Exposure to Valsartan Products Containing Nitrosamine Impurities in the United States, Canada, and Denmark.

BACKGROUND: Following the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the United States, Canada, and Denmark. METHODS: We conducted a retrospective cohort study using administrative healthcare data from the US FDA Sentinel System, four Canadian provinces that contribute to the Canadian Network for Observational Drug Effect Studies (CNODES), and the Danish National Prescription Registry. Patients, 18 years and older between May 2012 and December 2020 with a valsartan dispensing were identified in each database. Patients were followed from the date of valsartan dispensing until discontinuation. We defined four valsartan exposure categories based on nitrosamine impurity status; recalled generic products with confirmed NDMA/NDEA levels (recalled-tested); recalled generic products that were not tested (recalled); non-recalled generic and non-recalled branded products. In Denmark, the recalled-tested category was not included due to absence of testing data. The proportion and duration of use of valsartan episodes stratified by nitrosamine-impurity status was calculated. RESULTS: We identified 3.3 and 2.8 million (United States) and 51.3 and 229 thousand (Canada) recalled-tested and recalled valsartan exposures. In Denmark, where valsartan exposure was generally low, there were 10 747 recalled exposures. Immediately after the recall notices were issued, there was increased rates of switching to a non-valsartan ARB. The mean duration of use of the recalled-tested products was 167 (±223.1) and 146 (±255.8) days in the United States and Canada respectively. For the recalled products, mean cumulative duration of use was 178 (±249.6), 269 (±397.3) and 166 (±251.0) days in the United States, Canada, and Denmark, respectively. CONCLUSION: In this cohort study, despite widespread use of recalled generic valsartan between 2012 and 2018, the duration of use was relatively short and probably did not pose an elevated risk of nitrosamine-induced cancer. However, since products with nitrosamine impurity could have been on the market over a 6-year period, patients exposed to these products for longer durations could have a potentially different risk of cancer.

Treatment trajectories for Danish individuals with type 2 diabetes in the era of emerging glucose-lowering therapies.

AIM: To analyse patterns of glucose-lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023. MATERIALS AND METHODS: We examined time trends in the clinical profiles of people with T2D who initiated different glucose-lowering therapy classes for the first time. We furthermore investigated individual-level treatment trajectories following first-ever glucose-lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first-ever prescription for metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) or insulin, excluding those without HbA1c-confirmed T2D or probable type 1 diabetes. RESULTS: We included 260 393 individuals initiating a new glucose-lowering therapy class from 2016 to 2023, during which there were 6- and 3-fold increases in initiators of GLP-1RAs and SGLT-2is, respectively. The median HbA1c level at treatment initiation with GLP-1RAs or SGLT-2is decreased, from 67-68 mmol/mol in 2016-2017 to 57-58 mmol/mol in 2022-2023. Among individuals who initiated metformin as first-line therapy, the proportion who started additional glucose-lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first-ever glucose-lowering therapy in 2020, 22% used SGLT-2is and 18% GLP-1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively. CONCLUSIONS: Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP-1RAs and SGLT-2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease.

Changes in the Use of Hydrochlorothiazide and Other Antihypertensive Drugs in Switzerland in Association With the Swissmedic Safety Alert Regarding Non-melanoma Skin Cancer: An Interrupted Time-Series Analysis Using Swiss Claims Data.

PURPOSE: Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic. METHODS: We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population. RESULTS: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less. CONCLUSION: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland.

Real-World Use of Semaglutide for Weight Management: Patient Characteristics and Dose Titration-A Danish Cohort Study.

