Reducing perceived barriers to scaling up overdose education and naloxone distribution and medications for opioid use disorder in the United States in the HEALing (helping end addiction long-term®) communities study.

BACKGROUND: Scaling up overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD) is needed to reduce opioid overdose deaths, but barriers are pervasive. This study examines whether the Communities That HEAL (CTH) intervention reduced perceived barriers to expanding OEND and MOUD in healthcare/behavioral health, criminal-legal, and other/non-traditional venues. METHODS: The HEALing (Helping End Addiction Long-Term®) Communities Study is a parallel, wait-list, cluster randomized trial testing the CTH intervention in 67 communities in the United States. Surveys administered to coalition members and key stakeholders measured the magnitude of perceived barriers to scaling up OEND and MOUD in November 2019-January 2020, May-June 2021, and May-June 2022. Multilevel linear mixed models compared Wave 1 (intervention) and Wave 2 (wait-list control) respondents. Interactions by rural/urban status and research site were tested. RESULTS: Wave 1 respondents reported significantly greater reductions in mean scores for three outcomes: perceived barriers to scaling up OEND in Healthcare/Behavioral Health Venues (-0.26, 95% confidence interval, CI: -0.48, -0.05, p = 0.015), OEND in Other/Non-traditional Venues (-0.53, 95% CI: - 0.84, -0.22, p = 0.001) and MOUD in Other/Non-traditional Venues (-0.34, 95% CI: -0.62, -0.05, p = 0.020). There were significant interactions by research site for perceived barriers to scaling up OEND and MOUD in Criminal-Legal Venues. There were no significant interactions by rural/urban status. DISCUSSION: The CTH Intervention reduced perceived barriers to scaling up OEND and MOUD in certain venues, with no difference in effectiveness between rural and urban communities. More research is needed to understand facilitators and barriers in different venues.

Governing the Access to COVID-19 Tools Accelerator: towards greater participation, transparency, and accountability.

The Access to COVID-19 Tools Accelerator (ACT-A) is a multistakeholder initiative quickly constructed in the early months of the COVID-19 pandemic to respond to a catastrophic breakdown in global cooperation. ACT-A is now the largest international effort to achieve equitable access to COVID-19 health technologies, and its governance is a matter of broad public importance. We traced the evolution of ACT-A's governance through publicly available documents and analysed it against three principles embedded in the founding mission statement of ACT-A: participation, transparency, and accountability. We found three challenges to realising these principles. First, the roles of the various organisations in ACT-A decision making are unclear, obscuring who might be accountable to whom and for what. Second, the absence of a clearly defined decision making body; ACT-A instead has multiple centres of legally binding decision making and uneven arrangements for information transparency, inhibiting meaningful participation. Third, the nearly indiscernible role of governments in ACT-A, raising key questions about political legitimacy and channels for public accountability. With global public health and billions in public funding at stake, short-term improvements to governance arrangements can and should now be made. Efforts to strengthen pandemic preparedness for the future require attention to ethical, legitimate arrangements for governance.

Fight, flight, and free will: The effect of trauma informed psychoeducation on perceived culpability and punishment for juvenile and adult offenders.

Justifications for punishment are generally grounded in retribution or consequentialism. Retribution is rooted in and legitimized by common sense notions of free will, claiming that offenders freely and rationally choose to commit a criminal act, and are therefore deserving of punishment. Consequentialism does not necessitate a reliance on a belief in free will, and views punishment as means to a valuable end. In recent years, neuroscientific research has challenged the notion of free will, providing one pathway for a public shift away from retribution and towards consequentialism. To date, no studies have examined whether educating participants about biopsychosocial effects of trauma that are often outside of conscious awareness may contribute to free will doubt. This study used a 2 (biopsychosocial information, neutral information) × 2 (juvenile offender, adult offender) between subjects design and measured beliefs in free will, judgments of culpability, and justifications for punishment. Results showed a main effect of trauma informed psychoeducation on free will beliefs, such that individuals who watched a trauma video had lower free will beliefs compared to individuals who watched a control video. Direct effects of trauma informed psychoeducation on sentence severity and on justifications for punishment were nonsignificant. However, mediation analyses revealed that free will beliefs had an indirect effect on the relations between trauma informed psychoeducation and perceived culpability and that perceived culpability had an indirect effect on the relations between trauma informed psychoeducation and retribution, consequentialism, and punishment severity.

