The prevalence and moderators of clinical pain in people with schizophrenia: A systematic review and large scale meta-analysis

Background: People with schizophrenia frequently have physical comorbidities that can cause pain. Experimental studies report reduced pain sensitivity among schizophrenia patients, but it remains unclear if clinically relevant pain is less prevalent in schizophrenia. Method: We systematically searched major electronic databases from inception till 03/2014. Articles were included that reported the prevalence of clinical pain in people with schizophrenia. Two independent authors conducted searches, completed methodological quality assessment and extracted data. A random effects relative risks (RR) meta-analysis was conducted to determine the prevalence of all-cause and specific pain in schizophrenia, and the relative prevalence compared to the general population, and to assess moderators. Results: Altogether, 14 studies were included encompassing 242,703 individuals with schizophrenia (30.2–55.8 years) and 4,259,221 controls. Different types of pain were considered. The overall pooled prevalence of clinical pain in people with schizophrenia was 34.7% (95% CI = 23.6–46.6). In the comparative analysis involving 7 studies with controls, the RR was 0.99 (95% CI = 0.83–1.19). The pooled prevalence of headache among 94,043 individuals with schizophrenia was 29.9% (95% CI = 3–69%) and the RR compared to 4,248,284 controls was 1.32 (95% CI = 0.85–2.07). In moderator analyses, neither age, sex, study quality or pain assessment method influenced pain prevalence. Conclusion: Clinical pain affects a third of people with schizophrenia and levels are similar with age- and sex-comparable controls. Future research is needed to determine if similar clinical pain prevalences in schizophrenia occur despite having more painful conditions, resulting from under-reporting, higher pain thresholds or lower help seeking behaviours

Good Fat, Essential Cellular Requirements for Triacylglycerol Synthesis to Maintain Membrane Homeostasis in Yeast*

Storage triacylglycerols (TAG) and membrane phospholipids share common precursors, i.e. phosphatidic acid and diacylglycerol, in the endoplasmic reticulum. In addition to providing a biophysically rather inert storage pool for fatty acids, TAG synthesis plays an important role to buffer excess fatty acids (FA). The inability to incorporate exogenous oleic acid into TAG in a yeast mutant lacking the acyltransferases Lro1p, Dga1p, Are1p, and Are2p contributing to TAG synthesis results in dysregulation of lipid synthesis, massive proliferation of intracellular membranes, and ultimately cell death. Carboxypeptidase Y trafficking from the endoplasmic reticulum to the vacuole is severely impaired, but the unfolded protein response is only moderately up-regulated, and dispensable for membrane proliferation, upon exposure to oleic acid. FA-induced toxicity is specific to oleic acid and much less pronounced with palmitoleic acid and is not detectable with the saturated fatty acids, palmitic and stearic acid. Palmitic acid supplementation partially suppresses oleic acid-induced lipotoxicity and restores carboxypeptidase Y trafficking to the vacuole. These data show the following: (i) FA uptake is not regulated by the cellular lipid requirements; (ii) TAG synthesis functions as a crucial intracellular buffer for detoxifying excess unsaturated fatty acids; (iii) membrane lipid synthesis and proliferation are responsive to and controlled by a balanced fatty acid composition

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

International audienceAbstract Background Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO 2 ) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO 2 with patients’ outcome. Methods Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO 2  300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO 2 -AUC), for hyperoxemia was significantly associated with mortality ( p = 0.003). Conclusions In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration : clinicaltrials.gov NCT02908308 , Registered September 20, 2016

Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial

International audienc