Key clinical point: The addition of abemaciclib to endocrine therapy (ET) demonstrated robust treatment benefits regardless of menopausal status in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), high-risk early breast cancer (BC).

Major finding: Abemaciclib+ET significantly improved invasive disease-free survival (iDFS; hazard ratio 0.785; nominal P = .0268) in postmenopausal women with HR+/HER2− BC and led to even greater iDFS improvement (hazard ratio 0.578; P < .0001) in premenopausal women. No new safety events were reported.

Study details: Findings are from an exploratory analysis of the monarchE trial including 5637 patients with HR+/HER2−, node-positive, high-risk early BC who were randomly assigned to receive standard of care ET with/without adjuvant abemaciclib, of which 43.5% and 56.4% of patients were premenopausal and postmenopausal, respectively.

Disclosures: This study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. The other authors reported ties with several sources, including Eli Lilly.

Source: Paluch-Shimon S et al, on behalf of the monarchE investigators. Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2−, node-positive, high-risk early breast cancer. Ther Adv Med Oncol. 2023 (Feb 3). Doi: 10.1177/17588359231151840

Key clinical point: The addition of abemaciclib to endocrine therapy (ET) demonstrated robust treatment benefits regardless of menopausal status in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), high-risk early breast cancer (BC).

Major finding: Abemaciclib+ET significantly improved invasive disease-free survival (iDFS; hazard ratio 0.785; nominal P = .0268) in postmenopausal women with HR+/HER2− BC and led to even greater iDFS improvement (hazard ratio 0.578; P < .0001) in premenopausal women. No new safety events were reported.

Study details: Findings are from an exploratory analysis of the monarchE trial including 5637 patients with HR+/HER2−, node-positive, high-risk early BC who were randomly assigned to receive standard of care ET with/without adjuvant abemaciclib, of which 43.5% and 56.4% of patients were premenopausal and postmenopausal, respectively.

Disclosures: This study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. The other authors reported ties with several sources, including Eli Lilly.

Source: Paluch-Shimon S et al, on behalf of the monarchE investigators. Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2−, node-positive, high-risk early breast cancer. Ther Adv Med Oncol. 2023 (Feb 3). Doi: 10.1177/17588359231151840

Key clinical point: The addition of abemaciclib to endocrine therapy (ET) demonstrated robust treatment benefits regardless of menopausal status in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), high-risk early breast cancer (BC).

Major finding: Abemaciclib+ET significantly improved invasive disease-free survival (iDFS; hazard ratio 0.785; nominal P = .0268) in postmenopausal women with HR+/HER2− BC and led to even greater iDFS improvement (hazard ratio 0.578; P < .0001) in premenopausal women. No new safety events were reported.

Study details: Findings are from an exploratory analysis of the monarchE trial including 5637 patients with HR+/HER2−, node-positive, high-risk early BC who were randomly assigned to receive standard of care ET with/without adjuvant abemaciclib, of which 43.5% and 56.4% of patients were premenopausal and postmenopausal, respectively.

Disclosures: This study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. The other authors reported ties with several sources, including Eli Lilly.

Source: Paluch-Shimon S et al, on behalf of the monarchE investigators. Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2−, node-positive, high-risk early breast cancer. Ther Adv Med Oncol. 2023 (Feb 3). Doi: 10.1177/17588359231151840

Key clinical point: In patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC), adding endocrine therapy (ET) to dual anti-HER2 targeted therapy after chemotherapy improved progression-free survival (PFS) without increasing the rate of adverse events.

Major finding: There was a significant improvement in 5-year PFS with vs without the addition of ET (hazard ratio 0.59; P = .031). Nausea and vomiting were more common in patients who did not vs did receive ET (21% vs 7%; P = .010).

Study details: This study analyzed the real-world data of 147 patients with HER2+/HR+ metastatic BC from a prospective registry who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET.

Disclosures: This study did not receive any funding. Some authors declared serving on the advisory board for or receiving research funding, speaker honoraria, or travel grants from several sources.

Source: Loft M et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74 (Jan 9). Doi: 10.1007/s10549-022-06856-1

Key clinical point: In patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC), adding endocrine therapy (ET) to dual anti-HER2 targeted therapy after chemotherapy improved progression-free survival (PFS) without increasing the rate of adverse events.

