Key clinical point: First-line palbociclib plus letrozole proved to be a more effective treatment option than letrozole alone in a real-world population of older patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (BC).

Major finding: Real-world progression-free survival (22.2 vs 15.8 months; adjusted hazard ratio 0.59; P < .001) was significantly prolonged and real-world best tumor response rate was significantly higher (52.4% vs. 22.1%; adjusted odds ratio 2.0; P < .001) in patients receiving palbociclib+letrozole vs letrozole alone.

Study details: Findings are from a retrospective cohort study including 796 women aged ≥65 years with HR+/HER2− metastatic BC who initiated first-line treatment with palbociclib+letrozole or letrozole alone.

Disclosures: This study was sponsored by Pfizer Inc. Three authors declared being employees of and owning stocks in Pfizer Inc. The other authors declared receiving advisory board fees, consulting fees, honoraria, or research funding from Pfizer Inc and other sources.

Source: Rugo HS et al. Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer. Breast. 2023 (Mar 27). Doi: 10.1016/j.breast.2023.03.015

Key clinical point: First-line palbociclib plus letrozole proved to be a more effective treatment option than letrozole alone in a real-world population of older patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (BC).

Major finding: Real-world progression-free survival (22.2 vs 15.8 months; adjusted hazard ratio 0.59; P < .001) was significantly prolonged and real-world best tumor response rate was significantly higher (52.4% vs. 22.1%; adjusted odds ratio 2.0; P < .001) in patients receiving palbociclib+letrozole vs letrozole alone.

Study details: Findings are from a retrospective cohort study including 796 women aged ≥65 years with HR+/HER2− metastatic BC who initiated first-line treatment with palbociclib+letrozole or letrozole alone.

Disclosures: This study was sponsored by Pfizer Inc. Three authors declared being employees of and owning stocks in Pfizer Inc. The other authors declared receiving advisory board fees, consulting fees, honoraria, or research funding from Pfizer Inc and other sources.

Source: Rugo HS et al. Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer. Breast. 2023 (Mar 27). Doi: 10.1016/j.breast.2023.03.015

Key clinical point: First-line palbociclib plus letrozole proved to be a more effective treatment option than letrozole alone in a real-world population of older patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (BC).

Major finding: Real-world progression-free survival (22.2 vs 15.8 months; adjusted hazard ratio 0.59; P < .001) was significantly prolonged and real-world best tumor response rate was significantly higher (52.4% vs. 22.1%; adjusted odds ratio 2.0; P < .001) in patients receiving palbociclib+letrozole vs letrozole alone.

Study details: Findings are from a retrospective cohort study including 796 women aged ≥65 years with HR+/HER2− metastatic BC who initiated first-line treatment with palbociclib+letrozole or letrozole alone.

Disclosures: This study was sponsored by Pfizer Inc. Three authors declared being employees of and owning stocks in Pfizer Inc. The other authors declared receiving advisory board fees, consulting fees, honoraria, or research funding from Pfizer Inc and other sources.

Source: Rugo HS et al. Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer. Breast. 2023 (Mar 27). Doi: 10.1016/j.breast.2023.03.015

Key clinical point: Omission of surgical axillary staging (AS) worsened overall survival (OS) but not breast cancer-specific survival (BCSS) in older women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) early-stage breast cancer (BC).

Major finding: Women who did not undergo AS had similar BCSS (adjusted hazard ratio [HR] 0.98; 95% CI 0.77-1.25) but poorer OS (adjusted HR 1.14; 95% CI 1.04-1.25) compared with those who underwent AS.

Study details: Findings are from a population-based cohort study including 17,370 women aged 65-95 years with ER+/HER2− early-stage BC who underwent surgery, of which 1771 patients did not undergo AS.

Disclosures: This study was supported by the Ontario Ministry of Health and the Ministry of Long-Term Care, Canada. The authors declared no conflict of interests.

Source: Castelo M et al. The association between surgical axillary staging, adjuvant treatment use and survival in older women with early stage breast cancer: A population-based study. Ann Surg Oncol. 2023 (Mar 14). Doi: 10.1245/s10434-023-13274-0

Key clinical point: Omission of surgical axillary staging (AS) worsened overall survival (OS) but not breast cancer-specific survival (BCSS) in older women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) early-stage breast cancer (BC).

