In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.

Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).

334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.

TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.

Teva Branded Pharmaceutical Products R&D Inc.

Study Registration Number: NCT03893825

Due to different timing of drug launches across countries, published health technology assessment (HTA) findings from one country may impact HTA outcomes in other countries. The aim of our work was to identify the most influential HTA bodies by analyzing to what extent HTA bodies cross-reference each other in their HTA reports.

We analyzed the HTA reports on single drug assessments (SDA) published by 46 HTA bodies from 28 countries (and cross-country collaborations) with decision dates between January 2011 and November 2023. We searched the identified HTA reports by using natural language processing and a predefined set of keywords to identify whether, and to what extent, HTA bodies reference each other in their HTA reports. Additionally, we assessed if there is a trend over time in the cross-referencing, and whether any clusters could be identified.

Based on the analysis of 24,793 SDAs, the National Institute for Health and Care Excellence (NICE) was referenced the most (in 4,198 HTA reports across 39 HTA bodies), followed by the Canadian Agency for Drugs and Technologies in Health (in 2,034 reports across 35 HTA bodies), and the Scottish Medicines Consortium (SMC) (in 1,960 reports across 31 HTA bodies). The HTA bodies that most often referenced other HTAs were the Agency for Health Technology Assessment and Tariff System, the Haute Autorité de santé, and NICE. Seven HTA bodies were not referenced in any HTA report, while four did not reference any other HTA body.

Our research shows that most of the analyzed HTA agencies not only referenced other HTA bodies in their HTA reports but were also referenced by other HTA bodies. The most often referenced HTA agencies were mostly from English-speaking countries, were well recognized, and had well defined methodologies.

The role of lay health workers in data collection for clinical and translational research studies is not well described. We explored lay health workers as data collectors in clinical and translational research studies. We also present several methods for examining their work, i.e., qualitative interviews, fidelity checklists, and rates of unusable/missing data.

We conducted 2 randomized, controlled trials that employed lay health research personnel (LHR) who were employed by community-based organizations. In one study, n = 3 Latina LHRs worked with n = 107 Latino diabetic participants. In another study, n = 6 LHR worked with n = 188 Cambodian American refugees with depression. We investigated proficiency in biological, behavioral, and psychosocial home-based data collection conducted by LHR. We also conducted in-depth interviews with lay LHR to explore their experience in this research role. Finally, we described the training, supervision, and collaboration for LHR to be successful in their research role.

Independent observers reported a very high degree of fidelity to technical data collection protocols (>95%) and low rates of missing/unusable data (1.5%–11%). Qualitative results show that trust, training, communication, and supervision are key and that LHR report feeling empowered by their role. LHR training included various content areas over several weeks with special attention to LHR and participant safety. Training and supervision from both the academic researchers and the staff at the community-based organizations were necessary and had to be well-coordinated.

Carefully selected, trained, and supervised LHRs can collect sophisticated data for community-based clinical and translational research.

Routine patient care data are increasingly used for biomedical research, but such “secondary use” data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount.

For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs.

We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives.

After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.

To measure the impact of an automated hand hygiene monitoring system (AHHMS) and an intervention program of complementary strategies on hand hygiene (HH) performance in both acute-care and long-term care (LTC) units.

Prospective, nonrandomized, before-and-after intervention study.

Single Veterans Affairs Medical Center (VAMC), with 2 acute-care units and 6 LTC units.

An AHHMS that provides group HH performance rates was implemented on 8 units at a VAMC from March 2021 through April 2022. After a 4-week baseline period and 2.5-week washout period, the 52-week intervention period included multiple evidence-based components designed to improve HH compliance. Unit HH performance rates were expressed as the number of dispenses (events) divided by the number of patient room entries and exits (opportunities) × 100. Statistical analysis was performed with a Poisson general additive mixed model.

During the 4-week baseline period, the median HH performance rate was 18.6 (95% CI, 16.5–21.0) for all 8 units. During the intervention period, the median HH rate increased to 21.6 (95% CI, 19.1–24.4; P < .0001), and during the last 4 weeks of the intervention period (exactly 1 year after baseline), the 8 units exhibited a median HH rate of 25.1 (95% CI, 22.2–28.4; P < .0001). The median HH rate increased from 17.5 to 20.0 (P < .0001) in LTC units and from 22.9 to 27.2 (P < .0001) in acute-care units.

The intervention was associated with increased HH performance rates for all units. The performance of acute-care units was consistently higher than LTC units, which have more visitors and more mobile veterans.

It has been previously identified that levels of peripheral inflammatory proteins, such as cytokines, are altered in people with schizophrenia spectrum disorders (SSD).

