Life expectancy, mortality risks and cause of death in patients with serious mental illness in South East London: a comparison between 2008-2012 and 2013-2017.

BACKGROUND: People with serious mental illness (SMI) have a significantly shorter life expectancy than the general population. This study investigates whether the mortality rate in this group has changed over the last decade. METHODS: Using Clinical Record Interactive Search software, we extracted data from a large electronic database of patients in South East London. All patients with schizophrenia, schizoaffective disorder or bipolar disorder from 2008 to 2012 and/or 2013 to 2017 were included. Estimates of life expectancy at birth, standardised mortality ratios and causes of death were obtained for each cohort according to diagnosis and gender. Comparisons were made between cohorts and with the general population using data obtained from the UK Office of National Statistics. RESULTS: In total, 26 005 patients were included. In men, life expectancy was greater in 2013-2017 (64.9 years; 95% CI 63.6-66.3) than in 2008-2012 (63.2 years; 95% CI 61.5-64.9). Similarly, in women, life expectancy was greater in 2013-2017 (69.1 years; 95% CI 67.5-70.7) than in 2008-2012 (68.1 years; 95% CI 66.2-69.9). The difference with general population life expectancy fell by 0.9 years between cohorts in men, and 0.5 years in women. In the 2013-2017 cohorts, cancer accounted for a similar proportion of deaths as cardiovascular disease. CONCLUSIONS: Relative to the general population, life expectancy for people with SMI is still much worse, though it appears to be improving. The increased cancer-related mortality suggests that physical health monitoring should consider including cancer as well.

Prediction of the Duration to Next Admission for an Acute Affective Episode in Patients with Bipolar I Disorder.

Objective: Predicting disease relapse and early intervention could reduce symptom severity. We attempted to identify potential indicators that predict the duration to next admission for an acute affective episode in patients with bipolar I disorder. Methods: We mathematically defined the duration to next psychiatric admission and performed single-variate regressions using historical data of 101 patients with bipolar I disorder to screen for potential variables for further multivariate regressions. Results: Age of onset, total psychiatric admissions, length of lithium use, and carbamazepine use during the psychiatric hospitalization contributed to the next psychiatric admission duration positively. The all-in-one found that hyperlipidemia during the psychiatric hospitalization demonstrated a negative contribution to the duration to next psychiatric admission; the last duration to psychiatric admission, lithium and carbamazepine uses during the psychiatric hospitalization, and heart rate on the discharge day positively contributed to the duration to next admission. Conclusion: We identified essential variables that may predict the duration of bipolar I patients' next psychiatric admission. The correlation of a faster heartbeat and a normal lipid profile in delaying the next onset highlights the importance of managing these parameters when treating bipolar I disorder.

Age effect of antipsychotic medications on the risk of sudden cardiac death in patients with schizophrenia: A nationwide case-crossover study.

AIM: Research regarding the effects of age in patients with schizophrenia taking antipsychotics on the risk of sudden cardiac death is lacking. We determined the effect of patient age on the association between exposure to antipsychotics and the risk of sudden cardiac death in a nationwide schizophrenia cohort. METHODS: From the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, data of 1836 patients with schizophrenia who had experienced sudden cardiac death between 2000 and 2016 were included. A case-crossover design by using a 14-day window was applied, and subgroup analyses were performed by stratifying patients into three age subgroups (<45, 45-65, and >65 years) to assess the effect of age on the risk of sudden cardiac death in patients taking antipsychotics. RESULTS: No association between exposure to antipsychotic agents and sudden cardiac death risk was found in patients aged >65 years who were characterized by a high burden of medical illnesses. However, zotepine significantly increased the risk of sudden cardiac death in patients aged <45 years (adjusted relative risk [RR] = 2.68, P = 0.046). Flupentixol (adjusted RR = 5.30, P = 0.004) and risperidone (adjusted RR = 1.68, P = 0.01) significantly elevated the risk of sudden cardiac death in patients aged 45-65 years. CONCLUSION: This study suggests that individual antipsychotics pose different risks of sudden cardiac death in patients with schizophrenia across their lifespan. Clinicians should consider patient age when evaluating the risks and benefits of antipsychotic treatment.

Antipsychotic medications and the progression of upper respiratory infection to pneumonia in patients with schizophrenia.