Major finding: There was a significant improvement in 5-year PFS with vs without the addition of ET (hazard ratio 0.59; P = .031). Nausea and vomiting were more common in patients who did not vs did receive ET (21% vs 7%; P = .010).

Study details: This study analyzed the real-world data of 147 patients with HER2+/HR+ metastatic BC from a prospective registry who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET.

Disclosures: This study did not receive any funding. Some authors declared serving on the advisory board for or receiving research funding, speaker honoraria, or travel grants from several sources.

Source: Loft M et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74 (Jan 9). Doi: 10.1007/s10549-022-06856-1

Key clinical point: In patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC), adding endocrine therapy (ET) to dual anti-HER2 targeted therapy after chemotherapy improved progression-free survival (PFS) without increasing the rate of adverse events.

Major finding: There was a significant improvement in 5-year PFS with vs without the addition of ET (hazard ratio 0.59; P = .031). Nausea and vomiting were more common in patients who did not vs did receive ET (21% vs 7%; P = .010).

Study details: This study analyzed the real-world data of 147 patients with HER2+/HR+ metastatic BC from a prospective registry who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET.

Disclosures: This study did not receive any funding. Some authors declared serving on the advisory board for or receiving research funding, speaker honoraria, or travel grants from several sources.

Source: Loft M et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74 (Jan 9). Doi: 10.1007/s10549-022-06856-1

Key clinical point: Marking sentinel lymph nodes (SLN) with superparamagnetic iron oxide (SPIO) nanoparticles led to a substantial proportion of patients with ductal carcinoma in situ (DCIS) of the breast avoiding an upfront SLN dissection (SLND).

Major finding: Upfront SLND could be avoided in 78.3% of patients after marking SLN with SPIO nanoparticles. Among patients receiving delayed SLND, the detection rate was significantly better with SPIO vs radioisotope (⁹⁹Tc), both with (98.2% vs 63.6%) and without the concomitant use of blue dye (92.7% vs 50.9%; both P < .001).

Study details: Findings are from a prospective, multicenter cohort study including 254 patients with DCIS.

Disclosures: This study was funded by the Uppsala University. One author declared serving on an advisory board and receiving institutional grants and speaker honoraria from several sources.

Source: Karakatsanis A et al. Delayed sentinel lymph node dissection in patients with a preoperative diagnosis of ductal cancer in situ by preoperative injection with superparamagnetic iron oxide (SPIO) nanoparticles: The SentiNot study. Ann Surg Oncol. 2023 (Jan 31). Doi: 10.1245/s10434-022-13064-0

Key clinical point: Marking sentinel lymph nodes (SLN) with superparamagnetic iron oxide (SPIO) nanoparticles led to a substantial proportion of patients with ductal carcinoma in situ (DCIS) of the breast avoiding an upfront SLN dissection (SLND).

Major finding: Upfront SLND could be avoided in 78.3% of patients after marking SLN with SPIO nanoparticles. Among patients receiving delayed SLND, the detection rate was significantly better with SPIO vs radioisotope (⁹⁹Tc), both with (98.2% vs 63.6%) and without the concomitant use of blue dye (92.7% vs 50.9%; both P < .001).

Study details: Findings are from a prospective, multicenter cohort study including 254 patients with DCIS.

Disclosures: This study was funded by the Uppsala University. One author declared serving on an advisory board and receiving institutional grants and speaker honoraria from several sources.

Source: Karakatsanis A et al. Delayed sentinel lymph node dissection in patients with a preoperative diagnosis of ductal cancer in situ by preoperative injection with superparamagnetic iron oxide (SPIO) nanoparticles: The SentiNot study. Ann Surg Oncol. 2023 (Jan 31). Doi: 10.1245/s10434-022-13064-0

Key clinical point: Marking sentinel lymph nodes (SLN) with superparamagnetic iron oxide (SPIO) nanoparticles led to a substantial proportion of patients with ductal carcinoma in situ (DCIS) of the breast avoiding an upfront SLN dissection (SLND).

Major finding: Upfront SLND could be avoided in 78.3% of patients after marking SLN with SPIO nanoparticles. Among patients receiving delayed SLND, the detection rate was significantly better with SPIO vs radioisotope (⁹⁹Tc), both with (98.2% vs 63.6%) and without the concomitant use of blue dye (92.7% vs 50.9%; both P < .001).