OBJECTIVE: To determine patient characteristics and dose titration patterns of real-world Wegovy (semaglutide) users. RESEARCH DESIGN AND METHODS: We used a population-based cohort study including Danish adults who filled Wegovy prescriptions from 12 December 2022 to 31 December 2023. Outcomes were patient characteristics, prescriber type, and dose titration patterns. RESULTS: We identified 110,748 individuals (median age 49 years; 70% female) filling 773,708 prescriptions for Wegovy. General practitioners initiated treatment in 86%. Common comorbidities included hypertension (30%), dyslipidemia (17%), and arthrosis (17%). Only 13% reached the maximum dose of 2.4 mg by their fifth prescription, while 5.7% stopped after the first prescription. Few users (10%) followed recommended dose increases every 4 weeks. Overall, 25% filled at least one prescription of 2.4 mg, while 33-48% continued with the 1.0-mg dosage from the fourth prescription onward. CONCLUSIONS: Real-world Wegovy users generally resembled trial participants, but few follow the dose titration schemes tested in premarket clinical trials.

Medication management in Danish home health care: Mapping of tasks and time consumption.

We aimed to map tasks related to medication management and time consumption in Danish home health care. Nursing staff (n = 30) from five municipalities were followed during a 10-week period and tasks related to medication management, time consumption and information on citizens' medication were registered. A total of 269 courses were registered, including 163 (61%) home visits, 76 (28%) in-office courses, 29 (11%) in-clinic courses and 1 (0.4%) acute visit. Of defined categories related to medication management, 'record-keeping and communication' (62%, n = 167), 'dispensing' (48%, n = 129) and 'identification' (30%, n = 81) were most often performed. During half of courses (55%, n = 147), the nursing staff was interrupted at least one time. The median time spent on medication management was less than the time allocated in most of allocated time slots (82%), with a median excess time of 5.1 min (range 0.02-24 min). Citizens (n = 32) used a median of 11 (interquartile range [IQR] 9-13) regular medications and 2 (IQR 1-4) as-needed, and 69% (n = 22) used high-risk situation medications. In conclusion, employees in Danish home health care perform diverse medication-related tasks and are frequently interrupted in their work. Employees spend less time than allocated but do not fully solve all tasks according to best practice guidance.

Dicloxacillin is an inducer of intestinal P-glycoprotein but neither dicloxacillin nor flucloxacillin increases the risk of stroke/systemic embolism in direct oral anticoagulant users.

AIM: We aimed to assess if dicloxacillin/flucloxacillin reduces the therapeutic efficacy of direct oral anticoagulants (DOACs) and the underlying molecular mechanism. METHODS: In a randomized, crossover study, we assessed whether dicloxacillin reduces oral absorption of drugs through P-glycoprotein (P-gp) during 10 and 28 days of treatment. To study the impact of dicloxacillin/flucloxacillin on intestinal and hepatic expression of P-gp in vitro, we usd LS174T cells and 3D spheroids of primary human hepatocytes. Finally, we used nationwide Danish health registries and the UK's Clinical Practice Research Datalink to estimate hazard ratios (HRs) for the risk of stroke and systemic embolism following dicloxacillin/flucloxacillin exposure among DOAC users, using phenoxymethylpenicillin and amoxicillin as active comparators. RESULTS: Dicloxacillin reduced the area under the curve of dabigatran to a geometric mean ratio 10 days of 0.67 (95% confidence interval [CI]: 0.42-1.1) and geometric mean ratio 28 days of 0.72 (95% CI: 0.39-1.4), suggesting reduced oral absorption via increased P-gp expression. In vitro, dicloxacillin raised P-gp expression in both intestinal and liver cells, while flucloxacillin only affected liver cells. In the pharmacoepidemiologic study, dicloxacillin and flucloxacillin were not associated with increased risk of stroke/systemic embolism (dicloxacillin vs. phenoxymethylpenicillin HR: 0.93, 95% CI: 0.72-1.2; flucloxacillin vs. amoxicillin HR: 0.89, 95% CI: 0.51-1.5). CONCLUSIONS: Dicloxacillin increases expression of intestinal P-gp, leading to reduced oral absorption of dabigatran. However, concomitant use of dicloxacillin/flucloxacillin was not associated with stroke and systemic embolism among DOAC users, suggesting no clinical impact from the drug-drug interaction between dicloxacillin/flucloxacillin and DOACs.

