Nitric oxide and long-term outcomes after kidney transplantation: Results of the TransplantLines cohort study.

Impaired endogenous nitric oxide (NO) production may contribute to graft failure and premature mortality in kidney transplant recipients (KTR). We investigated potential associations of 24-h urinary NOx (NO3- + NO2-) excretion (uNOx) with long-term outcomes. uNOx was determined by HPLC and GC-MS in 698 KTR and in 132 kidney donors before and after donation. Additionally, we measured urinary nitroso species (RXNO) by gas-phase chemiluminescence. Median uNOx was lower in KTR compared to kidney donors (688 [393-1076] vs. 1301 [868-1863] before donation and 1312 [982-1853] µmol/24 h after donation, P < 0.001). During median follow-up of 5.4 [4.8-6.1] years, 150 KTR died (61 due to cardiovascular disease) and 83 experienced graft failure. uNOx was inversely associated with all-cause mortality (HR per doubling of uNOx: 0.84 [95% CI 0.75-0.93], P < 0.001) and cardiovascular mortality (HR 0.78 [95% CI 0.67-0.92], P = 0.002). The association of uNOx with graft failure was lost when adjusted for renal function (HR per doubling of uNOx: 0.89 [95% CI 0.76-1.05], P = 0.17). There were no significant associations of urinary RXNO with outcomes. Our study suggests that KTR have lower NO production than healthy subjects and that lower uNOx is associated with a higher risk of all-cause and cardiovascular mortality.

Functional vitamin K status and risk of incident chronic kidney disease and microalbuminuria: a prospective general population-based cohort study.

BACKGROUND: Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate (Gla) protein (dp-ucMGP), a marker of vitamin K status, is associated with renal function and may serve as a potentially modifiable risk factor for incident chronic kidney disease (CKD). We aimed to assess the association between circulating dp-ucMGP and incident CKD. METHODS: We included 3969 participants with a mean age of 52.3 ± 11.6 years, of whom 48.0% were male, enrolled in the general population-based Prevention of REnal and Vascular ENd-stage Disease study. Study outcomes were incident CKD, defined as either development of an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or microalbuminuria. Associations of dp-ucMGP with these outcomes were quantified using Cox proportional hazards models and were adjusted for potential confounders. RESULTS: Median plasma dp-ucMGP was 363 [interquartile range (IQR) 219-532] pmol/L and mean serum creatinine- and serum cystatin C-based eGFR (eGFRSCr-SCys) was 95.4 ± 21.8 mL/min/1.73 m2. During 7.1 years of follow-up, 205 (5.4%) participants developed incident CKD and 303 (8.4%) developed microalbuminuria. For every doubling of plasma dp-ucMGP, hazard ratios for the development of incident CKD and microalbuminuria were 1.85 [95% confidence interval (CI) 1.59-2.16; P < 0.001] and 1.19 (95% CI 1.07-1.32; P = 0.001), respectively. These associations lost significance after adjustment for baseline eGFRSCr-SCys [0.99 (95% CI 0.88-1.12; P = 0.86)] and baseline age [1.03 (95% CI 0.94-1.14; P = 0.50)], respectively. CONCLUSIONS: The associations of plasma dp-ucMGP with incident CKD and microalbuminuria were driven by the respective baseline effects of renal function and age.

Incidence, prognostic factors, and outcomes of venous thromboembolism in critically ill patients: data from two prospective cohort studies.

