The United Nation’s Sustainable Development Goals (SDGs) 7 (Affordable and Clean Energy), 9 (Industry, Innovation and Infrastructure), and 11 (Sustainable Cities and Communities) focus on the responsible use of energy across all industries in order to fight climate change and associated health consequences, with construction at the forefront. Throughout their life cycle, buildings emit significant amounts of carbon dioxide into the atmosphere, aggravating the greenhouse effect ¹; healthcare buildings have a particularly large impact on the environment given their 24/7 utilization. In addition to adapting their structure and infrastructure to climate change-related phenomena, the carbon footprint of healthcare can be mitigated through green hospital design and construction practices rooted in creative, innovative solutions ².

First, hospitals should ideally be built using environmentally sustainable materials acquired in energy-efficient manners. Cement has been used for most buildings since the 1940’s due to its convenience and relatively low cost: However, it requires substantial energy to prepare, releasing significant amounts of carbon dioxide into the atmosphere during the fuel-intensive kiln heating process required to make it – cement production alone accounted for 7% of total carbon dioxide emissions in 2019 ³. Carbon dioxide release from cement use can be curbed by using more efficient kilns, a lower clinker-to-cement ratio, or lower-carbon fuels. To this end, Germany’s HeidelbergCement aims to establish the world’s first carbon neutral cement plant by 2030 by both increasing the proportion of biomass fuel used to run the plant, all the while using carbon capture technologies to reduce its net carbon emissions⁴ – such efforts play a significant part in green hospital construction. In parallel, painting materials containing lead or cadmium should be avoided, as should any materials harboring persistent bio-accumulative toxic chemicals, including various types of plastics and flame retardants. Finally, construction materials should be acquired in an environmentally friendly way, such as by using local materials or renewable energy-fueled modes of transport ⁵.

Second, hospital design must be as energy efficient as possible. To this end, buildings should be engineered such as to maximize the use of daylight (for example, with many windows and South-facing if in the Northern hemisphere), while certain species of plants can be used to absorb pollution in a natural manner. Energy management systems should be established that leverage onsite renewable energy sources.

Finally, hospitals can be designed such as to respect and improve the local ecosystem: high reflectance roofing or “green roof” systems can be used in order to increase the albedo effect, reduce urban heat, and manage stormwater while promoting local ecosystems. In addition, local biodiversity in the form of floral and faunal life should be assessed and protected in the construction of healthcare facilities: These should be deliberately designed such as to respect and be best integrated into their local natural contexts.

Buoying such efforts, a number of countries to date have developed healthcare building-specific rating systems providing an effective framework to probe building environmental performance and integrate sustainable development into their construction. These systems, such as the United Kingdom’s BREEAM (Building Research Establishment’s Environmental Assessment Method), the United States’ LEED (Leadership in Energy and Environmental Design), and Australia’s GREEN STAR rating system, address all aspects of building construction, including but not limited to management, health and wellbeing, pollution, and land use and ecology ⁶.

Both within the United States and globally, a shift in standards will be required to ensure green hospital construction and a lower carbon footprint. New structural codes should be designed and adopted to promote decarbonized construction processes and energy-efficient buildings, potentially supported by government-regulated mandatory smart-building certifications or financial incentives to individuals and organizations.

References

1. Lu, K. & Wang, H. Estimation of Building’s Life Cycle Carbon Emissions Based on Life Cycle Assessment and Building Information Modeling: A Case Study of a Hospital Building in China. J. Geosci. Environ. Prot. (2019). doi:10.4236/gep.2019.76013
2. Khahro, S. H. et al. Optimizing energy use, cost and carbon emission through building information modelling and a sustainability approach: A case-study of a hospital building. Sustain. (2021). doi:10.3390/su13073675
3. Factbox-Cement: the carbon cost of construction | Reuters. Available at: https://www.reuters.com/article/climate-cement-factbox/factbox-cement-the-carbon-cost-of-construction-idUSKBN2H80D2.
4. HeidelbergCement to build the world’s first carbon-neutral cement plant. Available at: https://www.heidelbergcement.com/en/pr-02-06-2021.
5. Danilov, A., Benuzh, A., Yeye, O., Compaore, S. & Rud, N. Design of healthcare structures by green standards. doi:10.1051/e3sconf/202016405002
6. Green Assessment Criteria for Public Hospital Building Development in Malaysia | Elsevier Enhanced Reader.