Aim Research regarding the effect of antipsychotic medications on the risk of upper respiratory infection (URI) progression to pneumonia in patients with schizophrenia is rare. This study investigated the effect of antipsychotic use on the risk of URI progression to pneumonia in patients with schizophrenia. METHODS: This cohort study used the Taiwan's Nationwide Psychiatric Inpatient Medical Claims Database. From January 1, 1996 to December 31, 2012, 22,771 patients with schizophrenia were diagnosed as having the first URI episode after their first psychiatric admission and 135 of them developed pneumonia within 30 days. The duration and dosage of antipsychotics were assessed before and after URI. Cox regression with time-dependent model was used to assess the risk of antipsychotic use on the progression of URI to pneumonia. RESULTS: Among first- and second-generation antipsychotics, clozapine was the only medication associated with an increased risk of developing pneumonia before URI (adjusted hazard ratio [aHR] = 2.05, P = .024). Clozapine was also the only drug significantly associated with an increased risk after URI (aHR = 1.92, P = .027). Regarding medication use after URI, the dosage of clozapine was significantly associated with an increased risk based on Cox regression with a time-dependent model (aHR = 1.95, P = .003). CONCLUSIONS: The use of clozapine was associated with URI progression to pneumonia in patients with schizophrenia. The dosage of clozapine used in the post-URI period was also associated with an increased risk. Clinicians should consider lowering clozapine dosage in patients with URI to prevent them developing pneumonia.

Physical Illnesses Before Diagnosed as Schizophrenia: A Nationwide Case-Control Study.

Some physical illnesses are potentially associated with the development of schizophrenia. However, few studies have investigated these associations. Here, we examined physical illnesses and medical utilization patterns existing before patients received a diagnosis of schizophrenia. We enrolled a large representative cohort of the general population in Taiwan (N = 1 000 000) and identified 1969 young patients with a new diagnosis of schizophrenia from January 1, 2000 to December 31, 2013. We conducted a nested case-control study based on risk-set sampling. Each case was age-matched and sex-matched with 4 controls selected from the general population. The case and control groups were compared on the basis of various clinical characteristics. Conditional logistic regression was used to estimate the magnitude of risk associated with newly diagnosed schizophrenia. Within the 1 year before the schizophrenia diagnosis, the cases were most likely to visit the psychiatry department, followed by internal medicine and family medicine departments. According to multivariate analysis, compared with the controls, the cases had substantially higher risk of physical conditions in the prodromal phase, including hypertension (adjusted risk ratio [aRR] = 1.93, P = .001), other forms of heart disease (aRR = 2.07, P < .001), cerebrovascular diseases (aRR = 2.96, P = .001), chronic obstructive pulmonary disease (aRR = 1.50, P = .005), asthma (aRR = 1.76, P = .003), and irritable bowel syndrome (aRR = 2.00, P < .001). A wide range of psychiatric diseases and concomitant use of medications were significantly associated with schizophrenia development. In conclusion, several physical illnesses were identified to be associated with schizophrenia development, indicating that people with these illnesses could be vulnerable to schizophrenia.

Clinical Risk Factors for Therapeutic Lithium-Associated Electrocardiographic Changes in Patients With Bipolar Disorder.

PURPOSE/BACKGROUND: Lithium, a common medication used in bipolar disorder treatment, can exert an inhibitory effect on sodium and potassium channels and potentially cause cardiac electrical conduction disturbance and corrected QT (QTc) prolongation. This study aimed to examine whether lithium at therapeutic levels can change electrocardiographic parameters in different groups of patients with bipolar disorder and to identify the potential clinical risk factors. METHODS/PROCEDURES: Standard 12-lead electrocardiogram data before and after lithium treatment in bipolar disorder patients after at least 2-week dropout of psychotropic medications were analyzed. FINDINGS/RESULTS: A total of 39 patients with bipolar disorder receiving lithium treatment were enrolled. Nineteen patients (48.7%) exhibited increased from P wave beginning to QRS complex beginning intervals after lithium treatment (mean serum level, 0.653 ± 0.247 mmol/L). Twenty-four patients (61.5%) exhibited increased a combination of Q, R, and S waves complex durations and increased QTc intervals. Twenty-three patients (59.0%) exhibited increased corrected JT (JTc) intervals. The patient group with increased QTc or JTc intervals exhibited a higher mean systolic blood pressure than did the patient group without increased QTc (134.7 ± 19.2 mm Hg vs 115.7 ± 11.8 mm Hg, P = 0.020) or JTc intervals (134.4 ± 19.6 mm Hg vs 117.6 ± 13.3 mm Hg, P = 0.054), respectively. Biochemical and hemodynamic parameters were comparable between patients with and without increased a combination of Q, R, and S waves complex durations or from P wave beginning to QRS complex beginning intervals. IMPLICATIONS/CONCLUSIONS: Elevated systolic blood pressure may be the risk factor for the ventricular conduction delay in bipolar disorder patients receiving lithium at therapeutic levels.

