Validity of chronic disease diagnoses in Icelandic healthcare registries

Aims: To evaluate the validity of recorded chronic disease diagnoses in Icelandic healthcare registries. Methods: Eight different chronic diseases from multiple sub-specialties of medicine were validated with respect to accuracy, but not to timeliness. For each disease, 30 patients with a recorded diagnosis and 30 patients without the same diagnosis were randomly selected from >80,000 participants in the iStopMM trial, which includes 54% of the Icelandic population born before 1976. Each case was validated by chart review by physicians using predefined criteria. Results: The overall accuracy of the chronic disease diagnoses was 96% (95% CI 94–97%), ranging from 92 to 98% for individual diseases. After weighting for disease prevalence, the accuracy was estimated to be 98.5%. The overall positive predictive value (PPV) of chronic disease diagnosis was 93% (95% CI 89–96%) and the overall negative predictive value (NPV) was 99% (95% CI 96–100%). There were disease-specific differences in validity, most notably multiple sclerosis, where the PPV was 83%. Other disorders had PPVs between 93 and 97%. The NPV of most disorders was 100%, except for hypertension and heart failure, where it was 97 and 93%, respectively. Those who had the registered chronic disease had objective findings of disease in 96% of cases. Conclusions: When determining the presence of chronic disease, diagnosis data from the Icelandic healthcare registries has a high PPV, NPV and accuracy. Furthermore, most diagnoses can be confirmed by objective findings such as imaging or blood testing. These findings can inform the interpretation of studies using diagnostic data from the Icelandic healthcare registries.

Trends in the incidence and management of hypoxic-ischaemic encephalopathy in the therapeutic hypothermia era: a national population study

ObjectiveHypoxic-ischaemic encephalopathy (HIE) remains a leading cause of neonatal mortality and neurodisability. We aimed to determine the incidence of HIE and management patterns against national guidelines.DesignRetrospective cohort study using the National Neonatal Research Database.SettingNeonatal units in England and Wales.PatientsInfants 34–42 weeks gestational age (GA) with a recorded diagnosis of HIE.Main outcomesIncidence of HIE, mortality and treatment with therapeutic hypothermia (TH) were the main outcomes. Temporal changes were compared across two epochs (2011–2013 and 2014–2016).ResultsAmong 407 462 infants admitted for neonatal care, 12 195 were diagnosed with HIE. 8166 infants ≥36 weeks GA had moderate/severe HIE, 62.1% (n=5069) underwent TH and mortality was 9.3% (n=762). Of infants with mild HIE (n=3394), 30.3% (n=1027) underwent TH and 6 died. In late preterm infants (34–35 weeks GA) with HIE (n=635, 5.2%), 33.1% (n=210) received TH and 13.1% (n=83) died. Between epochs (2011–2013 vs 2014–2016), mortality decreased for infants ≥36 weeks GA with moderate/severe HIE (17.5% vs 12.3%; OR 0.69, 95% CI 0.59 to 0.81, p<0.001). Treatment with TH increased significantly between epochs in infants with mild HIE (24.9% vs 35.8%, p<0.001) and those born late preterm (34.3% vs 46.6%, p=0.002).ConclusionsMortality of infants ≥36 weeks GA with moderate/severe HIE has reduced over time, although many infants diagnosed with moderate/severe HIE do not undergo TH. Increasingly, mild HIE and late preterm infants with HIE are undergoing TH, where the evidence base is lacking, highlighting the need for prospective studies to evaluate safety and efficacy in these populations.

Epidemiology and the diagnostic challenge of extra-pulmonary tuberculosis in a teaching hospital in Ethiopia

Background Ethiopia reported a high rate of extra-pulmonary tuberculosis (EPTB) and the cases are increasing since the last three decades. However, diagnostic evidence to initiate TB treatment among EPTB cases is not well known. Therefore, we described the epidemiology and assessed how EPTB is diagnosed in a teaching hospital in Ethiopia. Methods We conducted a retrospective review among all adult EPTB cases diagnosed in Yekatit 12 Hospital Medical College from 2015 to 2019. Using a standardized data abstraction sheet, we collected data from patients’ medical records on sociodemographic, sites, and laboratory diagnosis of EPTB cases. Results Of the 965 total TB cases, 49.8%(481) had a recorded diagnosis of EPTB during the study period. The mean age of EPTB patients was 32.9 years (SD±13.9) and 50.7% were males. Tubercular lymphadenitis (40.3%), abdominal (23.4%), and pleural TB(13.5%) were the most common sites of EPTB involvement, followed in descending order by the genitourinary, skeletal, central nervous system, abscess, breast, and laryngeal TB. We found a histopathology finding consistent with EPTB in 59.1% of cases, Acid-fast bacilli positive in 1.5%, and the rest diagnosed on radiological grounds. In the majority of cases, more than one diagnostic method was used to diagnose EPTB cases. Conclusions Nearly half of TB patients had a recorded diagnosis of EPTB that comprise heterogeneous anatomical sites. All EPTB patients were started anti-TB therapy without definitive microbiology results. This indicates the diagnostic challenge of EPTB faced in our setting and proves to be significant for TB control in Ethiopia.