As there is considerable inconsistency in the literature with respect to how inflammatory profiles differ between acute and chronic stages of SSD, a systematic review and network meta-analysis was performed.

Records from CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and PsycINFO were systematically searched from inception until 31 March 2022 for published studies that had measured levels of inflammatory proteins in cases of SSD and healthy controls. Pairwise and network meta-analyses were performed to determine whether there were significant differences in mean peripheral protein concentrations between acute SSD, chronic SSD, and healthy controls.

After application of the screening process, 215 articles were included for data-analysis. One group of markers were consistently elevated (p<0·05) in both acute and chronic SSD, relative to healthy controls; this group comprised interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP). A second group of markers were inconsistently altered between illness stages: IL-2 and interferon (IFN)-γ were significantly elevated (p<0·05) in acute SSD, whilst IL-4, IL-12 and IFN-γ were significantly decreased (p<0·05) in chronic SSD.

These results indicate that a baseline level of inflammatory protein alteration occurs in SSD throughout the course of illness. This was evident from the group of markers that were consistently elevated in acute and chronic SSD (e.g., IL-6), representing possible trait markers. Moreover, superimposed immune activity may occur in acute SSD, given the group of possible state markers that were increased only in acute illness (e.g., IFN-γ). Further research is required to elucidate whether these peripheral changes are reflected within the central nervous system.

None Declared

Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response.

Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice.

We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response.

We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223–558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine.

Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.

To determine how engagement of the hospital and/or vendor with performance improvement strategies combined with an automated hand hygiene monitoring system (AHHMS) influence hand hygiene (HH) performance rates.

Prospective, before-and-after, controlled observational study.

The study was conducted in 58 adult and pediatric inpatient units located in 10 hospitals.

HH performance rates were estimated using an AHHMS. Rates were expressed as the number of soap and alcohol-based hand rub portions dispensed divided by the number of room entries and exits. Each hospital self-assigned to one of the following intervention groups: AHHMS alone (control group), AHHMS plus clinician-based vendor support (vendor-only group), AHHMS plus hospital-led unit-based initiatives (hospital-only group), or AHHMS plus clinician-based vendor support and hospital-led unit-based initiatives (vendor-plus-hospital group). Each hospital unit produced 1–2 months of baseline HH performance data immediately after AHHMS installation before implementing initiatives.

Hospital units in the vendor-plus-hospital group had a statistically significant increase of at least 46% in HH performance compared with units in the other 3 groups (P ≤ .006). Units in the hospital only group achieved a 1.3% increase in HH performance compared with units that had AHHMS alone (P = .950). Units with AHHMS plus other initiatives each had a larger change in HH performance rates over their baseline than those in the AHHMS-alone group (P < 0.001).

AHHMS combined with clinician-based vendor support and hospital-led unit-based initiatives resulted in the greatest improvements in HH performance. These results illustrate the value of a collaborative partnership between the hospital and the AHHMS vendor.

To determine how pharmacists with formal antimicrobial stewardship program (ASP) responsibilities prioritize their time and pharmacists without formal antimicrobial stewardship program responsibilities contribute to ASP activities.

A nationwide survey.

Members of the American College of Clinical Pharmacy who subscribe to the following practice and research network e-mail listservs: infectious diseases, adult medicine, cardiology, critical care, hematology–oncology, immunology and transplantation, and pediatrics.

A survey was distributed via listservs. Respondents were asked about their personal and institutional demographics and ASP activities.

In total, 245 pharmacists responded: 135 pharmacists with formal antimicrobial stewardship program responsibilities; 110 pharmacists without formal antimicrobial stewardship program responsibilities. Although most respondents had completed a general pharmacy residency (85%), only 20% had completed an infectious diseases (ID) specialty residency. Among pharmacists with formal antimicrobial stewardship program responsibilities, one-third had no formal training or certification in ID or ASP. Pharmacists without formal antimicrobial stewardship program responsibilities spent ∼12.5% of their time per week on ASP activities, whereas pharmacists with formal antimicrobial stewardship program responsibilities spent 28% of their time performing non-ASP activities. Pharmacists with formal antimicrobial stewardship program responsibilities were more likely than pharmacists without formal antimicrobial stewardship program responsibilities to perform antibiotic guideline development (P < .001), antibiotic-related education (P = .002), and direct notification of rapid diagnostic results (P = .018). Pharmacists with formal antimicrobial stewardship program responsibilities without formal ID training or certification spent less time on ASP activities and were more likely to perform lower-level interventions.

Many ASP activities are being performed by pharmacists without formal ID training. To ensure the future success of ASPs, pharmacists with formal antimicrobial stewardship program responsibilities should have adequate training to meet more advanced metrics, and more pharmacists without formal antimicrobial stewardship program responsibilities should be included in basic interventions.