The impact of spikes in handgun acquisitions on firearm-related harms.

BackgroundResearch has documented sharp and short-lived increases in firearm acquisitions immediately following high-profile mass shootings and specific elections, increasing exposure to firearms at the community level. We exploit cross-city variation in the estimated number of excess handgun acquisitions in California following the 2012 presidential election and the Sandy Hook school shooting 5 weeks later to assess whether the additional handguns were associated with increases in the rate of firearm-related harms at the city level.MethodsWe use a two-stage modeling approach. First, we estimate excess handguns as the difference between actual handgun acquisitions, as recorded in California's Dealer Record of Sales, and expected acquisitions, as predicted by a seasonal autoregressive integrated moving-average (SARIMA) time series model. We use Poisson regression models to estimate the effect of city-level excess handgun purchasing on city-level changes in rates of firearm mortality and injury.ResultsWe estimate there were 36,142 excess handguns acquired in California in the 11 weeks following the election (95% prediction interval: 22,780 to 49,505); the Sandy Hook shooting occurred in week 6. We find city-level purchasing spikes were associated with higher rates of firearm injury in the 52 weeks post-election: a relative rate of 1.044 firearm injuries for each excess handgun per 1,000 people (95% CI: 1.000 to 1.089). This amounts to approximately 290 (95% CI: 0 to 616) additional firearm injuries (roughly a 4% increase) in California over the year. We do not detect statistically significant associations for shorter time windows or for firearm mortality.ConclusionThis study provides evidence for an association between excess handgun acquisitions following high-profile events and firearm injury at the community level. This suggests that even marginal increases in handgun prevalence may be impactful

Researcher-Practitioner Partnerships to Implement and Evaluate Sexual and Relationship Violence Prevention Programs for Boys and Men.

Although male-focused sexual and relationship violence (SRV) prevention programs are widely promulgated, limited guidance concerning how programs should be implemented for rigorous evaluation exists. To help develop evidence for such guidance, this paper reports on 20 interviews with leaders at youth-serving community-based organizations (CBOs) and educational institutions, which are sites for male-focused SRV prevention programs. This study examined: (1) how programs can be designed to engage male participants; and (2) how youth-serving CBOs and educational institutions can partner with researchers for evaluations. Findings underscore the importance of attending to the unique needs of program participants, their parents/guardians, and host organizations

Associations between implementation of Project Lazarus and opioid analgesic dispensing and buprenorphine utilization in North Carolina, 2009–2014

Background Project Lazarus (PL) is a seven-strategy, community-coalition-based intervention designed to reduce opioid overdose and dependence. The seven strategies include: community education, provider education, hospital emergency department policy change, diversion control, support programs for patients with pain, naloxone policies, and addiction treatment expansion. PL was originally developed in Wilkes County, NC. It was made available to all counties in North Carolina starting in March 2013 with funding of up to $34,400 per county per year. We examined the association between PL implementation and 1) overall dispensing rate of opioid analgesics, and 2) utilization of buprenorphine. Buprenorphine is often used in connection with medication assisted treatment (MAT) for opioid dependence. Methods Observational interrupted time series analysis of 100 counties over 2009–2014 (n = 7200 county-months) in North Carolina. The intervention period was March 2013–December 2014. 74 of 100 counties implemented the intervention. Exposure data sources comprised process surveys, training records, Prescription Drug Monitoring Program (PDMP) data, and methadone treatment program quality data. Outcomes were PDMP-derived counts of opioid prescriptions and buprenorphine patients. Incidence Rate Ratios were estimated with adjusted GEE Poisson regression models of all seven PL strategies. Results In adjusted models, diversion control efforts were positively associated with increased dispensing of opioid analgesics (IRR: 1.06; 95% CI: 1.03, 1.09). None of the other PL strategies were associated with reduced prescribing of opioid analgesics. Support programs for patients with pain were associated with a non-significant decrease in buprenorphine utilization (IRR: 0.93; 95% CI: 0.85, 1.02), but addiction treatment expansion efforts were associated with no change in buprenorphine utilization (IRR: 0.98; 95% CI: 0.91, 1.06). Conclusions Implementation of PL strategies did not appreciably reduce opioid dispensing and did not increase buprenorphine utilization. These results are consistent with previous findings of limited impact of PL strategies on overdose morbidity and mortality. Future studies should analyze the uptake of MAT using a more expansive view of institutional barriers, treating community coalition activity around MAT as an effect modifier

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID‐19 during the course of the pandemic

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p =.02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p =.032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0–2.6, p =.04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0–11.3, p =.05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p <.001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98, p =.016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p <.001 and 50/571 [8.8%] vs. 213/402 [52.2%], p <.001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p <.001 and 73/571 [12.8%] vs. 5/402 [1.2%], p <.001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study

Replacement of Tyr-SO3H by a p-carboxymethyl-phenylalanine in a CCK8-derivative preserves its high affinity for CCK-B receptor.

International audienceThe sulfated tyrosine present in the sequence of CCK8 Asp26-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2, seems to play a critical role in the recognition of CCK-A binding sites. In this work, we have investigated whether the presence of an anionic charge on the tyrosine moiety is strictly necessary and whether the sulfate moiety interacts with a divalent cation in the receptor subsite. For this purpose, the novel amino acids (L,D)Phe(p-CH2CO2H) and (L,D) Phe(p-CH2CONHOH), as well as their L-resolved forms were introduced into the sequence of Ac[X27, Nle28, Nle31]-CCK27-33 by solid phase method. The biological activities of these new derivatives were compared to two almost equiactive analogues of CCK8, Ac[Phe(p-CH2SO3H)27, Nle28, Nle31]-CCK27-33 and Boc[Nle28, Nle31]-CCK27-33 (BDNL) and to the nonsulfated analogue of the latter peptide (BDNL NS). All these new CCK-related analogues behave as agonists in stimulating pancreatic amylase release and display high affinity for brain binding sites (KI approximately 3-11 nM) but the only peptides which retain affinity for CCK-A receptors (KI approximately 20 nM) are those containing a p-carboxymethyl phenylalanine. Thus, introduction of this amino acid under an esterified form on the side chain, into specific and potent CCK-B agonists could allow compounds endowed with good bioavailabilities to be obtained.The sulfated tyrosine present in the sequence of CCK8 Asp26-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2, seems to play a critical role in the recognition of CCK-A binding sites. In this work, we have investigated whether the presence of an anionic charge on the tyrosine moiety is strictly necessary and whether the sulfate moiety interacts with a divalent cation in the receptor subsite. For this purpose, the novel amino acids (L,D)Phe(p-CH2CO2H) and (L,D) Phe(p-CH2CONHOH), as well as their L-resolved forms were introduced into the sequence of Ac[X27, Nle28, Nle31]-CCK27-33 by solid phase method. The biological activities of these new derivatives were compared to two almost equiactive analogues of CCK8, Ac[Phe(p-CH2SO3H)27, Nle28, Nle31]-CCK27-33 and Boc[Nle28, Nle31]-CCK27-33 (BDNL) and to the nonsulfated analogue of the latter peptide (BDNL NS). All these new CCK-related analogues behave as agonists in stimulating pancreatic amylase release and display high affinity for brain binding sites (KI approximately 3-11 nM) but the only peptides which retain affinity for CCK-A receptors (KI approximately 20 nM) are those containing a p-carboxymethyl phenylalanine. Thus, introduction of this amino acid under an esterified form on the side chain, into specific and potent CCK-B agonists could allow compounds endowed with good bioavailabilities to be obtained