Major finding: Women who did not undergo AS had similar BCSS (adjusted hazard ratio [HR] 0.98; 95% CI 0.77-1.25) but poorer OS (adjusted HR 1.14; 95% CI 1.04-1.25) compared with those who underwent AS.

Study details: Findings are from a population-based cohort study including 17,370 women aged 65-95 years with ER+/HER2− early-stage BC who underwent surgery, of which 1771 patients did not undergo AS.

Disclosures: This study was supported by the Ontario Ministry of Health and the Ministry of Long-Term Care, Canada. The authors declared no conflict of interests.

Source: Castelo M et al. The association between surgical axillary staging, adjuvant treatment use and survival in older women with early stage breast cancer: A population-based study. Ann Surg Oncol. 2023 (Mar 14). Doi: 10.1245/s10434-023-13274-0

Key clinical point: Omission of surgical axillary staging (AS) worsened overall survival (OS) but not breast cancer-specific survival (BCSS) in older women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) early-stage breast cancer (BC).

Major finding: Women who did not undergo AS had similar BCSS (adjusted hazard ratio [HR] 0.98; 95% CI 0.77-1.25) but poorer OS (adjusted HR 1.14; 95% CI 1.04-1.25) compared with those who underwent AS.

Study details: Findings are from a population-based cohort study including 17,370 women aged 65-95 years with ER+/HER2− early-stage BC who underwent surgery, of which 1771 patients did not undergo AS.

Disclosures: This study was supported by the Ontario Ministry of Health and the Ministry of Long-Term Care, Canada. The authors declared no conflict of interests.

Source: Castelo M et al. The association between surgical axillary staging, adjuvant treatment use and survival in older women with early stage breast cancer: A population-based study. Ann Surg Oncol. 2023 (Mar 14). Doi: 10.1245/s10434-023-13274-0

Key clinical point: Patients with early breast cancer (BC) who achieve pathological complete response (pCR) with neoadjuvant chemotherapy can nevertheless be at risk for disease relapse if there is nodal involvement at diagnosis and tumors are large and have lobular histology.

Major finding: Disease-free survival (DFS) was worse in the overall cohort (hazard ratio [HR] 1.94; P < .001) and in patients with triple-negative BC (TNBC; HR 2.45; P < .001) who did vs did not have initial positive lymph node involvement. Lobular histology (HR 3.55; P = .003) and large tumors (cT3/4; HR 2.07; P = .033) were also associated with a higher risk for shorter DFS in patients with TNBC and human epidermal growth factor receptor 2-positive BC, respectively.

Study details: This retrospective pooled analysis included 2066 patients with BC who had achieved pCR.

Disclosures: This study was funded by Projekt DEAL, Germany. Some authors declared receiving consulting fees, honoraria, travel expenses, research grants, or honoraria or having other ties with several sources.

Source: Huober J et al. Identifying breast cancer patients at risk of relapse despite pathological complete response after neoadjuvant therapy. NPJ Breast Cancer. 2023;9:23 (Apr 7). Doi: 10.1038/s41523-023-00525-2

Key clinical point: Patients with early breast cancer (BC) who achieve pathological complete response (pCR) with neoadjuvant chemotherapy can nevertheless be at risk for disease relapse if there is nodal involvement at diagnosis and tumors are large and have lobular histology.

Major finding: Disease-free survival (DFS) was worse in the overall cohort (hazard ratio [HR] 1.94; P < .001) and in patients with triple-negative BC (TNBC; HR 2.45; P < .001) who did vs did not have initial positive lymph node involvement. Lobular histology (HR 3.55; P = .003) and large tumors (cT3/4; HR 2.07; P = .033) were also associated with a higher risk for shorter DFS in patients with TNBC and human epidermal growth factor receptor 2-positive BC, respectively.

Study details: This retrospective pooled analysis included 2066 patients with BC who had achieved pCR.

Disclosures: This study was funded by Projekt DEAL, Germany. Some authors declared receiving consulting fees, honoraria, travel expenses, research grants, or honoraria or having other ties with several sources.

