Arginine deprivation is a novel antimetabolite strategy for the treatment of arginine-dependent cancers that exploits differential expression and regulation of key urea cycle enzymes. Several studies have focused on inactivation of argininosuccinate synthetase 1 (ASS1) in a range of malignancies, including melanoma, hepatocellular carcinoma (HCC), mesothelial and urological cancers, sarcomas, and lymphomas. Epigenetic silencing has been identified as a key mechanism for loss of the tumor suppressor role of ASS1 leading to tumoral dependence on exogenous arginine. More recently, dysregulation of argininosuccinate lyase has been documented in a subset of arginine auxotrophic glioblastoma multiforme, HCC and in fumarate hydratase-mutant renal cancers. Clinical trials of several arginine depletors are ongoing, including pegylated arginine deiminase (ADI-PEG20, Polaris Group) and bioengineered forms of human arginase. ADI-PEG20 is furthest along the path of clinical development from combinatorial phase 1 to phase 3 trials and is described in more detail. The challenge will be to identify tumors sensitive to drugs such as ADI-PEG20 and integrate these agents into multimodality drug regimens using imaging and tissue/fluid-based biomarkers as predictors of response. Lastly, resistance pathways to arginine deprivation require further study to optimize arginine-targeted therapies in the oncology clinic.
Arginase ; Arginine ; Argininosuccinate Lyase ; Argininosuccinate Synthase ; Biomarkers ; Carcinoma, Hepatocellular ; Drug Combinations ; Epigenomics ; Glioblastoma ; Humans ; Kidney Neoplasms ; Lymphoma ; Melanoma ; Sarcoma ; Urea ; Urologic Neoplasms

Objective Describe the prevalence of depressive disorders (mood disorders with current depressive episode) among individuals treated in general hospitals in Beijing. Methods 2877 outpatients and 2925 inpatients ≥15 years of age from 50 general hospitals (selected by stratified random sampling) were screened by trained psychiatric nurses using a depression screening instrument and then the gold standard diagnosis of all subjects screened positive and 10% of those screened negative was determined by a trained psychiatrist who used a semi-structured interview schedule based on American psychiatric diagnostic criteria (DSM-IV). Results The adjusted point prevalence, one-year prevalence, and lifetime prevalence of any type of depressive disorder were 5.23%, 5.72% and 8.22%, respectively; corresponding prevalences of major depressive disorder were 2.94%, 3.46%, and 5.32%, respectively. Conclusions The prevalence of depressive disorders among patients in general hospitals in Beijing is not significantly higher than in the general population in China.

OBJECTIVEDescribe the prevalence and risk factors for suicidal ideation and suicide attempt among outpatients at general hospitals in Beijing.

METHODSTrained psychiatric nurses obtained data about the characteristics of suicidal thoughts and suicide attempts from 2877 persons 15 years of age or older who were consecutive outpatients at 35 level-1, 8 level-2 and 7 level-3 general hospitals selected from all hospitals in Beijing by stratified random sampling. Logistic regression analysis was used to identify risk factors for suicidal ideation and suicide attempt.

RESULTSThe lifetime prevalence of suicidal ideation and suicide attempt were 6.08% (95% CI: 5.25% - 7.25%) and 1.18% (0.82% - 1.65%), respectively. Mutivariate logistic analysis found that the most important risk factors for suicidal ideation were hopelessness in the prior year (OR = 7.96), current depression (OR = 3.41), younger age (OR for < 35 = 2.83; OR for 35 - 55 = 2.08), having a blood relative with prior suicidal behavior (OR = 2.58), and so forth; the most important risk factors for suicide attempt were younger age (OR for < 35 = 4.96; OR for 35 - 55 = 4.40), hopelessness in the prior year (OR = 4.02), self-report of health status in last weeks as poor (OR = 2.81), not currently married (never married, divorced, widowed, etc) (OR = 2.80), and so forth. Four variables were independent risk factors for both suicidal ideation and suicide attempt: hopelessness in the last year, younger age, having associates with prior suicidal behavior and female gender.

CONCLUSIONSMany patients treated at medical, surgical and other outpatient departments of general hospitals in Beijing are depressed and at risk for suicide; this is particularly true of young female patients who feel hopeless about their future. Outpatient clinicians need to be trained to identify such patients, to assess the severity of their psychological problems and, if necessary, to provide appropriate treatment or refer them for psychiatric evaluation.

Adult ; Age Factors ; China ; epidemiology ; Depression ; epidemiology ; Female ; Health Surveys ; Hospitals, General ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Outpatients ; psychology ; statistics & numerical data ; Prevalence ; Risk Factors ; Sex Factors ; Suicide ; psychology ; statistics & numerical data ; Suicide, Attempted ; psychology ; statistics & numerical data

OBJECTIVETo compare the characteristics of suicides in the four main demographic groups: urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in China.