BACKGROUND: The objective of this study was to describe the prevalence, incidence, prognostic factors, and outcomes of venous thromboembolism in critically ill patients receiving contemporary thrombosis prophylaxis. METHODS: We conducted a pooled analysis of two prospective cohort studies. The outcomes of interest were in-hospital pulmonary embolism or lower extremity deep vein thrombosis (PE-LDVT), in-hospital nonleg deep vein thrombosis (NLDVT), and 90-day mortality. Multivariable logistic regression analysis was used to evaluate the association between predefined baseline prognostic factors and PE-LDVT or NLDVT. Cox regression analysis was used to evaluate the association between PE-LDVT or NLDVT and 90-day mortality. RESULTS: A total of 2208 patients were included. The prevalence of any venous thromboembolism during 3 months before ICU admission was 3.6% (95% CI 2.8-4.4%). Out of 2166 patients, 47 (2.2%; 95% CI 1.6-2.9%) developed PE-LDVT and 38 patients (1.8%; 95% CI 1.2-2.4%) developed NLDVT. Renal replacement therapy (OR 3.5 95% CI 1.4-8.6), respiratory failure (OR 2.0; 95% CI 1.1-3.8), and previous VTE (OR 3.6; 95% CI 1.7-7.7) were associated with PE-LDVT. Central venous catheters (OR 5.4; 95% CI 1.7-17.8) and infection (OR 2.2; 95% CI 1.1-4.3) were associated with NLDVT. Occurrence of PE-LDVT but not NLDVT was associated with increased 90-day mortality (HR 2.7; 95% CI 1.6-4.6, respectively, 0.92; 95% CI 0.41-2.1). CONCLUSION: Thrombotic events are common in critically ill patients, both before and after ICU admittance. Development of PE-LDVT but not NLDVT was associated with increased mortality. Prognostic factors for developing PE-LDVT or NLDVT despite prophylaxis can be identified at ICU admission and may be used to select patients at higher risk in future randomized clinical trials. TRIAL REGISTRATION: NCT03773939.

Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study.

BACKGROUND: Serum free thiols (R-SH, sulfhydryl groups) reliably reflect systemic oxidative stress. Since serum free thiols are rapidly oxidized by reactive species, systemic oxidative stress is generally associated with reduced serum free thiol levels. Free thiols associate with favorable disease outcomes in many patient cohorts, and the current hypothesis is that oxidative stress might also play an important role in cardiovascular disease. In this study, we aimed to establish the role of serum free thiols in the general population by investigating their relationship with the risk of cardiovascular (CV) events and all-cause mortality. METHODS: Participants (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study from the general population were included. At baseline, serum levels of free thiols were quantified and adjusted to total protein levels. Protein-adjusted serum free thiol levels were studied for their associations with clinical and biochemical parameters, as well as with the risk of CV events and all-cause mortality. RESULTS: The mean protein-adjusted serum free thiol level was 5.05 ± 1.02 µmol/g of protein. Protein-adjusted serum free thiols significantly predicted the risk of CV events, even after adjustment for potential confounding factors (hazard ratio [HR] per doubling 0.68 [95% confidence interval [CI] 0.47-1.00], P = 0.048). Similarly, protein-adjusted serum free thiols were significantly predictive of the risk of all-cause mortality (HR per doubling 0.66 [95% CI 0.44-1.00], P = 0.050). Stratified analyses revealed lower HRs for subjects with a lower body mass index (BMI), without hypertension, and without diabetes. Conversely, HRs were lower in subjects with albuminuria. CONCLUSIONS: In this large population-based cohort study, serum free thiols significantly predicted the risk of CV events and all-cause mortality. Our results highlight the potential significance and clinical applicability of serum free thiols since they are amendable to therapeutic intervention.

Diagnostic accuracy of evaluation of suspected syncope in the emergency department: usual practice vs. ESC guidelines.

