COVID-19-related flexibility in methadone take-home doses associated with decreased attrition: Report from an opioid treatment program in central Pennsylvania.

INTRODUCTION: Pennsylvania saw a dramatic increase in take-home doses of methadone after the COVID-19 pandemic-related relaxation in regulations. We evaluated whether pandemic-initiated relaxation in take-home methadone dose regulations was associated with changes in attrition and urine drug test (UDT) results at one outpatient opioid treatment program (OTP) among adult patients treated with methadone for opioid use disorder (OUD). METHODS: We analyzed aggregated, retrospective clinical practice data, using data abstracted from the OTP's electronic health record (EHR) on the number of patients treated with methadone, those allowed take-home doses, the number of take-home methadone doses dispensed, and the number and type of patient discharge ("attrition") from treatments for 12 months before (March 2019-February 2020; "pre-pandemic") and 12 months after (March 2020-February 2021; "pandemic") the regulatory changes took place. We also examined monthly aggregate data on the number of urine samples testing positive for amphetamines, cocaine, benzodiazepines or illicit opioids, and compared these findings between the pre-pandemic and pandemic periods. RESULTS: Pre-pandemic, 229 patients were treated with methadone, compared to 278 patients during the pandemic period. They received 11,047 and 28,563 take-home daily-doses of methadone (p < 0.0001) during each assessment period, respectively. All-cause treatment attrition (discharge from the program for any reason) decreased from 27.1 % in the pre-pandemic to 15.5 % in the pandemic period (p < 0.001). Compared to pre-pandemic, during the pandemic period the urine toxicology testing showed reduced positivity rates for cocaine (26.4 % vs 18.9 %, p < 0.001), and oxycodone and morphine (1.8 % vs 1.1 %, p < 0.019), and increased for fentanyl (24.0 % vs 30.5 %, p < 0.007), without statistically significant changes for benzodiazepines or amphetamines. CONCLUSIONS: The relaxation of regulations guiding take-home methadone doses accompanied reduced treatment attrition and favorable changes in urine toxicology results in one OTP. Allowing OTPs to apply flexible decisions regarding take-home methadone doses could improve treatment retention, outcomes, and, in turn, save lives.

Tumorigenicity Testing in Athymic Mice of Cultured Human Melanocytes for Transplantation in Engineered Skin Substitutes.

Autologous engineered skin substitutes (ESS) have been shown to close excised, full-thickness burns, but are consistently hypopigmented due to depletion of human melanocytes (hM) during culture of keratinocytes. Hypothetically, addition of hM to ESS may restore uniform pigmentation, but may also promote neoplasia and tumor formation. To evaluate this risk, 16 strains of hM were isolated and propagated in selective culture medium, then injected subcutaneously into athymic mice (1 × 10(7) hM/animal; n = 6/strain) and followed for 24 weeks. Human melanoma cells (SK-Mel-2, SK-Mel-5) served as positive controls. No detectable tumors formed from hM strains derived from normal skin. In contrast, SK-Mel-2 formed tumors in 50% of mice, and SK-Mel-5 formed tumors in 83% of mice. Histopathology confirmed the tumorigenic anatomy of the controls and the presence of hM that were not tumorigenic in the test groups. These results support the safety of cultured hM for transplantation to restore uniform skin pigmentation in wounds closed with ESS.

The importance of coral larval recruitment for the recovery of reefs impacted by cyclone Yasi in the central Great Barrier Reef.