Study details: Findings are from a prospective, multicenter cohort study including 254 patients with DCIS.

Disclosures: This study was funded by the Uppsala University. One author declared serving on an advisory board and receiving institutional grants and speaker honoraria from several sources.

Source: Karakatsanis A et al. Delayed sentinel lymph node dissection in patients with a preoperative diagnosis of ductal cancer in situ by preoperative injection with superparamagnetic iron oxide (SPIO) nanoparticles: The SentiNot study. Ann Surg Oncol. 2023 (Jan 31). Doi: 10.1245/s10434-022-13064-0

Key clinical point: Contralateral prophylactic mastectomy (CPM) did not offer any survival benefit to patients with triple-negative breast cancer (TNBC) irrespective of the presence of BRCA mutations.

Major finding: The 5-year overall survival did not significantly improve with vs without CPM in the entire population of patients with TNBC (P = .05) and in the subgroups of patients with (P = .35) and without (P = .12) BRCA mutations.

Study details: Findings are from a multi-institutional database study including 796 patients with TNBC, of which 15.5% of patients underwent CPM.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Fasano GA et al. Survival outcomes in women with unilateral, triple-negative, breast cancer correlated with contralateral prophylactic mastectomy. Ann Surg Oncol. 2023 (Jan 21). Doi: 10.1245/s10434-022-13056-0

Key clinical point: Contralateral prophylactic mastectomy (CPM) did not offer any survival benefit to patients with triple-negative breast cancer (TNBC) irrespective of the presence of BRCA mutations.

Major finding: The 5-year overall survival did not significantly improve with vs without CPM in the entire population of patients with TNBC (P = .05) and in the subgroups of patients with (P = .35) and without (P = .12) BRCA mutations.

Study details: Findings are from a multi-institutional database study including 796 patients with TNBC, of which 15.5% of patients underwent CPM.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Fasano GA et al. Survival outcomes in women with unilateral, triple-negative, breast cancer correlated with contralateral prophylactic mastectomy. Ann Surg Oncol. 2023 (Jan 21). Doi: 10.1245/s10434-022-13056-0

Key clinical point: Contralateral prophylactic mastectomy (CPM) did not offer any survival benefit to patients with triple-negative breast cancer (TNBC) irrespective of the presence of BRCA mutations.

Major finding: The 5-year overall survival did not significantly improve with vs without CPM in the entire population of patients with TNBC (P = .05) and in the subgroups of patients with (P = .35) and without (P = .12) BRCA mutations.

Study details: Findings are from a multi-institutional database study including 796 patients with TNBC, of which 15.5% of patients underwent CPM.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Fasano GA et al. Survival outcomes in women with unilateral, triple-negative, breast cancer correlated with contralateral prophylactic mastectomy. Ann Surg Oncol. 2023 (Jan 21). Doi: 10.1245/s10434-022-13056-0

Key clinical point: Adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better disease-free survival (DFS) than tamoxifen-only or tamoxifen+AI in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor2-positive (HER2+) breast cancer (BC).

Major finding: Adjuvant ET with tamoxifen or tamoxifen+AI was associated with significantly worse DFS rates than AI in the entire population of women with HR+/HER2+ BC (hazard ratio 1.64; P = .025), with gonadotropin-releasing hormone being associated with improved DFS rates in premenopausal patients aged ≤45 years (hazard ratio 0.41; P = .023).

Study details: Findings are from a post hoc analysis of the ShortHER trial including 784 patients with HR+/HER2+ early BC who received adjuvant anthracycline/taxane-based chemotherapy plus trastuzumab.

Disclosures: This study was supported by Agenzia Italiana del Farmaco and other sources. Some authors declared receiving personal fees from several sources.

Source: Dieci MV et al. Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: Analysis from the phase III randomized ShortHER trial. NPJ Breast Cancer. 2023;9(1):6 (Feb 4). Doi: 10.1038/s41523-023-00509-2

Key clinical point: Adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better disease-free survival (DFS) than tamoxifen-only or tamoxifen+AI in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor2-positive (HER2+) breast cancer (BC).

Major finding: Adjuvant ET with tamoxifen or tamoxifen+AI was associated with significantly worse DFS rates than AI in the entire population of women with HR+/HER2+ BC (hazard ratio 1.64; P = .025), with gonadotropin-releasing hormone being associated with improved DFS rates in premenopausal patients aged ≤45 years (hazard ratio 0.41; P = .023).