METHODSA detailed psychological autopsy survey instrument was independently administered to 895 suicide victims in family members and close associates from 23 geographically representative locations from around the country.

RESULTSPesticide ingestion accounted for 58% (519) of all suicides and 61% (318/519) of deaths were due to unsuccessful medical resuscitation. A substantial proportion (37%) of suicide victims did not have a mental illness. Among the 563 victims with mental illness, only 13% (76/563) received psychiatric treatment. Compared to other demographic groups, young rural females who died from suicide had the highest rate of pesticide ingestion (79%), the lowest prevalence of mental illness (39%), and the highest acute stress from precipitating life events just prior to the suicide.

CONCLUSIONMany suicides in China are impulsive acts of deliberate self-harm following acute interpersonal crises. Prevention of suicides in China must focus on improving awareness of psychological problems, improving mental health services, providing alternative social support networks for managing acute interpersonal conflicts, limiting access to pesticides, and improving the resuscitation skills of primary care providers.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autopsy ; Child ; China ; epidemiology ; Female ; Humans ; Male ; Mental Disorders ; epidemiology ; psychology ; Middle Aged ; Rural Population ; Suicide ; psychology ; statistics & numerical data ; trends ; Urban Population

OBJECTIVEDescribe the mental health services provided at different types of general hospitals in Beijing.

METHODSDistribute the "Hospital Mental Health Services Survey" to all 508 hospitals in the 18 Beijing districts; the survey covers information for 2001 on the type of mental health services provided, the characteristics of the service providers, the number and diagnoses of first-visit mental health patients, and the prescription of psychotropic medications.

RESULTS73% (373/508) of the hospitals completed the survey, including 75% (325/436) of the general hospitals. Among the 325 general hospitals, 171 (53%) provided one or more types of mental health services; they had a total of 420 staff members who provide these services, but their educational level was relatively low and mental health training limited. 61 general hospitals had mental health outpatient departments that treated 50% (47,151/93,891) of all first-visit mental health patients seen in all hospitals (including psychiatric hospitals) in the municipality; 90% (42,578/47,151) of these first-visit patients in general hospitals were seen at 18 level-3 hospitals. Among the 44,441 first-visit patients for whom diagnostic information was available, the main diagnoses were neurosis (43%) and depression (30%). 103 of the participating general hospitals prescribed 73% of antidepressant medications prescribed at all hospitals in the municipality and 97% of all fluoxetine (Prozac and others).

CONCLUSIONSGeneral hospitals-particularly level-1 and level-2 general hospitals-need to put more emphasis on mental health services, increase training of staff who provide the services and open relevant departments. Monitoring the development of mental health services in general hospitals and increasing the quality of their mental health services will require periodic assessment of the types and range of mental health services provided and of the diagnostic accuracy and treatment standards of the staff providing these services.

Adult ; Antidepressive Agents ; therapeutic use ; China ; Drug Utilization ; statistics & numerical data ; Female ; Hospitals, General ; statistics & numerical data ; Humans ; Male ; Mental Health Services ; statistics & numerical data ; Middle Aged ; Surveys and Questionnaires

OBJECTIVETo describe the current prevalence and distribution of all types of mental disorders in Zhejiang Province and use this data to develop a provincial mental health plan.

METHODSStratified multi-stage cluster randomization was used to identify 14 counties (cities), 70 townships (urban districts), 140 villages (urban neighborhoods) and 15,000 subjects > or = 15 years of age. Psychiatric nurses used an expanded version of the General Health Questionnaire (GHQ) to identify subgroups of subjects at high, moderate and low risk of having a mental disorder, then psychiatrists determined their diagnoses by administering a structured psychiatric examination (SCID) that employs American diagnostic criteria for mental disorders (DSM-IV) to 100% of high-risk, 40% of moderate-risk and 10% of low-risk subjects.

RESULTS14 639 subjects completed the screening and 4,788 completed the psychiatric examination. The adjusted overall current rate of mental disorders was 17.3% (95% CI = 16.0%-18.7%), which dropped to 13.4% (12.2%-14.7%) if the non-specific (NOS) disorders were excluded. The most common diagnostic groups were affective disorders (8.6%, 7.9%-9.5%), anxiety disorders (4.3%, 3.6%-5.1%), and substance use disorders (3.0%, 2.4%-3.8%). The most common specific disorders were major depressive disorder (4.3%, 3.7%-4.9%), alcohol use disorder (2.9%, 2.3%-3.7%), dysthymia (1.6%, 1.3%-1.9%) and specific phobias (1.2%, 0.8%-1.8%). The overall prevalence was higher in rural than in urban areas (RR = 1.23, 95% CI = 1.11-1.37) and slightly higher in women than in men (RR = 1.11, 1.00-1.22).

