Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

There are currently no widely used guidelines to determine which older patients with acute respiratory conditions require hospital admission. This study assessed the need for clinical decision rules to help determine whether hospital admission is required for patients over 50 years for three common respiratory conditions: chronic obstructive pulmonary disease (COPD), heart failure (HF), and community-acquired pneumonia (CAP).

Postal survey.

Emergency physicians (EPs) from the United States, Canada, and Australasia.

A random sample of EPs from the United States, Canada, and Australasia.

A modified Dillman technique with a prenotification letter and up to three postal surveys.

EP opinions regarding the need for and willingness to use clinical decision rules for emergency department (ED) patients over 50 years with COPD, HF, or CAP to predict hospital admission. We assessed the required sensitivity of each rule for return ED visit or death within 14 days.

A total of 801 responses from 1,493 surveys were received, with response rates of 55%, 60%, and 46% for Australasia, Canada, and the United States, respectively. Over 90% of EPs reported that they would consider using clinical decision rules for HF, CAP, and COPD. The median required sensitivity for death within 14 days was 97 to 98% for all conditions.

EPs are likely to adopt highly sensitive clinical decision rules to predict the need for hospital admission for patients over 50 years with COPD, HF, or CAP.

Four to 10% of patients with transient ischemic attack (TIA) suffer a stroke or die within 7 days. Our objectives were to determine (1) current practice for investigating and treating emergency department (ED) patients with TIA, (2) willingness to use a clinical decision rule to identify patients at high risk of impending stroke or death, and (3) the required sensitivity of this rule.

We administered a mail survey to a random sample of members of three national emergency physician associations in Australia, Canada, and the United States using a modified Dillman technique. A prenotification letter and up to three surveys were sent.

A total of 801 responses (53.7%) from 1,493 surveys were received; 53.6% (95% CI 47.5–59.7) of emergency physicians reported routinely admitting TIA patients, ranging from 6.6% in Canada to 56.7% in the United States, and 9.9% of emergency physicians have a stroke prevention clinic, with 4.7% estimating that patients are seen within 7 days. A sensitive clinical decision rule for TIA patients would be used by 96.3% (95% CI 93.9–98.7) of emergency physicians. The median required sensitivity of this rule for stroke or death within 7 days was 97%.

Almost half of all TIA patients are managed as outpatients,which is neither expedited nor in a dedicated stroke clinic. Emergency physicians indicate a willingness to use a highly sensitive clinical decision rule to triage TIA patients.