The Incidence of Pulmonary Embolism in Hospitalized Non-ICU Patients with COVID-19 during the First Wave: A Multicenter Retrospective Cohort Study in the Netherlands.

INTRODUCTION: During the first COVID-19 outbreak in 2020 in the Netherlands, the incidence of pulmonary embolism (PE) appeared to be high in COVID-19 patients admitted to the intensive care unit (ICU). This study was performed to evaluate the incidence of PE during hospital stay in COVID-19 patients not admitted to the ICU. METHODS: Data were retrospectively collected from 8 hospitals in the Netherlands. Patients admitted between February 27, 2020, and July 31, 2020, were included. Data extracted comprised clinical characteristics, medication use, first onset of COVID-19-related symptoms, admission date due to COVID-19, and date of PE diagnosis. Only polymerase chain reaction (PCR)-positive patients were included. All PEs were diagnosed with computed tomography pulmonary angiography (CTPA). RESULTS: Data from 1,852 patients who were admitted to the hospital ward were collected. Forty patients (2.2%) were diagnosed with PE within 28 days following hospital admission. The median time to PE since admission was 4.5 days (IQR 0.0-9.0). In all 40 patients, PE was diagnosed within the first 2 weeks after hospital admission and for 22 (55%) patients within 2 weeks after onset of symptoms. Patient characteristics, pre-existing comorbidities, anticoagulant use, and laboratory parameters at admission were not related to the development of PE. CONCLUSION: In this retrospective multicenter cohort study of 1,852 COVID-19 patients only admitted to the non-ICU wards, the incidence of CTPA-confirmed PE was 2.2% during the first 4 weeks after onset of symptoms and occurred exclusively within 2 weeks after hospital admission.

The effect of current antithrombotic therapy on mortality in nursing home residents with COVID-19: a multicentre retrospective cohort study.

BACKGROUND: The first wave of COVID led to an alarmingly high mortality rate among nursing home residents (NHRs). In hospitalised patients, the use of anticoagulants may be associated with a favourable prognosis. However, it is unknown whether the use of antithrombotic medication also protected NHRs from COVID-19-related mortality. OBJECTIVES: To investigate the effect of current antithrombotic therapy in NHRs with COVID-19 on 30-day all-cause mortality during the first COVID-19 wave. METHODS: We performed a retrospective cohort study linking electronic health records and pharmacy data in NHRs with COVID-19. A propensity score was used to match NHRs with current use of therapeutic dose anticoagulants to NHRs not using anticoagulant medication. The primary outcome was 30-day all-cause mortality, which was evaluated using a logistic regression model. In a secondary analysis, multivariable logistic regression was performed in the complete study group to compare NHRs with current use of therapeutic dose anticoagulants and those with current use of antiplatelet therapy to those without such medication. RESULTS: We included 3521 NHRs with COVID-19 based on a positive RT-PCR for SARS-CoV-2 or with a well-defined clinical suspicion of COVID-19. In the matched propensity score analysis, NHRs with current use of therapeutic dose anticoagulants had a significantly lower all-cause mortality (OR = 0.73; 95% CI: 0.58-0.92) compared to NHRs who did not use therapeutic anticoagulants. In the secondary analysis, current use of therapeutic dose anticoagulants (OR: 0.62; 95% CI: 0.48-0.82) and current use of antiplatelet therapy (OR 0.80; 95% CI: 0.64-0.99) were both associated with decreased mortality. CONCLUSIONS: During the first COVID-19 wave, therapeutic anticoagulation and antiplatelet use were associated with a reduced risk of all-cause mortality in NHRs. Whether these potentially protective effects are maintained in vaccinated patients or patients with other COVID-19 variants, remains unknown.

Control in the Hospital by Extensive Clinical rules for Unplanned hospitalizations in older Patients (CHECkUP); study design of a multicentre randomized study.

