Apathy Symptoms, Physical and Cognitive Function, Health-Related Quality of Life, and Mortality in Older Patients With CKD: A Longitudinal Observational Study.

RATIONALE & OBJECTIVE: Apathy reflects diminished motivation, goal-directed behavior, and emotions, as well as less engagement in social interactions. Apathy overlaps with depression and is associated with cognitive decline. In the older individuals with chronic kidney disease (CKD), both depression and cognitive impairments are common, but apathy symptoms have been underreported. We investigated the occurrence of apathy symptoms and their associations with physical and cognitive functioning, health-related quality of life (HRQoL), and mortality in older patients with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 180 outpatients aged≥65 years with estimated glomerular filtration rate≤20mL/min/1.73m2 from 5 Dutch nephrology centers. EXPOSURE: Apathy symptoms at baseline were considered present when a Geriatric Depression Scale's 3-item apathy subscale score was≥2 points. OUTCOME: Physical and cognitive functioning, HRQoL (assessed in annual geriatric assessments), and 4-year mortality. ANALYTICAL APPROACH: Linear regression for cross-sectional associations, linear regression models for longitudinal associations, and Cox regression models for mortality over 4 years of observation. RESULTS: Apathy symptoms were present in 64 patients (36%; 67% men; median age 75.5 years), of whom 32 (50%) had no depressive symptoms. At baseline, the presence of apathy symptoms was associated with significantly more frailty, more functional dependence, less physical capacity, lower visuoconstructive performance, worse delayed recall, and lower HRQoL scores. The presence of apathy symptoms at baseline was also associated with a higher mortality risk (hazard ratio, 2.3 [95% CI, 1.3-4.2], P=0.005 adjusted for age, sex, and high education level), but not with changes in physical and cognitive functioning or HRQoL during the follow-up period. LIMITATIONS: Risk of selection bias and residual confounding. CONCLUSIONS: Apathy symptoms were highly prevalent and associated with concurrent lower physical and cognitive status, lower HRQoL, and increased mortality. These findings highlight apathy as a potentially important clinical phenotype in older CKD patients. PLAIN-LANGUAGE SUMMARY: We observed that older kidney patients often present apathy symptoms, such as less motivation, fewer goal-directed behaviors, fewer emotions, and less social engagement. Prior research has not extensively described apathy in kidney disease. We investigated the link between apathy symptoms and poor outcomes. We measured physical functioning, cognitive functioning, and quality of life. We learned that one-third of our older kidney patients showed symptoms of apathy, only half of whom had symptoms of depression. Patients with apathy symptoms showed lower quality of life and lower physical and cognitive performance. They also had a higher risk of death. These findings highlight the need for awareness of apathy symptoms in older kidney patients.

Impact of geriatric co-management on outcomes in hospitalised cardiology patients aged 85 and over.

OBJECTIVE: Cardiovascular disease and frailty are common among the population aged 85+. We hypothesised these patients might benefit from geriatric co-management, as has been shown in other frail patient populations. However, there is limited evidence supporting geriatric co-management in older, hospitalised cardiology patients. METHODS: A retrospective cohort study was performed in a large teaching hospital in the Netherlands. We compared patients aged 85 and over admitted to the cardiology ward before (control group) and after the implementation of standard geriatric co-management (intervention group). Data on readmission, mortality, length of stay, number of consultations, delirium, and falls were analysed. RESULTS: The data of 1163 patients were analysed (n = 542 control, n = 621 intervention). In the intervention group, 251 patients did not receive the intervention because of logistic reasons or the treating physician's decision. Baseline characteristics were comparable in the intervention and control groups. Patients in the intervention group had a shorter length of stay (-1 day, p = 0.01) and were more often discharged to a geriatric rehabilitation facility (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.10-3.54, p = 0.02) compared with the control patients. Other outcomes were not significantly different between the groups. CONCLUSIONS: After implementation of standard geriatric co-management for hospitalised cardiology patients aged 85 and over, the length of hospital stay shortened and the number of patients discharged to a geriatric rehabilitation facility increased. The adherence to geriatric team recommendations was high. Geriatric co-management would appear to optimise care for older hospitalised patients with cardiac disease.

Concurrent lithium and haemodialysis treatment: Clinical recommendations based on the literature and a multicentre survey.

