Reassessing long-term risk of suicide after a first episode of psychosis

BackgroundThe long-term risk of suicide after a first episode of psychosis is unknown, because previous studies have often been based on prevalence cohorts, have been biased to more severely ill, hospitalised patients, have extrapolated from a short follow-up time, and have made a distinction between schizophrenia and other psychoses. The aim of this study was to determine the epidemiology of suicide in a clinically representative, retrospective inception cohort of patients with a first episode of psychosis.MethodsAll 2723 patients who presented for the first time to secondary care services with psychosis in three defined geographical catchment areas in London (1965–2004, n=2056), Nottingham (1997–1999, n=203), and Dumfries and Galloway (1979–1998, n=464) were traced after a mean follow-up of 11·5 years. The main outcome measure was number of deaths by suicide and open verdicts according to International Classification of Diseases, editions 7–10.FindingsCase fatality from suicide was considerably lower than expected from previous studies: 1·9% (53/2723); proportionate mortality was 11·9% (53/444). Although the rate of suicide was highest in the first year after presentation, risk persisted late into follow-up, with median time to suicide being 5·6 years. Suicide occurred nearly 12 times more than expected from the general population of England and Wales (standardised mortality ratio 11·65, 95%CI 8·73–15·24), and 49 of the 53 suicides were excess deaths. Even a decade after first presentation, suicide risk remained almost four times higher than in the general population (3·92, 95%CI 2·22–6.89), a time when there may be less intense clinical monitoring of risk.InterpretationThe highest risk of suicide after a psychotic episode occurs soon after presentation, yet clinicians should still be vigilant in assessing risk a decade or more after first contact. The widely held view that 10–15% die from suicide is misleading because it refers to proportionate mortality rather than lifetime risk. Nonetheless, after a first espisode of psychosis, risk of suicide is substantially increased compared with that in the general population.FundingUK Medical Research Council.     

Clinical psychological tests useful for differentiating depressive state with Alzheimer's disease from major depression of the elderly

Background:  A depressive state with Alzheimer's disease (AD) is difficult to differentiate from major depression (MD) in many cases. The purpose of this study was to identify differences between the two disorders using a battery of clinically available psychological tests.
Methods:  We evaluated depression and apathy using the Geriatric Depression Scale consisting of 30 items (GDS30) and Apathy Scale in 38 patients with AD and 31 with MD who were diagnosed based on clinical symptoms and radiological findings. In addition, the Cornel Medical Index (CMI) was employed to compare the psychological features of the two disorders.
Results:  In AD patients, the Apathy Scale score was greater than the GDS30 score, suggesting a strong tendency toward apathy. There was a significant difference in the GDS30/Apathy Scale score ratio between the two groups ( P  < 0.05, OR: 3.11). When examining the downstream mental items of the CMI, the values of tension-category parameters were significantly greater in AD patients, whereas those of depression-category parameters were significantly higher in MD patients. In individual patients, we compared the scores for the two categories, and there was a marked difference ( P  < 0.001, OR: 10.6).
Conclusion:  These results suggest that the GDS30, Apathy Scale, and CMI are useful for differentiating MD from AD and evaluating their psychological features.     

E-selectin ligand–1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-β

The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. As TGF-β signaling is a critical determinant of growth plate homeostasis, skeletal dysplasias are often associated with dysregulation of this pathway. The context-dependent action of TFG-β signaling is tightly controlled by numerous mechanisms at the extracellular level and downstream of ligand-receptor interactions. However, TGF-β is synthesized as an inactive precursor that is cleaved to become mature in the Golgi apparatus, and the regulation of this posttranslational intracellular processing and trafficking is much less defined. Here, we report that a cysteine-rich protein, E-selectin ligand–1 (ESL-1), acts as a negative regulator of TGF-β production by binding TGF-β precursors in the Golgi apparatus in a cell-autonomous fashion, inhibiting their maturation. Furthermore, ESL-1 inhibited the processing of proTGF-β by a furin-like protease, leading to reduced secretion of mature TGF-β by primary mouse chondrocytes and HEK293 cells. In vivo loss of Esl1 in mice led to increased TGF-β/SMAD signaling in the growth plate that was associated with reduced chondrocyte proliferation and delayed terminal differentiation. Gain-of-function and rescue studies of the Xenopus ESL-1 ortholog in the context of early embryogenesis showed that this regulation of TGF-β/Nodal signaling was evolutionarily conserved. This study identifies what we believe to be a novel intracellular mechanism for regulating TGF-β during skeletal development and homeostasis.     

