An Economic Evaluation of Coordinated Specialty Care (CSC) Services for First-Episode Psychosis in the U.S. Public Sector.

BACKGROUND: Schizophrenia spectrum disorders exert a large and disproportionate economic impact. Early intervention services may be able to alleviate the burden of schizophrenia spectrum disorders on diagnosed individuals, caregivers, and society at large. Economic analyses of observational studies have supported investments in specialized team-based care for early psychosis; however, questions remain regarding the economic viability of first-episode services in the fragmented U.S. healthcare system. The clinic for Specialized Treatment Early in Psychosis (STEP) was established in 2006, to explicitly model a nationally-relevant U.S. public-sector early intervention service. The purpose of this study was to conduct an economic evaluation of STEP, a Coordinated Specialty Care service (CSC) based in a U.S. State-funded community mental health center, relative to usual treatment (UT). METHODS: Eligible patients were within 5 years of psychosis onset and had no more than 12 weeks of lifetime antipsychotic exposure. Participants were randomized to STEP or UT. The annual per-patient cost of the STEP intervention per se was estimated assuming a steady-state caseload of 30 patients. A cost-offset analysis was conducted to estimate the net value of STEP from a third-party payer perspective. Participant healthcare service utilization was evaluated at 6 months and over the entire 12 months post randomization. Generalized linear model multivariable regressions were used to estimate the effect of STEP on healthcare costs over time, and generate predicted mean costs, which were combined with the per-patient cost of STEP. RESULTS: The annual per-patient cost of STEP was $1,984. STEP participants were significantly less likely to have any inpatient or ED visits; among individuals who did use such services in a given period, the associated costs were significantly lower for STEP participants at month 12. We did not observe a similar effect with regard to other healthcare services. The predicted average total costs were lower for STEP than UT, indicating a net benefit for STEP of $1,029 at month 6 and $2,991 at month 12; however, the differences were not statistically significant. CONCLUSIONS: Our findings are promising with regard to the value of STEP to third-party payers.

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study.

BACKGROUND: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams ('First-episode Services' or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? METHODS/DESIGN: The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREP(R)) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREP(R) over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. DISCUSSION: STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02069925 . Registered 20 February 2014.

Travel-associated disease among US residents visiting US GeoSentinel clinics after return from international travel.

BACKGROUND: US residents make 60 million international trips annually. Family practice providers need to be aware of travel-associated diseases affecting this growing mobile population. OBJECTIVE: To describe demographics, travel characteristics and clinical diagnoses of US residents who present ill after international travel. METHODS: Descriptive analysis of travel-associated morbidity and mortality among US travellers seeking care at 1 of the 22 US practices and clinics participating in the GeoSentinel Global Surveillance Network from January 2000 to December 2012. RESULTS: Of the 9624 ill US travellers included in the analysis, 3656 (38%) were tourist travellers, 2379 (25%) missionary/volunteer/research/aid workers (MVRA), 1580 (16%) travellers visiting friends and relatives (VFRs), 1394 (15%) business travellers and 593 (6%) student travellers. Median (interquartile range) travel duration was 20 days (10-60 days). Pre-travel advice was sought by 45%. Hospitalization was required by 7%. Compared with other groups of travellers, ill MVRA travellers returned from longer trips (median duration 61 days), while VFR travellers disproportionately required higher rates of inpatient care (24%) and less frequently had received pre-travel medical advice (20%). Illnesses of the gastrointestinal tract were the most common (58%), followed by systemic febrile illnesses (18%) and dermatologic disorders (17%). Three deaths were reported. Diagnoses varied according to the purpose of travel and region of exposure. CONCLUSIONS: Returning ill US international travellers present with a broad spectrum of travel-associated diseases. Destination and reason for travel may help primary health care providers to generate an accurate differential diagnosis for the most common disorders and for those that may be life-threatening.

Adopting a Novel Approach to Prevent and Address Patient Mistreatment of Staff in a Community Mental Health Center.

Verbal mistreatment of staff by patients is common in health care settings. Experiencing or witnessing mistreatment can have harmful psychological impacts, affecting well-being and clinical practice. As part of an effort to become an antiracist organization, an academic community mental health center based in Connecticut developed an initiative to address verbal mistreatment. Training in the Expect, Recognize, Address, Support, Establish (ERASE) framework was provided to 140 staff members. This training and subsequent actions to enhance the culture of safety were perceived as helpful by staff. Further development of the initiative is proceeding as the center's primary performance improvement program.

Risk of deaths due to injuries in travellers: a systematic review.