Comparison of sociodemographic factors, healthcare utilisation by general practitioner visits, somatic hospital admissions, and medication use in Norway, Sweden, and Denmark.

PURPOSE: The healthcare systems in Scandinavia inform nationwide registers and the Scandinavian populations are increasingly combined in research. We aimed to compare Norway (NO), Sweden (SE), and Denmark (DK) regarding sociodemographic factors and healthcare. METHODS: In this cross-sectional study, we analyzed aggregated data from the nationwide Scandinavian registers. We calculated country-specific statistics on sociodemographic factors and healthcare use (general practitioner visits, admissions to somatic hospitals, and use of medicines). RESULTS: In 2018, population were 5295,619 (NO), 10,120,242 (SE), and 5781,190 (DK). The populations were comparable regarding sex, age, education, and income distribution. Overall, medication use was comparable, while there was more variation in hospital admissions and general practitioner visits. For example, per 1000 inhabitants, 703 (NO), 665 (SE), and 711 (DK) individuals redeemed a prescription, whereas there were 215 (NO), 134 (SE), and 228 (DK) somatic hospital admissions per 1000 inhabitants. General practitioner contacts per 1000 inhabitants were 7082 in DK and 5773 in NO (-data from SE). CONCLUSION: The Scandinavian countries are comparable regarding aggregate-level sociodemographic factors and medication use. Variations are noted in healthcare utilisation as measured by visits to general practitioners and admissions to hospitals. This variation should be considered when comparing data from the Scandinavian countries.

Diagnostic accuracy of dipsticks for urinary tract infections in acutely hospitalised patients: a prospective population-based observational cohort study.

OBJECTIVE: To determine the added diagnostic value of dipsticks for urinary tract infections (UTI) in acutely hospitalised individuals. DESIGN: Prospective population-based cohort study. SETTING: North Denmark. PARTICIPANTS: All adults (≥18 years) examined with dipsticks at emergency departments in North Denmark Region from September 20 through 23 October 2021. MAIN OUTCOME MEASURES: UTI was defined as ≥1 symptom of new-onset frequency, dysuria or suprapubic tenderness combined with a positive urine culture. Positive dipsticks were defined as any reaction for leucocyte esterase and/or nitrite. RESULTS: Dipsticks were used in 1052/2495 (42%) of acutely hospitalised patients with a median age of 73 years (IQR 57-82) and 540 (51%) were female. Overall, 89/1052 (8%) fulfilled the UTI criteria and urine cultures were done in 607/1052 (58%) patients. Among patients examined with both dipstick and urine culture, sensitivity and specificity for UTI were 87% (95% CI 78% to 93%) and 45% (95% CI 41% to 50%). Positive and negative predictive values were 21% (95% CI 17% to 26%) and 95% (95% CI 92% to 98%), whereas positive and negative likelihood ratios were 1.58 (95% CI 1.41 to 1.77) and 0.30 (95% CI 0.18 to 0.51). Pretest probabilities of UTI ranged from 29% to 60% in participants with specific UTI symptoms with corresponding post-test probabilities of 35-69% if dipsticks were positive and 12-27% if dipsticks were negative. Results remained comparable if final clinical diagnosis was used as outcome among all patients examined with dipsticks. Modified Poisson regression yielded an adjusted relative risk of 4.41 (95% CI 2.40 to 8.11) for empirical antibiotics for UTI in participants without specific UTI symptoms and a positive dipstick. CONCLUSIONS: Dipsticks yielded limited clinical decision support compared with a symptom-driven approach in this study and were independently associated with excess antibiotics for UTI.

Short-term and long-term stroke risk following SARS-CoV-2 infection in relation to disease severity: a Danish national cohort study.

