Care Cohort Research Articles

Methods of Bloodless Care, Clinical Outcomes, and Costs for Adult Patients Who Decline Allogeneic Transfusions.

Providing bloodless medical care for patients who wish to avoid allogeneic transfusion can be challenging; however, previous studies have demonstrated favorable outcomes when appropriate methods are used. Here, we report one of the largest series of patients receiving bloodless care, along with the methods used to provide such care, and the resulting outcomes. In a retrospective cohort study, 1111 adult inpatients (age ≥18 years) at a single institution who declined allogeneic transfusion for religious or personal reasons between June 2012 and June 2016 were included, and the patient blood management methods are described. Patient characteristics, laboratory data, and transfusion rates, as well as clinical outcomes (morbidity, mortality, and length of stay) were compared to all other patients in the hospital who received standard care, including transfusions if needed (n = 137,009). Medical and surgical patients were analyzed as subgroups. The primary outcome was composite morbidity (any morbid event: infectious, thrombotic, ischemic, renal, or respiratory). Secondary outcomes included individual morbid events, in-hospital mortality, length of stay, total hospital charges, and costs. The bloodless cohort had more females and a lower case mix index, but more preadmission comorbidities. Mean nadir hemoglobin during hospitalization was lower in the bloodless (9.7 ± 2.6 g/dL) compared to the standard care (10.1 ± 2.4 g/dL) group (P < .0001). Composite morbidity occurred in 14.4% vs 16.0% (P = .16) of the bloodless and standard care patients, respectively. Length of stay and in-hospital mortality were similar between the bloodless and standard care patients. After Bonferroni adjustment for multiple comparisons, hospital-acquired infection occurred less frequently in the bloodless compared to the standard care cohort (4.3% vs 8.3%) (P < .0001) in the medical patient subgroup, but not in the surgical subgroup. After propensity score adjustment in a multivariable model and adjustment for multiple comparisons, bloodless care was associated with less risk of hospital-acquired infection (OR, 0.56; 95% CI, 0.35-0.83; P = .0074) in the medical subgroup, but not in the surgical subgroup. Median total hospital charges (by 8.5%; P = .0017) and costs (by 8.7%; P = .0001) were lower in the bloodless compared to the standard care cohort, when all patients were included. Overall, adult patients receiving bloodless care had similar clinical outcomes compared to patients receiving standard care. Medical (but not surgical) bloodless patients may be at less risk for hospital-acquired infection compared to those receiving standard care. Bloodless care is cost-effective and should be considered as high-value practice.

Dynamics of multimorbidity and frailty, and their contribution to mortality, nursing home and home care need: A primary care cohort of 1 456 052 ageing people.

SummaryBackgroundPrevalence of both multimorbidity and frailty increases with age, but more evidence is needed to elucidate their relationship and their association with other health-related outcomes. We analysed the dynamics of both conditions as people age and calculate the associated risk of death, nursing home admission, and need for home care.MethodsData were drawn from the primary care electronic health records of a longitudinal cohort of people aged 65 or older in Catalonia in 2010–2019. Frailty and multimorbidity were measured using validated instruments (eFRAGICAP, a cumulative deficit model; and SNAC-K, respectively), and their longitudinal evolution was described. Cox regression models accounted for the competing risk of death and adjusted by sex, socioeconomical status, and time-varying age, alcohol and smoking.FindingsWe included 1 456 052 patients. Prevalence of multimorbidity was consistently high regardless of age, while frailty almost quadrupled from 65 to 99 years. Frailty worsened and also changed with age: up to 84 years, it was more related to concurrent diseases, and afterwards, to frailty-related deficits. While concurrent diseases contributed more to mortality, frailty-related deficits increased the risk of institutionalisation and the need for home care.InterpretationThe nature of people’s multimorbidity and frailty vary with age, as does their impact on health status. People become frailer as they age, and their frailty is more characterised by disability and other symptoms than by diseases. Mortality is most associated with the number of comorbidities, whereas frailty-related deficits are associated with needing specialised care.FundingInstituto de Salud Carlos III through PI19/00535, and the PFIS Grant FI20/00040 (Co-funded by European Regional Development Fund/European Social Fund).

Non-fatal overdose risk during and after opioid agonist treatment: A primary care cohort study with linked hospitalisation and mortality records.