INTRODUCTION: Lithium has an irreplaceable role in the treatment of severe mood disorders, but declining renal function associated with its use leads to clinical dilemmas. Although not often applied, and requiring close monitoring and multidisciplinary actions, concurrent lithium and haemodialysis treatment (CLHT) is a feasible option. To our knowledge, however, there are no detailed consensus- or evidence-based treatment guidelines or directives on its delivery. METHODS: To fill this gap, we reviewed the literature and surveyed psychiatrists and nephrologists with experience in CLHT using a self-designed questionnaire. Our goal was to form an integrated picture of the current knowledge and clinical practices of CLHT and formulate practical recommendations for colleagues being confronted with patients with renal dysfunction requiring lithium to help manage their mood disorder. RESULTS: We identified 14 case reports and case series describing CLHT and one systematic review concluding CLHT to be effective. Ten nephrologists and six psychiatrists practising in the Netherlands completed our questionnaire, providing details on collaboration, lithium dosing regimens, serum level evaluations and additional amenities and services they deemed necessary during CLHT delivery. DISCUSSION: We found that CLHT appears to be safe and effective and argue that delivery is a shared responsibility and needs continuous multidisciplinary finetuning. To facilitate delivery, we provide a flowchart for the initiation or reinstatement of lithium therapy in haemodialysis patients and a practical guide for CLHT, including an easy-to-use rule of thumb for calculating the lithium target dose.

Kidney transplantation or dialysis in older adults-an interview study on the decision-making process.

BACKGROUND: In older patients with end-stage kidney disease (ESKD), the choice between kidney transplantation (KT) and dialysis may be more complex than in younger patients because of a higher prevalence of comorbidities and frailty. This study aims to provide greater insight into the current decision-making process by exploring the expectations, experiences and health outcome priorities of all stakeholders. METHODS: We performed semi-structured interviews with patients ≥65 years with ESKD (eGFR <15 ml/min/1.73m2, KT recipient or treated with dialysis), patients' relatives and healthcare professionals (nephrologists, nurses and medical social workers). Interviews were conducted until data saturation and thematically analysed. RESULTS: We performed 36 interviews (patients n = 18, relatives n = 5, healthcare professionals n = 13). Thematic analysis revealed five themes. Older patients' health outcome priorities were mostly related to quality of life (QOL). Individual older patients showed marked differences in the preferred level of engagement during the decision-making process (varying from 'wants to be in the lead' to 'follows the nephrologist') and in informational needs (varying from evidence-based to experience-based). On the contrary, healthcare professionals were quite unanimous on all aspects. They focused on determining eligibility for KT as start of the decision-making process, on clear and extensive information provision and on classical, medical outcomes. CONCLUSIONS: The decision-making process could benefit from early identification of older patients' values, needs and health outcome priorities, in parallel with assessment of KT eligibility and before discussing the treatment options, and the explicit use of this information in further steps of the decision-making process.

Mechanosensitive MiRs regulated by anabolic and catabolic loading of human cartilage.

OBJECTIVE: Elucidation of whether miRs are involved in mechanotransduction pathways by which cartilage is maintained or disturbed has a particular importance in our understanding of osteoarthritis (OA) pathophysiology. The aim was to investigate whether mechanical loading influences global miR-expression in human chondrocytes and to identify mechanosensitive miRs responding to beneficial and non-beneficial loading regimes as potential to obtain valuable diagnostic or therapeutic targets to advance OA-treatment. METHOD: Mature tissue-engineered human cartilage was subjected to two distinct loading regimes either stimulating or suppressing proteoglycan-synthesis, before global miR microarray analysis. Promising candidate miRs were selected, re-evaluated by qRT-PCR and tested for expression in human healthy vs OA cartilage samples. RESULTS: After anabolic loading, miR microarray profiling revealed minor changes in miR-expression while catabolic stimulation produced a significant regulation of 80 miRs with a clear separation of control and compressed samples by hierarchical clustering. Cross-testing of selected miRs revealed that miR-221, miR-6872-3p, miR-6723-5p were upregulated by both loading conditions while others (miR-199b-5p, miR-1229-5p, miR-1275, miR-4459, miR-6891-5p, miR-7150) responded specifically after catabolic loading. Mechanosensitivity of miR-221 correlated with pERK1/2-activation induced by both loading conditions. The miR-response to loading was transient and a constitutive deregulation of mechano-miRs in OA vs healthy articular cartilage was not observed. CONCLUSIONS: MiRs with broader vs narrower mechanosensitivity were discovered and the first group of mechanosensitive miRs characteristic for non-beneficial loading was defined that may shape the proteome differentially when cartilage tissue is disturbed. The findings prompt future investigations into miR-relevance for mechano-responsive pathways and the corresponding miR-target molecules.