BACKGROUND: Due to ageing of the population the incidence of multimorbidity and polypharmacy is rising. Polypharmacy is a risk factor for medication-related (re)admission and therefore places a significant burden on the healthcare system. The reported incidence of medication-related (re)admissions varies widely due to the lack of a clear definition. Some medications are known to increase the risk for medication-related admission and are therefore published in the triggerlist of the Dutch guideline for Polypharmacy in older patients. Different interventions to support medication optimization have been studied to reduce medication-related (re)admissions. However, the optimal template of medication optimization is still unknown, which contributes to the large heterogeneity of their effect on hospital readmissions. Therefore, we implemented a clinical decision support system (CDSS) to optimize medication lists and investigate whether continuous use of a CDSS reduces the number of hospital readmissions in older patients, who previously have had an unplanned probably medication-related hospitalization. METHODS: The CHECkUP study is a multicentre randomized study in older (≥60 years) patients with an unplanned hospitalization, polypharmacy (≥5 medications) and using at least two medications from the triggerlist, from Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. Patients will be randomized. The intervention consists of continuous (weekly) use of a CDSS, which generates a Medication Optimization Profile, which will be sent to the patient's general practitioner and pharmacist. The control group will receive standard care. The primary outcome is hospital readmission within 1 year after study inclusion. Secondary outcomes are one-year mortality, number of emergency department visits, nursing home admissions, time to hospital readmissions and we will evaluate the quality of life and socio-economic status. DISCUSSION: This study is expected to add evidence on the knowledge of medication optimization and whether use of a continuous CDSS ameliorates the risk of adverse outcomes in older patients, already at an increased risk of medication-related (re)admission. To our knowledge, this is the first large study, providing one-year follow-up data and reporting not only on quality of care indicators, but also on quality-of-life. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register on October 14, 2018, identifier: NL7449 (NTR7691). https://www.trialregister.nl/trial/7449 .

Mortality in hip fracture patients after implementation of a nurse practitioner-led orthogeriatric care program: results of a 1-year follow-up.

BACKGROUND: Hip fractures are a major cause of mortality and disability in frail older adults. Therefore, orthogeriatrics has been embraced to improve patient outcomes. With the optimal template of orthogeriatric care still unknown, and to curtail rising healthcare expenditure we implemented a nurse practitioner-led orthogeriatric care program (NPOCP). The objective was to evaluate NPOCP by measuring 3-month and 1-year mortality, compared to usual care (UC). In addition, length of stay (LOS) and location of hospital discharge were reported. METHODS: An anonymised data set, of hip fracture patients (n = 300) who presented to Maastricht University Medical Centre, the Netherlands, a level-1 trauma centre, was used. NPOCP was implemented on one of two surgical wards, while the other ward received UC. Patient allocation to these wards was random. RESULTS: In total, 144 patients received NPOCP and 156 received UC. In the NPOCP, 3-month and 1-year mortality rates were 9.0% and 13.9%, compared to 24.4% and 34.0% in the UC group (P < 0.001). The adjusted hazard ratio (aHR) for 3-month (aHR 0.50 [95%CI: 0.26-0.97]) and 1-year mortality (aHR 0.50 [95%CI: 0.29-0.85]) remained lower in NPOCP compared to UC. Median LOS was 9 days [IQR 5-13] in patients receiving UC and 7 days [IQR 5-13] in patients receiving NPOCP (P = 0.08). Thirty-eight (27.5%) patients receiving UC and fifty-seven (40.4%) patients receiving NPOCP were discharged home (P = 0.023). CONCLUSION: Implementation of NPOCP was associated with significantly reduced mortality in hip fracture patients and may contribute positively to high-quality care and improve outcomes in the frail orthogeriatric population.

Medication adherence among gout patients initiated allopurinol: a retrospective cohort study in the Clinical Practice Research Datalink (CPRD).

Objectives: When urate lowering therapy is indicated in patients with gout, medication adherence is essential. This study assesses non-persistence and non-adherence in patients with newly diagnosed gout, and identifies factors associated with poor medication adherence. Methods: A retrospective data analysis was performed within the UK Clinical Practice Research Datalink (1987-2014) among incident gout patients, aged ⩾40 years and starting allopurinol (n = 48 280). The proportion of patients non-persistent (a first medication gap of ⩾90 days) after 1 and 5 years, and median time until a first 90-day gap was estimated using Kaplan-Meier statistics in those starting allopurinol and restarting after a first interruption. Non-adherence (proportion of days covered <80%) over the full observation period was calculated. Multivariable Cox- or logistic regressions assessed factors associated with non-persistence or non-adherence, respectively. Results: Non-persistence increased from 38.5% (95% CI: 38.1, 38.9) to 56.9% (95% CI: 56.4, 57.4) after 1 and 5 years of initiation. Median time until a first 90-day gap was 1029 days (95% CI: 988, 1078) and 61% were non-adherent. After a first gap, 43.3% (95% CI: 42.7, 43.9) restarted therapy within 1 year, yet only 52.3% (95% CI: 51.4, 53.1) persisted for 1 year. Being female and a current smoker increased the risk for non-persistence and non-adherence, while older age, overweight, receiving anti-hypertensive medication or colchicine and suffering from dementia, diabetes or dyslipidaemia decreased the risk. Conclusion: Medication adherence among gout patients starting allopurinol is poor, particularly among females and younger patients and patients with fewer comorbidities. Medication adherence remains low in those reinitiating after a first gap.