Risk of death among people with rare autoimmune diseases compared to the general population in England during the 2020 COVID-19 pandemic

Objectives To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. Methods We conducted a cohort study in Hospital Episode Statistics for England 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. Results We included 168 691 people with a recorded diagnosis of RAIRD alive on 01/03/2020. Their median age was 61.7 (IQR 41.5–75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. 1,815 (1.1%) participants died during March and April 2020. The age-standardised mortality rate (ASMR) among people with RAIRD (3669.3, 95% CI 3500.4–3838.1 per 100 000 person-years) was 1.44 (95% CI 1.42–1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. Conclusion The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to healthcare services.

Effects of Thyroid Status on Regional Brain Volumes: A Diagnostic and Genetic Imaging Study in UK Biobank

Background Thyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit/hyperactivity disorder (ADHD). However, the brain structures involved are unknown and it is unclear if the adult brain is also susceptible to changes in thyroid status. Methods We used International Classification of Disease-10 codes, polygenic thyroid scores at different thresholds of association with thyroid traits (PT-values), and image-derived phenotypes in UK Biobank (n = 18 825) to investigate the effects of a recorded diagnosis of thyroid disease and genetic risk for thyroid status on cerebellar and subcortical gray matter volume. Regional genetic pleiotropy between thyroid status and ADHD was explored using the GWAS-pairwise method. Results A recorded diagnosis of hypothyroidism (n = 419) was associated with significant reductions in total cerebellar and pallidum gray matter volumes (β [95% CI] = −0.14[−0.23, −0.06], P = 0.0005 and β [95%CI] = −0.12 [−0.20, −0.04], P = 0.0042, respectively), mediated in part by increases in body mass index. While we found no evidence for total cerebellar volume alterations with increased polygenic scores for any thyroid trait, opposing influences of increased polygenic scores for hypo- and hyperthyroidism were found in the pallidum (PT &lt; 1e−3: β [95% CI] = −0.02 [−0.03, −0.01], P = 0.0003 and PT &lt; 1e−7: β [95% CI] = 0.02 [0.01, 0.03], P = 0.0003, respectively). Neither hypo- nor hyperthyroidism showed evidence of regional genetic pleiotropy with ADHD. Conclusions Thyroid status affects gray matter volume in adults, particularly at the level of the cerebellum and pallidum, with potential implications for the regulation of motor, cognitive, and affective function.

Pregabalin prescribing patterns in Australian general practice, 2012–2018: a cross-sectional study

BackgroundIn 2013 pregabalin was subsidised by Australia’s Pharmaceutical Benefits Scheme (PBS) for neuropathic pain. Since the subsidy, pregabalin prescribing has been increasing in Australia and so has related harm. There are concerns it is being prescribed for indications other than neuropathic pain, which have little evidence of efficacy.AimTo describe pregabalin prescribing in Australian general practice.Design & settingA cross-sectional study of patients attending 445 general practice sites in the national MedicineInsight database from March 2012–February 2018.MethodThe following aspects were calculated: the proportion of prescriptions that were for pregabalin per year; the prevalence of pain conditions in patients prescribed pregabalin; and same-day prescribing of pregabalin with opioids or benzodiazepines.ResultsPrescribing increased from 13 per 10 000 to 104 per 10 000 prescriptions between 2012–2013 and 2017–2018. A total of 1 891 623 patients were identified of whom 114 123 (6.0%) were prescribed pregabalin; 49.7% (n = 56 772) had a recorded diagnosis of neuropathic pain. Among people prescribed pregabalin without a recorded diagnosis of neuropathic pain, 43.5% (n = 24 927) had a diagnosis of back problems, 8.8% (n = 5073) chronic pain, and 26.4% (n = 30 146) had no pain diagnosis. Pregabalin was prescribed the same day as an opioid to 38.1% of patients (95% confidence interval [CI] = 37.1% to 39.1%) and a benzodiazepine to 13.1% of patients (95% CI = 12.5% to 13.7%). Patients with a diagnosis of chronic pain had the highest rate of same-day prescribing of pregabalin with an opioid (70.4%, 95% CI = 68.9% to 71.9%) or a benzodiazepine (25.8%, 95% CI = 24.2% to 27.4%)ConclusionSubstantial increases in pregabalin prescribing were identified in Australian general practice, but only half of patients had a neuropathic pain diagnosis recorded, the only approved indication for subsidy. High rates of same-day prescribing with opioids and benzodiazepines may put patients at increased risk of harm.

