sulfonated in women with PCOS. CONCLUSION: All women with PCOS had increased serum levels of LHdi, compared with those in the follicular phase. The percentage of LHdi was increased and that of FSHtri decreased in women with PCOS. The increased LHdi leads to maintenance of the abnormal early follicular development of the polycystic ovary, and the decreased FSHtri contributes to the arrested follicle growth.

Gonadotropin Glycoforms Circulating in Women Using Progestins of the Levonorgestrel Family for Contraception.

CONTEXT: The progestins of the levonorgestrel family are 13-ethylgonane progestins, commonly used for contraception in women. One contraceptive effect of these progestins is inhibition of ovulation, which may be a result of changes in gonadotropin glycosylation patterns. Gonadotropin glycoforms differ in number of glycans and bioactivity: more bioactive low-N-glycosylated glycoforms, diglycosylated luteinizing hormone (LHdi) and triglycosylated follicle-stimulating hormone (FSHtri), and less bioactive fully N-glycosylated glycoforms, LHtri and FSHtetra. OBJECTIVE: Characterize the glycosylation patterns on the circulating gonadotropin glycoforms in women using 13-ethylgonane progestins for contraception. DESIGN SUBJECTS MAIN OUTCOME MEASURES: Serum samples, collected from 92 healthy women using 13-ethylgonane progestins for contraception, were included. Forty women used progestin-only continuously and 52 used progestins combined with ethinylestradiol (EE) for 3 weeks followed by a hormone-free week. Concentration, sulfonation, and sialylation of each glycoform were determined and compared with follicular phase values of normal menstrual cycles. RESULTS: The progestin-only group had significantly increased serum levels, decreased sulfonation, and increased sialylation of LHdi. The LHdi/FSHtri ratio was increased. The progestin+EE group had significantly decreased gonadotropin glycoform concentrations and decreased sialylation of FSHtri. The progestin+EE effect on sialylation of FSHtri occurred later during the treatment cycle in contrast to the effect on FSHtri concentration. CONCLUSIONS: The 2 different progestin treatments induced different effects on the glycan synthesis and concentrations of more bioactive low-glycosylated gonadotropins. Progestin-only treatment increased sialylation and decreased sulfonation of LHdi molecules, contributing to sustained higher levels of bioactive LHdi molecules. Progestin+EE treatment decreased sialylation of FSHtri, contributing to a shorter half-life and decreased levels of bioactive FSHtri.

Unique Pattern of N-Glycosylation, Sialylation, and Sulfonation on TSH Molecules in Serum of Children Up to 18 Months.

CONTEXT: N-glycosylation and glycan composition of human TSH molecules modulate the biological properties of TSH in different physiological and clinical situations. The degree of sialylation of serum TSH was reported to be very low in normal third-trimester fetuses compared with normal adults. The circulating TSH glycoforms and their glycan compositions in young children have hitherto not been determined. OBJECTIVE: To characterize N-glycosylation and glycan composition of circulating TSH molecules in young children. DESIGN, PARTICIPANTS, MAIN OUTCOME MEASURES: Serum samples were obtained from euthyroid individuals: 33 children, age 2 weeks to 3 years, and 264 adults. The di-glycosylated TSH and tri-glycosylated TSH glycoforms were determined and characterized with respect to sialylation and sulfonation. The TSH N-glycosylation was also examined in pituitary extracts of 75 individuals. RESULTS: In children up to 18 months of age, most TSH molecules were low-N-glycosylated, high-sulfonated, and low-sialylated compared with older children and adults. The degree of N-glycosylation was similar in serum and pituitary extracts up to 3 months of age and after that was higher in serum than in pituitary extracts. CONCLUSIONS: Children up to age 18 months had low-sialylated TSH molecules, similar to those reported for third-trimester fetuses. Most TSH molecules in young children were of smaller size and less negatively charged, favoring transport into their target tissues. The low sialylation favors a high biopotency at thyroid and extrathyroidal TSH receptors. A delayed development of the liver SO3-N-acetylgalactosamine receptor function after birth is a likely explanation of the highly sulfonated TSH molecules in serum samples of infants.

Low-glycosylated forms of both FSH and LH play major roles in the natural ovarian stimulation.

BACKGROUND: The natural ovarian stimulation is mediated by four gonadotrophin glycoforms: FSHtri with three, FSHtetra with four, LHdi with two, and LHtri with three N-glycans. The aim of the study was to determine the serum concentrations of the four glycoforms and their contents of anionic monosaccharides (AMS), i.e. sialic acid (SA) and sulfonated N-acetylgalactosamine (SU) residues throughout the menstrual cycle. METHODS: Serum samples were collected from 78 healthy women with regular menstrual cycles. The serum glycoform molecules were identified by their distributions at electrophoreses. Analyses were also performed after removal of terminal SA. The hormones were measured with time-resolved sandwich fluoroimmunoassays. RESULTS: The concentration profiles of the four glycoforms were markedly different. FSHtri, which had a 3-fold higher biopotency than FSHtetra, had peak levels on cycle day 5 and at midcycle and nadirs on cycle days 9 and 21-23. FSHtetra had a raised level on cycle days 5-12, followed by a decrease. LHdi and LHtri had similar patterns, but the peak/nadir ratio was much more pronounced for LHdi than for LHtri, 18 versus 4. The numbers of SA residues per molecule were at a maximum around midcycle when the corresponding numbers of SU were at a minimum. The SU/SA ratio was at a minimum on cycle day 12. CONCLUSION: The results indicate that the LHdi and the FSHtri molecules play major roles in the natural ovarian stimulation. The SU/SA ratios per molecule favoured a prolonged circulatory half-life of all glycoforms at the midcycle phase. The observations may lead to more successful inductions of ovulation in anovulatory women.