Cells under pressure - the relationship between hydrostatic pressure and mesenchymal stem cell chondrogenesis.

Early osteoarthritis (OA), characterised by cartilage defects, is a degenerative disease that greatly affects the adult population. Cell-based tissue engineering methods are being explored as a solution for the treatment of these chondral defects. Chondrocytes are already in clinical use but other cell types with chondrogenic properties, such as mesenchymal stem cells (MSCs), are being researched. However, present methods for differentiating these cells into stable articular-cartilage chondrocytes that contribute to joint regeneration are not effective, despite extensive investigation. Environmental stimuli, such as mechanical forces, influence chondrogenic response and are beneficial with respect to matrix formation. In vivo, the cartilage is subjected to multiaxial loading involving compressive, tensile, shear and fluid flow and cellular response. Tissue formation mechanobiology is being intensively studied in the cartilage tissue-engineering research field. The study of the effects of hydrostatic pressure on cartilage formation belongs to the large area of mechanobiology. During cartilage loading, interstitial fluid is pressurised and the surrounding matrix delays pressure loss by reducing fluid flow rate from pressurised regions. This fluid pressurisation is known as hydrostatic pressure, where a uniform stress around the cell occurs without cellular deformation. In vitro studies, examining chondrocytes under hydrostatic pressure, have described its anabolic effect and similar studies have evaluated the effect of hydrostatic pressure on MSC chondrogenesis. The present review summarises the results of these studies and discusses the mechanisms through which hydrostatic pressure exerts its effects.

Degenerative isolated cartilage defects of the patellofemoral joint are associated with more severe symptoms compared to trauma-related defects: results of the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: The purpose of this study was to utilize data from the German Cartilage Registry (KnorpelRegister DGOU) to examine the hypothesis that degenerative cartilage defects of the patellofemoral joint are associated with more severe clinical symptoms compared to trauma-related defects. METHODS: All patients with isolated focal cartilage defects of the patellofemoral joint registered in the German Cartilage Registry until May 2017 were included in the study. Patients with previous surgery of the ipsilateral knee were excluded. Baseline data including etiology (traumatic, degenerative), size, location and ICRS grade of the cartilage defects as well as the duration of symptoms were analyzed. Clinical symptoms were evaluated by means of the numeric analog scale (NAS) for pain and the Knee injury and Osteoarthritis Outcome Score (KOOS). Group comparisons were performed using the Mann-Whitney-U test along with the Chi-squared test and Fisher's exact test. A bivariate correlation analysis and a multivariable linear regression analysis were performed to investigate the association between the defect characteristics and the clinical scores. RESULTS: A total of 423 patients (203 traumatic and 220 degenerative defects) were included. Isolated degenerative cartilage defects were found to have significantly more trochlear locations (28% vs. 18%; p = 0.006), significantly less ICRS grade 4 lesions (50% vs. 73%; p = 0.002) and a significantly smaller defect size [median 300 (IQR 105-400) vs. 300 (200-400) mm2] when compared to those from traumatic etiology. Traumatic defects showed significantly better KOOS-ADL [77 (60-90) vs. 69 (56-82); p = 0.005], KOOS-pain [69 (56-81) vs. 61 (47-75); p = 0.001] and NAS [2 (1-5) vs. 4 (1-6); p = 0.005] scores compared to degenerative defects. The correlation analysis revealed only weak correlations between the quantitative defect characteristics and clinical scores. CONCLUSIONS: Degenerative isolated cartilage defects in the patellofemoral joint are associated with more severe clinical symptoms in comparison to trauma-related defects. Additionally, they show a larger variance regarding their location with more trochlear defects. LEVEL OF EVIDENCE: III.

Bone block augmentation from the iliac crest for treatment of deep osteochondral defects of the knee resembles biomechanical properties of the subchondral bone.