BACKGROUND: Syncope is a frequent reason for referral to the emergency department. After excluding a potentially life-threatening condition, the second objective is to find the cause of syncope. The objective of this study was to assess the diagnostic accuracy of the treating physician in usual practice and to compare this to the diagnostic accuracy of a standardised evaluation, consisting of thorough history taking and physical examination by a research physician. METHODS: This prospective cohort study included suspected (pre) syncope patients without an identified serious underlying condition who were assessed in the emergency department. Patients were initially seen by the initial treating physician and the usual evaluation was performed. A research physician, blinded to the findings of the initial treating physician, then performed a standardised evaluation according to the ESC syncope guidelines. Diagnostic accuracy (proportion of correct diagnoses) was determined by expert consensus after long-term follow-up. RESULTS: One hundred and one suspected (pre) syncope patients were included (mean age 59 ± 20 years). The usual practice of the initial treating physicians did not in most cases follow ESC syncope guidelines, with orthostatic blood pressure measurements made in only 40% of the patients. Diagnostic accuracy by the initial treating physicians was 65% (95% CI 56-74%), while standardised evaluation resulted in a diagnostic accuracy of 80% (95% CI 71-87%; p = 0.009). No life-threatening causes were missed. CONCLUSIONS: Usual practice of the initial treating physician resulted in a diagnostic accuracy of 65%, while standardised practice, with an emphasis on thorough history taking, increased diagnostic accuracy to 80%. Results suggest that the availability of additional resources does not result in a higher diagnostic accuracy than standardised evaluation, and that history taking is the most important diagnostic test in suspected syncope patients. Netherlands Trial Registration: NTR5651. Registered 29 January 2016, https://www.trialregister.nl/trial/5532.

Intermediate Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis: Systematic Review with Meta-Analysis and Trial Sequential Analysis.

Different doses of low-molecular-weight heparin (LMWH) are registered and used for thrombosis prophylaxis. We assessed benefits and harms of thrombosis prophylaxis with a predefined intermediate-dose LMWH compared with placebo or no treatment in patients at risk of venous thromboembolism (VTE). We performed a systematic review with meta-analyses and trial sequential analyses (TSA) following The Cochrane Handbook for Systematic Reviews of Interventions. Medline, Cochrane CENTRAL, Web of Science, and Embase were searched up to December 2018. Trials were evaluated for risk of bias and quality of evidence was assessed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Seventy randomized trials with 34,046 patients were included. Eighteen (26%) had overall low risk of bias. There was a small statistically significant effect of LMWH on all-cause mortality (risk ratio [RR]: 0.96; TSA-adjusted confidence interval [TSA-adjusted CI]: 0.94-0.98) which disappeared in sensitivity analyses excluding ambulatory cancer patients (RR: 0.99; TSA-adjusted CI: 0.84-1.16). There was moderate-quality evidence for a statistically significant beneficial effect on symptomatic VTE (odds ratio [OR]: 0.59; TSA-adjusted CI: 0.53-0.67; number needed to treat [NNT]: 76; 95% CI: 60-106) and a statistically significant harmful effect on major bleeding (Peto OR: 1.66; TSA-adjusted CI: 1.31-2.10; number needed to harm [NNH]: 212; 95% CI: 142-393). There were no significant intervention effects on serious adverse events. The use of intermediate-dose LMWH for thrombosis prophylaxis compared with placebo or no treatment was associated with a small statistically significant reduction of all-cause mortality that disappeared in sensitivity analyses excluding trials that evaluated LMWH for anticancer treatment. Intermediate-dose LMWH provides benefits in terms of VTE prevention while it increases major bleeding.

Feasibility of hospital-initiated non-facilitator assisted advance care planning documentation for patients with palliative care needs.

BACKGROUND: Advance Care Planning (ACP) and its documentation, accessible to healthcare professionals regardless of where patients are staying, can improve palliative care. ACP is usually performed by trained facilitators. However, ACP conversations would be more tailored to a patient's specific situation if held by a patient's clinical healthcare team. This study assesses the feasibility of ACP by a patient's clinical healthcare team, and analyses the documented information including current and future problems within the palliative care domains. METHODS: This multicentre study was conducted at the three Groningen Palliative Care Network hospitals in the Netherlands. Patients discharged from hospital with a terminal care indication received an ACP document from clinical staff (non-palliative care trained staff at hospitals I and II; specialist palliative care nurses at hospital III) after they had held ACP conversations. An anonymised copy of this ACP document was analysed. Documentation rates of patient and contact details were investigated, and documentation of current and future problems were analysed both quantitatively and qualitatively. RESULTS: One hundred sixty ACP documents were received between April 2013 and December 2014, with numbers increasing for each consecutive 3-month time period. Advance directives were frequently documented (82%). Documentation rates of current problems in the social (24%), psychological (27%) and spiritual (16%) domains were low compared to physical problems (85%) at hospital I and II, but consistently high (> 85%) at hospital III. Of 545 documented anticipated problems, 92% were physical or care related in nature, 2% social, 5% psychological, and < 1% spiritual. Half of the anticipated non-physical problems originated from hospital III. CONCLUSIONS: Hospital-initiated ACP documentation by a patient's clinical healthcare team is feasible: the number of documents received per time period increased throughout the study period, and overall, documentation rates were high. Nonetheless, symptom documentation predominantly regards physical symptoms. With the involvement of specialist palliative care nurses, psychological and spiritual problems are addressed more frequently. Whether palliative care education for non-palliative care experts will improve identification and documentation of non-physical problems remains to be investigated.

