Ending the War on People with Substance Use Disorders in Health Care

Earp et al. (2021) provide a robust justification for the decriminalization of drugs based on the systemic racism that fuels the “war on drugs” and the ongoing harms of drug policies to individuals. The authors’ call for decriminalization is a necessary but insufficient step in addressing the entrenched structural, institutional, and individual discrimination that leads to the inequitable and unjust treatment of people with substance use disorder (PWSUD). Nothing short of robust enforcement of existing legal protections and sweeping legal reforms in the regulation of addiction treatment, controlled substances, health care finance, and civil rights law will be adequate to achieve equity and remedy the malignant injustice in this area. This commentary addresses the widespread subrogation of PWSUD in the health care system, which is characterized by the disempowerment, disparagement, and sometimes outright abandonment of patients—a persistent pattern of mistreatment that would spark outrage and condemnation for people with any other health condition

Substance Use Disorder, Discrimination, and The CARES Act: Using Disability Law to Strengthen New Protections

The COVID-19 pandemic is having devastating consequences for people with substance use disorders (SUD). SUD is a chronic health condition—like people with other chronic health conditions, people with SUD experience periods of remission and periods of exacerbation and relapse. Unlike people with most other chronic conditions, people with SUD who experience a relapse may face criminal charges and incarceration. They are chronically disadvantaged by pervasive social stigma, discrimination, and structural inequities. People with SUD are also at higher risk for both contracting the SARS-CoV-19 virus and experiencing poorer outcomes. Meanwhile, there are early indications that pandemic conditions have led to new and increased drug use, and overdose deaths are surging. More than ever, people with SUDs need access to evidence-based treatment and other services without structural barriers and with civil rights protections. To that end, a new provision in the Coronavirus Aid, Relief, and Economic Securities Act (CARES Act) strengthens penalties for the wrongful disclosure of SUD treatment records as well as addresses discrimination in multiple settings based on the misuse of those records. People with SUD reasonably fear negative treatment and discrimination if their condition is exposed. To address this barrier, federal law strictly protects the confidentiality of SUD treatment records. These protections have existed for nearly 50 years; however, the stringent requirements have been blamed for hampered and even deadly treatment decisions by health care providers who do not have access to SUD treatment records. Section 3221 of the CARES Act, effective March 2021, enacts the first major statutory changes to SUD treatment record confidentiality since 1992 and is aimed at improving information sharing among SUD treatment providers and other health care providers. But increased information sharing also creates concerns about information misuse and discrimination, and the possibility of renewed treatment avoidance. To address the tension between the benefits of information sharing and the possible harms of discrimination after disclosure, Section 3221 strengthens the disclosure penalties to align with HIPAA. It also adds an entirely new nondiscrimination provision which prohibits discriminatory use by recipients of disclosed SUD treatment information in areas including health care, employment and receipt of worker’s compensation, rental or sale of housing, access to courts, and social services and benefits funded by federal, state, or local governments. This essay provides the first analysis of the new nondiscrimination protections in Section 3221 of CARES Act for individuals with SUD using the framework of existing protections against disability-based discrimination in the Americans with Disabilities Act, Section 504 of the Rehabilitation Act, Section 1557 of the Patient Protection and Affordable Care Act, and the Fair Housing Act. We propose that as the new protections of Section 3221 are implemented through regulations, guidance, and enforcement, they should be understood within the context of existing disability nondiscrimination laws as well as the specific purpose of Section 3221 to ensure that discrimination against such people does not continue to serve as a barrier to seeking treatment. We offer three insights to achieve this goal. First, the new protections should be understood to include current illegal substance users and should be construed broadly. Second, the scope of entities covered by the new protections should be interpreted consistently with existing definitions in laws that prohibit disability-based discrimination in employment, public programs, services, and activities, health care, and housing. Finally, robust enforcement must be coupled with educational initiatives about the pervasive discrimination faced by people with SUDs, and new and existing nondiscrimination requirements that protect them

Substance Use Disorder Discrimination and The CARES Act: Using Disability Law to Inform Part 2 Rulemaking