PURPOSE: Bone block augmentation from the iliac crest can be used for reconstruction of the osteochondral unit to restore the underlying subchondral bone upon restoration of the cartilaginous layer via matrix-induced chondrocyte transplantation. To critically understand the successful restoration of the defect, biomechanical and histological analysis of the implanted bone blocks is required. The aim of the study was to analyse the ability of the bone block technique to restore huge bone defects by mimicking the physiological subchondral zone. METHODS: The experiments were performed using lateral femoral condyles and iliac crest bone grafts from the same cadavers (n = 6) preserved using the Thiel method. CT scans were made to evaluate bone pathology. Bone mineral density of all specimens was evaluated in the femoral head prior to testing. A series of tests were conducted for each pair of specimens. A static compression test was performed using an electro dynamic testing machine with maximal strength and failure behavior analyzed. Biomechanical tests were performed in the medial-lateral direction for iliac crest and for femoral condyles with and without removal of the cartilage layer. Histological analysis was performed on decalcified specimens for comparison of the condyle at lesion site and the graft. RESULTS: No significant difference in failure load could be found for iliac crest (53.3-180.5 N) and femoral condyle samples upon cartilage removal (38.5-175.1 N) (n.s.). The femoral condyles with an intact cartilage layer showed significantly higher loads (118.3-260.4N) compared to the other groups indicating that native or regenerated cartilage can further increase the failure load (p < 0.05). Bone mineral density significantly influenced failure load in all study groups (p < 0.05). Histological similarity of the cancellous bone in the femoral condyle and in the iliac crest was observed. However, within the subchondral zone, there was a higher density of sponge like organized trabeculae in the bone samples from the iliac crest. Tide mark was only detected at the osteochondral interface in femoral condyles. CONCLUSION: This study demonstrated that, bone blocks derived from the iliac crest allow a biomechanical appropriate and stable restoration of huge bony defects by resembling the subchondral zone of the femoral condyle. Therefore, bone augmentation from the iliac crest combined with matrix-induced autologous chondrocyte transplantation seems to be a reasonable method to treat these challenging injuries.

Timing of anterior cruciate ligament reconstruction within the first year after trauma and its influence on treatment of cartilage and meniscus pathology.

PURPOSE: Anterior cruciate ligament (ACL) ruptures are often associated with primary meniscal and cartilage lesions. Late reconstruction of ACL-deficient knees may increase the risk of developing secondary meniscal and cartilage lesions; hence, the timing of ACL repair is of the utmost importance. Because meniscus outcome is also a potential predictor for osteoarthritis (OA), this study compared ACL repair within the first 6 months after injury to that of surgery conducted 7-12 months after injury with regard to the incidence of meniscal and cartilage lesions. METHODS: This prospective cross-sectional study included all complete isolated primary ACL ruptures treated in our institution within 1 year after trauma over a 12-month period. Exclusion criteria were revision ACL, complex ligament injuries, previous knee surgery, and missing injury data. Cartilage lesions were classified according to the score established by the International Cartilage Repair Society (ICRS score) and meniscal tears according to their treatment options. RESULTS: Two hundred and thirty-three of 730 patients (162 men, 71 women) with ACL repair met the inclusion criteria. 86.3 % of surgical interventions were conducted within 6 months and 13.7 % after 6 months of trauma. Severe cartilage lesions grade III-IV did not significantly differ between the different time points of ACL repair (<6 months 39.9 %; >6 months 31.3 %; p = n.s.). Medial meniscus lesions received significantly higher meniscal repair in early compared to delayed ACL repair. Significantly higher rate of meniscal repair of the medial meniscus was seen in cases of early ACL repair compared to delayed (<6 months 77.2 %, >6 months 46.7; p = 0.022). The rate of medial meniscal repair in early ACL repair was significantly higher for women (89.5-0 %; p = 0.002), however, not for men (73.3-53.8 %; p = n.s.). No differences were found for lateral meniscal lesions, with regard to neither the different time points (p = n.s.) nor the sex (p = n.s.). CONCLUSIONS: Because of the significantly higher rate of prognostically advantageous meniscal repair, the recommendation for an ACL reconstruction within 6 months after trauma was made to preserve the meniscus and reduce the risk of developing OA. LEVEL OF EVIDENCE: Prospective cross-sectional cohort study, Level II.

Non-surgical treatment of pubic overload and groin pain in amateur football players: a prospective double-blinded randomised controlled study.

