1- Versus 3-Month DAPT in Older Patients at a High Bleeding Risk Undergoing PCI: Insights from the XIENCE Short DAPT Global Program.

This analysis aimed to evaluate the effect of 1- versus 3-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in older patients. Data from 3 prospective, single-arm studies (XIENCE Short DAPT Program), including patients with high bleeding risk successfully treated with an everolimus-eluting stent (XIENCE, Abbott) were analyzed. DAPT was discontinued at 1 or at 3 months in patients free from ischemic events and adherent to DAPT. Patients were stratified according to age (≥75 and <75 years). The primary end point was all-cause death or myocardial infarction (MI). The key secondary end point was Bleeding Academic Research Consortium type 2 to 5 bleeding. The outcomes were assessed from 1 to 12 months after index PCI. Of 3,364 patients, 2,241 (66.6%) were aged ≥75 years. The risk of death or MI was similar with 1- versus 3-month DAPT in patients aged ≥75 (8.5% vs 8.0%, adjusted hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69 to 1.30) and <75 years (6.9% vs 7.8%, adjusted HR 0.97, 95% CI 0.60 to 1.57, interaction p = 0.478). Bleeding Academic Research Consortium type 2 to 5 bleeding was consistently lower with 1- than with 3-month DAPT in patients aged ≥75 years (7.2% vs 9.4%, adjusted HR 0.66, 95% CI 0.48 to 0.91) and <75 years (9.7% vs 11.9%, adjusted HR 0.86, 95% CI 0.57 to 1.29, interaction p = 0.737). In conclusion, in patients at high bleeding risk who underwent PCI, patients older and younger than 75 years derived a consistent benefit from 1- compared with 3-month DAPT in terms of bleeding reduction, with no increase in all-cause death or MI at 1 year.

Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System.

Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the "memory" to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that "memory" of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions.IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal with such complexity. In this study, we examined the molecular "memory" that is generated by previous exposure to stimulus. Under our experimental conditions, activating effects of autoregulated two-component signaling and inhibitory effects of the stress response counterbalanced the transcriptional output to approach response homeostasis whether or not cells had been preexposed to stimulus. Modeling allows prediction of response behavior in different scenarios and demonstrates both the robustness of the system output and its sensitivity to historical parameters such as timing and levels of exposure to stimuli.

Depressed mood as a risk factor for unprotected sex in young people.

OBJECTIVES: Young people may place themselves and others at risk of sexually transmitted infections (STI) and/or the human immunodeficiency virus (HIV) through engaging in unprotected sex. Mental health problems may play an important role in sex-related risk behaviour. The current research was an investigation of depressed mood and condom use in a help-seeking sample of young people in Melbourne, Australia. METHOD: The sample comprised 76 sexually active young people aged 15-24 years who were referred to ORYGEN Youth Health, a public mental health service in Melbourne, Australia. Controlling for demographic characteristics and substance use, multivariate logistic regression examined depressed mood as a predictor of condom use at last sexual intercourse. RESULTS: Half of the sample reported condom use the last time they had sexual intercourse. Depressed mood, female gender and unemployment increased the likelihood that participants engaged in unprotected sex. CONCLUSION: A high proportion of young people, particularly those who are depressed, are failing to protect themselves from STI/HIV. Mental health services working with young people have the opportunity to implement initiatives aimed at reducing risk of STI/HIV infection.

Psychotic-like experiences in nonpsychotic help-seekers: associations with distress, depression, and disability.

Psychotic-like experiences (PLEs) increase the risk of schizophrenia and other psychotic disorders yet are common in the community. Some PLEs, such as those associated with depression, distress, and poor functioning, may confer increased risk. The aim of this study is to determine the prevalence of PLEs in a nonpsychotic clinical sample and to investigate whether any subtypes of PLEs are associated with the above factors. Consecutive referrals to a youth psychiatric service (N = 140) were assessed to measure PLEs, depression, and functioning. PLE data were factor analyzed, and the associations of psychotic subtypes and distress, depression, and disability were analyzed. Three subtypes of PLEs were identified: Bizarre Experiences, Persecutory Ideas, and Magical Thinking. Bizarre Experiences and Persecutory Ideas were associated with distress, depression, and poor functioning. Magical Thinking was not, unless accompanied by distress. Bizarre Experiences and Persecutory Ideas may be more malignant forms of psychotic symptoms, as they are associated with current disability, and may confer increased risk of development of full-blown psychotic disorder.

Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States.

OBJECTIVE: Recognizing the prodrome of a first psychotic episode prospectively creates the opportunity of intervention, which could delay, ameliorate or even prevent onset. Valid criteria and a reliable methodology for identifying possible prodromes are needed. This paper describes an instrument, the Comprehensive Assessment of At-Risk Mental States (CAARMS), which has been designed for such a purpose. It has two functions: (i) to assess psychopathology thought to indicate imminent development of a first-episode psychotic disorder; and (ii) to determine if an individual meets criteria for being at ultra high risk (UHR) for onset of first psychotic disorder. This paper describes the pilot evaluation of the CAARMS. METHOD: Several methodologies were used to test the CAARMS. First, CAARMS scores in a group of UHR young people and the association between CAARMS scores and the risk of transition to psychotic disorder, were analysed. Second, CAARMS scores in a UHR group were compared to a control group. To assess concurrent validity, CAARMS-defined UHR criteria were compared to the existing criteria for identifying the UHR cohort. To assess predictive validity, the CAARMS-defined UHR criteria were applied to a sample of 150 non-psychotic help-seekers and rates of onset of psychotic disorder at 6-month follow-up determined for the CAARMS-positive (i.e. met UHR criteria) group and the CAARMS-negative (i.e. did not meet UHR criteria) group. The inter-rater reliability of the CAARMS was assessed by using pairs of raters. RESULTS: High CAARMS score in the UHR group was significantly associated with onset of psychotic disorder. The control group had significantly lower CAARMS scores than the UHR group. The UHR criteria assessed by the CAARMS identified a similar group to the criteria measured by existing methodology. In the sample of non-psychotic help-seekers those who were CAARMS-positive were at significantly increased risk of onset of psychotic disorder compared to those who were CAARMS-negative (relative risk of 12.44 (95% CI = 1.5-103.41, p = 0.0025)). The CAARMS had good to excellent reliability. CONCLUSIONS: In these preliminary investigations, the CAARMS displayed good to excellent concurrent, discriminant and predictive validity and excellent inter-rater reliability. The CAARMS instrument provides a useful platform for monitoring subthreshold psychotic symptoms for worsening into full-threshold psychotic disorder.

Patterns of current comorbidity in young help-seekers: implications for service planning and delivery.

OBJECTIVE: To identify the pattern of current comorbidity in young help-seekers referred to a specialist mental health service. METHOD: One hundred and forty-nine participants were assessed for current psychiatric diagnoses following their referral to ORYGEN Youth Health. RESULTS: Seventy-eight per cent of the sample rated for at least one diagnosis with almost half the sample presenting with two or more disorders. Next to comorbid depression and anxiety, comorbidity between substance use disorders and mood and anxiety disorders was the most prominent pattern of comorbidity in the sample. CONCLUSIONS: The present findings suggest that integration between mental health and substance abuse services is well overdue and must be addressed at policy, service system and clinical levels.