Source: Huober J et al. Identifying breast cancer patients at risk of relapse despite pathological complete response after neoadjuvant therapy. NPJ Breast Cancer. 2023;9:23 (Apr 7). Doi: 10.1038/s41523-023-00525-2

Key clinical point: Patients with early breast cancer (BC) who achieve pathological complete response (pCR) with neoadjuvant chemotherapy can nevertheless be at risk for disease relapse if there is nodal involvement at diagnosis and tumors are large and have lobular histology.

Major finding: Disease-free survival (DFS) was worse in the overall cohort (hazard ratio [HR] 1.94; P < .001) and in patients with triple-negative BC (TNBC; HR 2.45; P < .001) who did vs did not have initial positive lymph node involvement. Lobular histology (HR 3.55; P = .003) and large tumors (cT3/4; HR 2.07; P = .033) were also associated with a higher risk for shorter DFS in patients with TNBC and human epidermal growth factor receptor 2-positive BC, respectively.

Study details: This retrospective pooled analysis included 2066 patients with BC who had achieved pCR.

Disclosures: This study was funded by Projekt DEAL, Germany. Some authors declared receiving consulting fees, honoraria, travel expenses, research grants, or honoraria or having other ties with several sources.

Source: Huober J et al. Identifying breast cancer patients at risk of relapse despite pathological complete response after neoadjuvant therapy. NPJ Breast Cancer. 2023;9:23 (Apr 7). Doi: 10.1038/s41523-023-00525-2

Key clinical point: Data from a multi-institutional US database of more than 2.5 million screening mammograms showed that digital breast tomosynthesis (DBT) was superior to digital mammography (DM) for the purpose of breast cancer (BC) screening.

Major finding: Compared with DM, DBT led to significantly higher cancer detection rates (adjusted odds ratio [OR] 1.24), biopsy rate (adjusted OR 1.33), and positive predictive value of recall (adjusted OR 1.33; all P < .001).

Study details: Findings are from a retrospective study including 2,528,063 screening mammograms in 1,100,447 women aged 40-79 years.

Disclosures: This study did not report the source of funding. Some authors declared receiving grants, travel support, consulting fees, or payments from various sources.

Source: Conant EF et al. Mammographic screening in routine practice: Multisite study of digital breast tomosynthesis and digital mammography screenings. Radiology. 2023 (Mar 14). Doi: 10.1148/radiol.221571

Key clinical point: Data from a multi-institutional US database of more than 2.5 million screening mammograms showed that digital breast tomosynthesis (DBT) was superior to digital mammography (DM) for the purpose of breast cancer (BC) screening.

Major finding: Compared with DM, DBT led to significantly higher cancer detection rates (adjusted odds ratio [OR] 1.24), biopsy rate (adjusted OR 1.33), and positive predictive value of recall (adjusted OR 1.33; all P < .001).

Study details: Findings are from a retrospective study including 2,528,063 screening mammograms in 1,100,447 women aged 40-79 years.

Disclosures: This study did not report the source of funding. Some authors declared receiving grants, travel support, consulting fees, or payments from various sources.

Source: Conant EF et al. Mammographic screening in routine practice: Multisite study of digital breast tomosynthesis and digital mammography screenings. Radiology. 2023 (Mar 14). Doi: 10.1148/radiol.221571

Key clinical point: Data from a multi-institutional US database of more than 2.5 million screening mammograms showed that digital breast tomosynthesis (DBT) was superior to digital mammography (DM) for the purpose of breast cancer (BC) screening.

Major finding: Compared with DM, DBT led to significantly higher cancer detection rates (adjusted odds ratio [OR] 1.24), biopsy rate (adjusted OR 1.33), and positive predictive value of recall (adjusted OR 1.33; all P < .001).

Study details: Findings are from a retrospective study including 2,528,063 screening mammograms in 1,100,447 women aged 40-79 years.

Disclosures: This study did not report the source of funding. Some authors declared receiving grants, travel support, consulting fees, or payments from various sources.

Source: Conant EF et al. Mammographic screening in routine practice: Multisite study of digital breast tomosynthesis and digital mammography screenings. Radiology. 2023 (Mar 14). Doi: 10.1148/radiol.221571

Key clinical point: In patients with early, operable breast cancer (BC), peritumoral injection of a local anesthetic (lidocaine) prior to surgery improved survival outcomes.