OBJECTIVES: Studies have reported high incidences of stroke in patients hospitalised with SARS-CoV-2, but the impact of disease severity is unexplored. We aimed to estimate the risk of incident ischaemic stroke in SARS-CoV-2 test-positive individuals compared with test-negative individuals stratified by disease severity during acute infection and post infection. DESIGN: A register-based cohort study. SETTING: A Danish nationwide study. PARTICIPANTS: All Danish adults who had PCR tests for SARS-CoV-2 performed between 1 March 2020 and 30 November 2021. Test-positive individuals were included at their first positive test. For individuals tested prior to 30 November 2021, we randomly sampled an index date from the distribution of test dates among SARS-CoV-2 test-positive individuals. Test-positive individuals were followed during the acute phase of infection (days 0-14) and post infection (180 days after the acute phase). Test-negative individuals were followed in equivalent time periods. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident ischaemic stroke risk in SARS-CoV-2 test-positive individuals compared with test-negative individuals during acute infection and post infection. We calculated subdistribution HRs (SHR) with death as a competing risk using propensity score weighting as confounder control. The risk was stratified according to disease severity: community managed, hospitalised, or admission to the intensive care unit. RESULTS: Among 3 910 219 SARS-CoV-2 PRC-tested individuals, 356 421 test-positive and 3 067 456 test-negative individuals were included. A positive SARS-CoV-2 test was associated with an SHR of 3.32 (95% CI 2.60 to 4.25) overall for stroke compared with test negative in the acute phase. In the postinfection period, the risk of stroke remained increased in individuals hospitalised during the acute phase (SHR 1.85, 95% CI 1.45 to 2.37). Individuals with community-managed SARS-CoV-2 had no increased long-term risk of stroke (SHR 1.01, 95% CI 0.88 to 1.16). CONCLUSION: SARS-CoV-2 infection is associated with increased stroke risk. Disease severity seems to be an important factor. Individuals with community-managed SARS-CoV-2 had no increased stroke risk.

Challenges related to transitioning from hospital to temporary care at a skilled nursing facility: a descriptive study.

PURPOSE: With decreasing number of hospital beds, more citizens are discharged to temporary care at skilled nursing facilities, requiring increasingly complex care in a non-hospital setting. We mapped challenges related to the transition of citizens from hospital to temporary care at a skilled nursing facility in relation to medication management, responsibility of medical treatment, and communication. METHODS: Descriptive study of citizens discharged from Odense University Hospital to temporary care from May 2022 to March 2023. RESULTS: We included 209 citizens (53% women, median age 81 years). Most citizens (97%; n = 109/112) had their medication changed during hospital admission. Citizens used a median of eight medications, including risk medications (96%, n = 108). Medication-related challenges occurred for 37% (n = 77) of citizens and most often concerned missing alignment of medication records. Half of citizens (47%, n = 99) moved into temporary care with all medication needed for further dispensing. Nurses conducted in median three telephone calls (interquartile range [IQR 1-4]) and sent in median two correspondences (IQR 1-3) per citizen within the first 5 days. Nurses most often called the hospital physician (41% of telephone calls, n = 265/643) and sent correspondences to the general practitioner (55% of correspondences, n = 257/469). For 31% (n = 29/95) of citizens requiring action from nursing staff, this could have been avoided if the nurses had had access to the discharge letter. CONCLUSION: We identified several challenges related to the transition of patients from hospital to temporary care, most often related to medication. A third of actions related to medication management were considered avoidable with improved practices around communication.

Use of antibiotics for urinary tract infections up to and after care home admission in Denmark: a nationwide study.