Mood stabilisers and risk of stroke in bipolar disorder.

BACKGROUND: Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.AimsIn this study, we investigated the risk of stroke following the exposure to mood stabilisers in patients with bipolar disorder. METHOD: Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case-crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder. RESULTS: Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke. CONCLUSIONS: Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.Declaration of interestNone.

Dysregulation of glucose metabolism since young adulthood increases the risk of cardiovascular diseases in patients with bipolar disorder.

Aging patients with bipolar disorder (BD) are at a high risk of cardiovascular diseases (CVDs). However, few studies have directly examined the association between metabolic risks and CVDs in patients with BD across the lifespan. Therefore, the aim of this study was to determine lifetime metabolic risk factors for CVDs in patients with BD. We recruited BD-I patients who were more than 50 years old and had had at least one psychiatric hospitalization. Patients who had a cardiologist-confirmed CVD diagnosis (ICD-9 code 401-414) were assigned to the case group. Fifty-five cases were matched with 55 control patient without CVDs based on age and sex. Clinical data were obtained by retrospectively reviewing 30 years of hospital records. Compared to control subjects, a significantly higher proportion of cases had impaired fasting glucose between ages 31 and 40 (44.0% versus 17.4%, p = 0.046), diabetes mellitus between ages 41 and 50 (25.6% versus 8.6%, p = 0.054), and diabetes mellitus after age 51 (36.3% versus 12.7%, p = 0.005). No significant difference was found in overweight, obesity, or dyslipidemia. After adjusting for years of education, first episode as mania, and second generation antipsychotic use, lifetime diabetes mellitus remained a risk factor for CVDs (OR = 4.45, 95% CI = 1.89-10.66, p = 0.001). The findings suggest that glucose dysregulation across the adult age span is probably the major metabolic risk contributing to CVDs in patients with BD. Clinicians therefore have to notice the serum fasting glucose levels of BD patients since young adulthood.

Diabetes mellitus and first episode mania associated with cardiovascular diseases in patients with older-age bipolar disorder.

Patients with bipolar disorder (BD) are at high risk for developing cardiovascular diseases (CVDs) during aging process. However, investigations are lacking regarding the risk factors for CVDs specific to BD patients. The aim of this study was to examine the relationship between CVDs and traditional risk factors in association with the characteristics of BD in older age. Totally, we recruited 124 patients with BD-I (DSM-IV) who had at least one psychiatric admission and cardiologist-confirmed CVD diagnosis (ICD-9 code 401-414) at mean age of 61.7+4.9 years. Each case subject was matched with one BD-I patient without CVDs based on age, sex, and date of the most recent psychiatric admission (+2 years). Clinical data were obtained by retrospectively reviewing the medical record. A multiple logistic regression model showed that not only traditional risk factor (e.g., diabetes mellitus) but also non-traditional one associated with BD (e.g., first episode mania) significantly increased the risk of CVDs. Given the limitation of this cross-sectional study, longitudinal investigations are needed to elucidate the contributions of both traditional risk factors and the BD characteristics for CVD risk in patients with BD.

Roles of amino acids in the Escherichia coli octaprenyl diphosphate synthase active site probed by structure-guided site-directed mutagenesis.

Octaprenyl diphosphate synthase (OPPS) catalyzes consecutive condensation reactions of farnesyl diphosphate (FPP) with five molecules of isopentenyl diphosphates (IPP) to generate C(40) octaprenyl diphosphate, which constitutes the side chain of ubiquinone or menaquinone. To understand the roles of active site amino acids in substrate binding and catalysis, we conducted site-directed mutagenesis studies with Escherichia coli OPPS. In conclusion, D85 is the most important residue in the first DDXXD motif for both FPP and IPP binding through an H-bond network involving R93 and R94, respectively, whereas R94, K45, R48, and H77 are responsible for IPP binding by providing H-bonds and ionic interactions. K170 and T171 may stabilize the farnesyl carbocation intermediate to facilitate the reaction, whereas R93 and K225 may stabilize the catalytic base (MgPP(i)) for H(R) proton abstraction after IPP condensation. K225 and K235 in a flexible loop may interact with FPP when the enzyme becomes a closed conformation, which is therefore crucial for catalysis. Q208 is near the hydrophobic part of IPP and is important for IPP binding and catalysis.