SummaryBackgroundThe initiation and cessation of opioid agonist treatment (OAT) have both been associated with elevated risk of fatal overdose. We examined risk of non-fatal overdose during OAT initiation and cessation and specifically between methadone versus buprenorphine recipients.MethodsWe utilised primary care electronic health records from the Clinical Practice Research Datalink to delineate a study cohort of adults aged 18-64 who were prescribed OAT between Jan 1, 1998 and Dec 31, 2017. These records were linked to hospitalisation, mortality records and patient neighbourhood and practice-level Index of Multiple Deprivation quintiles. With inverse probability treatment weights applied and negative binomial regression models we estimated incidence rate ratios for hospital admissions among patients who experienced multiple overdoses.FindingsA total of 20898 patients were prescribed methadone or buprenorphine over 83856 person-years of follow-up. Compared with periods in treatment, patients not in treatment were 51% more likely to experience a non-fatal overdose that required hospitalisation (weighted rate ratio, wRR 1·51; 95% CI 1·42, 1·60), especially during the four weeks of OAT initiation (5·59; 5·31, 5·89) and following cessation (13·39; 12·78, 14·03). The wRR of overdose during (0·37; 0·34, 0·39) and after treatment (0·36; 0·34, 0·38) favoured buprenorphine compared to methadone.InterpretationOAT is associated with decreased non-fatal overdose risk. Buprenorphine may act more protectively than methadone, especially during the first four weeks of treatment.FundingNational Institute for Health and Care Research (NIHR) Greater Manchester Patient Safety Translational Research Centre (PSTRC-2016-003).

Chlamydia Trachomatis/Neisseria Gonorrhea Retesting Among Adolescents and Young Adults in a Primary Care Network

PurposeChlamydia trachomatis/Neisseria gonorrhea (CT/NG) retesting three months after diagnosis is a guideline-recommended strategy to detect re-infections. Adolescents and young adults are priority populations in the U.S. Sexually Transmitted Infections National Strategic Plan, but there is a lack of research examining CT/NG retesting among these populations. This study describes retesting following CT/NG diagnosis among adolescent and young adult patients at Title X and non-Title X clinics and measures the association of patient-level factors with CT/NG retesting. MethodsWe evaluated electronic medical records from 2014 to 2020 from an academic urban-suburban primary care network. The primary outcome was retesting, defined as a diagnostic test for CT or NG ordered 8–16 weeks after index diagnosis. Mixed effects logistic regression modeling stratified by Title X funding was conducted to evaluate the association of patient-level factors with CT/NT retesting. ResultsOverall, 23.5% (n = 731) of patients were retested within 8–16 weeks following index CT/NG diagnosis. A significantly greater proportion of Title X patients were retested compared to non-Title X patients. Males were significantly less likely to be retested compared to females, and the proportion of patients retested decreased significantly over the study period. DiscussionGuideline-recommended retesting following CT/NG diagnosis was low in this young primary care cohort, especially among male and non-Title X clinic patients. Decreases in CT/NG retesting over the study period may be contributing to worsening of the STI epidemic. Our results provide insights into CT/NG retesting that can inform efforts to end the STI epidemic.

Factors associated with statin discontinuation near end of life in a Danish primary health care cohort.

Long-term preventive treatment such as treatment with statins should be reassessed among patients approaching end of life. The aim of the study was to describe the rate of discontinuation of statin treatment and factors associated with discontinuation in the 6 months before death. This study is a retrospective cohort study using national registers and blood test results from primary health care patients. Patients in the Copenhagen municipality, Denmark who died between 1997 and 2018 and were statin users during the 10-year period before death were included. We calculated the proportion who remained statin users in the 6-month period before death. Factors associated with discontinuation were tested using logistic regression. A total of 55,591 decedents were included. More patients continued treatment (64%, n = 35,693) than discontinued (36%, n = 19,898) the last 6 months of life. The 70 and 80 age groups had the lowest odds of discontinuing compared to the 90 (OR 1.59, 95% CI 0.93-2.72) and 100 (OR 3.11, 95% CI 2.79-3.47) age groups. Increasing comorbidity score (OR 0.89, 95% CI 0.87; 0.90 per 1-point increase) and use of statins for secondary prevention (OR 0.89, 95% CI 0.85; 0.93) reduced the likelihood of discontinuation as did a diagnosis of dementia, heart failure, or cancer. A substantial portion of patients continued statin treatment near end of life. Efforts to promote rational statin use and discontinuation are required among patients with limited life expectancy, including establishing clear, practical recommendations about statin discontinuation, and initiatives to translate recommendations into clinical practice.