A new SARS-CoV-2 variant, B.1.1.529 a.k.a. Omicron, was recently reported to the World Health Organization (WHO) after being first detected on November 11, 2021 in Botswana and shortly thereafter in South Africa. The variant was identified in the U.S. on December 1, 2021, and in close to 60 countries spanning every continent except Antarctica since ¹.

The Omicron variant has been classified as a variant of concern by the WHO, primarily reflecting predictions and preliminary data of increased transmissibility. The estimated doubling time for Omicron cases reaches as little as 2 days, while its estimated reproduction (R) number is above 2, meaning that every person infected with this variant is expected to, on average, infect at least 2 others. This is consistent with current COVID-19 spreading dynamics in South Africa’s Gauteng province, whereby the early doubling time in this fourth COVID-19 wave has exceeded that of all three previous waves ².

This variant harbors a number of deletions and over 30 mutations, a few of which overlap with those found in the Alpha, Beta, Gamma, and Delta SARS-CoV-2 variants. It is distinguished by two genetically differentiated lineages, BA.1 and BA.2, that may behave quite differently.

For the BA.1 Omicron variant, one of the three genes targeted in a common PCR test is not detected (in a phenomenon known as S-gene target failure), similar to that observed for the Alpha variant ³. This PCR test can thus be used to identify infections by this variant while awaiting confirmation from sequencing. However, BA.2 Omicron, or the “stealth variant”, does not harbor this genetic signature and is thus not distinguishable from other variants by PCR.

Anecdotal reports from South African clinicians highlight that patients infected with Omicron tend to be younger individuals than the previous norm for COVID-19 infections. Many individuals having already survived COVID-19 still fall ill from a new infection, and researchers have estimated that the risk of reinfection with Omicron is five times greater than that with other variants. However, infected patients have so far presented with a clinical phenotype similar to that of past COVID-19  variants ⁴.

A recent Pfizer-BioNTech study found that, since 80% of the spike protein regions targeted by CD8+ T cells remain unchanged in the Omicron variant, two doses of its mRNA-based BNT152b2 vaccine are able to induce protection against severe Omicron-associated disease. In addition, a third dose of the vaccine can neutralize antibody titers 25 times more strongly than can two doses – emphasizing the continued importance of booster shots ⁵. In parallel, the mRNA-based Moderna vaccine is being tweaked to better neutralize the Omicron variant. Robust data remains to be collected with regard to the efficacy of other vaccines against this variant.

To date, monoclonal antibodies as well as antiviral treatments (e.g. remdesevir and molnupiravir, which respectively target the virus’ RNA polymerase and other proteins which have remained mostly unchanged) are expected to remain effective in the treatment of an Omicron variant infection.

Researchers are developing predictive models of the Omicron variant’s epidemiological dynamics in the next few months. Meanwhile, in the U.S., the Centers for Disease Control (CDC) are using genomic surveillance tools to monitor all SARS-CoV-2 variants in order to best inform public health policies. It is best, in the meantime, that individuals continue to protect themselves and others by getting vaccinated, including with booster shots, while maintaining safe distancing, keeping windows open when possible to improve ventilation, and wearing masks.

References

1. Omicron Variant: What You Need to Know | CDC. Available at: https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron-variant.html.
2. Karim, S. S. A. & Karim, Q. A. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet (London, England) 398, 2126–2128 (2021). doi: 10.1016/S0140-6736(21)02758-6.
3. Volz, E. et al. Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature 593, 266–269 (preprint). doi: 10.1101/2020.12.30.20249034.
4. Frequently asked questions for the B.1.1.529 mutated SARS-CoV-2 lineage in South Africa – NICD. Available at: https://www.nicd.ac.za/frequently-asked-questions-for-the-b-1-1-529-mutated-sars-cov-2-lineage-in-south-africa/.
5. Pfizer and BioNTech Provide Update on Omicron Variant | Business Wire. Available at: https://www.businesswire.com/news/home/20211208005542/en/.
6. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. Available at: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern.