Study details: Findings are from a post hoc analysis of the ShortHER trial including 784 patients with HR+/HER2+ early BC who received adjuvant anthracycline/taxane-based chemotherapy plus trastuzumab.

Disclosures: This study was supported by Agenzia Italiana del Farmaco and other sources. Some authors declared receiving personal fees from several sources.

Source: Dieci MV et al. Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: Analysis from the phase III randomized ShortHER trial. NPJ Breast Cancer. 2023;9(1):6 (Feb 4). Doi: 10.1038/s41523-023-00509-2

Key clinical point: Adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better disease-free survival (DFS) than tamoxifen-only or tamoxifen+AI in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor2-positive (HER2+) breast cancer (BC).

Major finding: Adjuvant ET with tamoxifen or tamoxifen+AI was associated with significantly worse DFS rates than AI in the entire population of women with HR+/HER2+ BC (hazard ratio 1.64; P = .025), with gonadotropin-releasing hormone being associated with improved DFS rates in premenopausal patients aged ≤45 years (hazard ratio 0.41; P = .023).

Study details: Findings are from a post hoc analysis of the ShortHER trial including 784 patients with HR+/HER2+ early BC who received adjuvant anthracycline/taxane-based chemotherapy plus trastuzumab.

Disclosures: This study was supported by Agenzia Italiana del Farmaco and other sources. Some authors declared receiving personal fees from several sources.

Source: Dieci MV et al. Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: Analysis from the phase III randomized ShortHER trial. NPJ Breast Cancer. 2023;9(1):6 (Feb 4). Doi: 10.1038/s41523-023-00509-2

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

If the pandemic served as a window into our health, what it revealed was a U.S. population that is not only sick but also seemingly only getting sicker. Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.

Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.

Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
 

Microplastics

“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.

Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.

According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.

Pressure also is mounting for a ban on microbeads in personal care products.

Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
 

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.

Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.

To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.

The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.

Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
 

Bisphenol A (BPA)

BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.

Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.

As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.

Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
 

Dioxins and polychlorinated biphenyls (PCBs)

Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.

Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
 

Pesticides

The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.

Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.

A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.

Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
 

Per- and polyfluoroalkyl substances (PFAS)

PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”

PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.

The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.

Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”

In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”

Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University’s Grossman School of Medicine, where I’m the director.

It’s flu season, yet again. For many parts of the country, we’re already in the thick of it, and for other places, we’re going to have flu outbreaks continuing and intensifying. I’ve long believed that every health care institution – nursing homes, hospitals, clinics, home care, hospice – should require flu shots for all doctors and all nurses because it is the easiest, cheapest, and most ethical way to protect the workforce, who you need to be in there when flu outbreaks take place, and to protect patients against getting the flu when they come into hospital settings and get exposed to health care workers who may have the flu already but don’t know it.

In a recent poll, I was happy to see that the majority of physicians surveyed agreed with me: 65% said they supported mandatory flu vaccination in hospitals and only 23% said they did not. I think flu vaccination is something that has already been shown to be useful and important, not only in stopping people from getting the flu but also in making sure that they don’t get as sick when they get the flu.

Just like COVID-19 vaccination, it doesn’t always prevent somebody from getting infected, but if you get it, it keeps you from winding up sick at home, or worse – from dying and winding up in the morgue. Flu kills many, many people every year. We don’t want that to happen. A flu vaccine will really help prevent deaths, help prevent the number of symptoms that somebody gets, and will get people back to work. The benefits are pretty clear.

Does the flu vaccine work equally well every year? It does not. Some years, the strains that are picked for the vaccine don’t match the ones that circulate, and we don’t get as much protection as we hoped for. I think the safety side is so strong that it’s worth making the investment and the effort to promote mandatory flu vaccination.

Can you opt out on religious grounds? Well, some hospitals permit that at New York University. You have to go before a committee and make a case that your exemption on religious grounds is based on an authentic set of beliefs that are deeply held, and not just something you thought up the day before flu vaccine requirements went into effect.

There may be room for some exemptions – obviously, for health reasons. If people think that the flu vaccine is dangerous to them and can get a physician to agree and sign off that they are not appropriate to vaccinate, okay.