BACKGROUND: Annual global travel reached an all-time high of 1.4 billion international tourist visits in 2019. It is estimated that injury accounts for close to 25% of deaths in travellers, most of which are theoretically preventable. However, there are limited data available on injury occurrence and outcomes in travellers. Our objective was to better understand the relative risk of dying from injury that arises from the novel environments and behavioural changes associated with foreign travel. METHODS: A systematic literature review was conducted (PubMed, Embase and Scopus) according to PRISMA guidelines that included studies published in English since 1990 that reported injury deaths in tourists per 100 000-person years or as a proportion of total tourist deaths in comparison to a non-traveller population. We also included studies that reported data allowing calculation of these rates. Relative rates or proportions of overall injury mortality, mortality due to traffic accidents, drowning and homicide were summarized. RESULTS: In total, 1847 articles were identified, 105 underwent full-text review, and 10 articles were suitable for data extraction. There was great variability of relative risk reported, but overall, travellers appear to have a higher risk of injury mortality than domestic populations, with relative rates of injury death ranging from 1.04 to 16.7 and proportionate mortality ratios ranging from 1.43 to 3. CONCLUSIONS: Tourists should be aware of the increased risk of dying from road traffic hazards, drowning and homicide while traveling abroad. Specific geographies and activities associated with higher risk should be emphasized. Travel medicine practitioners and organizations that send people abroad should counsel travellers regarding these risks and seek ways to reduce them, including encouraging potential risk-mitigating behaviours. There is a need to improve systems of data collection and reporting on injury deaths in travellers and to study the impact of pre-travel and institutional interventions aimed at reducing this risk.

Reducing the Duration of Untreated Psychosis (DUP) in a US Community: A Quasi-Experimental Trial.

Objective: Duration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign ("Mindmap") can reduce DUP in a US community setting. Methods: In this nonrandomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Greater New Haven) from 2015 to 2019, while usual detection efforts continued at a control FES (PREP, Greater Boston). Mindmap targeted diverse sources of delay through mass & social media messaging, professional outreach & detailing, and rapid enrollment of referrals. Both FES recruited 16-35 years old with psychosis onset ≤3 years. Outcome measures included DUP-Total (onset of psychosis to FES enrollment), DUP-Demand (onset of psychosis to first antipsychotic medication), and DUP-Supply (first antipsychotic medication to FES enrollment). Results: 171 subjects were recruited at STEP and 75 at PREP. Mindmap was associated with an increase in the number of referrals and in efficiency of engagement at STEP. Pre-campaign DUP (2014-2015) was equivalent, while Mindmap was associated with DUP reductions at STEP but not PREP. DUP-Total fell significantly in both the first and the second quartile (11.5 and 58.5 days reduction per campaign year, respectively). DUP-Demand and DUP-Supply fell in the third quartiles only (46.3 and 70.3 days reduction per campaign year, respectively). No reductions were detectable across all quartiles at PREP, but between site comparisons were not significant. Conclusions: This is the first controlled demonstration of community DUP reduction in the US, and can inform future early detection efforts across diverse settings.

Electrophysiological indices of abnormal error-processing in adolescents with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Impaired cognitive control has been frequently observed in children and young people with attention deficit hyperactivity disorder (ADHD) and might underlie the excessive hyperactivity and impulsivity in this population. We investigated behavioural and electrophysiological indices relevant to one domain of cognitive control; namely error processing. METHODS: Adolescents aged 14 to 17 with ADHD (n = 23) and a typically developing control group (HC; n = 19) performed a visual go/no-go task. Electro-encephalography (EEG) data were collected simultaneously and response-locked error trials were averaged to derive two event-related potentials, the error-related negativity (ERN) and error positivity (Pe). Evoked theta power and inter-trial phase coherence (ITC) were measured in two time windows ('early' and 'late') equivalent to those used for detection of the ERN and Pe. RESULTS: Analysis revealed normal ERN amplitude and a statistical trend for smaller Pe amplitude at a fronto-central electrode site in the ADHD group. The group also showed significant reductions in late evoked theta power and early and late theta ITC. Relationships between behavioural measures and ITC were different between groups, particularly for post-error slowing, a measure of strategic response adjustment on trials immediately following an error. CONCLUSIONS: The results reveal abnormalities in behavioural and electrophysiological indices of error processing in adolescents with ADHD and suggest that ITC is more sensitive than traditional ERP measures to error-processing abnormalities.

Tetanus Vaccination 2020 and Collateral Protections against Pertussis and Diphtheria.

Tetanus is a life-threatening but vaccine-preventable disease caused by the toxin of the bacterium Clostridium tetani and is characterized by muscle spasms and autonomic nervous system dysfunction. It is prevented through vaccination with tetanus toxoid, but because the causative agent is widespread in the environment, eradication is impossible. Therefore, efforts to reduce incidence are aimed at reaching elimination, rather than eradication. This article reviews the pathogenesis, clinical manifestation and treatment of tetanus, and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus in the United States.