PURPOSE: Older people have the highest use of antibiotics for acute and chronic urinary tract infection (UTI), despite diagnostic uncertainty and the growing problem of antibiotic resistance. We aim to describe use-patterns of UTI antibiotics two years prior to and following care home admission in Denmark. METHODS: This was a register-based nationwide drug-utilization study. In a cohort comprising all Danish residents admitted into a care home from 2015 to 2021, we described the use of UTI antibiotics, and examined differences between regions and individual care homes in rates of UTI antibiotic use. Further, we described trends in UTI-related contacts with hospitals in the two years prior to and following care home admission. RESULTS: The cohort comprised 101,297 residents (61% female; median age 84 years). UTI antibiotic use doubled from 7 to 14 treatments/100 residents/month two months prior to care home admission and remained at 10 treatments/100 residents/month the following two years. Prescription of pivmecillinam (55%) was most common. Primary care practitioners prescribed the majority (92%) of UTI antibiotics. UTI-related hospital contacts peaked at two months prior to care home admission, with 6 admissions/100 residents/month, subsequently dropping to 2 admission/100 residents/month. We found considerable variation in UTI antibiotic use, with 10% of care homes responsible for 20% of treatments in 2021. CONCLUSION: Use of UTI antibiotics increased prior to and remained at a stable high level following care home admission in Denmark. Despite variation in use across regions and individual care homes, an overall decrease was seen throughout the years 2016-2021.

Mental health and use of psychotropic prescription drugs in adult patients with primary immune thrombocytopenia: a nationwide population-based cohort study.

Patients with primary immune thrombocytopenia (ITP) suffer from reduced survival and quality of life, but the underlying reasons for this are largely undescribed. Mental health and the use of psychotropic drugs in ITP is unknown. We investigated the risk of hospital-registered mental health events including fatigue and the use of psychotropic drugs in adult patients with ITP compared with the general population, using nationwide registry-data. We identified 3,749 patients with ITP and 149,849 age- and sex-matched general population comparators in the Danish Health Registries in the period 1997-2016. The median age was 60 years (interquartile range [IQR], 40-73) and 53% were women. We followed the individuals for incident mental health events and estimated the use of psychotropic drugs over calendar-years and in temporal relation to diagnosis of ITP. The first year cumulative incidence of any mental health event was 2.3% (95% confidence interval [CI]: 1.9-2.9) in patients and 0.7% (95% CI: 0.6-0.7) in comparators, yielding an adjusted cause-specific hazard ratio (csHR) of 3.57 (95% CI: 2.84-4.50). The corresponding estimates for depression were 1.2% (95% CI: 0.9-1.6) and 0.3% (0.3-0.4) respectively, with an adjusted csHR of 3.53 (95% CI: 2.56-4.85). We found similar findings for anxiety and fatigue, but risks generally diminished after 1-5 years. The use of opioids, antidepressants, and benzodiazepines increased in temporal relation to diagnosis of ITP. The risk of mental health events and the use of psychotropic drugs is higher in adult patients with ITP compared with the general population, and has a temporal relation to diagnosis of ITP emphasizing that mental health in ITP is a concern.

Does LDL-C determination method affect statin prescribing for primary prevention? A register-based study in Southern Denmark.

AIMS: Examine whether low-density lipoprotein cholesterol (LDL-C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease. METHODS AND RESULTS: We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the Region directly measure LDL-C whereas four laboratories calculate LDL-C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL-C determined during 2018-2019. There were 202,807 people who had LDL-C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL-C measurement. The median reported LDL-C was 3.40 mmol/L (IQR 2.90 to 4.00) for those with a direct measurement versus 3.00 mmol/L (IQR 2.40 to 3.50) for those with calculated LDL-C. For those with direct measurement, re-calculated LDL-C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL-C measurement. Among those with directly measured LDL-C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL-C. Direct LDL-C measurement led to higher odds of having a statin initiated compared to calculated LDL-C (adjusted odds ratio 1.23, 95% CI 1.17 to 1.30); for those with triglycerides > 1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30 to 1.52). CONCLUSION: Differences in the reporting of LDL-C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.

Building transparency and reproducibility into the practice of pharmacoepidemiology and outcomes research.

Real-world evidence (RWE) studies are increasingly used to inform policy and clinical decisions. However, there remain concerns about the credibility and reproducibility of RWE studies. Observational researchers should highlight the level of transparency of their studies by providing a succinct statement addressing study transparency with the publication of every paper, poster, or presentation that reports on a RWE study. In this paper, we propose a framework for an explicit transparency statement that declares the level of transparency a given RWE study has achieved across five key domains: 1) protocol, 2) pre-registration, 3) data, 4) code sharing, and 5) reporting checklists.