High-sensitivity troponin I with or without ultra-sensitive copeptin for the instant rule-out of acute myocardial infarction.

BackgroundThe instant, single-sampling rule-out of acute myocardial infarction (AMI) is still an unmet clinical need. We aimed at testing and comparing diagnostic performance and prognostic value of two different single-sampling biomarker strategies for the instant rule-out of AMI.MethodsFrom the Biomarkers in Acute Cardiac Care (BACC) cohort, we recruited consecutive patients with acute chest pain and suspected AMI presenting to the Emergency Department of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany. We compared safety, effectiveness and 12-month incidence of the composite endpoint of all-cause death and myocardial infarction between (i) a single-sampling, dual-marker pathway combining high-sensitivity cardiac troponin I (hs-cTnI) and ultra-sensitive copeptin (us-Cop) at presentation (hs-cTnI ≤ 27 ng/L, us-Cop < 10 pmol/L and low-risk ECG) and (ii) a single-sampling pathway based on one-off hs-cTnI determination at presentation (hs-cTnI < 5 ng/L and low-risk ECG). As a comparator, we used the European Society of Cardiology (ESC) 0/1-h dual-sampling algorithm.ResultsWe enrolled 1,136 patients (male gender 65%) with median age of 64 years (interquartile range, 51–75). Overall, 228 (20%) patients received a final diagnosis of AMI. The two single-sampling instant rule-out pathways yielded similar negative predictive value (NPV): 97.4% (95%CI: 95.4–98.7) and 98.7% (95%CI: 96.9–99.6) for dual-marker and single hs-cTnI algorithms, respectively (P = 0.11). Both strategies were comparably safe as the ESC 0/1-h dual-sampling algorithm and this was consistent across subgroups of early-comers, low-intermediate risk (GRACE-score < 140) and renal dysfunction. Despite a numerically higher rate of false-negative results, the dual-marker strategy ruled-out a slightly but significantly higher percentage of patients compared with single hs-cTnI determination (37.4% versus 32.9%; P < 0.001). There were no significant between-group differences in 12-month composite outcome.ConclusionsInstant rule-out pathways based on one-off determination of hs-cTnI alone or in combination with us-Cop are comparably safe as the ESC 0/1 h algorithm for the instant rule-out of AMI, yielding similar prognostic information. Instant rule-out strategies are safe alternatives to the ESC 0/1 h algorithm and allow the rapid and effective triage of suspected AMI in patients with low-risk ECG. However, adding copeptin to hs-cTn does not improve the safety of instant rule-out compared with the single rule-out hs-cTn at very low cut-off concentrations.

Residual risk of major adverse cardiovascular and limb events among different atherosclerotic cardiovascular disease phenotypes receiving guideline-recommended antiplatelet monotherapy: The resrisk study

Background and Aims : To quantify the long-term residual atherothrombotic risk among a routine care cohort with coronary artery disease (CAD), ischaemic stroke (IS) or peripheral artery disease (PAD) on guideline-recommended antiplatelet monotherapy (APMT).

Outcomes of COVID-19 Among High-Risk Individuals: A Study Comparing Febrile and Afebrile Presentation.

BackgroundFever is one of the most frequent symptoms of coronavirus disease 2019 (COVID-19) and clinicians are faced with a practice question on whether fever is a risk for progression of disease especially in persons with risk factors for severe illness. We studied if a difference exists in the clinical course and outcome between febrile and afebrile (symptomatic) presentation.MethodsPatients aged > 18 years with confirmed COVID-19 with at least one risk factor for severe illness were studied. Enrolment was done from a home COVID-19 care cohort between May 2020 and March 2022. Participants were divided into febrile and afebrile groups and further divided into six sub-groups based on their comorbidities (diabetes mellitus, hypertension, chronic lung disease, chronic kidney disease, liver disease and others) using a pre-specified inclusion method. Severity of illness was classified as non-hypoxic or hypoxic and clinical course was monitored.ResultsA total of 3,752 patients were studied, of whom 965 (25.7%) had severe illness and 117 (3.1%) died. Persons with obesity (P < 0.001), chronic kidney disease (P = 0.003) and chronic liver disease (P = 0.02) more frequently had presentation without fever. No significant difference in hypoxia (P = 0.35) or mortality (P = 0.50) was observed between febrile (n = 1,240) and afebrile (n = 2,512) presentation.ConclusionFever in COVID-19 was not associated with severe illness or mortality. The overall and risk factor specific mortality observed in our study is substantially low, probably due to lesser bias in selection of study participants or due to ethnicity of study population.

Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study

BackgroundWhile the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as ‘mild’, ‘moderate’ or ‘severe’ based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights.MethodsWe developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (< 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation.ResultsSix stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with ‘moderate’ TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with ‘severe’ GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p < 0.001).ConclusionsSix stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care.Trial registrationThe core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

Behavioral and Cognitive Problems as Determinants of Malnutrition in Long-Term Care Facilities, a Cross-Sectional and Prospective Study

ObjectivesTo investigate the cross-sectional and prospective associations between behavior and cognitive problems and malnutrition in long-term care facilities (LTCF).DesignCross-sectional and prospective routine care cohort study.Setting6874 Residents in Dutch LTCFs (period 2005–2020).ParticipantsData were obtained from the InterRAI-LTCF instrument. Cross-sectional analyses on prevalence of malnutrition at admission included 3722 residents. Prospective analyses studied incident malnutrition during stay (total follow-up time 7104 years) and included data of 1826 residents with first measurement on admission (‘newly-admitted’) and n=3152 with first measurement on average ∼1 year after admission (‘existing’).MeasurementsInterRAI scales for communication problems (CS), aggressive behavior (ABS), social engagement (RISE), depressive symptoms (DRS), cognitive performance (CPS) and the total number of behavior and cognitive problems were investigated as independent variables and malnutrition (ESPEN 2015 definition) as dependent variable in regression analyses. Results were stratified for gender and group ‘newly-admitted’ vs. ‘existing’.ResultsOn admission, 9.5% of residents was malnourished. In men, low social engagement was associated with prevalence of malnutrition. In women, all behavior and cognitive problems except depression were associated with malnutrition in the unadjusted analyses, but this attenuated in the full model taking all problems into account. The incidence of malnutrition during stay amounted to 8.9%. No significant associations of behavior and cognitive problems with malnutrition incidence were seen in ‘newly-admitted’ male residents while in ‘existing’ male residents all determinants were significantly associated. In ‘newly-admitted’ female residents CS, ABS and CPS, and in ‘existing’ female residents CS, RISE, ABS and CPS were significantly associated with incident malnutrition. All associations slightly attenuated after adjustment. Malnutrition incidence increased with increasing number of combined behavior and cognitive problems.ConclusionResidents with behavior and cognitive problems are at an increased risk of being malnourished at admission, or becoming malnourished during stay in a LTCF, especially residents with multiple behavior and cognitive problems.

Penicillin Allergy Delabeling Program: an exploratory economic evaluation in the Australian context.

Internationally, clinical and economic advantages of low-risk penicillin delabelling have been explored, supporting changes to healthcare delivery systems where penicillin delabelling is embedded into inpatient usual care. To determine if economic advantages of low-risk inpatient penicillin delabelling, described in the international literature, are realised in the Australian context. This explorative economic evaluation had prospective patient data collection between January and August 2019, across two Australian health services. Part 1: determine the cost per effectively delabelled patient for Penicillin Allergy Delabeling Program inpatients (PADP cohort) compared with Outpatient Antibiotic Allergy Testing Service outpatients (OAATS cohort). Part 2: a cost analysis to compare hospital costs for inpatients with low-risk penicillin allergy who did (PADP cohort) and did not (usual care cohort) undergo PADP delabelling. Part 1: the PADP (n = 350) and OAATS (n = 27 patients, n = 36 individual visits) cohorts were comparable. In PADP, costs/proportion delabelled was $20.10/0.98, equating to $20.51 per effectively delabelled patient; in OAATS, it was $181.24/0.50, equating to $362. Compared with OAATS, PADP was associated with savings of $341.97 per effectively delabelled patient, indicating the outpatient testing was the dominated strategy, being more costly and less effective. Part 2: the PADP (n = 218) and usual care (n = 32) cohorts were comparable. Significantly favouring the delabelled PADP cohort, the mean difference per patient was -4.41 days (95% confidence interval: -7.64, -1.18) and -$9467.72 (95% confidence interval: -$15 419.98, -$3515.46). Consistent with international literature, delabelling low-risk penicillin allergies in the inpatient setting had economic advantages in the Australian context. Fully powered economic evaluations are urgently required to consolidate these findings.