CONCLUSIONSMental disorders seriously affect the social and economic development of Zhejiang Province; they are a major public health problem that urgently needs to be addressed. To do this, it is necessary to develop and implement a comprehensive province-wide mental health plan and regularly evaluate its effectiveness.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Male ; Mental Disorders ; diagnosis ; epidemiology ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Young Adult

OBJECTIVEUnderstand the public's current attitudes and knowledge about suicide and, thus, provide essential information to the development of targeted public education programs-important components of the suicide prevention effort.

METHODSSeventeen mental health professionals who were extensively trained in the methods of conducting focus groups used a pre-tested focus group outline on attitudes and knowledge about suicide to conduct 101 focus groups and 18 individual in-depth interviews with a total of 842 community respondents from 6 regions in northern China. The focus groups and in-depth interviews were audio-taped, transcribed and analyzed using the QSR Nvivo text analysis software.

RESULTSMost respondents believed that suicide was a greater problem in rural areas and among women and identified physical illnesses, economic problems and interpersonal conflicts (particularly family conflicts) as the main causes of suicide. Rural residents and women were believed to exhibit impulsive suicidal behavior because of their personal limitations and over-sensitiveness. Most thought that suicide was understandable and a small proportion felt that it was acceptable behavior in certain circumstances. Almost all felt that suicide resulted in the stigmatization and a loss of 'face' for the family. Most believed that one should show concern for persons who have suicidal behavior and their family members and expressed a willingness to have superficial social relationships with them but were unwilling to establish close personal relations with them. The vast majority believed that suicide was either very difficult or impossible to prevent.

CONCLUSIONSIn China the community is tolerant, sympathetic and, in some cases, accepting of suicide but there remains a substantial underlying stigmatization of suicide. Community members have some misunderstandings about suicide; the most obvious misunderstanding is the underestimation of the importance of mental illness as a cause of suicide. The content of public health messages used in suicide prevention programs should be developed by combining findings from both qualitative and quantitative research.

China ; Health Knowledge, Attitudes, Practice ; Humans ; Social Support ; Suicide ; prevention & control ; psychology ; Surveys and Questionnaires

OBJECTIVETo identify the most common life events that occurred prior to suicide in elderly individuals and the relationship of these life events to depressive symptoms.

METHODSA detailed study considering life events in the year prior to death, the presence of mental illness at the time of death and the level of depressive symptoms in the 2 weeks prior to death was undertaken with the family members and other associates of 304 persons at 55 years of age and older who died of suicide.

RESULTSThe three most common negative life events were acute or chronic physical illness or injury (59.2%), major changes in diet, sleeping or other daily routines (37.8%) and financial difficulties (34.5%). The severity of depressive symptoms was significantly greater among persons who had experienced these life events both for persons with or without definite mental illness.

CONCLUSIONMost elderly persons who died of suicide events had experienced multiple negative life events in the year prior to death and these life events were closely related to the severity of depressive symptoms at the time of death.

Aged ; psychology ; statistics & numerical data ; China ; Depression ; psychology ; Humans ; Life Change Events ; Quality of Life ; Retrospective Studies ; Risk Factors ; Suicide ; psychology

Age Factors ; China ; Female ; Forecasting ; Humans ; Male ; Research ; trends ; Research Design ; Risk Factors ; Rural Population ; Suicide ; prevention & control ; statistics & numerical data

OBJECTIVETo evaluate the accuracy of reports of suicide in the national death registry systems and to estimate a more accurate suicide rate.

METHODSTwenty-three sites from the Disease Surveillance Points Network-one of the national death registry systems-were selected and 1 932 of the deaths that occurred at these sites from August 1995 through August 2000 in which the official cause was classified as "accidental" or "mental illness" were selected for detailed household surveys focusing on reassessing the cause of death. Valid interviews were completed in 1 653 of these cases. The original cause of death recorded on the death certificate was compared with the finding of the detailed household survey and the result was used to adjust the suicide rate.

RESULTSAfter detailed investigation, 16 of the 857 (1.87%) deaths reported on the death certificate as suicide were considered accidental deaths, 39 of the 721 (5.41%) accidental deaths were considered suicide, 17 of the 35 (48.57%) cases reported as undetermined accidents were considered suicide, and 6 of the 40 (15.00%) cases in which mental illness was the recorded cause of death were considered suicide. After adjustments for errors in the reported cause of death and for missing deaths, the reported crude suicide rate of 13.65/100 000 in China was adjusted to 22.99/100 000 (95% CI: 21.78/100 000 - 24.25/100 000).

CONCLUSIONAfter adjustments the actual suicide rate for China was higher than the reported rate indicating that suicide was an increasingly important public health problem for China.

China ; epidemiology ; Humans ; Public Health ; Suicide ; statistics & numerical data