Self-Compassion, Social Constraints, and Psychosocial Outcomes in a Pet Bereavement Sample.

This study investigated self-compassion in the context of grief following the death of a companion animal in a recently bereaved sample (N = 431). We addressed social contexts and individual differences focusing on how psychosocial outcomes vary as a function of social constraints, as well as individual differences in self-compassion and use of continuing bonds (CB). We observed that self-compassion related to the frequency of engagement in CB. Self-compassion also moderated relationships between grief severity and depression as well as social constraints and depression. We recommend future research on self-compassion training and psychosocial outcomes, especially for those experiencing social constraints or disenfranchised grief.

International best practice for the evaluation of responsiveness to sapropterin dihydrochloride in patients with phenylketonuria.

Phenylketonuria (PKU) is an inherited metabolic disease caused by phenylalanine hydroxylase (PAH) deficiency. As the resulting high blood phenylalanine (Phe) concentration can have detrimental effects on brain development and function, international guidelines recommend lifelong control of blood Phe concentration with dietary and/or medical therapy. Sapropterin dihydrochloride is a synthetic preparation of tetrahydrobiopterin (6R-BH4), the naturally occurring cofactor of PAH. It acts as a pharmacological chaperone, reducing blood Phe concentration and increasing dietary Phe tolerance in BH4-responsive patients with PAH deficiency. Protocols to establish responsiveness to sapropterin dihydrochloride vary widely. Two meetings were held with an international panel of clinical experts in PKU management to develop recommendations for sapropterin dihydrochloride response testing. At the first meeting, regional differences and similarities in testing practices were discussed based on guidelines, a literature review, outcomes of a global physician survey, and case reports. Statements developed based on the discussions were sent to all participants for consensus (>70% of participants) evaluation using a 7-level rating system, and further discussed during the second meeting. The experts recommend sapropterin dihydrochloride response testing in patients with untreated blood Phe concentrations of 360-2000 µmol/L, except in those with two null mutations. For neonates, a 24-h sapropterin dihydrochloride loading test is recommended; responsiveness is defined as a decrease in blood Phe ≥30%. For older infants, children, adolescents, and adults, a test duration of ≥48 h or a 4-week trial is recommended. The main endpoint for a 48-h to 7-day trial is a decrease in blood Phe, while improved Phe tolerance is the endpoint to be assessed during a longer trial. Longer trials may not be feasible in some locations due to lack of reimbursement for hospitalization, while a 4-week trial may not be possible due to limited access to sapropterin dihydrochloride or public health regulation. A 48-h response test should be considered in pregnant patients who cannot achieve blood Phe ≤360 µmol/L with a Phe-restricted diet. Durability of response and clinical benefits of sapropterin dihydrochloride should be assessed over the long term. Harmonization of protocols is expected to improve identification of responders and comparability of test results worldwide.

Actual frequency of imaging during follow-up of testicular cancer in Israel-a comparison with the guidelines.