Cyclone Yasi, one of the most severe tropical storms on record, crossed the central Great Barrier Reef (GBR) in February 2011, bringing wind speeds of up to 285 km hr⁻¹ and wave heights of at least 10 m, and causing massive destruction to exposed reefs in the Palm Island Group. Following the cyclone, mean (± S.E.) hard coral cover ranged from just 2.1 (0.2) % to 5.3 (0.4) % on exposed reefs and no reproductively mature colonies of any species of Acropora remained. Although no fragments of Acropora were found at impacted exposed sites following the cyclone, small juvenile colonies of Acropora (<10 cm diameter) were present, suggesting that their small size and compact morphologies enabled them to survive the cyclone. By contrast, sheltered reefs appeared to be unaffected by the cyclone. Mean (± S.E.) hard coral cover ranged from 18.2 (2.4) % to 30.0 (1.0) % and a large proportion of colonies of Acropora were reproductively mature. Macroalgae accounted for 8 to 16% of benthic cover at exposed sites impacted by cyclone Yasi but were absent at sheltered sites. Mean (± S.E.) recruitment of acroporids to settlement tiles declined from 25.3 (4.8) recruits tile⁻¹ in the pre-cyclone spawning event (2010) to 15.4 (2.2) recruits tile⁻¹ in the first post-cyclone spawning event (2011). Yet, post-cyclone recruitment did not differ between exposed (15.2±2.1 S.E.) and sheltered sites (15.6±2.2 S.E.), despite the loss of reproductive colonies at the exposed sites, indicating larval input from external sources. Spatial variation in impacts, the survival of small colonies, and larval replenishment to impacted reefs suggest that populations of Acropora have the potential to recover from this severe disturbance, provided that the Palm Islands are not impacted by acute disturbances or suffer additional chronic stressors in the near future.

Histone-like nucleoid-structuring protein represses transcription of the ehx operon carried by locus of enterocyte effacement-negative Shiga toxin-expressing Escherichia coli.

Shiga toxin-producing Escherichia coli (STEC) are a significant cause of zoonotic foodborne diarrheal disease in industrialized nations. In addition to Shiga toxin most STEC produce the enterohemolysin (EhxA) toxin. The EhxA toxin is encoded by the ehxCABD operon located on the large plasmid carried by STEC, yet its role in pathogenesis is unknown. A histone-like nucleoid-structuring protein (H-NS) null mutant of STEC O91:H21 strain B2F1 displayed a hyper-hemolytic phenotype, was defective in binding to human colonic epithelial cells, and was non-motile. We concluded that H-NS modulated expression of several genes in B2F1 including the ehx operon. Electrophoretic mobility shift assays indicate that H-NS binds to an 88bp region of DNA upstream of the ehxC start codon. To determine if the same region of DNA was sensitive to repression by H-NS, a transcriptional fusion was constructed between the putative promoter region of ehx and a promoterless lacZ gene. The beta-galactosidase activity detected was low in E. coli that produced H-NS but was significantly higher in the H-NS null background. Taken together, the data indicates that in STEC the 88bp region upstream of the ehx operon contains a cis-acting element to which H-NS binds and negatively regulates expression of enterohemolysin.

Doctors' new tool to fight lawsuits: saying 'I'm sorry.' Malpractice insurers find owning up to errors soothes patient anger. 'The risks are extraordinary'.

A lot of attention and energy has been spent over the past several years on reducing the amount of settlements and awards in malpractice cases. Of course these are important issues, but the best situation for physicians is not to be sued at all. Therefore, the medical community needs to start focusing on ways to prevent lawsuits from being filed in the first place. Recent studies and publications indicate that physicians may have more control over the lawsuit lottery than they realize. An article that appeared on the front page of the May 18, 2004 edition of the Wall Street Journal is reprinted below with permission. This article supports the proposition that the best tool to minimize the possibility of being sued may be as simple as expressing condolence and empathy when there is a bad outcome. The lawsuit reform bill that recently passed the Oklahoma legislature, H.B. 2661, contains an "I'm Sorry Law" that permits physicians to express condolence without those statements being used against them in court. For more information regarding the power of an apology, physicians may want to obtain the book by Michael S. Woods, M.D. (a speaker at the OSMA Physician Survival Summit) titled: "Healing Words: The Power of Apology in Medicine." The book can be obtained from: Doctors in Touch, 708.697.6447 or info@doctorsintouch.com.