On the other hand, if you’re working with an especially vulnerable population – newborns, people who are immunosuppressed – then I think you’ve got to be vaccinated and you shouldn’t be working around people who are at huge risk of getting the flu if you refuse to be vaccinated or, for that matter, can’t be vaccinated.

Would I extend these mandates? Yes, I would. I’d extend them to COVID-19 vaccination and to measles vaccination. I think physicians and nurses should be good role models. They should get vaccinated. We know that the best available evidence says that vaccination for infectious disease is safe. It is really the best thing we can do to combat a variety of diseases such as the flu and COVID-19.

It seems to me that, in addition, the data that are out there in terms of risks from flu and COVID-19 – deaths in places like nursing homes – are overwhelming about the importance of trying to get staff vaccinated so they don’t bring flu into an institutionalized population. This is similar for prison health and many other settings where people are kept close together and staff may move from place to place, rotating from institution to institution, spreading infectious disease.

I’m going to go with the poll. Let’s keep pushing for health care workers to do the right thing and to be good role models. Let’s get everybody a flu vaccination. Let’s extend it to a COVID-19 vaccination and its boosters.

Let’s try to show the nation that health care is going to be guided by good science, a duty to one’s own health, and a duty to one’s patients. It shouldn’t be political. It should be based on what works best for the interests of health care providers and those they care for.

I’m Art Caplan at the New York University Grossman School of Medicine. Thanks for watching.
 

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape. A version of this article originally appeared on Medscape.com.

More on ‘intellectual constipation’

Regarding your editorial, “From debate to stalemate and hate: An epidemic of intellectual constipation” (Current Psychiatry, January 2023, p. 3-4, doi:10.12788/cp.0321): fantastic and so very well put. As you (we) get older, we get more forceful in presenting our ideas. Your presentation is perfect for the times, and I hope your editorial is read by many. I have started a group of doctors (Psychiatrists of the Realm) that will be available to teach physicians and nonphysicians at no charge. It is our responsibility as the elder statesmen of medicine to make sure what wisdom we have acquired can be shared with others.

Robert W. Pollack, MD, ABPN, DLFAPA
Fort Myers, Florida

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on SWOT analysis of psychiatry

I loved your recent analysis of psychiatry (“Contemporary psychiatry: A SWOT analysis,” Current Psychiatry, January 2023, p. 16-19,27, doi:10.12788/cp.0320). What a great idea! It looks very complete to me. It occurs to me to consider adding a very simple but I think profound strength: the fact that one’s mental health affects every decision a person makes for their entire life. Taking this stance opens many doors and makes our input and expertise as a profession relevant to all aspects of society. Mental health is personal and matters deeply to all of us.

Paul R. Crosby, MD, MBA
President and CEO of the Frances and Craig Lindner Center of HOPE
Associate Professor and Vice Chair
Department of Psychiatry and Behavioral Neuroscience
University of Cincinnati College of Medicine
Cincinnati, Ohio

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on evolution’s triumphs and blunders

I enjoyed your editorial, “Is evolution’s greatest triumph its worst blunder?” (Current Psychiatry, November 2022, p. 5,10-11, doi:10.12788cp.0301). I commend you for the bravery and freshness of the view you suggest we reconsider. It is interesting that observation of humans' propensity for violence didn't cause Darwin to wonder how that fit into his survival paradigm since we were not likely to have been under threat of extinction while the human neocortex was undergoing its novel evolutionary design. Being born in 1809 would have given him enough time to have his doubts about undesired human evolutionary trajectories with potential extinction outcomes. I’m no expert, but I’ve never heard he considered that human potential could lean in that direction. You may have seen the article by Kirsch¹ about people who are advocating that humans voluntarily move toward extinction and let the planet live. I would be interested in a follow-up article on the type of comments and ideas inspired by your editorial. Kudos to you for your creativity.

Michele A. Packard, PhD
Boulder, Colorado

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on ‘intellectual constipation’

Regarding your editorial, “From debate to stalemate and hate: An epidemic of intellectual constipation” (Current Psychiatry, January 2023, p. 3-4, doi:10.12788/cp.0321): fantastic and so very well put. As you (we) get older, we get more forceful in presenting our ideas. Your presentation is perfect for the times, and I hope your editorial is read by many. I have started a group of doctors (Psychiatrists of the Realm) that will be available to teach physicians and nonphysicians at no charge. It is our responsibility as the elder statesmen of medicine to make sure what wisdom we have acquired can be shared with others.

