Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency.

BACKGROUND: Congenital fibrinogen deficiency (CFD) is a rare, inherited disorder affecting normal blood clotting function, where patients can experience severe and/or frequent bleeding episodes (BEs). Treatment with human fibrinogen concentrate (HFC) can prevent/arrest bleeding. There is a need for more data on the efficacy, pharmacokinetics (PK) and safety of HFC treatment in paediatric patients with CFD. METHODS: Haemostatic efficacy of HFC (Fibryga® , Octapharma AG) for on-demand treatment of bleeding and surgical prophylaxis in patients <12 years old was assessed by investigators and an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) based on an objective 4-point efficacy scale. Maximum clot firmness (MCF; surrogate marker of haemostatic efficacy), single-dose PK and safety were also assessed. RESULTS: Of 14 patients receiving HFC (median [range] age 6.0 years [1.0-10.0]), eight received HFC for 10 BEs, three for surgical prophylaxis and 13 for PK. The IDMEAC rated haemostatic efficacy as 100% successful for on-demand BE treatment (95% CI 69.15-100.00) and surgical prophylaxis (95% CI 29.24-100.00). After a mean first dose of 70.78 mg/kg for BEs, mean (±SD) MCF significantly increased from pre-treatment to 1-hour post-infusion (3.3 mm [±1.77]; P = 0.0002), coinciding with haemostatic efficacy. PK parameters were favourable. Two possibly related adverse events occurred, including one serious (portal vein thrombosis). No allergic/hypersensitivity reactions or deaths were observed. CONCLUSION: HFC treatment for on-demand treatment of BEs and surgical prophylaxis was efficacious for this ultra-rare paediatric population with congenital afibrinogenaemia and showed a favourable PK and safety profile.

Fifteen years of heroin-assisted treatment in a Swiss prison-a retrospective cohort study.

BACKGROUND: In the context of the current US opioid crisis and the compelling fact that a quarter to a third of all those addicted to heroin pass through its prisons and jails each year, the care of incarcerated opioid-using individuals (OUI) needs to be improved. AIMS: Little has been published on the effectiveness or outcomes of heroin-assisted treatment (HAT), a treatment option for severely dependent OUI delivered in a prison setting. The aim of this study was therefore to evaluate such treatment since its implementation. The primary objective was to investigate whether heroin-assisted treatment was associated with severe detrimental health outcomes. The secondary objective was to compare the heroin-assisted treatment group with the general prison population in terms of occupational functioning. DESIGN: Retrospective cohort study SETTING: An open prison with 120 places SUBJECTS: Data on 1885 male prisoners with a total of 2239 imprisonment periods between 2000 and 2015 was available. Ninety-seven inmates in heroin-assisted treatment were compared with 1788 inmates from the general prison population (reference group). MEASUREMENTS: Mortality, medical complications (including overdoses), and work performance (days worked, sick days, and monthly wages earned). FINDINGS: Inmates receiving HAT were on average 1 year younger (33.8 vs. 34.9 years), had longer prison stays (7.3 vs. 3.0 months), were more often of Swiss nationality (68.0% vs. 28.9%), and had committed more drug- and property-related offenses (49.5% vs. 23.2% and 63.9% vs. 38.3%, respectively) compared to the reference group. No serious heroin-related medical complication occurred during the 15-year window of observation among inmates with heroin-assisted treatment. Their work performance was comparable to that of the reference group. CONCLUSIONS: This study shows that heroin-assisted treatment can be a valuable treatment option for severely dependent OUI during imprisonment, can be delivered safely by prison health staff over extended periods of time, and allows OUI in treatment to achieve work performance rates comparable to that of the general prison population.

Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency: an interim analysis of a Phase III trial.

BACKGROUND: Fibrinogen concentrate is the preferred choice for fibrinogen replacement in congenital fibrinogen deficiency. This study investigated hemostatic efficacy of a new plasma-derived, double virus-inactivated (using two dedicated virus inactivation/elimination steps) human fibrinogen concentrate for on-demand treatment of bleeding episodes (BEs) and surgical prophylaxis. STUDY DESIGN AND METHODS: In this planned interim analysis of a prospective, multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia (≥12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic efficacy was assessed by investigators and an independent data monitoring and endpoint adjudication committee (IDMEAC) using objective four-point criteria and by thromboelastometry maximum clot firmness (MCF). RESULTS: Fibrinogen concentrate was used on-demand to treat 23 BEs in 11 patients, with 21 (91.3%) requiring a single infusion only. Treatment success was 95.7% (90% confidence interval [CI], 0.81-1.00; assessment missing for one BE) by investigators and 100% (90% CI, 0.88-1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to 6.5 mm (95% CI, 5.65-7.40; p < 0.0001) at 1 hour postinfusion of a median (range) dose of 58.8 (33.9-101.7) mg/kg per BE. Four patients received fibrinogen concentrate as surgical prophylaxis, with intraoperative and postoperative treatment success rated 100% (90% CI, 0.50-1.00) by investigators and IDMEAC (median [range] dose per surgery 93.5 [34.1-225.4] mg/kg). No additional hemostatic interventions were required. No deaths, thromboses, or seroconversions were reported. CONCLUSION: These data showed that the new fibrinogen concentrate was efficacious for on-demand treatment of acute bleeding and surgical prophylaxis in congenital afibrinogenemia patients.