Use of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: There have been increasing numbers of case reports and observational studies of adverse events in patients receiving long-term therapy with proton pump inhibitors (PPIs). The effects of PPI therapy on risks of fundic gland polyps (FGPs) and gastric cancer have received considerable attention. We performed a systematic review with a meta-analysis of randomized controlled trials and observational studies that assessed these risks. METHODS: We searched the PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials databases for relevant studies published through July 2015. We calculated pooled odds ratio for FGPs and the risk ratio for gastric cancer in PPI users compared with PPI nonusers using fixed- and random-effects models. RESULTS: We analyzed data from 12 studies, comprising more than 87,324 patients: 1 randomized controlled trial reporting the effect of PPIs on gastric polyps (location not specified), 6 cohort and 1 case-control studies on FGPs, and 1 cohort and 3 case-control studies on gastric cancer. Pooled odds ratios for FGPs were 1.43 (95% confidence interval, 1.24-1.64) and 2.45 (95% confidence interval, 1.24-4.83) from fixed- and random-effects models, respectively. The pooled risk ratio for gastric cancer was 1.43 (95% confidence interval, 1.23-1.66) from each model. We observed significant heterogeneity among studies reporting on FGPs, but not among studies reporting on gastric cancer. CONCLUSIONS: Based on a systematic review with meta-analysis, long-term use of PPIs (≥12 months) is associated with an increased risk of FGPs. PPI therapy might also increase the risk of gastric cancer, but this association could be biased, because of the limited number of studies and possible confounding factors.

Content and construct validity of the Rheumatic Diseases Comorbidity Index in patients with gout.

OBJECTIVE: Gout has been associated with a large number of co-morbidities. As yet, no co-morbidity measure has been validated for use in clinical studies in gout. This study aims to evaluate the content and construct validity of the Rheumatic Diseases Comorbidity Index (RDCI) and a gout-specifically modified RDCI (mRDCI) in patients with gout. METHODS: In a cross-sectional sample of 122 patients with gout, data on co-morbidities were obtained during an interview, chart review and clinical examination. The data were used to compute the RDCI/mRDCI, a simple co-morbidity count, the Charlson Comorbidity Index (CCI) and the Functional Comorbidity Index (FCI). Content and construct validity was explored by assessing Spearman correlations between the two RDCI versions and between RDCI/mRDCI and the other co-morbidity indices, as well as demographic and clinical outcomes. In addition, we assessed the independent association between the RDCI/mRDCI and physical functioning (HAQ disability index), physical health (36-Item Short Form Health Survey) and direct health care and non-health care costs using multivariable regression analyses. RESULTS: The correlation between the RDCI and mRDCI was 0.86. Correlations between the RDCI/mRDCI and simple co-morbidity count, CCI or FCI varied between 0.72 and 0.88. Correlations with generic and gout-specific health outcomes were moderate and weak, respectively, with slightly better results for the mRDCI. Multivariable analyses showed that both the RDCI and mRDCI contributed to the variation in physical functioning, physical health and direct health care and non-health care costs. CONCLUSION: Both the RDCI and mRDCI have appropriate content and construct validity to evaluate the influence of co-morbidity on outcome in patients with gout.

The Gout Assessment Questionnaire 2.0: cross-cultural translation into Dutch, aspects of validity and linking to the International Classification of Functioning, Disability and Health.

OBJECTIVES: The Gout Assessment Questionnaire 2.0 (GAQ2.0) is a disease-specific patient-reported outcome measure for gout that distinguishes five different subscales and comprises overall 31 questions. The aims of this study were to translate the GAQ2.0 into Dutch and to test clinimetric properties. METHODS: Recommendations for translation and cross-cultural adaptation were followed and no cultural adaptations were needed. The resulting Dutch GAQ2.0 was administered to patients registered at the rheumatology outpatient clinic diagnosed with gout. Internal consistency was tested using Cronbach's α, reliability using intraclass correlation coefficient (ICC), content validity by linkage to the International Classification of Functioning, Disability and Health (ICF) and construct validity by correlating the subscales of the GAQ2.0 with the HAQ disability index (HAQ-DI) and 36-item Short Form Health Survey (SF-36). RESULTS: A total of 126 patients [106 (84%) male, mean age 66.6 years (s.d. 10.4), mean disease duration 11.2 years (s.d. 10.6)] completed a number of questionnaires, including the GAQ2.0, HAQ-DI and SF-36, and underwent a clinical examination. Internal consistency was sufficient (Cronbach's α = 0.83-0.94), except for the subscale gout medication side effects (Cronbach's α = 0.51). Test-retest reliability was good (ICCs 0.73-0.86) for all subscales, but moderate for the subscale unmet gout treatment need (ICC 0.56). Gout impact (GI) subscale scores showed only weak to moderate correlations with HAQ-DI and SF-36, but stronger emphasis on the emotional consequences of gout. Also, it correlated better with gout-specific outcomes such as the number of gout flares and pain. CONCLUSION: The Dutch GAQ2.0 shows sufficient evidence of validity to assess disease-specific functioning and health in patients with gout and seems to capture different aspects than those represented in the HAQ and SF-36.