Buprenorphine is a semi-synthetic opioid derived from the opioid thebaine. [1] Buprenorphine was originally developed to provide analgesia but is much more commonly used for the management of opioid dependence. [2] It functions as a partial agonist for the mu receptor, to which addictive opioids bind, and can thus manage opioid addiction by decreasing the physiological responses typically associated with opioid tolerance. It produces effects such as euphoria and respiratory depression at low to moderate doses, but the effects are much less significant than those produced by opioids such as heroin. [3]

Buprenorphine may be better known for its use in treating opioid overuse disorder, but it is also effective  at providing analgesia. In 2018, Aiyer et al. reviewed the literature on the efficacy of five different buprenorphine formulations in patients with chronic pain. [4] The researchers found that 14 of the 25 studies they reviewed showed a clinically significant benefit in the treatment of chronic pain by buprenorphine. Transdermal (application through the skin) buprenorphine was the most effective form of treatment, producing greater pain relief than intravenous, sublingual (applied under the tongue), and buccal (cheek) buprenorphine. According to Leffler et al., transdermal buprenorphine is ideal due to the drug’s low molecular weight, high lipophilicity, and high potency: these characteristics facilitate transdermal absorption. [5]

Buprenorphine is the first medication to treat opioid overuse disorder that can be prescribed in physicians’ offices, as per the Drug Addiction Treatment Act of 2000. [3] Physicians must receive approval from the Substance Abuse and Mental Health Services Administration before administering buprenorphine and must undergo training should they wish to simultaneously treat more than 30 patients with the opioid, but the fact that it can be administered in settings other than opioid treatment programs greatly increases access to treatment. [3]

Prior to the introduction of buprenorphine, methadone was commonly used to treat opioid overuse disorder. Unlike buprenorphine, methadone is a full agonist for the mu opioid receptor and causes higher levels of euphoria and analgesia, increasing the likelihood that patients treated with methadone will experience severe withdrawal when treatment stops. [6] Buprenorphine has a “ceiling effect,” which means that its effects plateau at higher concentrations.

Like virtually any opioid, buprenorphine can be abused, which may lead to the development of tolerance and withdrawal. The data on buprenorphine abuse, however, have been thus far encouraging. In 2019, nearly three-fourths of American adults using buprenorphine did not misuse the drug in the past 12 months. [7] Additionally, buprenorphine abuse decreased during 2015-2019, despite an increase in the number of people receiving buprenorphine treatment.

Patients presenting to the emergency room with untreated opioid overuse disorder often require high doses of buprenorphine. Herring et al. recently found that buprenorphine doses exceeding 12 mg very rarely caused respiratory depression, excessive sedation, or withdrawal. [8] Buprenorphine is also used in emergency medicine to treat opioid withdrawal. While rarely life-threatening, withdrawal can be extremely uncomfortable, and buprenorphine can provide relief by inducing mild and long-lasting euphoric effects. [9] Emergency departments, as well as general physicians and opioid treatment programs, have used buprenorphine extensively in the past two decades, to the great benefit of their patients.

References 

1. Jasinski, D. R., Pevnick, J. S. & Griffith, J. D. Human Pharmacology and Abuse Potential of the Analgesic Buprenorphine: A Potential Agent for Treating Narcotic Addiction. Arch. Gen. Psychiatry 35, 501–516 (1978). 

2. Welsh, C. & Valadez-Meltzer, A. Buprenorphine. Psychiatry Edgmont2, 29–39 (2005). 

3. Buprenorphine. https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine.

4. Aiyer, R., Gulati, A., Gungor, S., Bhatia, A. & Mehta, N. Treatment of Chronic Pain With Various Buprenorphine Formulations: A Systematic Review of Clinical Studies. Anesth. Analg.127, 529–538 (2018). 

5. Leffler, A.et al.Local Anesthetic-like Inhibition of Voltage-gated Na+Channels by the Partial μ-opioid Receptor Agonist Buprenorphine. Anesthesiology 116, 1335–1346 (2012). 

6. Whelan, P. J. & Remski, K. Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds. J. Neurosci. Rural Pract.3, 45–50 (2012). 

7. Abuse, N. I. on D. Buprenorphine misuse decreased among U.S. adults with opioid use disorder from 2015-2019. National Institute on Drug Abuse. https://www.drugabuse.gov/news-events/news-releases/2021/10/buprenorphine-misuse-decreased-among-us-adults-with-opioid-use-disorder-from-2015-2019 (2021). 