OBJECTIVES: Computed tomography (CT) examinations are frequent in follow-up care of testicular cancer (TC) but may increase the risk for other cancers. We wanted to assess the actual number of CT and X-ray examinations within the first 5 years after a diagnosis of TC in Israel during 2003-2007. METHODS: The database of Maccabi Healthcare Services, Israel, was searched for TC patients diagnosed in 2003 to 2007 by direct linkage with the Israel National Cancer Registry. Data on diagnostic imaging examinations (CT of chest, abdomen, or pelvis, unspecified sites; X-ray of chest) were extracted during a 5-year follow-up for 226 incident patients. The actual number of CT and X-ray examinations was compared to the National Comprehensive Cancer Network (NCCN) guideline. We tabulated the median with 10th and 90th percentiles (P10, P90) for the number of CTs and X-rays considering histology, stage, and adjuvant strategy. RESULTS: The number of abdomen or pelvis CTs for TC patients receiving chemo- or radiotherapy was in accordance with the NCCN guideline. The median of abdomen or pelvis CTs for surveillance patients was 8.5 (P10, P90: 3; 13) for nonseminoma and 5.0 (P10, P90: 5; 13) for seminoma patients compared to 14 to 17 CTs recommended. The number of chest X-rays was lower than recommended in the guideline for all adjuvant strategies. CONCLUSIONS: The NCCN guidelines regarding CTs were met for TC patients treated with chemo- or radiotherapy but fell below recommendations for surveillance. Guidelines from 2011 and 2012 were updated in favor of fewer CTs during surveillance. KEY POINTS: • The number of CTs followed the NCCN guidelines in patients treated with chemo- or radiotherapy. • Surveillance patients received fewer CTs and X-rays than recommended in the NCCN guidelines from 2005. • The number of applied CT examinations corresponded to a radiation dose that did not substantially raise the lifetime risk for cancer.

Associations of sociodemographic and clinical factors with perinatal depression among Israeli women: a cross-sectional study.

BACKGROUND: Perinatal depression is a common problem that affects about 18% of women worldwide, though the heterogeneity between countries is great. The aims of this study were to assess the prevalence of perinatal depressive symptoms in a national sample of women in Israel, and to investigate associations of these symptoms with demographic, medical and lifestyle factors. METHODS: The study included all members of Maccabi Health Services, the second largest health maintenance organization in Israel, who filled the Edinburgh Postnatal Depression Scale (EPDS) during 2015-2016. Crude odds ratios (ORs) and adjusted ORs (aORs) are presented for associations of sociodemographic, medical and lifestyle factors with perinatal depressive symptoms, according to a score ≥ 10 on the EPDS. RESULTS: Of 27,520 women who filled the EPDS, 1346 (4.9%) met the criteria for perinatal depression. In a logistic regression analysis we found the following factors associated with perinatal depression: the use of antidepressant medications (aOR = 2.34, 95% CI 1.94-2.82, P < 0.001 and aOR = 3.44; 95% CI 2.99-3.97, P < 0.001 for ≤3 months and > 3 months respectively), a diagnosis of chronic diabetes mellitus (aOR = 2.04; 95% CI 1.22-3.43, P = 0.007), Arab background (aOR = 2.28; 95% CI 1.82-2.86, P < 0.001), current and past smoking (aOR = 1.62; 95% CI 1.35-1.94, P < 0.001 and aOR = 1.36; 95% CI 1.05-1.76, P = 0.021, respectively), and anaemia (aOR = 1.17; 95% CI 1.04-1.32, P = 0.011). Orthodox Jewish affiliation and residence in the periphery of the country were associated with lower perinatal depression (aOR = 0.48; 95% CI 0.36-0.63, P < 0.001 and aOR = 0.72; 95% CI 0.57-0.92, P = 0.007, respectively). CONCLUSIONS: The prevalence of perinatal depression in this study was 4.9%. Perinatal depression was associated with a number of demographic, medical and lifestyle factors, including the use of antidepressant medication, chronic diabetes mellitus, Arab background, current or past smoking, and anaemia. These risk factors may help identify women at risk of perinatal depression.

Sea water desalination and removal of iodine: effect on thyroid function.