Semaglutide (Ozempic®) Use in Denmark 2018 Through 2023 ‒ User Trends and off-Label Prescribing for Weight Loss.

Purpose: A surge in the use of semaglutide injection (Ozempic®) approved to treat type 2 diabetes (T2D) has led to a global supply shortage. We investigated contemporary user rates and clinical characteristics of semaglutide (Ozempic®) users in Denmark, and the extent of "off-label" prescribing for weight loss. Patients and Methods: Nationwide population-based cross-sectional study based on linked health registries January 2018 through December 2023. All adults who received a first prescription of semaglutide once weekly (Ozempic®) were included. We examined quarterly rates of new users and total user prevalences, using other glucagon-like peptide-1 receptor agonists and weight loss medications as comparison. We also investigated user characteristics including T2D, glucose control, comedications, and cardiorenal disease. Results: The new user rate of semaglutide (Ozempic®) remained stable at approximately 4 per 1000 adult person-years between 2019 and 2021 and then accelerated, peaking at 10 per 1000 in the first quarter of 2023 after which it declined sharply. User prevalence increased to 91,626 users in Denmark in 2023. The proportion of semaglutide (Ozempic®) new users who had a record of T2D declined from 99% in 2018 to only 67% in 2022, increasing again to 87% in 2023. Among people with T2D who initiated semaglutide (Ozempic®) in 2023, 52% received antidiabetic polytherapy before initiation, 39% monotherapy, and 8% no antidiabetic therapy. Most T2D initiators had suboptimal glucose control, with 83% having an HbA1c ≥48 mmol/mol and 68% ≥53 mmol/mol despite use of antidiabetic medication, and 29% had established atherosclerotic cardiovascular disease or kidney disease. Conclusion: The use of semaglutide (Ozempic®) in Denmark has increased dramatically. Although not approved for weight loss without T2D, one-third of new users in 2022 did not have T2D. Conversely, most initiators with T2D had a clear medical indication for treatment intensification, and "off-label" use can only explain a minor part of the supply shortage.

Critical evaluation of cohort study results.

Being able to critically evaluate modern cohort studies is important when being presented with claims based on observational evidence. In this review article, key aspects of the cohort design are presented using an example of a cohort study investigating the association between the use of SGLT2 inhibitors and gout. We describe the active comparator, new user design, modern methods used to address confounding, how to identify the most common sources of bias, and how to interpret study results appropriately.

Critical evaluation of articles on case-control studies.

The case-control design is one of the key designs used in observational research. In this review, we discuss common pitfalls of case-control studies and describe how case-control studies can be critically evaluated. We further assert that a well-conducted case-control study provides the same results, precision, and level of evidence as a corresponding cohort study.

Considerations for the use of biochemical laboratory registry data in clinical and public health research.

OBJECTIVES: To inform researchers of central considerations and limitations when applying biochemical laboratory-generated registry data in clinical and public health research. STUDY DESIGN AND SETTING: After review of literature on registry-based studies and the utilization of clinical laboratory registry data, relevant paragraphs and their applicability toward the creation of considerations for the use of biochemical registry data in research were evaluated. This led to the creation of an initial ten considerations. These were elaborated, edited, and merged after several read-throughs by all authors and discussed thoroughly under influence by the authors' personal experiences with laboratory databases and research registries in Denmark, leading to the formulation of five central considerations with corresponding items and illustrative examples. RESULTS: We recommend that the following considerations should be addressed in studies relying on biochemical laboratory-generated registry data: why are biochemical laboratory data relevant to examine the hypothesis, and how were the variable(s) utilized in the study? What were the primary indications for specimen collection in the study population of interest? Were there any pre-analytical circumstances that could influence the test results? Are data comparable between producing laboratories and within the single laboratory over time? Is the database representative in terms of completeness of study populations and key variables? CONCLUSION: It is crucial to address key errors in laboratory registry data and acknowledge potential limitations.