Major finding: Peritumoral infiltration of lidocaine at the time of surgery led to 26% improvement in disease-free survival (hazard ratio [HR] 0.74; P = .017) and 29% improvement in overall survival (HR 0.71; P = .019) at a median follow-up of 68 months. No adverse events related to injection of lidocaine were reported.

Study details: Findings are from the phase 3 study including 1583 patients with early, operable BC who did not receive prior neoadjuvant treatment and were randomly assigned to undergo surgery with or without a peritumoral injection of 0.5% lidocaine 7-10 minutes preoperatively.

Disclosures: This study was supported by Department of Atomic Energy, India. Dr. Sudeep Gupta declared receiving research funding from several sources.

Source: Badwe RA et al. Effect of peritumoral infiltration of local anesthetic before surgery on survival in early breast cancer. J Clin Oncol. 2023 (Apr 6). Doi: 10.1200/JCO.22.01966

Key clinical point: In patients with early, operable breast cancer (BC), peritumoral injection of a local anesthetic (lidocaine) prior to surgery improved survival outcomes.

Major finding: Peritumoral infiltration of lidocaine at the time of surgery led to 26% improvement in disease-free survival (hazard ratio [HR] 0.74; P = .017) and 29% improvement in overall survival (HR 0.71; P = .019) at a median follow-up of 68 months. No adverse events related to injection of lidocaine were reported.

Study details: Findings are from the phase 3 study including 1583 patients with early, operable BC who did not receive prior neoadjuvant treatment and were randomly assigned to undergo surgery with or without a peritumoral injection of 0.5% lidocaine 7-10 minutes preoperatively.

Disclosures: This study was supported by Department of Atomic Energy, India. Dr. Sudeep Gupta declared receiving research funding from several sources.

Source: Badwe RA et al. Effect of peritumoral infiltration of local anesthetic before surgery on survival in early breast cancer. J Clin Oncol. 2023 (Apr 6). Doi: 10.1200/JCO.22.01966

Key clinical point: In patients with early, operable breast cancer (BC), peritumoral injection of a local anesthetic (lidocaine) prior to surgery improved survival outcomes.

Major finding: Peritumoral infiltration of lidocaine at the time of surgery led to 26% improvement in disease-free survival (hazard ratio [HR] 0.74; P = .017) and 29% improvement in overall survival (HR 0.71; P = .019) at a median follow-up of 68 months. No adverse events related to injection of lidocaine were reported.

Study details: Findings are from the phase 3 study including 1583 patients with early, operable BC who did not receive prior neoadjuvant treatment and were randomly assigned to undergo surgery with or without a peritumoral injection of 0.5% lidocaine 7-10 minutes preoperatively.

Disclosures: This study was supported by Department of Atomic Energy, India. Dr. Sudeep Gupta declared receiving research funding from several sources.

Source: Badwe RA et al. Effect of peritumoral infiltration of local anesthetic before surgery on survival in early breast cancer. J Clin Oncol. 2023 (Apr 6). Doi: 10.1200/JCO.22.01966

Key clinical point: In women with 2-3 ipsilateral foci of breast cancer (BC), breast-conserving surgery (BCS; lumpectomy plus adjuvant radiation) resulted in a local recurrence rate that was below the a priori determined clinically acceptable threshold of 8%.

Major finding: BCS resulted in a highly acceptable 5-year local recurrence rate of 3.1% (95% CI 1.3%-6.4%) in patients with multiple ipsilateral BC.

Study details: Findings are from the phase 2 American College of Surgeons Oncology Group Z11102 (Alliance) trial including 204 women aged ≥40 years with multiple ipsilateral BC who underwent BCS.

Disclosures: This study was supported by the US National Institutes of Health. Some authors declared owning stocks; serving on editorial boards, in leadership positions, or as employees; receiving research funding, honoraria, or travel and accommodation expenses; or having other ties with various sources.

Source: Boughey JC et al. Local recurrence after breast-conserving therapy in patients with multiple ipsilateral breast cancer: Results from ACOSOG Z11102 (Alliance). J Clin Oncol. 2023 (Mar 28). Doi: 10.1200/JCO.22.02553

Key clinical point: In women with 2-3 ipsilateral foci of breast cancer (BC), breast-conserving surgery (BCS; lumpectomy plus adjuvant radiation) resulted in a local recurrence rate that was below the a priori determined clinically acceptable threshold of 8%.