In Israel, about 55% of drinking water is derived from desalination (DSW) which removes all iodine. A recent study from Israel demonstrated high rates of iodine deficiency among school-aged children and pregnant women. There are concerns that low iodine may lead to impaired thyroid function. However, to date, the impact of consuming DSW on body iodine status has not been studied. The objective was to assess whether the increased use of DSW is associated with increased rates of hypothyroidism. Using data from a large health fund in Israel, we compared proportions of patients with higher than normal thyroid stimulating hormone (TSH), and lower than normal T3 and T4 levels before and after a massive desalination project became operational in August 2013 in areas with high vs. low use of DSW. Over 400,000 cases were compared in 2010-2013 vs. 2014-2016. Overall, there was no increase in the proportion of individuals with higher than normal TSH levels, or lower than normal T3 and T4 levels. In conclusion, in this population-based study, following the introduction of DSW, there was no evidence of increased incidence of low thyroid function tests, and the trends were similar in both areas highly consuming, or not consuming, DSW.

[RATES OF MICROCEPHALY AMONG NEONATES IN AIR POLLUTED REGIONS OF HAIFA BAY].

BACKGROUND: In 2016 Israeli news media reported preliminary results of research claiming higher incidence of microcephaly among newborns in air polluted areas in Haifa Bay. These news prompted high levels of anxiety and anger. OBJECTIVES: To quantify the incidence of microcephaly in Haifa Bay and compare it to the rest of Israel. METHODS: Employing Maccabi electronic health records to compare rates of microcephaly among neonates followed up in Maccabi's well-baby clinics to the same clinics in the rest of Israel. RESULTS: Mean head circumference percentile was similar in Haifa Bay and the rest of Israel (38.09+/- 26.42 vs 37.59+-25.62), as was the rate of microcephaly (4.92% vs. 4.83%). CONCLUSIONS: These findings do not support air pollution as an etiological factor of microcephaly in Haifa Bay. DISCUSSION: Air pollution is not associated with higher rates of microcephaly in Haifa Bay.

A Framework for Modeling Emerging Diseases to Inform Management.

The rapid emergence and reemergence of zoonotic diseases requires the ability to rapidly evaluate and implement optimal management decisions. Actions to control or mitigate the effects of emerging pathogens are commonly delayed because of uncertainty in the estimates and the predicted outcomes of the control tactics. The development of models that describe the best-known information regarding the disease system at the early stages of disease emergence is an essential step for optimal decision-making. Models can predict the potential effects of the pathogen, provide guidance for assessing the likelihood of success of different proposed management actions, quantify the uncertainty surrounding the choice of the optimal decision, and highlight critical areas for immediate research. We demonstrate how to develop models that can be used as a part of a decision-making framework to determine the likelihood of success of different management actions given current knowledge.

Impact of quadrivalent human papillomavirus vaccine on genital warts in an opportunistic vaccination structure.

OBJECTIVE: Genital warts are the most common sexually transmitted disease and have a detrimental impact on quality of life. Genital warts could be prevented by prophylactic HPV vaccination. The objective was to study real-life benefit of opportunistic HPV vaccination on age and gender specific incidence of genital warts. METHODS: We performed a register-based population cohort study from publicly funded health-care provider in Israel. The incidence of genital warts was assessed during three time frame intervals: 2006-2008 (pre-vaccination effect period) 2009-2012 (early post-vaccination effect period) and 2013-2015 (late post-vaccination effect period), with an average annual number of members of 1,765,481, 1,906,774 and 2,042,678 in the years 2006-2008, 2009-2012 and 2013-2015, respectively. RESULTS: Among females, annual incidence of genital warts per 100,000 women decreased from 210.43 to 161.71 (OR 0.76, 95%CI 0.71-0.82, p<0.001) and to 146.8 (OR 0.69, 95%CI 0.66-0.72, p<0.001) between pre-vaccination period and early and late post-vaccination periods, respectively. Among males, annual incidence of genital warts per 100,000 men decreased from 262.85 to 232.40 (OR 0.88, 95%CI 0.83-0.93, p<0.001) and to 234.01 (OR 0.88, 95%CI 0.86-0.91, p<0.001) between pre-vaccination period and early and late post-vaccination periods, respectively. CONCLUSIONS: There is a potential benefit in reducing incidence of genital warts even in opportunistic HPV vaccination structure. This information may be relevant for health-care providers in countries where national immunization programs do not include HPV vaccines.