Orthostatic blood pressure recovery patterns in suspected syncope in the emergency department.

INTRODUCTION: Orthostasis is a frequent trigger for (pre)syncope but some forms of orthostatic (pre)syncope have a worse prognosis than others. Routine assessment of orthostatic BP in the ED can detect classic orthostatic hypotension, but often misses these other forms of orthostatic (pre)syncope. This study aimed to determine the frequency of abnormal orthostatic BP recovery patterns in patients with (pre)syncope by using continuous non-invasive BP monitoring. METHODS: We performed a prospective cohort study in suspected patients with (pre)syncope in the ED of a tertiary care teaching hospital between January and August 2014. Orthostatic BP was measured during the active lying-to-standing test with Nexfin, a continuous non-invasive finger arterial pressure measurement device. Orthostatic BP recovery patterns were defined as normal BP recovery, initial orthostatic hypotension, delayed BP recovery, classic orthostatic hypotension and reflex-mediated hypotension. RESULTS: Of 116 patients recruited, measurements in 111 patients (age 63 years, 51% male) were suitable for analysis. Classic orthostatic hypotension was the most prevalent abnormal BP pattern (19%), but only half of the patients received a final diagnosis of orthostatic hypotension. Initial orthostatic hypotension and delayed BP recovery were present in 20% of the patients with (pre)syncope of whom 45% were diagnosed as unexplained syncope. Reflex-mediated hypotension was present in 4% of the patients. CONCLUSION: Continuous non-invasive BP measurement can potentially identify more specific and concerning causes of orthostatic (pre)syncope. Correct classification is important because of different short-term and long-term clinical implications.

Urinary sulfur metabolites associate with a favorable cardiovascular risk profile and survival benefit in renal transplant recipients.

In post-transplant conditions, sulfur may be protective by intermediate conversion to hydrogen sulfide and thiosulfate. However, sulfate, the end product of sulfur-containing amino acids (SAAs), contributes to metabolic acid load and may adversely influence acid-base homeostasis. We investigated the association of urinary sulfur metabolites with cardiometabolic parameters in renal transplant recipients (RTRs) and analyzed their predictive capacity for mortality. We studied urinary sulfate and thiosulfate excretion in 24-hour urine samples from 707 RTRs at a median 5.4 years (interquartile range, 1.9 to 12.2) after transplantation as well as from 110 controls. Diet was assessed for SAA content and various risk factors were measured. Urinary sulfate was similar, whereas thiosulfate was higher in RTRs versus controls. SAA intake was lower in RTRs compared with controls and correlated with sulfate but not thiosulfate excretion. Sulfate beneficially associated with eGFR, net acid excretion, systolic BP, high-sensitivity C-reactive protein, N-terminal probrain natriuretic peptide, and proteinuria (all P≤0.01). Thiosulfate beneficially associated with eGFR, serum acidity, high-sensitivity C-reactive protein, and N-terminal probrain natriuretic peptide (all P≤0.001). During a median 27 months (interquartile range, 22-36) of follow-up, 47 RTRs died. After adjustment for age, sex, and eGFR, hazard ratios for mortality were 0.87 (95% confidence interval, 0.82 to 0.92; P<0.001) for urinary sulfate and 0.60 (95% confidence interval, 0.41 to 0.59; P=0.01) for thiosulfate. Thus, despite the association of urinary sulfate with metabolic acid load, urinary sulfate and thiosulfate beneficially associated with survival in RTRs, possibly by influencing cardiovascular parameters. Intervention studies with exogenous sulfur are warranted to elucidate mechanisms underlying these promising associations in RTRs.