PURPOSE: The incidence of groin pain in athletes is steadily increasing. Symptomatic pubic overload with groin pain and aseptic osteitis pubis represent well-known and frequently misdiagnosed overuse injuries in athletes. This study investigated the benefits of standardised non-surgical treatment for swift return-to-football. METHODS: In a prospective double-blinded controlled study, 143 amateur football players with groin pain as well as radiological signs and clinical symptoms of pubic overload were analysed for 1 year. Two randomised study groups participated in an intensive physical rehabilitation programme, either with or without shock wave therapy. The control group did not participate in any standardised rehabilitation programme but only stopped participating in sports activity. Follow-up examinations took place 1, 3 months and 1 year after the beginning of therapy. Endpoints were visual analogue scale (VAS), functional tests, the time of return-to-football, recurrent complaints and changes in the MR image. RESULTS: Forty-four football players with groin pain and aseptic osteitis pubis were randomised into two study groups; 26 received shock wave therapy, 18 did not. Clinical examination showed pubic overload as a multi-located disease. Players receiving shock wave therapy showed earlier pain relief in the VAS (p < 0.001) and returned to football significantly earlier (p = 0.048) than players without this therapy. Forty-two of 44 players of both study groups returned to football within 4 months after the beginning of therapy and had no recurrent groin pain within 1 year after trauma. Fifty-one players of the control group returned to football after 240 days (p < 0.001), of whom 26 (51%) experienced recurrent groin pain. Follow-up MRI scans did not show any effect of shock wave therapy. CONCLUSION: Non-surgical therapy is successful in treating pubic overload and osteitis pubis in athletes. Shock wave therapy as a local treatment significantly reduced pain, thus enabling return-to-football within 3 months after trauma. Early and correct diagnosis is essential for successful intensive physiotherapy. LEVEL OF EVIDENCE: I.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery]. / Nachbehandlung bei der autologen Chondrozytentransplantation: Eine Bestandsaufnahme und Empfehlung der AG Klinische Geweberegeneration der DGU/DGOOC.

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

Effect of conventional hemodialysis on the apixaban plasma concentration.

PURPOSE: Apixaban is a factor Xa inhibitor used in patients undergoing hemodialysis treatment. The objective of this study is to investigate the effect of hemodialysis on apixaban plasma concentrations. METHODS: This observational study is on patients treated with apixaban 2.5 mg twice daily on conventional hemodialysis with standard low-molecular-weight heparin (LMWH) anticoagulation (nadroparin 3800-7600 IU). Plasma blood samples were collected before starting dialysis (t1), 2 h after starting dialysis (t2), and directly after dialysis (t3). Apixaban concentration was measured before and after dialysis. Anti-Xa activity was measured for all three samples. RESULTS: A significant difference was observed between the apixaban concentration before and after dialysis (mean before dialysis 141.03 ng/mL; mean after dialysis 102.71 ng/mL; p = 0.003). Nonetheless, both apixaban plasma concentrations and anti-Xa levels remained within the reference range. Anti-Xa levels had a strong correlation with the apixaban concentrations (r = 0.935, p = 0.000). Thus, anti-Xa activity might be used as a surrogate for apixaban plasma concentration. CONCLUSION: There seems to be no need for dose adjustments of apixaban; co-administration of LMWH next to apixaban might also be unnecessary.

SERT and TPH-1 mRNA expression are reduced in irritable bowel syndrome patients regardless of visceral sensitivity state in large intestine.

Colorectal visceral hypersensitivity has been demonstrated in a subset of irritable bowel syndrome (IBS) patients. Serine protease and serotonergic signaling modulate gastrointestinal visceral sensitivity. We evaluated whether altered mucosal serine protease and serotonergic pathway components are related to rectal visceral hypersensitivity in IBS patients. Colorectal mucosal biopsies of 23 IBS patients and 15 controls were collected. Gene transcripts of protease-activated receptor (PAR)-2, trypsinogen IV, tryptophan hydroxylase (TPH)-1, and serotonin reuptake transporter (SERT) were quantified using real-time polymerase chain reaction. Substance P and 5-HT contents were measured by ELISA. The number of enterochromaffin cells, mast cells, and intraepithelial lymphocytes was determined using immunohistochemistry. Rectal visceral sensitivity was determined in IBS patients using barostat programmed for phasic ascending distension. Rectal hypersensitivity (+) and (-) IBS patients showed lower TPH-1 and SERT mRNA levels in the rectum compared with controls (P ≤ 0.05). Rectal hypersensitivity (+) IBS patients (n = 12) showed lower TPH-1 mRNA level in the sigmoid compared with controls (P = 0.015). No significant differences were observed in PAR-2 and trypsinogen IV expression between controls and IBS patients. Rectal substance P content was increased in IBS patients compared with controls (P = 0.045). No significant differences were found in transcript levels, cell counts, and substance P and 5-HT contents between rectal hypersensitivity (+) and (-) IBS patients. In conclusion, regardless of visceral hypersensitivity state, several serotonergic signaling components are altered in IBS patients.