8. Herring, A. A.et al.High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder. JAMA Netw. Open 4, e2117128 (2021). 

9. Herring, A. A., Perrone, J. & Nelson, L. S. Managing Opioid Withdrawal in the Emergency Department With Buprenorphine. Ann. Emerg. Med.73, 481–487 (2019). 

While COVID-19 vaccines confer a certain degree of immunity to the virus, they are not 100% effective in all cases ¹. As such, there remains a need to develop treatments for individuals who contract COVID-19. To this end, COVID-19 anti-viral treatments have been gaining clinical momentum, recently shown by clinical trials in various phases to be highly effective in rapidly treating symptoms of COVID-19.

In 2021, British regulators were the first to approve of an orally administered anti-viral COVID-19 medication, molnupiravir, manufactured by Merck & Co. and Ridgeback Biotherapeutics ². Initially designed by researchers at Emory University to treat infections of the Venezuelan equine encephalitis virus, it resembles building blocks of the SARS-CoV-2 genome, fooling the virus into producing copies of its genetic code that are plagued with mutations – ultimately leading to its self-inflicted death and significantly reducing viral load. A phase II/III randomized trial found that, among individuals with mild or moderate COVID-19 who had at least one risk factor for severe COVID-19, molnupiravir resulted in a 50% reduction in the risk of hospitalization or death when administered within five days of symptom onset ³. Although data have yet to be published in peer-reviewed journals, in light of these promising results, an emergency use authorization application was submitted to the US Food and Drug Administration (FDA).

More recently, a similar antiviral treatment, Paxlovid, has been studied by Pfizer ⁴. Administered alongside an older antiviral, ritonavir, twice daily, the treatment inhibits the main protease key to SARS-CoV-2 replication ⁵. Preliminary data were assessed in over 1,200 COVID-19-positive individuals at high risk of developing severe illness ⁶and found that the treatment led to an 89% reduction in the risk of hospitalization or death. However, the research has also yet to be peer-reviewed.

Finally, a third anti-viral, AT-527, has been produced by Roche and Atea Pharmaceuticals. Despite working according to a mechanism similar to that of molnupiravir, the drug failed to show a significant drop in SARS-CoV-2 viral load in patients with mild or moderate COVID-19 in clinical trials.

Interestingly, a different line of anti-viral research has pointed to a novel strategy. SARS-CoV-2 infection was found to induce the activation of the unfolded protein response (UPR), and inhibition of the UPR was found to reduce viral replication in vitro. This UPR pathway is also associated with COVID-19-associated pulmonary complications. Its potential as a focal point for both anti-viral and therapeutic effects has thus prompted rigorous research on its use as a completely novel and particularly powerful clinical tool against COVID-19 ^7,8.

The development of these anti-viral treatments holds particular promise beyond the only other antiviral drug approved  to treat COVID-19 as of early November, remdesivir, which needs to be delivered intravenously. First, if used to prevent the virus from gaining a foothold in the first place, anti-viral medications may be a powerful tool to thwart full-blown COVID-19 prior to becoming more virulent, thereby curtailing the duration of the disease and transmissibility. Second, their oral administration route makes them easy and non-invasive to administer. Third, they could be particularly powerful in regions in which vaccination rates remain low, such as lower-income countries.

In the end, fighting the COVID-19 pandemic will warrant a multipronged effort, including but not limited to vaccination, monoclonal antibody treatments, anti-viral medications, and ongoing public and patient education.

References

1. Olliaro, P., Torreele, E. & Vaillant, M. COVID-19 vaccine efficacy and effectiveness—the elephant (not) in the room. The Lancet Microbe (2021). doi:10.1016/S2666-5247(21)00069-0
2. Willyard, C. How antiviral pill molnupiravir shot ahead in the COVID drug hunt. Nature (2021). doi:10.1038/d41586-021-02783-1
3. Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study – Merck.com. Available at: https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/.
4. Pfizer’s Novel COVID-19 Oral Antiviral Treatment Candidate Reduced Risk of Hospitalization or Death by 89% in Interim Analysis of Phase 2/3 EPIC-HR Study | Business Wire. Available at: https://www.businesswire.com/news/home/20211105005260/en/.
5. Jin, Z. et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature (2020). doi:10.1038/s41586-020-2223-y
6. A Study of PF-07321332/Ritonavir in Nonhospitalized High Risk Adult Participants With COVID-19 – Full Text View – ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04960202.
7. Barabutis, N. Unfolded protein response in the COVID-19 context. Aging Heal. Res. (2021). doi:10.1016/j.ahr.2020.100001
8. Echavarría-Consuegra, L. et al. Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection. PLoS Pathog. (2021). doi:10.1371/journal.ppat.1009644