Beyond Watches and Chocolate-Global Mental Health Elective in Switzerland.

Despite increasing interest in global mental health training opportunities, only a few psychiatry residency programs offer global mental health training experiences in developing countries and even fewer programs offer it in other first-world countries. The authors developed a global mental health elective giving US psychiatry residents the opportunity to visit Switzerland to study and experience the mental health care system in this European country. This elective focuses on four major learning objectives: (1) the system of training and curriculum of postgraduate psychiatry education in Switzerland, (2) clinical and organizational aspects of Swiss mental health, (3) administrative aspects of Swiss mental health care delivery, and (4) scholarly activity. This program was uniquely tailored for psychiatry residents. The preliminary experiences with US psychiatry residents show that they value this learning experience, the opportunity to access a different mental health care system, as well as the potential to build international connections with peers.

The Tarrytown Chief Residents Leadership Conference: a long-term follow-up.

OBJECTIVE: Creating training opportunities for the development of effective leaders is an increasingly important goal in psychiatry residency training programs. This article examines the long-term perceived impact of the Tarrytown Chief Residents Leadership Conference on preparing psychiatric residents for future leadership positions. METHODS: Self-report surveys from attendees who participated in the conference between 1998 and 2011 were examined. RESULTS: Five hundred and forty-one completed surveys were returned (43 % response rate). Eighty-six percent of respondents reported moderate to extreme improvement in leadership confidence post-conference. Most respondents indicated at least moderate improvement in self-awareness (93 %), understanding of group process (92 %), and willingness to address conflict (89 %). Ninety percent felt the conference was important to their residency training, and 80 % indicated increased interest in leadership post-conference. CONCLUSIONS: Responders reported lasting improvements in their confidence in and perceived ability to utilize skills necessary for effective leadership, demonstrating the value of this experiential learning opportunity.

Impact of New York State's Health Home Model on Health Care Utilization.

The Affordable Care Act established Medicaid health homes to provide care management and coordination for high-need individuals, including many with serious mental illness. The authors used data from the Medicaid Data Warehouse to examine health care utilization over 3 years among 10,193 individuals who enrolled in a New York State health home and had at least one outpatient mental health visit during the year prior to enrollment. Results for postenrollment year 2 indicated a 43% decrease in inpatient mental health discharges, a 38% decrease in substance use discharges, and a 7% reduction in general medical discharges, whereas mental health outpatient treatment and behavioral and nonbehavioral medication utilization increased. Further research is needed to determine the effectiveness of health home care management for individuals with serious mental illness.

Protocol for a multicentre, randomised, parallel-control, superiority trial comparing administration of clotting factor concentrates with a standard massive haemorrhage protocol in severely bleeding trauma patients: the FiiRST 2 trial (a 2020 EAST multicentre trial).

INTRODUCTION: Acute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma. METHODS AND ANALYSIS: The factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study. ETHICS AND DISSEMINATION: The study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma. TRIAL REGISTRATION NUMBER: NCT04534751, pre results.

Substance use disorders and employability among welfare recipients.

The 2006 welfare reform legislation (Deficit Reduction Act of 2005) imposed more stringent work requirements and defined the amount of time cash assistance recipients are allowed to be exempted from the work requirement because of substance use treatment. As there is little empirical literature on the employability of substance users, it is difficult to know whether it is realistic to expect individuals with substance use disorders to meet the increased work requirement. Based on a comprehensive evaluation of nearly 9,000 substance-misusing welfare recipients from 2001 to 2007, University Behavioral Associates (UBA) Comprehensive Services Model program in Bronx, New York, found that 60% of recipients were not exempted from the work requirement owing to substance misuse at the outset, and an additional 24% were found nonexempt after 3 months of intensive outpatient treatment coupled with case management, resulting in a total of 84% of the UBA clients not being exempted from the work requirement because of substance misuse by Day 90. UBA also found that 25% of substance-misusing clients were able to obtain employment, and most successfully retained those jobs over the course of 6 months. These findings are discussed in relation to the new law's work requirements and the issue of the employability of substance misusers. Finally, the value of case management in serving this hard-to-engage population is discussed.

Treatment of Serious Mental Illness in Medical and Mental Health Settings.