The temporal relationship between severe mental illness diagnosis and chronic physical comorbidity: a UK primary care cohort study of disease burden over 10 years

Despite increased rates of physical health problems in people with schizophrenia, bipolar disorder, and other psychotic illnesses, the temporal relationship between physical disease acquisition and diagnosis of a severe mental illness remains unclear. We aimed to determine the cumulative prevalence of 24 chronic physical conditions in people with severe mental illness from 5 years before to 5 years after their diagnosis. In this cohort study, we used the UK Clinical Practice Research Datalink (CPRD) to identify patients aged 18-100 years who were diagnosed with severe mental illness between Jan 1, 2000, and Dec 31, 2018. Each patient with severe mental illness was matched with up to four individuals in the CPRD without severe mental illness by sex, 5-year age band, primary care practice, and year of primary care practice registration. Individuals in the matched cohort were assigned an index date equal to the date of severe mental illness diagnosis in the patient with severe mental illness to whom they were matched. Our primary outcome was the cumulative prevalence of 24 physical health conditions, based on the Charlson and Elixhauser comorbidity indices, at 5 years, 3 years, and 1 year before and after severe mental illness diagnosis and at the time of diagnosis. We used logistic regression to compare people with severe mental illness with the matched cohort, adjusting for key variables such as age, sex, and ethnicity. We identified 68 789 patients diagnosed with a severe mental illness between Jan 1, 2000, and Dec 31, 2018, and we matched them to 274 827 patients without a severe mental illness diagnosis. In both cohorts taken together, the median age was 40·90 years (IQR 29·46-56·00), 175 138 (50·97%) people were male, and 168 478 (49·03%) were female. The majority of patients were of White ethnicity (59 867 [87·03%] patients with a severe mental illness and 244 566 [88·99%] people in the matched cohort). The most prevalent conditions at the time of diagnosis in people with severe mental illness were asthma (10 581 [15·38%] of 68 789 patients), hypertension (8696 [12·64%]), diabetes (4897 [7·12%]), neurological disease (3484 [5·06%]), and hypothyroidism (2871 [4·17%]). At diagnosis, people with schizophrenia had increased odds of five of 24 chronic physical conditions compared with matched controls, and nine of 24 conditions were diagnosed less frequently than in matched controls. Individuals with bipolar disorder and other psychoses had increased odds of 15 conditions at diagnosis. At 5 years after severe mental illness diagnosis, these numbers had increased to 13 conditions for schizophrenia, 19 for bipolar disorder, and 16 for other psychoses. Elevated odds of multiple conditions at the point of severe mental illness diagnosis suggest that early intervention on physical health parameters is necessary to reduce morbidity and premature mortality. Some physical conditions might be under-recorded in patients with schizophrenia relative to patients with other severe mental illness subtypes. UK Office For Health Improvement and Disparities.

Assessing the external validity of the SAFEHEART risk prediction model in patients with familial hypercholesterolaemia in an English routine care cohort

Background and aimsThe SAFEHEART tool has shown good discrimination in predicting cardiovascular events in a bespoke genotyped cohort with familial hypercholesterolaemia (FH). We assessed whether the tool could aid clinical decision making in an English routine care cohort with FH. MethodsA historical (2000–2017) open cohort of 3643 participants aged 18–79 years and ≥6-months since FH diagnosis was derived from the Clinical Practice Research Datalink. Individual 10-year cardiovascular risks were predicted using the SAFEHEART model, with multiple imputation used to manage missing data. Outcomes were the first occurrence of myocardial infarction, coronary revascularisation, ischaemic stroke, carotid revascularisation, peripheral arterial revascularisation, non-traumatic lower limb amputation, or cardiovascular death. Model performance was assessed using standard measures of calibration and discrimination, and decision curve analysis. Results147 outcome events were observed over a median 3.73 (IQR 1.59–6.48) years follow-up. While the model had some discriminatory value (Harrell's c-statistic 0.67 (95% CI 0.61–0.72)), observed outcome risks departed substantially from predicted risks. Calibration slopes for men and women by age decile were 10.09 (95% CI 7.40–12.77) and 2.85 (1.25–4.45), respectively. Recalibration-in-the-large led to closer alignment of observed and predicted risks (recalibration slopes 3.48 (2.55–4.41) and 1.14 (0.50–1.79), respectively). Decision curve analysis suggested the recalibrated model had net benefit at predicted risks of 10–30%. ConclusionsThe original SAFEHEART model has limited generalisability to the routinely identifiable English primary care FH population. With recalibration it appears to have moderate utility at 10–30% predicted risk. It may have greater validity in more bespoke genetically defined FH populations.