Unlocking Deprescribing Potential in Nursing Homes: Insights from a Focus Group Study with Healthcare Professionals.

BACKGROUND: The nursing home population is characterized by multimorbidity and disabilities, which often result in extensive prescription of medication and subsequent polypharmacy. Deprescribing, a planned and supervised process of dose reduction or total cessation of medication, is a solution to combat this. OBJECTIVE: This study aimed to identify barriers and enablers of deprescribing as experienced by nursing home physicians (NHPs) and collaborating pharmacists in the specific nursing home setting. METHODS: This qualitative study utilized a semi-structured interview format with two focus groups consisting of a mix of NHPs and pharmacists. Directed content analysis was performed based on the Theoretical Domains Framework, a validated framework for understanding determinants of behavior change among health care professionals. RESULTS: Sixteen health care professionals participated in two focus groups, including 13 NHPs and three pharmacists. The participating NHPs and pharmacists believed that deprescribing is a valuable process with enablers, such as multidisciplinary collaboration, good communication with patients and family, and involvement of the nursing staff. NHPs and pharmacists view deprescribing as a core task and feel assured in their ability to carry it out successfully. However, they also noted barriers: deprescribing is time-consuming; communication with residents, their relatives or medical specialists is difficult; and electronic patient systems often do not adequately support it. CONCLUSIONS: This study provides insight into the various barriers and enablers faced by NHPs and pharmacists when deprescribing in nursing homes. Specific for this population, deprescribing barriers focus on communication (with residents and their relatives, and also with medical specialists) and resources, while knowledge and expertise are mentioned as enablers.

Evaluation of a multifaceted medication review in older patients in the outpatient setting: a before-and-after study.

BACKGROUND: The prevalence of medication-related emergency department visits and acute hospital admissions in older patients is rising due to the ageing of the population and increasing prevalence of multimorbidity and associated polypharmacy. AIM: To explore whether a combined medication review performed in the outpatient setting reduces the number of medication-related emergency department visits and hospital (re)admissions. METHOD: All consecutive patients visiting the geriatric outpatient clinic underwent a multifaceted medication review (i.e. evaluation by at least a geriatrician, and/or pharmacist and use of clinical decision support system). Subsequently, we analysed the number of, and reason for, emergency department visits, acute hospital admissions and readmissions in the year prior to and the year following the index-date (date of first presentation and medication review). RESULTS: A multifaceted medication review reduced the number of potentially medication-related emergency department visits (38.9% vs. 19.6%, p < 0.01), although the total number of ED visits or acute hospital admissions per patient in the year before and after medication review did not differ. CONCLUSION: A multifaceted medication review performed in the outpatient clinic reduced the number of potentially medication-related emergency department visits and could therefore reduce negative health outcomes and healthcare costs.

Clinical Decision Support Systems in Hospitalized Older Patients: An Exploratory Analysis in a Real-Life Clinical Setting.