Sandwich Technique for Large Osteochondral Lesions of the Knee.

OBJECTIVE: To evaluate whether a sandwich technique procedure for large osteochondral lesions (OCL) of the medial femur condyle reduces clinical symptoms and improves activity level as well as to assess repair tissue integration on MRI over 2 years. DESIGN: Twenty-one patients (median age: 29 years, 18-44 years) who received matrix-associated autologous chondrocyte transplantation (MACT) combined with cancellous bone grafting at the medial femur condyle in a 1-step procedure were prospectively included. Patients were evaluated before surgery (baseline) as well as 3, 6, 12, and 24 months postoperatively, including clinical evaluation, Lysholm score, Tegner Activity Rating Scale, and MRI with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). RESULTS: Seventeen patients were available for the 24-month (final) follow-up (4 dropouts). Lysholm significantly improved from 48 preoperatively stepwise to 95 at final follow-up (P < 0.05). Tegner improvement from 2.5 at baseline to 4.0 at final follow-up was not significant (P = 1.0). MOCART score improved significantly and stepwise from 65 at 3 months to 90 at 24 months (P < 0.05). Total WORMS improved from 14.5 at surgery to 7.0 after 24 months (P < 0.05). Body mass index and defect size at surgery correlated with total WORMS at final follow-up (P < 0.05) but did not correlate with clinical scores or defect filling. CONCLUSION: MACT combined with cancellous bone grafting at the medial femoral condyle reduces symptoms continuously over 2 years. A 1-step procedure may reduce perioperative morbidity. However, despite improvements, patients' activity levels remain low, even 2 years after surgery.

Registered report protocol: A scoping review to identify potential predictors as features for developing automated estimation of the probability of being frail in secondary care.

INTRODUCTION: The impact of frailty surges, as the prevalence increases with age and the population age is rising. Frailty is associated with adverse health outcomes and increased healthcare costs. Many validated instruments to detect frailty have been developed. Using these in clinical practice takes time. Automated estimation of the probability of being frail using routinely collected data from hospital electronic health records (EHRs) would circumvent that. We aim to identify potential predictors that could be used as features for modeling algorithms on the basis of routine hospital EHR data to incorporate in an automated tool for estimating the probability of being frail. METHODS: PubMed (MEDLINE), CINAHL Plus, Embase, and Web of Science will be searched. The studied population consists of older people (≥65 years). The first step is searching articles published ≥2018. Second, we add two published literature reviews (and the articles included therein) [Bery 2020; Bouillon, 2013] to our search results. In these reviews, articles on potential predictor variables in frailty screening tools were included from inception until March 2018. The goal is to identify and extract all potential predictors of being frail. Domain experts will be consulted to evaluate the results. DISCUSSION: The results of the intended study will increase the quality of the developed algorithms to be used for automated estimation of the probability of being frail in secondary care. This is a promising perspective, being less labor-intensive compared to screening each individual patient by hand. Also, such an automated tool may raise awareness of frailty, especially in those patients who would not be screened for frailty by hand because they seem robust. CONCLUSION: The identified potential predictors of being frail can be used as evidence-based input for machine learning based automated estimation of the probability of being frail using routine EHR data in the near future.

Dialysis or kidney transplantation in older adults? A systematic review summarizing functional, psychological, and quality of life-related outcomes after start of kidney replacement therapy.