Families' importance in nursing care-families' opinions: a cross-sectional survey study in the homecare setting.

BACKGROUND: Informal care is an essential part of support provided in the homecare setting. To ensure effective healthcare provision, good communication and collaboration between informal and formal care providers are crucial. To achieve this aim, it is necessary to have a clear understanding of the perspectives of all stakeholders. In the scientific literature, limited knowledge is available regarding family members' opinions about their involvement in care. To date, no instruments have been developed that accurately measure these opinions. This study aims to elucidate the opinions of family members about their involvement in nursing care. METHODS: A cross-sectional survey approach was employed. The methodological steps in this study were (1) convert the Families' Importance in Nursing Care-Nurses' Attitudes (FINC-NA) from a nurses' perspective to a family perspective and thus develop the Families' Importance in Nursing Care-Families' Opinions (FINC-FO) and (2) measure families' opinions regarding their involvement in home nursing care. The questionnaire was sent to 3,800 patients with activated patient portals, which accounts for about 17% of the total patient base. Responses were received from 1,339 family members, a response rate of 35%. RESULTS: The developed FINC-FO questionnaire showed homogeneity and internal consistency. The results of the questionnaire indicate that family members consider it important to be involved in care and that they wish to be acknowledged as participants in discussions about care (planning) but are less inclined to actively participate in the provision of care by nurses. Family members expressed less explicit opinions about their own support needs. Factors such as level of education, type of partnership, and amount of care provided are seemingly associated with these opinions. CONCLUSIONS: Family members in the homecare setting wish to be involved in discussions about care (planning). The transition in care from primarily formal to more informal care necessitates an awareness and clear definition-on part of both healthcare professionals and families-of their respective roles in the provision of care. Communication about wishes, expectations, and the need for support in care is essential to ensure quality of care and that the family can sustain caregiving.

Validity and diagnostic overlap of functional somatic syndrome diagnoses.

OBJECTIVE: We present the first study that investigates the validity and the diagnostic overlap of the three main functional somatic syndrome (FSS) diagnoses, i.e. chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), irrespective of help-seeking behaviour or diagnostic habits, and irrespective of differences in diagnostic thresholds for chronicity or symptom interference. METHODS: This cross-sectional analysis was performed in 89,781 participants of the general-population cohort Lifelines. Diagnostic criteria for CFS (Centers for Disease Control and Prevention), FM (American College of Rheumatology) and IBS (Rome IV) were assessed by questionnaire. Additional items were added to enable studying the effects of differences in thresholds for minimum symptom chronicity (varying from three for FM to six months for CFS and IBS), and symptom interference (required for CFS but not for FM and IBS). RESULTS: The diagnostic criteria were met by 3.1% for CFS, 6.6% for FM, and 5.5% for IBS participants. The number of participants that met criteria for all three diagnoses was 45 times higher than what would have been expected based on chance. After alignment of the chronicity and symptom interference criteria to circumvent differences in diagnostic thresholds, the overlap between diagnoses increased to 152 times. Furthermore, there was a similar pattern of symptom occurrence, particularly for those fulfilling diagnostic criteria for CFS and FM. CONCLUSION: The diagnostic overlap of different FSS was much higher than would be expected by chance, and substantially increased when FSS were more chronic and serious in nature.

The impact of socioeconomic factors, social determinants, and ethnicity on the utilization of glucose sensor technology among persons with diabetes mellitus: a narrative review.