In vitro sensitivity of Plasmodium falciparum to conventional and novel antimalarial drugs in Papua New Guinea

Objective Recent clinical studies have shown high rates of malaria treatment failure in endemic areas of Papua New Guinea (PNG), necessitating a change of treatment from chloroquine (CQ) or amodiaquine (AQ) plus sulphadoxine‐pyrimethamine to the artemisinin combination therapy (ACT) artemether plus lumefantrine (LM). To facilitate the monitoring of antimalarial drug resistance in this setting, we assessed the in vitro sensitivity of Plasmodium falciparum isolates from Madang Province. Methods A validated colorimetric lactate dehydrogenase assay was used to assess growth inhibition of 64 P. falciparum isolates in the presence of nine conventional or novel antimalarial drugs [CQ, AQ, monodesethyl‐amodiaquine (DAQ), piperaquine (PQ), naphthoquine (NQ), mefloquine (MQ), LM, dihydroartemisinin and azithromycin (AZ)]. Results The geometric mean (95% confidence interval) concentration required to inhibit parasite growth by 50% (IC₅₀) was 167 (141–197) nm for CQ, and 82% of strains were resistant (threshold 100 nm ), consistent with near‐fixation of the CQ resistance‐associated pfcrt allele in PNG. Except for AZ [8.351 (5.418–12.871) nm ], the geometric mean IC₅₀ for the other drugs was <20 nm . There were strong associations between the IC₅₀s of 4‐aminoquinoline (CQ, AQ, DAQ and NQ), bisquinoline (PQ) and aryl aminoalcohol (MQ) compounds suggesting cross‐resistance, but LM IC₅₀ only correlated with that of MQ. Conclusions Most PNG isolates are resistant to CQ in vitro but not to other ACT partner drugs. The non‐isotopic semi‐automated high‐throughput nature of the Plasmodium lactate dehydrogenase assay facilitates the convenient serial assessment of local parasite sensitivity, so that emerging resistance can be identified with relative confidence at an early stage.     

内蒙古呼伦贝尔地区气候性滴状角膜变性流行病学调查

目的调查气候性滴状角膜变性（CDK）在内蒙古呼伦贝尔地区的发病情况，并初步分析其相关因素。方法对内蒙古呼伦贝尔地区牧业四旗进行人群抽样调查，共调查2558人，其中游牧人群1210人，农耕人群1348人，并对可能相关因素进行问卷调查。结果调查人群中发病年龄最小为20岁，总患病率为21．6％，男性为21．7％，女性为21．6％，男女患病率和严重程度差异无统计学意义（χ^2=2．88，1．87，P=0．090，0．3929）；患病率随年龄增加而增高，40岁以上人群患病率为38．9％；20岁以上人群中1级病变311人，占15．3％，2级病变242人，占11．9％，未发现3级病变患者；牧业四旗之间患病率比较，差异有统计学意义（χ^2=38．12，P=0．00）；游牧人群患病率和严重程度明显高于农耕人群，二者比较差异有统计学意义（，=630．41，P=0．00）；调查发现：巴尔虎蒙古族患病率最高（52．8％），其次为布力亚特蒙古族（46．5％）、鄂温克族（40．8％），达斡尔族（1．6％）、汉族（1．3％）和科尔沁蒙古族（0．8％）最低，各民族患病率比较差异有统计学意义（χ^2=646．19，P=0．00）；通过相关因素分析发现CDK与年龄、放牧时间、民族及生活方式相关。结论CDK在内蒙古呼伦贝尔地区患病率较高，游牧人群高于农耕人群；不同民族患病率不同，其发生及严重程度与放牧时间、年龄、民族及生活方式有关。     

The critical care pharmacist: an essential intensive care practitioner

Clinical pharmacy services in the critical care setting have expanded dramatically and include assisting physicians in pharmacotherapy decision making, providing pharmacokinetic consultations, monitoring patients for drug efficacy and safety, providing drug information, and offering medical education to physicians, nurses, and patients. Measurable clinical effects of these services include reduced drug errors and adverse drug events, decreased morbidity and mortality rates, and a positive pharmacoeconomic impact by decreasing overall health care costs.     

Newborn hearing screening using the evoked otoacoustic emission: The Philippine General Hospital experience

The evoked otoacoustic emission (EOAE) test is a universally well-known and established procedure for screening the hearing of babies during the newborn period. It has been documented in foreign literature that the prevalence of hearing loss is significantly higher in high-risk neonates. In the Philippine General Hospital, 301 high-risk neonates and 105 non high-risk neonates were screened for hearing loss using the EOAE during a period of one year from March 2000 to March 2001. The initial failure rate in the high-risk population was 33% and 11% in the non high-risk population.