In the United States, the Health Insurance Portability and Accountability Act of 1996 (HIPAA) governs the use and disclosure of protected health information (PHI). Under HIPAA, entities like healthcare providers must carefully protect PHI from disclosure. However, providers are not barred from sharing other kinds of health information. In fact, HIPAA contains guidelines for the release of health information, which facilitates data sharing, commerce, and research. If the identifying information is removed from patient data through a process called deidentification, HIPAA protections no longer apply, and entities are free to use or disclose such deidentified health information.

Drawing on statistics, algorithms, and machine learning, academic researchers have devised many methods for deidentification of patient data. For example, some methods use manually crafted patterns to classify what information is “PHI-like” or “not PHI-like”. Other methods use supervised machine learning to automatically determine patterns as to what qualifies as PHI [1]. Regardless, the end goal is the same: deidentified data must be immune to reverse-engineering (called reidentification) that could compromise patient privacy. Under HIPAA, providers are liable if they fail to take reasonable deidentification measures [2]. On the other hand, HIPAA standards strive to minimize the risk of reidentification without unduly burdening providers.

Providers can deidentify data using what HIPAA calls the expert determination method. Under this method, a person with sufficient experience analyzes the data to determine whether the risk of reidentification is “very small” [3]. The expert does not need a specific education credential or professional certification, but they should have experience with statistics, mathematics, data science, or a similar field. To improve accountability, the expert must maintain documentation of their methods and results. By hiring an expert to make these determinations, healthcare providers can have greater assurance that their patient data is HIPAA-compliant.

Without access to a qualified expert, providers can also deidentify data through the safe harbor method. In this case, the provider must remove eighteen different types of data that could identify a patient [3]. These data include names, street addresses, telephone numbers, email addresses, Social Security numbers, full-face photographs, and others. HIPAA contains specific provisions for handling certain kinds of data, like birthdates and ZIP codes. Additionally, providers must take additional steps to remove information that they know could be identifiable [3]. For example, if one patient has a specific and unique occupation title, the provider should not include occupation data in their dataset. If healthcare providers cannot readily hire an expert, performing the safe harbor method in-house should ensure HIPAA compliance.

In summary, US federal law standardizes the handling of protected health information and deidentified health information. Yet, questions remain about whether HIPAA’s standards for the deidentification of patient data are sufficient. In the statistics literature, reidentification has been performed on many kinds of datasets outside the healthcare space. For example, reidentification was performed on an anonymized dataset of Netflix subscribers by cross-referencing Netflix watch data with public IMDB movie/television ratings [4]. Researchers have not systematically studied whether current reidentification methods are effective on patient data, and further research is needed to assist expert determinations and healthcare policymakers [5]. Future research may inform new standards for improving patient privacy or new paradigms for handling patient data.

References 

[1] S. M. Meystre, et al. Automatic De-identification of Textual Documents in the Electronic Health Record: A Review of Recent Research. BMC Medical Research Methodology 2010; 10: 70. DOI: 10.1186/1471-2288-10-70.  

[2] US Department of Health and Human Services. Special Topics: Research. HHS.gov 2018. URL: https://www.hhs.gov/hipaa/for-professionals/special-topics/research/index.html.  

[3] US Department of Health and Human Services. Guidance Regarding Methods for De-identification of Protected Health Information in Accordance with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. HHS.gov 2015. URL: https://www.hhs.gov/hipaa/for-professionals/privacy/special-topics/de-identification/index.html. 

[4] A. Narayanan and V. Shmatikov. How To Break Anonymity of the Netflix Prize Dataset. ArXiv.org 2006. ArXiv:cs/0610105.  

[5] K. El Emam, et al. A Systematic Review of Re-Identification Attacks on Health Data. PLOS One 2011. DOI: 10.1371/journal.pone.0028071.