OBJECTIVE: This study investigated service use by individuals with serious and nonserious mental illness receiving mental health care in medical and mental health settings. METHODS: Claims data from the New York State Medicaid Data Warehouse were examined for 8,988 patients who received at least one mental health service at an urban academic medical center during 2017 at a mental health setting, a medical setting, or both. RESULTS: Most patients (59%) received all of their mental health care in medical settings and from unaffiliated providers, including a large portion (16%) with serious mental illness. Despite the availability of integrated care in the medical setting and use of unaffiliated mental health providers, rates of mental health inpatient admissions were high among all patients in this setting (including those with serious and with nonserious mental illness), considerably higher than for patients treated in a mental health clinic within the system. Rates of medical and substance abuse inpatient admissions were also much higher for patients treated in the medical setting and by unaffiliated providers, compared with those treated in the system's mental health clinics. CONCLUSIONS: Findings suggest that when mental health services are available in medical and mental health settings within the same system, either patients with more severe physical illnesses are more likely to receive their mental health care in medical settings and from unaffiliated providers and thus have more hospitalizations of all types or affiliated mental health settings more effectively address clinical needs and thus reduce hospitalizations.

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients.

BACKGROUND: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. METHODS: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA® , Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. RESULTS: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. CONCLUSIONS: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.

The Swiss Mental Health Care System.

The United States and Switzerland are among the world's wealthiest countries. Both are highly innovative and entrepreneurial, ranking high in global competitiveness and innovation and with similar liberal economies. This column highlights features of the health care system in Switzerland, a country with an exclusively private health insurance system, with federally mandated universal health insurance. Residents can choose from about 58 insurance companies. Switzerland regulates these companies and negotiates reimbursement rates. The Swiss model of health care and its provision of comprehensive psychiatric and substance abuse treatment could inform policy as the United States considers major changes to its health care laws. Switzerland could serve as an example for developing a mental health care model that ensures appropriate services, with a high density of psychiatric inpatient facilities and mental health care providers, while maintaining affordable care.

Second Opinions in Psychiatry: A Review.

BACKGROUND: Although second opinions are rather restricted to the surgical disciplines, they have become more and more important to the health system in the last 20 years. The demand has been triggered by rising health costs and the economization of the field. The Internet has also made a considerable contribution to the demand for patient-initiated second opinions. Given these developments, it is surprising that second opinions have not become more important in the field of psychiatry. This article highlights the special situation of second opinions in psychiatry, discusses possible barriers to the adoption of second opinions in psychiatry, and the potential for greater use of second opinions in this field. OBJECTIVE: In psychiatry, second opinions have been neglected by the typical drivers of innovations in health care, including insurers and other commercial drivers as well as psychiatrists and patients themselves. This review identifies current barriers to widespread adoption of second opinions in psychiatric practice, discusses the benefits of second opinions that have been demonstrated in other disciplines, and outlines the potential gains to be realized through use of second opinions in psychiatry. METHODS: Literature in the area was reviewed through a search of the main medical databases. This literature review was supported by in-depth interviews with health care personnel and insurers. CONCLUSIONS: Second opinions are rarely obtained in psychiatry and there is little literature on this subject. The stigmatization of psychiatric disorders and patients and the uniqueness of the patient-doctor relationship in psychiatry, especially in psychotherapeutic care, may pose considerable obstacles to the use of second opinions in this field. In addition, more stakeholders, such as social workers, government agencies and regulators, health care and disability insurers, and social security agencies, are involved in the mental health compared with the somatic health sector, which may make it more difficult to achieve a coordinated approach in psychiatric care. However, we have found no convincingly good reason why second opinions have not been at least discussed in psychiatry. Psychiatry could benefit from ongoing discussions concerning the outcomes of second opinions in other medical disciplines.

TARPSY: A New System of Remuneration for Psychiatric Hospitalization in Switzerland.

As financing mental health care is becoming more challenging, governments are progressively introducing new remuneration systems. At the beginning of 2018, Switzerland introduced TARPSY, a new tariff system based on diagnosis-related psychiatric cost groups that takes into consideration ratings of severity and complexity. TARPSY is expected to provide incentives for medically and economically meaningful treatment, increase transparency, and improve the quality of the provided services by triggering competition between hospitals. Yet some fear that TARPSY will lead to an economization of mental health, encouraging a reduction in length of stay and medically indicated treatment.

Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.

BACKGROUND: Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio. METHODS: Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death. RESULTS: The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent. CONCLUSIONS: Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.

Lessons learned from a colocation model using psychiatrists in urban primary care settings.

OBJECTIVES: Comorbid psychiatric illness has been identified as a major driver of health care costs. The colocation of psychiatrists in primary care practices has been proposed as a model to improve mental health and medical care as well as a model to reduce health care costs. METHODS: Financial models were developed to determine the sustainability of colocation. RESULTS: We found that the population studied had substantial psychiatric and medical burdens, and multiple practice logistical issues were identified. CONCLUSION: The providers found the experience highly rewarding and colocation was financially sustainable under certain conditions. The colocation model was effective in identifying and treating psychiatric comorbidities.