Seawater desalination and serum magnesium concentrations in Israel.

With increasing shortage of fresh water globally, more countries are consuming desalinated seawater (DSW). In Israel >50% of drinking water is now derived from DSW. Desalination removes magnesium, and hypomagnesaemia has been associated with increased cardiac morbidity and mortality. Presently the impact of consuming DSW on body magnesium status has not been established. We quantified changes in serum magnesium in a large population based study (n = 66,764), before and after desalination in regions consuming DSW and in regions where DSW has not been used. In the communities that switched to DSW in 2013, the mean serum magnesium was 2.065 ± 0.19 mg/dl before desalination and fell to 2.057 ± 0.19 mg/dl thereafter (p < 0.0001). In these communities 1.62% of subjects exhibited serum magnesium concentrations ≤1.6 mg/dl between 2010 and 2013. This proportion increased by 24% between 2010-2013 and 2015-2016 to 2.01% (p = 0.0019). In contrast, no such changes were recorded in the communities that did not consume DSW. Due to the emerging evidence of increased cardiac morbidity and mortality associated with hypomagnesaemia, it is vital to consider re-introduction of magnesium to DSW.

Effective Research Mentorship for Residents: Meeting the Needs of Early Career Physicians.

OBJECTIVE: Challenges in pursuing research during residency may contribute to the shortage of clinician-scientists. Although the importance of mentorship in facilitating academic research careers has been described, little is understood about early career research mentorship for residents. The aim of this study was to better understand the mentorship process in the context of psychiatry residency. METHOD: Semi-structured interviews were conducted with experienced faculty mentors in a psychiatry department at a large academic medical center. Interviews were analyzed using inductive thematic analysis. Results from faculty interviews identified several key themes that were explored with an additional sample of resident mentees. RESULTS: Five themes emerged in our study: (1) being compatible: shared interests, methods, and working styles; (2) understanding level of development and research career goals in the context of residency training; (3) establishing a shared sense of expectations about time commitment, research skills, and autonomy; (4) residents' identity as a researcher; and (5) the diverse needs of a resident mentee. There was considerable congruence between mentor and mentee responses. CONCLUSIONS: There is an opportunity to improve research mentoring practice by providing guidance to both mentors and mentees that facilitates a more structured approach to the mentorship relationship.

Posttraumatic Growth Following the Loss of a Pet.

The current study examined posttraumatic growth (PTG) experienced by bereaved pet owners following the death of their pet. Using qualitative methodology, we analyzed responses of 308 participants who answered yes to a question about experiencing PTG. Within the five factors model of PTG, the most endorsed included the following: Relating to Others ( n = 76), Appreciation of Life ( n = 52), Personal Strength ( n = 51), Spiritual Change ( n = 32), and New Possibilities ( n = 29). Other themes not captured by the PTG included as follows: relating to animals ( n = 70), continuing bonds ( n = 53), attachment relationship ( n = 44), and unconditional love ( n = 13). Our findings support the notion that PTG occurs for people who have experienced pet loss, with new emergent themes.

Posttraumatic Growth Following the Loss of a Pet.

The current study examined Posttraumatic Growth (PTG) experienced by bereaved pet owners in the United States, French-Canada, Japan, and Hong Kong following the death of their pet. Using qualitative methodology, we analyzed responses of participants who answered "yes" to a question about experiencing PTG and explored to what extent the cross-cultural responses mapped onto the five factors of the Posttraumatic Growth Inventory (PTGI). For the U.S. sample, 58% of responses mapped onto the PTGI. For French-Canada, 72% of responses mapped onto the PTGI. For Japan, 50% of responses mapped onto the PTGI and for Hong Kong, 39% of responses mapped onto the PTGI. We also explored emergent categories related to PTG for individuals who have lost a pet and discerned the unique aspects for PTG across cultures.