Burden of disease and management of osteoarthritis and chronic low back pain: healthcare utilization and sick leave in Sweden, Norway, Finland and Denmark (BISCUITS): study design and patient characteristics of a real world data study.

Osteoarthritis (OA) and chronic low back pain (CLBP) are common musculoskeletal disorders with substantial patient and societal burden. Nordic administrative registers offer a unique opportunity to study the impact of these conditions in the real-world setting. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study was designed to study disease prevalence and the societal and economic burden in broad OA and CLBP populations. Patients in Sweden, Norway, Finland and Denmark with diagnoses of OA or CLBP (low back pain record plus≥2 pain relief prescriptions to indicate chronicity) were identified in specialty care, in primary care (Sweden and Finland) and in a quality-of-care register (Sweden). Matched controls were identified for the specialty care cohort. Longitudinal data were extracted on prevalence, treatment patterns, patient-reported outcomes, social and economic burden. Almost 1.4 million patients with OA and 0.4 million with CLBP were identified in specialty care, corresponding to a prevalence in the Nordic countries of 6.3 and 1.9%, respectively. The prevalence increased to 11-14% for OA and almost 6% for CLBP when adding patients identified in primary care. OA patients had a higher Elixhauser comorbidity index (0.66 vs. 0.46) and were using opioids (44.7 vs. 10.2%) or long-term nonsteroidal anti-inflammatory drug (NSAIDs) (20.9 vs. 4.5%) more than four times as often as compared to controls. The differences were even larger for CLBP patients compared to their controls (comorbidity index 0.89 vs. 0.39, opioid use 77.7 vs. 9.4%, and long-term NSAID use 37.2 vs. 4.8%). The BISCUITS study offers an unprecedented, longitudinal healthcare data source to quantify the real-world burden of more than 1.8 million patients with OA or CLBP across four countries. In subsequent papers we aim to explore among others additional outcomes and subgroups of patients, primarily those patients who may benefit most from better healthcare management.

Impact of Medicare eligibility on informal caregiving for surgery and stroke.

To assess whether the intensity of family and friend care changes after older individuals enroll in Medicare at age 65. Health and Retirement Study survey data (1998-2018). We compared informal care received by patients hospitalized for stroke, heart surgery, or joint surgery and who were stratified into propensity-weighted pre- and post-Medicare eligibility cohorts. A regression discontinuity design compared the self-reported likelihood of any care receipt, weekly hours of overall informal care, and intensity of informal care (hours among those receiving any care) at Medicare eligibility. Not applicable. A total of 2270 individuals were included; 1674 (73.7%) stroke, 240 (10.6%) heart surgery, and 356 (15.7%) joint surgery patients. Mean (SD) care received was 20.0 (42.1) weekly hours. Of the 1214 (53.5%) patients who received informal care, the mean (SD) care receipt was 37.4 (51.7) weekly hours. Mean (SD) overall weekly care received was 23.4 (45.5), 13.9 (35.8), and 7.8 (21.6) for stroke, heart surgery, and joint surgery patients, respectively. The onset of Medicare eligibility was associated with a 13.6 percentage-point decrease in the probability of informal care received for stroke patients (p=0.003) but not in the other acute care cohorts. Men had a 16.8 percentage-point decrease (p=0.002) in the probability of any care receipt. Medicare coverage was associated with a substantial decrease in family and friend caregiving use for stroke patients. Informal care may substitute for rather than complement restorative care, given that Medicare is known to expand the use of postacute care. The observed spillover effect of Medicare coverage on informal caregiving has implications for patient function and caregiver burden and should be considered in episode-based reimbursement models that alter professional rehabilitative care intensity.