Substance use disorder (SUD) is a chronic health condition—like people with other chronic health conditions, people with SUDs experience periods of remission and periods of exacerbation or recurrence. Unlike people with most other chronic conditions, people with SUDs may be more likely to garner law enforcement attention than medical attention during a recurrence. They are also chronically disadvantaged by pervasive social stigma, discrimination, and structural inequities. The COVID-19 pandemic has had devastating consequences for people with SUDs, who are at higher risk for both contracting the SARS-CoV-19 virus and experiencing poorer outcomes. Meanwhile, there are early indications that pandemic conditions have led to new and increased drug use, and overdose deaths are surging. More than ever, people with SUDs need access to evidence-based treatment and other services without structural barriers and with civil rights protections. To that end, a new provision in the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) strengthens penalties for the wrongful disclosure of SUD treatment records as well as addresses discrimination in multiple settings based on the misuse of those records. People with SUDs reasonably fear negative treatment and discrimination if their condition is exposed. To address this barrier, federal law strictly protects the confidentiality of SUD treatment records. These protections have existed for nearly fifty years; however, the stringent requirements have been blamed for hampered and even deadly treatment decisions by health care providers who do not have access to SUD treatment records. Section 3221 of the CARES Act, effective March 2021, enacts the first major statutory changes to SUD treatment record confidentiality since 1992 and is aimed at improving information sharing among SUD treatment providers and other health care providers. But increased information sharing also creates concerns about information misuse and discrimination and the possibility of renewed treatment avoidance. To address the tension between the benefits of information sharing and the possible harms of discrimination after disclosure, Section 3221 strengthens the disclosure penalties to align with the Health Insurance Portability and Accountability Act of 1996 (HIPAA). It also adds an entirely new nondiscrimination provision, which prohibits discriminatory use by recipients of disclosed SUD treatment information in areas including health care; employment and receipt of worker’s compensation; rental or sale of housing; access to courts; and social services and benefits funded by federal, state, or local governments. This essay provides the first analysis of the new nondiscrimination protections in Section 3221 of the CARES Act for individuals with SUDs using the framework of existing protections against disability-based discrimination in the Americans with Disabilities Act (ADA), Section 504 of the Rehabilitation Act, Section 1557 of the Patient Protection and Affordable Care Act (ACA), and the Fair Housing Act (FHA). We propose that as the new protections of Section 3221 are implemented through regulations, guidance, and enforcement, they should be understood within the context of existing disability nondiscrimination laws as well as the specific purpose of Section 3221 to ensure that discrimination against such people does not continue to serve as a barrier to seeking treatment. We offer three insights to achieve this goal. First, the new protections should be understood to include current illegal substance users and should be construed broadly. Second, the scope of entities covered by the new protections should be interpreted consistently with existing definitions in laws that prohibit disability-based discrimination in employment; public programs, services and activities; health care; and housing. Finally, robust enforcement must be coupled with educational initiatives about the pervasive discrimination faced by people with SUDs and new and existing nondiscrimination requirements that protect them

Congenital monocular elevation deficiency associated with a novel TUBB3 gene variant

Background The genetic basis of monocular elevation deficiency (MED) is unclear. It has previously been considered to arise due to a supranuclear abnormality.Methods Two brothers with MED were referred to Leicester Royal Infirmary, UK from the local opticians. Their father had bilateral ptosis and was unable to elevate both eyes, consistent with the diagnosis of congenital fibrosis of extraocular muscles (CFEOM). Candidate sequencing was performed in all family members.Results Both affected siblings (aged 7 and 12 years) were unable to elevate the right eye. Their father had bilateral ptosis, left esotropia and bilateral limitation of elevation. Chin up head posture was present in the older sibling and the father. Bell’s phenomenon and vertical rotational vestibulo-ocular reflex were absent in the right eye for both children. Mild bilateral facial nerve palsy was present in the older sibling and the father. Both siblings had slight difficulty with tandem gait. MRI revealed hypoplastic oculomotor nerve. Left anterior insular focal cortical dysplasia was seen in the older sibling. Sequencing of TUBB3 revealed a novel heterozygous variant (c.1263G>C, p.E421D) segregating with the phenotype. This residue is in the C-terminal H12 α-helix of β-tubulin and is one of three putative kinesin binding sites.Conclusion We show that familial MED can arise from a TUBB3 variant and could be considered a limited form of CFEOM. Neurological features such as mild facial palsy and cortical malformations can be present in patients with MED. Thus, in individuals with congenital MED, consideration may be made for TUBB3 mutation screening

Development of Cancer Surveillance Guidelines in Ataxia Telangiectasia: A Delphi-Based Consensus Survey of International Experts

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents\u27 professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres\u27. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials

Performance characteristics of methods for quantifying spontaneous intracerebral haemorrhage: data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial

Background: Poor prognosis after intracerebral haemorrhage (ICH) is related to haemorrhage characteristics. Along with developing therapeutic interventions, we sought to understand the performance of haemorrhage descriptors in large clinical trials.Methods: Clinical and neuroimaging data were obtained for 548 participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Independent observers performed visual categorisation of the largest diameter, measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS), fully automatic measurement methods; shape, density and intraventricular haemorrhage were also assessed. Intraobserver and interobserver reliability were determined for these measures.Results: ICH volume was significantly different among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2), 12.8 (13.1) cm3, respectively (p less than 0.0001). There was excellent agreement for haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation coefficient (ICC) 0.96–0.97, interobserver ICC 0.88; modified ABC/2 intraobserver ICC 0.95–0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95–0.99, interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82, (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC 0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC 0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly correlated. Using modified ABC/2, ICH volume was underestimated in regular (by 2.2-2.5 cm3, p less than 0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm3, p less than 0.0001). Fully automated measurement of haemorrhage volume was possible in only 5% of cases.Conclusions: Formal measurement of haemorrhage characteristics and visual estimates are reproducible. The standard ABC/2 method is superior to the modified ABC/2 method for quantifying ICH volume

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population