Epidemiology of Rabies and Current US Vaccine Guidelines.

Rabies is an acute encephalitis that is caused by rabies virus (RABV) infection, which belongs to the Rhabdoviridae family of viruses. It causes about 59,000 human deaths per year (although this number may be under-reported) and is generally fatal, once signs and symptoms begin to appear. Rabies is still very prevalent and under- reported, particularly in low to middle-income countries such as Asia and Africa, where there is lack of access to healthcare and domestic dogs are not widely vaccinated. Although not commonplace in the USA, rabies is mostly transmitted by wild animals such as bats, raccoons, skunks and foxes. Domesticated cats and dogs are also at risk of acquiring rabies, if they have not been vaccinated. Larger carnivores, such as coyotes, bobcats, mountain lions, wolves, bears, woodchucks, and beavers, should also be considered rabid (unless proven otherwise) if they are involved in an unprovoked attack on a person. The rabies vaccine can prevent 99% of deaths if administered promptly after exposure. There are two main vaccination strategies for rabies prevention: pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). This article reviews background and epidemiology of rabies and current guidelines for rabies PrEP and PEP regimens for the United States.

Predictive validity of conversion from the clinical high risk syndrome to frank psychosis.

Although the clinical high risk for psychosis (CHR) paradigm has become well-established over the past two decades, one key component has received surprisingly little investigative attention: the predictive validity of the criteria for conversion or transition to frank psychosis. The current study evaluates the predictive validity of the transition to psychosis as measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR individuals. Participants included 33 SIPS converters and 399 CHR non-converters both from the North American Prodromal Longitudinal Study (NAPLS-2), as well as a sample of 67 separately ascertained first-episode psychosis (FEP) patients from the STEP program. Comparisons were made at baseline and one-year follow-up on demographic, diagnostic stability (SCID), and available measurement domains relating to severity of illness (psychotropic medication, psychosocial treatment, and resource utilization). Principal findings are: 1) a large majority of cases in both SIPS converters (n = 27/33, 81.8%) and FEP (n = 57/67, 85.1%) samples met criteria for continued psychosis at one-year follow-up; 2) follow-up prescription rates for current antipsychotic medication were higher in SIPS converters (n = 17/32, 53.1%) compared to SIPS non-converters (n = 81/397, 20.4%), and similar as compared to FEP cases (n = 39/65, 60%); and 3) at follow-up, SIPS converters had higher rates of resource utilization (psychiatric hospitalizations, day hospital admissions, and ER visits) than SIPS non-converters and were similar to FEP in most categories. The results suggest that the SIPS definition of psychosis onset carries substantial predictive validity. Limitations and future directions are discussed.

The Psychiatric Consequences of Cannabinoids.

With rising rates of cannabis use in the general population and an increasing number of US states legalizing both recreational and medical cannabis use, it is important to be informed about the adverse consequences of cannabinoids. This Commentary provides an overview of the psychiatric effects of plant-based and synthetic cannabinoids, differentiating acute effects from effects associated with persistent use. Cannabinoids produce multiphasic and dose-dependent effects on anxiety, mood, and perception, in addition to impairing cognition and psychomotor function. Generally, in healthy individuals, the acute negative psychiatric effects of cannabinoids are rated as milder in severity compared with those in individuals with pre-existing psychiatric disorders. With chronic exposure to cannabinoids, the probability of developing tolerance and dependence can increase. A problematic pattern of cannabis use can lead to clinically significant impairment and distress. Cessation of cannabis use in individuals who are tolerant and dependent can lead to a withdrawal syndrome. Studies report long-term cannabis exposure has been linked to psychiatric disorders, such as anxiety, psychotic and mood disorders. Limitations to the existing evidence notwithstanding, the plausibility of a causal relationship between cannabinoid exposure and persistent negative psychiatric outcomes, and the potential for long-term brain changes by regular exposure, especially for adolescents, are sufficient to warrant discussions with clinicians and the public. Implications for clinicians who certify, prescribe, or care for patients receiving cannabinoids are discussed, and a case is made for further research to better understand the impact of legalization on public mental health.

The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans.