Safety profile and outcome after ultrasound-guided suprainguinal fascia iliaca catheters for hip fracture: a single-centre propensity-matched historical cohort study.

Peripheral nerve blocks improve analgesia following hip fracture; however, there are little published data on safety and outcomes of continuous regional anesthetic techniques. Our institution offers pre- and perioperative, anesthesiologist-delivered ultrasound-guided suprainguinal fascia iliaca catheters (FICs) to patients with hip fracture. We aimed to document the safety profile of this technique and establish whether there are any significant clinical benefits in outcomes measured by the UK National Hip Fracture Database. We performed a single-centre historical cohort study of 2,187 patients admitted to our institution with hip fracture over a 5.75-year period. Of these, 915 were treated with FIC and 1,272 received standard care (single-shot block). To control for baseline differences between these two cohorts, we used propensity score matching and exact matching, resulting in two well-matched groups of 728 patients treated with an FIC and standard care. No serious complications were observed as a result of an FIC. Unplanned removal occurred in 146/852 (17.1%) patients with documented data. No differences in 30-day mortality, pressure ulcer rates, or hospital length of stay were observed between the matched groups. The percentage of patients who were discharged to their usual residence was 79.3% in the FIC cohort vs 75.1% in the standard care cohort (difference, 4.2%; 95% confidence interval, -0.1 to 8.4; P = 0.06). Our single-centre propensity-matched historical cohort study suggests that ultrasound-guided suprainguinal fascia iliaca catheterization is a safe technique for patients with hip fracture and that our service is deliverable and sustainable within the UK's National Health Service. This study did not show statistically significant differences in outcomes between patients treated with FIC and standard care. An adequately powered multicentre randomized controlled trial comparing these approaches is warranted.

Clinical relevance of double-arm blood pressure measurement and prevalence of clinically important inter-arm blood pressure differences in Indian primary care.

Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter‐arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort.A number of 134 678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib).On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs 134.2 mmHg (p < .01) and diastolic BP 82.7 vs 82.6 mmHg (p < .01), respectively.Prevalence of significant mean systolic IAD between 10 and 15 mmHg was 7,813 (5.8%). Systolic IAD ≥ 15 mmHg 2,980 (2.2%) and diastolic IAD ≥ 10 mmHg 7,151 (5.3%). In total, there were 7,595 (5.6%) and 8,548 (6.3%) participants with BP above the 140/90 mmHg threshold in only the left or right arm, respectively. Prevalence of participants with elevated BP on one arm only was highest in patients with a systolic IAD ≥ 15 mmHg; 19.1% and 13.7%, for left and right arm, respectively.This study shows that a substantial prevalence of IAD exists in Indian primary care patients. BP is above the diagnostic threshold for hypertension in one arm only for 6% of participants. These findings emphasize the importance of undertaking bilateral BP measurement in routine clinical practice.

Panobinostat in combination with bortezomib and dexamethasone in multiply relapsed and refractory myeloma; UK routine care cohort.

The combination of panobinostat, bortezomib and dexamethasone (PanBorDex) is available as a treatment option for relapsed refractory multiple myeloma (RRMM) based on the PANORAMA-1 trial which investigated this triplet in early relapse. In routine clinical care, PanBorDex is used primarily in later relapses and is commonly administered in attenuated dosing schedules to mitigate the treatment-related toxicity. We set out to evaluate efficacy and safety outcomes with PanBorDex later in the disease course and evaluate the role of attenuated dosing schedules. This was a retrospective evaluation of patients treated in routine clinical practice between 2016–2019 across seven heamatology centres in the UK; patients who received at least one dose of PanBorDex were eligible for inclusion. The dosing schedule of panobinostat (10mg, 15mg or 20mg, twice or three times a week) and bortezomib (0.7mg/m2, 1mg/m2 or 1.3mg/m2 once or twice weekly) was as per treating physician choice. Patients received treatment until disease progression or unacceptable toxicity. The primary outcome is response rates according to IMWG criteria. Key secondary endpoints include progression-free survival (PFS) and overall survival (OS). Other secondary endpoints include rates of adverse events according to CTCAE criteria. In total, 61 patients were eligible for inclusion and received PanBorDex primarily as ≥5th line of treatment. One third of patients received PanBorDex at full dose, for the remaining two thirds, treatment was given in reduced dose intensities. The overall response rate was 44.2%, including 14.7% very good partial response (VGPR) rates; 68.8% of patients derived clinical benefit with stable disease or better. The median PFS was 3.4 months; non-refractory patients and those who achieved VGPR benefited from prolonged PFS of 11.4 months and 17.7 months, respectively. The median OS was 9.5 months. The triplet was associated with 45% and 18% incidence of grade 3–4 thrombocytopenia and diarrhea, respectively.