Major finding: BCS resulted in a highly acceptable 5-year local recurrence rate of 3.1% (95% CI 1.3%-6.4%) in patients with multiple ipsilateral BC.

Study details: Findings are from the phase 2 American College of Surgeons Oncology Group Z11102 (Alliance) trial including 204 women aged ≥40 years with multiple ipsilateral BC who underwent BCS.

Disclosures: This study was supported by the US National Institutes of Health. Some authors declared owning stocks; serving on editorial boards, in leadership positions, or as employees; receiving research funding, honoraria, or travel and accommodation expenses; or having other ties with various sources.

Source: Boughey JC et al. Local recurrence after breast-conserving therapy in patients with multiple ipsilateral breast cancer: Results from ACOSOG Z11102 (Alliance). J Clin Oncol. 2023 (Mar 28). Doi: 10.1200/JCO.22.02553

Key clinical point: In women with 2-3 ipsilateral foci of breast cancer (BC), breast-conserving surgery (BCS; lumpectomy plus adjuvant radiation) resulted in a local recurrence rate that was below the a priori determined clinically acceptable threshold of 8%.

Major finding: BCS resulted in a highly acceptable 5-year local recurrence rate of 3.1% (95% CI 1.3%-6.4%) in patients with multiple ipsilateral BC.

Study details: Findings are from the phase 2 American College of Surgeons Oncology Group Z11102 (Alliance) trial including 204 women aged ≥40 years with multiple ipsilateral BC who underwent BCS.

Disclosures: This study was supported by the US National Institutes of Health. Some authors declared owning stocks; serving on editorial boards, in leadership positions, or as employees; receiving research funding, honoraria, or travel and accommodation expenses; or having other ties with various sources.

Source: Boughey JC et al. Local recurrence after breast-conserving therapy in patients with multiple ipsilateral breast cancer: Results from ACOSOG Z11102 (Alliance). J Clin Oncol. 2023 (Mar 28). Doi: 10.1200/JCO.22.02553

Key clinical point: A dose of 25 mg exemestane 3 times weekly was noninferior to the standard once-daily dose in decreasing serum estradiol levels in postmenopausal women with stage 0-II estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Compared with once-daily exemestane, 3-times-weekly exemestane was noninferior (difference in percentage change 2.0%; P for noninferiority = .02) whereas once-weekly exemestane was less effective in decreasing serum estradiol levels in participants who received ≥80% of the active scheduled pills and underwent blood testing as per protocol. The adverse event rate was similar across all treatment arms.

Study details: This phase 2b trial included 180 postmenopausal women with stage 0-II, ER+ BC who were randomly assigned to receive 25 mg exemestane once daily, 3 times weekly, or once weekly for 4-6 weeks before surgery.

Disclosures: This study was supported by the US National Cancer Institute and other sources. Two authors declared being principal investigators, holding stocks, or receiving partial salary support or personal fees from various sources.

Source: Serrano D et al. Efficacy of alternative dose regimens of exemestane in postmenopausal women with stage 0 to II estrogen receptor-positive breast cancer: A randomized clinical trial. JAMA Oncol. 2023 (Mar 23). Doi: 10.1001/jamaoncol.2023.0089

Key clinical point: A dose of 25 mg exemestane 3 times weekly was noninferior to the standard once-daily dose in decreasing serum estradiol levels in postmenopausal women with stage 0-II estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Compared with once-daily exemestane, 3-times-weekly exemestane was noninferior (difference in percentage change 2.0%; P for noninferiority = .02) whereas once-weekly exemestane was less effective in decreasing serum estradiol levels in participants who received ≥80% of the active scheduled pills and underwent blood testing as per protocol. The adverse event rate was similar across all treatment arms.

Study details: This phase 2b trial included 180 postmenopausal women with stage 0-II, ER+ BC who were randomly assigned to receive 25 mg exemestane once daily, 3 times weekly, or once weekly for 4-6 weeks before surgery.

Disclosures: This study was supported by the US National Cancer Institute and other sources. Two authors declared being principal investigators, holding stocks, or receiving partial salary support or personal fees from various sources.