BACKGROUND: Binding studies have demonstrated that levels of the cannabinoid receptor type-1 are highest in the basal ganglia and cerebellum, two areas critical for motor control. However, no studies have systematically examined the dose-related effects of intravenous delta-9-tetrahydrocannabinol, the primary cannabinoid receptor type-1 partial agonist in cannabis, on broad domains of psychomotor function in humans. AIMS: Therefore, three domains of psychomotor function were assessed in former cannabis users (cannabis abstinent for a minimum of three months; n=23) in a three test-day, within-subject, double-blind, randomized, cross-over, and counterbalanced study during which they received intravenous delta-9-tetrahydrocannabinol (placebo, 0.015 mg/kg, and 0.03 mg/kg). METHODS: Gross motor function was assessed via the Cambridge Neuropsychological Test Automated Battery Motor Screening Task, fine motor control via the Lafayette Instrument Grooved Pegboard task, and motor timing via a Paced Finger-Tapping Task. In addition, the Cambridge Neuropsychological Test Automated Battery Rapid Visual Processing Task was utilized to determine whether delta-9-tetrahydrocannabinol-induced motor deficits were confounded by disruptions in sustained attention. RESULTS/OUTCOMES: Delta-9-tetrahydrocannabinol resulted in robust dose-dependent deficits in fine motor control (Grooved Pegboard Task) and motor timing (Paced Finger-Tapping Task), while gross motor performance (Motor Screening Task) and sustained attention (Rapid Visual Processing Task) were unimpaired. Interestingly, despite the observed dose-dependent increases in motor impairment and blood levels of delta-9-tetrahydrocannabinol, subjects reported similar levels of intoxication in the two drug conditions. CONCLUSIONS/INTERPRETATION: These data suggest that while several domains of motor function are disrupted by delta-9-tetrahydrocannabinol, subjective feelings of intoxication are dissociable from cannabinoid-induced psychomotor effects. Results are discussed in terms of the potential neural mechanisms of delta-9-tetrahydrocannabinol in motor structures.

The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

BACKGROUND: Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. METHODS: Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. RESULTS: Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. CONCLUSIONS: At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC.

Transcranial magnetic stimulation of Wernicke's and Right homologous sites to curtail "voices": a randomized trial.

BACKGROUND: Auditory/verbal hallucinations (AVHs) are accompanied by activation in Wernicke's and right homologous regions. Efficacy in curtailing AVHs via 1-Hz repetitive magnetic stimulation (rTMS) targeting a site in each region ("W" and "rW") was therefore studied. METHODS: Patients with schizophrenia and AVHs (N = 83) were randomly allocated to double-masked rTMS versus sham stimulation, with blocks of five sessions given to W and rW in random order, followed by five sessions to the site yielding greater improvement. The primary outcome measure was the Hallucination Change Score (HCS). Hallucination frequency, total auditory hallucination rating scale score, and clinical global improvement were secondary outcome measures. Attentional salience of AVHs and neuropsychological measures of laterality were studied as predictors of site-specific response. RESULTS: After 15 sessions, rTMS produced significant improvements relative to sham stimulation for hallucination frequency and clinical global improvement but not for HCS. After limiting analyses to patients whose motor threshold was detected consistently: 1) endpoint HCS demonstrated significantly greater improvement for rTMS compared with sham stimulation; 2) for high-salience AVHs, rTMS to rW after the first five sessions yielded significantly improved HCS scores relative to sham stimulation, whereas for low salience AVHs, rTMS to W produced this finding. Nondominant motor impairment correlated positively with hallucination improvement following rW rTMS. CONCLUSIONS: One-hertz rTMS per our site-optimization protocol produced some clinical benefit in patients with persistent AVHs as a group, especially when motor threshold was consistently detected. Level of hallucination salience may usefully guide selection of W versus rW as intervention sites.

Effects of motivation and medication on electrophysiological markers of response inhibition in children with attention-deficit/hyperactivity disorder.

BACKGROUND: Theories of attention-deficit/hyperactivity disorder (ADHD) posit either executive deficits and/or alterations in motivational style and reward processing as core to the disorder. Effects of motivational incentives on electrophysiological correlates of inhibitory control and relationships between motivation and stimulant medication have not been explicitly tested. METHODS: Children (9-15 years) with combined-type ADHD (n = 28) and matched typically developing children (CTRL) (n = 28) performed a go/no-go task. Electroencephalogram data were recorded. Amplitude of two event-related potentials, the N2 and P3 (markers of response conflict and attention), were measured. The ADHD children were all stimulant responders tested on and off their usual dose of methylphenidate; CTRLs were never medicated. All children performed the task under three motivational conditions: reward; response cost; and baseline, in which points awarded/deducted for inhibitory performance varied. RESULTS: There were effects of diagnosis (CTRL > ADHD unmedicated), medication (on > off), and motivation (reward and/or response cost > baseline) on N2 and P3 amplitude, although the N2 diagnosis effect did not reach statistical significance (p = .1). Interactions between motivation and diagnosis/medication were nonsignificant (p > .1). CONCLUSIONS: Motivational incentives increased amplitudes of electrophysiological correlates of response conflict and attention in children with ADHD, towards the baseline (low motivation) amplitudes of control subjects. These results suggest that, on these measures, motivational incentives have similar effects in children with ADHD as typically developing CTRLs and have additive effects with stimulant medication, enhancing stimulus salience and allocation of attentional resources during response inhibition.