Negotiating Hegemonic Masculinities and Mutual Exoticization within Grindr Tourism Interactions: "Everyone in Tel Aviv is a Muscle God".

Dating apps are spaces where masculinities are communicated digitally, affecting inequalities around gender expressions. This study aims to identify the masculinities communicated within Grindr tourism interactions in Tel Aviv and analyze how masculinities shape relations among international tourists and locals. Methods consist of interviews and audio diaries with nineteen tourist, local, and immigrant Grindr users in Tel Aviv. Theories of affordances, hegemonic masculinities, and relational sociology are used to analyze the data. In discussion of the results, the concept of mutual exoticization is put forth to interpret the social dynamics valued within Grindr tourism interactions, thereby revealing oppositional fantasies tied to nationalities and masculinities. The study also explores ethnicity's association with social and erotic capital in digital circulations of a localized Mizrahi masculinity. Findings reveal that while hegemonic masculinities are circulated on Grindr, resistance is also a part of Grindr tourism relations around masculinities. This research concludes by shedding light on masculinity inequalities within digital spaces where different nationalities co-congregate, revealing everyday negotiations of gender regimes. Grindr is the site of both reproduction of and resistance to social inequalities around masculinities.

Neurogenic Cell Behavior in 3D Culture Enhanced Within a Highly Compliant Synthetic Hydrogel Platform Formed via Competitive Crosslinking.

Purpose: Scaffold materials that better support neurogenesis are still needed to improve cell therapy outcomes for neural tissue damage. We have used a modularly tunable, highly compliant, degradable hydrogel to explore the impacts of hydrogel compliance stiffness on neural differentiation. Here we implemented competitive matrix crosslinking mechanics to finely tune synthetic hydrogel moduli within soft tissue stiffnesses, a range much softer than typically achievable in synthetic crosslinked hydrogels, providing a modularly controlled and ultrasoft 3D culture model which supports and enhances neurogenic cell behavior. Methods: Soluble competitive allyl monomers were mixed with proteolytically-degradable poly(ethylene glycol) diacrylate derivatives and crosslinked to form a matrix, and resultant hydrogel stiffness and diffusive properties were evaluated. Neural PC12 cells or primary rat fetal neural stem cells (NSCs) were encapsulated within the hydrogels, and cell morphology and phenotype were investigated to understand cell-matrix interactions and the effects of environmental stiffness on neural cell behavior within this model. Results: Addition of allyl monomers caused a concentration-dependent decrease in hydrogel compressive modulus from 4.40 kPa to 0.26 kPa (natural neural tissue stiffness) without influencing soluble protein diffusion kinetics through the gel matrix. PC12 cells encapsulated in the softest hydrogels showed significantly enhanced neurite extension in comparison to PC12s in all other hydrogel stiffnesses tested. Encapsulated neural stem cells demonstrated significantly greater spreading and elongation in 0.26 kPa alloc hydrogels than in 4.4 kPa hydrogels. When soluble growth factor deprivation (for promotion of neural differentiation) was evaluated within the neural stiffness gels (0.26 kPa), NSCs showed increased neuronal marker expression, indicating early enhancement of neurogenic differentiation. Conclusions: Implementing allyl-acrylate crosslinking competition reduced synthetic hydrogel stiffness to provide a supportive environment for 3D neural tissue culture, resulting in enhanced neurogenic behavior of encapsulated cells. These results indicate the potential suitability of this ultrasoft hydrogel system as a model platform for further investigating environmental factors on neural cell behavior. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-024-00794-2.