BACKGROUND: Inappropriate prescribing is associated with negative patient outcomes. In hospitalized patients, the use of Clinical Decision Support Systems (CDSSs) may reduce inappropriate prescribing and thereby improve patient-related outcomes. However, recently published large clinical trials (OPERAM and SENATOR) have shown negative results on the use of CDSSs and patient outcomes and strikingly low acceptance of recommendations. OBJECTIVE: The purpose of the present study was to investigate the use of a CDSS in a real-life clinical setting of hospitalized older patients. As such, we report on the real-life pattern of this in-hospital implemented CDSS, including (i) whether generated alerts were resolved; (ii) whether a recorded action by the pharmacist led to an improved number of resolved alerts; and (iii) the natural course of generated alerts, in particular of those in the non-intervention group; as these data are largely lacking in current studies. METHODS: Hospitalized patients, aged 60 years and older, admitted to Zuyderland Medical Centre, the Netherlands, in 2018 were included. The evaluation of the CDSS was investigated using a database used for standard care. Alongside demographic and clinical data, we also collected the total numbers of CDSS alerts, the number of alerts 'handled' by the pharmacist, those that resulted in an action by the pharmacist, and finally the outcome of the alerts at day 1 and day 3 after the alert was generated. RESULTS: A total of 3574 unique hospitalized patients, mean age 76.7 (SD 8.3) years and 53% female, were included. From these patients, 8073 alerts were generated, of which 7907 (97.9% of total) were handled by the pharmacist (day 1). In 51.6% of the alerts handled by the pharmacist, an action was initiated, resulting in 36.1% of the alerts resolved after day 1, compared with 27.3% if the pharmacist did not perform an action (p < 0.001). On day 3, in 52.6% of the alerts an action by the pharmacist was initiated, resulting in 62.4% resolved alerts, compared with 48.0% when no action was performed (p < 0.001). In the category renal function, the percentages differed significantly between an action versus no action of the pharmacist at day 1 and at day 3 (16.6% vs 10.6%, p < 0.001 [day 1]; 29.8% vs 19.4%, p < 0.001 [day 3]). CONCLUSION: This study demonstrates the pattern and natural course of clinical alerts of an in-hospital implemented CDSS in a real-life clinical setting of hospitalized older patients. Besides the already known beneficial effect of actions by pharmacists, we have also shown that many alerts become resolved without any specific intervention. As such, our study provides an important insight into the spontaneous course of resolved alerts, since these data are currently lacking in the literature.

Low Levels of Serum and Intracellular Vitamin C in Hospitalized COVID-19 Patients.

Vitamin C is a crucial micronutrient for human immune cell function and has potent antioxidant properties. It is hypothesized that vitamin C serum levels decline during infection. However, the precise mechanisms remain unknown. To gain deeper insights into the true role of vitamin C during infections, we aimed to evaluate the body's vitamin C storage during a SARS-CoV-2 infection. In this single-center study, we examined serum and intracellular vitamin C levels in peripheral blood mononuclear cells (PBMCs) of 70 hospitalized COVID-19 patients on the first and fifth days of hospitalization. Also, clinical COVID-19 severity was evaluated at these timepoints. Our findings revealed a high prevalence of hypovitaminosis C and vitamin C deficiency in hospitalized COVID-19 patients (36% and 15%). Moreover, patients with severe or critical disease exhibited a higher prevalence of low serum vitamin C levels than those with moderate illness. Serum vitamin C levels had a weak negative correlation with clinical COVID-19 severity classification on the day of hospitalization; however, there was no correlation with intracellular vitamin C. Intracellular vitamin C levels were decreased in this cohort as compared to a healthy cohort and showed further decline during hospitalization, while serum levels showed no relevant change. Based on this observation, it can be suggested that the reduction of intracellular vitamin C may be attributed to its antioxidative function, the need for replenishing serum levels, or enhanced turnover by immune cells. These data give an incentive to further investigate the role of intracellular vitamin C in a larger and more heterogeneous cohort as well as the underlying mechanisms.

Associations between presence of diabetes, mortality and fracture type in individuals with a hip fracture.

AIMS: An overlooked aspect of diabetes is an increased risk of hip fractures, with associated mortality. We investigated whether fracture type and/or burden of comorbidities explains the increased risk of mortality in diabetes after hip fracture. METHODS: For this cohort study, we used a de-identified data set of hip fracture patients registered in a quality-of-care registry (2017/2018) included in Maastricht University Medical Centre. RESULTS: Among 594 hip fracture patients, 90 (15.2 %) had diabetes. Median (IQR) age was 82 (71-87) years and 63.8 % were women. Compared to patients without, patients with diabetes had higher median Charlson Comorbidity Index [1 (0-2) vs 0 (0-2), P < 0.001)] and were more likely to sustain intertrochanteric/subtrochanteric fractures [54.4 vs 38.7 %, P = 0.02]. Over a median follow-up of 2.7 (1.6-3.3) years, crude mortality rate was 30.8 % in patients without and 50.0 % in patients with diabetes. This association remained unaltered after adjustment for age, sex, BMI, fracture type or burden of co-morbidities. CONCLUSION: Individuals with diabetes display a greatly increased absolute mortality risk after hip fracture. This association was not attenuated after adjustment for fracture type or non-diabetes associated co-morbidity. These findings have important implications for diabetes care in hip fracture patients, and underline the importance of fracture prevention.

A flickering cutaneous lesion occurring after an insect bite.

Many exaggerated skin reactions after insect bites have been described and due to global warming the incidence of these cases will increase. This clinical video promotes its recognition by showing an unusual cutaneous phenomenon after an insect bite.