Continuous glucose monitoring (CGM) usage has been shown to improve disease outcomes in people living with diabetes by facilitating better glycemic management. However, previous research has suggested that access to these devices can be influenced by nonmedical factors such as socioeconomic status and ethnicity. It is critical that equitable access to CGM devices is ensured as people from those groups experience poorer diabetes-related health outcomes. In this narrative review, we provide an overview of the various healthcare systems worldwide and how socioeconomic status, social context, and ethnicity shape device usage and the associated health outcomes. In general, we found that having a lower socioeconomic status and belonging to an ethnic minority group negatively impact CGM usage. While financial means proved to be an important mediator in this process, it was not the sole driver as disparities persisted even after adjustment for factors such as income and insurance status. Recommendations to increase CGM usage for people of a lower socioeconomic status and ethnic minorities include increasing the availability of financial, administrative, and educational support, for both patients and healthcare providers. However, recommendations will vary due to local country-specific circumstances, such as reimbursement criteria and healthcare ecosystems.

The effects of income, education, social factors and ethnicity on the use of glucose sensors by people with diabetes mellitus: a narrative review Over the recent years, glucose sensors have transformed the monitoring of glucose levels in people with diabetes. However, access to these devices has been determined by the healthcare systems and the associated rules and regulations, as well as perceptions from providers and patients about who would benefit most from these devices. In this narrative review, we performed an expansive literature search into what is known about factors that negatively impact the access to glucose sensors, and how these factors might be addressed. From this, we learn that, depending on the healthcare system, financial means form a major driver behind the disparities in glucose sensor use. However, factors such as ethnicity and provider and patient perceptions also can negatively affect one's chances to obtain a glucose sensor. Furthermore, we found that a successful program aimed at resolving the found disparities in glucose sensor use must be multi-faceted, and must include measures aimed at financial support, the use of objective and simple criteria for sensor eligibility, as well as educational support for both patients and providers.

Creatinine, cystatin C, muscle mass, and mortality: Findings from a primary and replication population-based cohort.

BACKGROUND: Serum creatinine is used as initial test to derive eGFR and confirmatory testing with serum cystatin C is recommended when creatinine-based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of serum creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision-making. METHODS: We included 8437 community-dwelling adults enrolled in the Dutch PREVEND study and 5033 in the US NHANES replication cohort. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification. RESULTS: Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1-Q3) serum creatinine and cystatin C were 71 (61-80) and 80 (62-88) µmol/L and 0.87 (0.78-0.98) and 0.91 (0.80-1.10) mg/L, respectively. Higher serum creatinine was associated with greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1636 (19%) deaths were registered over a median follow-up of 12.9 (5.8-16.3) years with a 10-year mortality rate (95% CI) of 7.6% (7.1-8.2%). In the NHANES, 1273 (25%) deaths were registered over a median follow-up of 17.9 (17.3-18.5) years with a 10-year mortality rate of 13.8% (12.8-14.7%). Both markers were associated with increased mortality. Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality, while the association between serum cystatin C and increased mortality strengthened. The shapes of the associations in the PREVEND study and NHANES were almost identical. CONCLUSIONS: The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.

Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.

OBJECTIVE: To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and TTR variant (TTRv) carriers. METHODS: sNfL levels were assessed longitudinally in persistently asymptomatic TTRv carriers (N = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (N = 8), in TTRv carriers who developed polyneuropathy (N = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (N = 20) or TTR-silencer (N = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay. RESULTS: sNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic TTRv carriers. In all TTRv carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment. CONCLUSION: sNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic TTRv carriers and in monitoring of disease progression and treatment effect.

Heart rate variability parameters do not correlate with pain intensity in healthy volunteers.