Group B Streptococcal disease in England (1998 – 2017): a population based observational study

Background and Objectives Group B Streptococcus (GBS) is the leading cause of sepsis and meningitis in infants &lt;90 days. In this study, the burden of GBS disease and mortality in young infants in England was assessed. Methods Using linked hospitalisation records from every National Health Service (NHS) hospital from 1 April 1998 to 31 March 2017, we calculated annual GBS incidence in infants aged &lt;90 days and, using regression models, compared their perinatal factors, rates of hospital-recorded disease outcomes and all-cause infant mortality rates with those of the general infant population. Results 15,429 infants aged &lt;90 days had a hospital-recorded diagnosis of GBS, giving an average annual incidence of 1.28 per 1000 live births (95% CI 1.26-1.30) with no significant trend over time. GBS-attributable mortality declined significantly from 0.044 (95%CI 0.029–0.065) per 1000 live births in 2001 to 0.014 (95%CI 0.010–0.026) in 2017 (annual percentage change -6.6, 95%CI -9.1 to -4.0). Infants with GBS had higher relative rates of visual impairment (HR 7.0 95% CI 4.1-12.1), cerebral palsy (HR 9.3 95% CI 6.6-13.3), hydrocephalus (HR 17.3 95% CI 13.8-21.6) and NEC (HR 18.8 95% CI 16.7-21.2) compared with those without GBS. Conclusions Annual rates of GBS disease in infants have not changed over 19 years. The reduction in mortality is likely multifactorial and due to widespread implementation of antibiotics in at-risk mothers and babies as well as advances in managing acutely unwell infants. New methods for prevention, such as maternal vaccination, must be prioritised.

Incidence and Prevalence of Microscopic Colitis Between 2001 and 2016: A Danish Nationwide Cohort Study

Background and Aims Epidemiological studies suggest an increasing global incidence of microscopic colitis, including collagenous colitis and lymphocytic colitis. We aimed to investigate the incidence and prevalence of microscopic colitis in Denmark. Methods In a nationwide cohort study, we included all incident patients with a recorded diagnosis of collagenous colitis or lymphocytic colitis in the Danish Pathology Register between 2001 and 2016. Results A total of 14 302 patients with microscopic colitis—8437 [59%] with collagenous and 5865 [41%] with lymphocytic colitis—were identified during the study period. The prevalence in December 2016 was estimated to be 197.9 cases per 100 000 inhabitants. Microscopic colitis was more prevalent among females (n = 10 127 [71%]), with a mean annual incidence of 28.8, compared with 12.3 per 100 000 person-years among males. The overall mean incidence during the study period was 20.7 per 100 000 person-years. Mean age at time of diagnosis was 65 years (standard deviation [SD]:14) for microscopic colitis, 67 [SD:13] for collagenous colitis, and 63 [SD:15] for lymphocytic colitis. The overall incidence increased significantly from 2.3 cases in 2001 to 24.3 cases per 100 000 person-years in 2016. However, the highest observed incidence of microscopic colitis was 32.3 cases per 100 000 person-years in 2011. Large regional differences were found, with the highest incidence observed in the least populated region. Conclusions The incidence of microscopic colitis in Denmark has increased 10-fold during the past 15 years and has now surpassed that of Crohn’s disease and ulcerative colitis. However, incidence has stabilised since 2012, suggesting that a plateau has been reached.

Synthetic cannabinoid use in psychiatric patients and relationship to hospitalisation: A retrospective electronic case register study

Introduction and objectives: Cannabis use has been associated with psychosis and with poor outcome in patients with mental illness. Synthetic cannabinoids (SCs) have been suggested to pose an even greater risk to mental health, but the effect on clinical outcome has not been directly measured. In this study, we aimed to investigate the demographics and hospitalisation of psychiatric patients who were SC users. Methods: We searched the Biomedical Research Centre Clinical Record Interactive Search register for SC users and age- and sex-matched SC non-users who had been psychiatric patients under the South London and Maudsley NHS Trust. We recorded diagnosis, homelessness, cannabis use and the total number of days admitted as an inpatient to secondary and tertiary mental-health services. Results: We identified 635 SC users and 635 age- and sex-matched SC non-users. SC users were significantly more likely to be homeless (χ2=138.0; p<0.0001) and to use cannabis (χ2=257.3; p<0.0001) than SC non-users. SC users had significantly more inpatient days after their first recorded use of SCs than controls ( M ( SD)=85.5 (199.7) vs. 25.4 (92.32); p<0.0001). Post hoc tests revealed that SC non-users who used cannabis had fewer inpatient days than SC users ( p<0.0001), and that non-users of both SC and cannabis had fewer inpatient days than SC non-using cannabis users ( p=0.02). Conclusions: SC use may lead to an increase in the number of days spent in hospital in patients with psychiatric illness. This highlights the need for clinicians to ask specifically about SC use.