Robert W. Pollack, MD, ABPN, DLFAPA
Fort Myers, Florida

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on SWOT analysis of psychiatry

I loved your recent analysis of psychiatry (“Contemporary psychiatry: A SWOT analysis,” Current Psychiatry, January 2023, p. 16-19,27, doi:10.12788/cp.0320). What a great idea! It looks very complete to me. It occurs to me to consider adding a very simple but I think profound strength: the fact that one’s mental health affects every decision a person makes for their entire life. Taking this stance opens many doors and makes our input and expertise as a profession relevant to all aspects of society. Mental health is personal and matters deeply to all of us.

Paul R. Crosby, MD, MBA
President and CEO of the Frances and Craig Lindner Center of HOPE
Associate Professor and Vice Chair
Department of Psychiatry and Behavioral Neuroscience
University of Cincinnati College of Medicine
Cincinnati, Ohio

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on evolution’s triumphs and blunders

I enjoyed your editorial, “Is evolution’s greatest triumph its worst blunder?” (Current Psychiatry, November 2022, p. 5,10-11, doi:10.12788cp.0301). I commend you for the bravery and freshness of the view you suggest we reconsider. It is interesting that observation of humans' propensity for violence didn't cause Darwin to wonder how that fit into his survival paradigm since we were not likely to have been under threat of extinction while the human neocortex was undergoing its novel evolutionary design. Being born in 1809 would have given him enough time to have his doubts about undesired human evolutionary trajectories with potential extinction outcomes. I’m no expert, but I’ve never heard he considered that human potential could lean in that direction. You may have seen the article by Kirsch¹ about people who are advocating that humans voluntarily move toward extinction and let the planet live. I would be interested in a follow-up article on the type of comments and ideas inspired by your editorial. Kudos to you for your creativity.

Michele A. Packard, PhD
Boulder, Colorado

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on ‘intellectual constipation’

Regarding your editorial, “From debate to stalemate and hate: An epidemic of intellectual constipation” (Current Psychiatry, January 2023, p. 3-4, doi:10.12788/cp.0321): fantastic and so very well put. As you (we) get older, we get more forceful in presenting our ideas. Your presentation is perfect for the times, and I hope your editorial is read by many. I have started a group of doctors (Psychiatrists of the Realm) that will be available to teach physicians and nonphysicians at no charge. It is our responsibility as the elder statesmen of medicine to make sure what wisdom we have acquired can be shared with others.

Robert W. Pollack, MD, ABPN, DLFAPA
Fort Myers, Florida

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on SWOT analysis of psychiatry

I loved your recent analysis of psychiatry (“Contemporary psychiatry: A SWOT analysis,” Current Psychiatry, January 2023, p. 16-19,27, doi:10.12788/cp.0320). What a great idea! It looks very complete to me. It occurs to me to consider adding a very simple but I think profound strength: the fact that one’s mental health affects every decision a person makes for their entire life. Taking this stance opens many doors and makes our input and expertise as a profession relevant to all aspects of society. Mental health is personal and matters deeply to all of us.

Paul R. Crosby, MD, MBA
President and CEO of the Frances and Craig Lindner Center of HOPE
Associate Professor and Vice Chair
Department of Psychiatry and Behavioral Neuroscience
University of Cincinnati College of Medicine
Cincinnati, Ohio

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

More on evolution’s triumphs and blunders

I enjoyed your editorial, “Is evolution’s greatest triumph its worst blunder?” (Current Psychiatry, November 2022, p. 5,10-11, doi:10.12788cp.0301). I commend you for the bravery and freshness of the view you suggest we reconsider. It is interesting that observation of humans' propensity for violence didn't cause Darwin to wonder how that fit into his survival paradigm since we were not likely to have been under threat of extinction while the human neocortex was undergoing its novel evolutionary design. Being born in 1809 would have given him enough time to have his doubts about undesired human evolutionary trajectories with potential extinction outcomes. I’m no expert, but I’ve never heard he considered that human potential could lean in that direction. You may have seen the article by Kirsch¹ about people who are advocating that humans voluntarily move toward extinction and let the planet live. I would be interested in a follow-up article on the type of comments and ideas inspired by your editorial. Kudos to you for your creativity.

Michele A. Packard, PhD
Boulder, Colorado

Disclosures
The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.