OBJECTIVE: When patients cannot indicate pain, physiological parameters may be useful. We tested whether heart rate variability (HRV) parameters, as reflection of sympathetic and vagal tone, can be used to quantify pain intensity. DESIGN: Prospective study. SUBJECTS AND SETTING: A standardized heat stimulus was applied to the forearm in 75 healthy volunteers during three study periods of 2 minutes. METHODS: Before and after each application, pain intensity was measured by a visual analog scale (VAS) and inter beat interval (IBI) was recorded. Standard deviation of normal to normal beat intervals (SDNN) of the IBI, the power of the low (LF, 0.07-0.14 Hz) and high frequency (HF, 0.15-0.50 Hz) band, and LF/HF ratio were calculated. Log transformation resulted in normal distribution. Correlation between HRV parameters and pain intensity was assessed by Pearson's correlation coefficient. RESULTS: Data from 73 volunteers (44 women) could be analyzed. The mean age was 30 ± 11 years. Compared with baseline, during all heat periods, pain intensity measured by VAS increased from 2 ± 3 mm, 3 ± 5 mm, and 2 ± 4 mm, to 40 ± 20 mm, 42 ± 21 mm, and 44 ± 22 mm, respectively. Log transformed SDNN (lnSDNN) and LF (lnLF) decreased; lnSDNN from 4.0 ± 0.4 to 3.9 ± 0.5, P = 0.002; 4.0 ± 0.4 to 3.9 ± 0.5, P = 0.016; and 4.1 ± 0.4 to 3.9 ± 0.4, P = 0.004, respectively; lnLF from 6.3 ± 1.0 to 6.1 ± 1.2, P = 0.001; 6.4 ± 1.0 to 6.2 ± 1.1, P = 0.019; and 6.5 ± 1.0 to 6.2 ± 1.1, P = 0.020, respectively. No correlation of any HRV parameter with VAS score was found. CONCLUSION: HRV parameters may detect responses to heat pain, but are not suitable to assess pain intensity.

The added value of family-centered rounds in the hospital setting: A systematic review of systematic reviews.

BACKGROUND: Family engagement in care for adult inpatients may improve shared decision making in the hospital and the competence and preparedness of informal caregivers to take over the care at home. An important strategy to involve family members in hospital care processes is to include them in (ward) rounds, also called 'family-centered rounds'(FCRs). OBJECTIVES: Summarize the evidence regarding the added value of FCRs from the perspectives of patients, family, and healthcare professionals. METHODS: A review protocol was registered a priori with PROSPERO (number CRD42022320915). The electronic databases PubMed, CINAHL, and PsycInfo were searched for English-written systematic reviews with a focus on FCRs. The results and methods were presented in line with the PRISMA guidelines, and the methodological quality of the included reviews was assessed using the adapted version of the AMSTAR tool. RESULTS: Of the 207 initial records, four systematic reviews were identified covering a total of 67 single studies, mainly performed in critical and pediatric care. Added values of FCR were described at review level, with references to single studies. All four systematic reviews reported an improvement in satisfaction among patients, family, and healthcare professionals, whereby satisfaction is linked to improved communication and interaction, improved situational understanding, inclusion of family in the decision-making process, and improved relationships within the care situation. CONCLUSION: Although only limited research has been conducted on the value of FCRs in the adult non-critical care setting, and despite the existence of a variety of outcome measures, the results available from the pediatric and acute care setting are positive. The findings of the sole study in an adult non-critical patient population are in line with these results. Further research in adult non-critical care is required to verify its effects in this setting.

Plasma bilirubin and late graft failure in renal transplant recipients.

Exogenous bilirubin has been shown to protect against oxidative stress in ischemia-reperfusion injury. Oxidative stress has been implicated in the pathophysiology of chronic transplant dysfunction leading to late graft failure after renal transplantation. We prospectively investigated whether high endogenous bilirubin is protective against development of late graft failure in renal transplant recipients (RTR). Baseline data were collected between August 2001 and July 2003 in nonicteric outpatient RTR with a functioning graft for >1 year. At baseline, bilirubin and liver enzymes were measured using routine assays on a Merck Mega analyzer. Graft failure was prospectively recorded until May 19 2009. During follow-up for 7.1 [6.2-7.2] years, 55 RTR developed graft failure. We found that circulating levels of bilirubin are inversely associated with late graft failure in RTR (HR = 0.29 [95% CI: 0.16-0.52], P < 0.001). This association was independent of potential confounders, including creatinine clearance, urinary protein excretion, calcineurin inhibitors, and gender (HR = 0.31 [95% CI: 0.15-0.62] P = 0.001). Our findings are consistent with a protective effect of increased endogenous bilirubin against development of late graft failure in RTR. If our findings are confirmed by other studies, intervention with endogenous or exogenous bilirubin may be of interest for long-term preservation of renal function in RTR.