BACKGROUND: In older patients, the choice between kidney transplantation (KT) and dialysis may be complicated because of a high prevalence of comorbidities and geriatric syndromes. Ideally, this decision-making process focusses on older patients' outcome priorities, which frequently include functional, psychological, and quality of life (QOL)-related outcomes. PURPOSE: This systematic review aims to summarize functional, psychological (including cognition), and QOL-related outcomes after start of kidney replacement therapy (KRT) in older adults. METHODS: We searched PubMed and Embase for research that investigated change in these variables after start of KRT in patients aged ≥ 60 years. Data were extracted using the summary measures reported in the individual studies. Risk of bias was assessed with the ROBINS-I tool. RESULTS: Sixteen observational studies (prospective n = 9, retrospective n = 7; KT-recipients n = 3, dialysis patients n = 13) were included. The results show that QOL improves in the majority of the older KT recipients. After start of dialysis, QOL improved or remained stable for most patients, but this seems less prevalent than after KT. Functional status decreases in a substantial part of the older dialysis patients. Furthermore, the incidence of serious fall injuries increases after start of dialysis. Nutritional status seems to improve after start of dialysis. CONCLUSION: The interpretability and comparability of the included studies are limited by the heterogeneity in study designs and significant risk of bias in most studies. Despite this, our overview of functional, psychological (including cognition), and QOL-related outcomes is useful for older adults and their clinicians facing the decision between KT and dialysis.

Integrating healthcare for follow-up of adult COVID-19 patients in an outpatient clinic: A matter of cooperation.

RATIONALE AIMS AND OBJECTIVES: A large number of patients infected with SARS-CoV-2 (COVID-19) need outpatient follow-up after hospitalization. As these patients may experience a broad range of symptoms, as do patients infected with the related SARS-CoV-1 virus, we set up a multidisciplinary outpatient clinic involving pulmonologists, internists, and geriatricians. Patients were allocated to a specialist based on symptoms reported on a self-developed questionnaire of expected symptoms of COVID-19. This study aimed to evaluate the effectiveness of this outpatient clinic. METHODS: In this retrospective study, the medical records of patients who presented to the outpatient clinic for follow-up after hospitalization for COVID-19 up to 31 August 2020, were reviewed. RESULTS: In total, 266 patients were seen at the outpatient clinic at least once. Overall, 100 patients were seen by a pulmonologist, 97 by an internist, and 65 by a geriatrician. A referral between these 3 medical specialists was needed for only 14 patients (5.3%). Fifty patients were seen by a psychologist, mostly those with a HADS score >10. Only 5 (2.2%) of the 221 patients who were not directly referred to a psychologist based on triage needed psychological support. Forty-eight patients (18%) were also seen by a physiatrist. CONCLUSION: Identifying which medical specialist (pulmonologist, internist, and/or geriatrician) should see patients attending a post-COVID outpatient clinic based on patient-reported symptoms proved an effective approach to managing the flow of post-COVID patients.

Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.

OBJECTIVES: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. METHODS: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). RESULTS: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. CONCLUSIONS: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19.

Few bacterial co-infections but frequent empiric antibiotic use in the early phase of hospitalized patients with COVID-19: results from a multicentre retrospective cohort study in The Netherlands.

BACKGROUND: Knowledge on bacterial co-infections in COVID-19 is crucial to use antibiotics appropriately. Therefore, we aimed to determine the incidence of bacterial co-infections, antibiotic use and application of antimicrobial stewardship principles in hospitalized patients with COVID-19. METHODS: We performed a retrospective observational study in four hospitals (1 university, 2 non-university teaching, 1 non-teaching hospital) in the Netherlands from March to May 2020 including consecutive patients with PCR-confirmed COVID-19. Data on first microbiological investigations obtained at the discretion of the physician and antibiotic use in the first week of hospital admission were collected. RESULTS: Twelve (1.2%) of the 925 patients included had a documented bacterial co-infection (75.0% pneumonia) within the first week. Microbiological testing was performed in 749 (81%) patients: sputum cultures in 105 (11.4%), blood cultures in 711 (76.9%), pneumococcal urinary antigen testing in 202 (21.8%), and Legionella urinary antigen testing in 199 (21.5%) patients, with clear variation between hospitals. On presentation 556 (60.1%; range 33.3-73.4%) patients received antibiotics for a median duration of 2 days (IQR 1-4). Intravenous to oral switch was performed in 41 of 413 (9.9%) patients who received intravenous treatment >48 h. Mean adherence to the local guideline on empiric antibiotic therapy on day 1 was on average 60.3% (range 45.3%-74.7%). CONCLUSIONS: On presentation to the hospital bacterial co-infections are rare, while empiric antibiotic use is abundant. This implies that in patients with COVID-19 empiric antibiotic should be withheld. This has the potential to dramatically reduce the current overuse of antibiotics in the COVID-19 pandemic.