The impact of remission duration on the long-term economic burden of acute myeloid leukemia among patients without hematopoietic stem cell transplant in the United States

Background and aims Acute myeloid leukemia (AML) prognosis is poor, with sustained remission occurring in <35% of young adults and <15% of older adults. This descriptive study examined the potential benefit of prolonged remission on the economic burden of AML. Methods Using the IBM MarketScan Commercial and Medicare Supplemental databases, we identified newly diagnosed patients with AML without hematopoietic stem cell transplantation from January 1, 2012 to December 31, 2018; AML diagnosis was the index date. Patients had 6 months of pre-index eligibility and were followed until the end of continuous eligibility, study data, or death. Active treatment and supportive care cohorts were defined; duration-of-remission subgroups (0 to <3, 3 to <6, 6 to <12, and ≥12 months) were established among active treatment patients with remission. Healthcare service utilization and costs were reported over follow-up and mutually exclusive treatment, remission, and post-relapse periods. Results This study included 1,558 active treatment and 1,127 supportive care patients who were followed for a median of 232 and 62 days, respectively. Over follow-up, active treatment and supportive care patients incurred mean ± standard deviation all-cause healthcare costs of $55,723 ± $61,994 and $68,596 ± $100,375 per-patient-per-month (PPPM), respectively. Decreasing PPPM costs were observed with increased remission duration (0 to <3 months: $71,823 ± $62,635; 3 to <6 months: $54,262 ± $44,734; 6 to <12 months: $35,287 ± $23,699; and ≥12 months: $15,615 ± $10,560). Although median follow-up varied by up to 5-fold, total costs were largely similar across duration-of-remission subgroups (0 to <3 months: $438,569 ± $332,675; 3 to <6 months: $590,411 ± $598,245; 6 to <12 months: $482,902 ± $369,115; and ≥12 months: $448,867 ± $316,133). Conclusions The economic burden of AML is substantial, even among untreated patients. Further, among patients with remission, longer durations in remission are associated with reduced PPPM healthcare costs, suggesting that remission-prolonging treatments could help mitigate healthcare costs.

Quality outcome of diabetes care during COVID-19 pandemic: a primary care cohort study

AimManagement of diabetes care can be affected by COVID-19 pandemic control measures. This study aimed to determine the impact of the pandemic, during 17.03.2020–16.03.2021, on quality outcomes of diabetes care in general practice in Switzerland.MethodsIn this retrospective cohort study, diabetes mellitus patients (≥ 18 years) with at least one consultation at a general practitioner, during 17.03.2018–16.03.2019 (cohort 1) and 17.03.2019–16.03.2020 (cohort 2) were included and followed-up for two years. Quality indicators and outcomes of diabetes care, at patient and practitioner level, were compared before and during the pandemic. Logistic regression was performed to identify patient’s risk factors for dropout from follow-up.ResultsData from 191 practices, 23,903 patients, cohort 1 and 25,092 patients, cohort 2, were analyzed. The fraction of patients lost to follow-up, attributable to the pandemic, was 28% (95% confidence interval: 25%, 30%). During the pandemic, compared to the previous year, regular measurement of weight, HbA1c, blood pressure and serum creatinine were less frequent and less patients per practitioner reached HbA1c and blood pressure target outcomes. Factors associated with continuity of care during the pandemic were: patient age 41–80 years, longer diabetes duration, diagnosis of hypertension or dyslipidemia, influenza vaccination during the last year. Risk factors for dropout were age > 80 and receiving only insulin as anti-diabetic medication.ConclusionA considerable quality reduction in diabetes mellitus care could be observed during the pandemic. Though the most vulnerable patients were not the most affected by the pandemic, key factors that might reduce dropout from follow-up were identified.