Source: Serrano D et al. Efficacy of alternative dose regimens of exemestane in postmenopausal women with stage 0 to II estrogen receptor-positive breast cancer: A randomized clinical trial. JAMA Oncol. 2023 (Mar 23). Doi: 10.1001/jamaoncol.2023.0089

Key clinical point: A dose of 25 mg exemestane 3 times weekly was noninferior to the standard once-daily dose in decreasing serum estradiol levels in postmenopausal women with stage 0-II estrogen receptor-positive (ER+) breast cancer (BC).

Major finding: Compared with once-daily exemestane, 3-times-weekly exemestane was noninferior (difference in percentage change 2.0%; P for noninferiority = .02) whereas once-weekly exemestane was less effective in decreasing serum estradiol levels in participants who received ≥80% of the active scheduled pills and underwent blood testing as per protocol. The adverse event rate was similar across all treatment arms.

Study details: This phase 2b trial included 180 postmenopausal women with stage 0-II, ER+ BC who were randomly assigned to receive 25 mg exemestane once daily, 3 times weekly, or once weekly for 4-6 weeks before surgery.

Disclosures: This study was supported by the US National Cancer Institute and other sources. Two authors declared being principal investigators, holding stocks, or receiving partial salary support or personal fees from various sources.

Source: Serrano D et al. Efficacy of alternative dose regimens of exemestane in postmenopausal women with stage 0 to II estrogen receptor-positive breast cancer: A randomized clinical trial. JAMA Oncol. 2023 (Mar 23). Doi: 10.1001/jamaoncol.2023.0089

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

The sex of a red blood cell donor has no effect on the survival of a transfusion recipient, data suggest.

In a randomized clinical trial with almost 9,000 patients, the adjusted hazard ratio of death among recipients of female donors’ blood, compared with recipients of male donors’ blood, was 0.98. The data contradict the finding of previous observational studies that donor sex is associated with recipient outcomes.

“The key finding was that we actually had a null result,” study author Dean Fergusson, MD, PhD, senior scientist at the Ottawa Hospital Research Institute, said in an interview. “We went in thinking that male donor blood would confer a benefit over female donor blood, and we found that there’s absolutely no difference between the donor sexes on recipient outcomes – mortality and other major secondary outcomes,” Dr. Fergusson added.

The study was published in the New England Journal of Medicine.
 

Differences ‘don’t matter’

A 2015 article from the National Heart, Lung, and Blood Institute identified a potential effect of donor sex on transfusion recipient survival. Since then, several observational studies have suggested that donor sex may influence survival after transfusion. This research includes two large studies, one from Canada and one from the Netherlands, that reported a heightened risk of death among recipients of red-cell units from female donors or donors who had been pregnant. Other studies, however, yielded conflicting results.

“The rationale was that female blood, because of biochemical properties, different hormones, exposure to babies and other males, all led to a different product, if you will, and these subtle changes could affect the blood product in terms of shelf life and potency,” said Dr. Fergusson. “That itself would have downstream effects on the recipient.”

The current double-blind study included 8,719 patients who received transfusions from September 2018 to December 2020 at three academic medical centers in Canada. Of this group, 5,190 received male donor blood, and 3,529 received blood from female donors.

The researchers randomly assigned patients in a 60:40 ratio to male and female donor groups. Data collection and follow-up were performed by the Ottawa Hospital Data Warehouse, Canadian Blood Services, and ICES, an independent research institute. Patient characteristics were similar in both trial groups at baseline.

After an average follow-up of 11.2 months, with a maximum follow-up of 29 months, 1,141 patients in the female donor group and 1,712 in the male donor group died. The study found no statistically significant difference in overall survival between the two groups. The unadjusted HR for death, with the male group as the reference, was 0.97, and the adjusted HR was 0.98. The rates of overall survival were 58% and 56.1% in the female and male donor groups, respectively.

The study did not prove that differences in outcome based on donor sex do not exist, said Dr. Fergusson. “But those differences really don’t matter in the recipient.”

The design of the trial itself was unique, Dr. Fergusson said. After patients consented to participate and underwent randomization, the study used routinely collected data from the participating hospitals’ electronic medical records rather than collect data anew for each patient. “That had a profound effect on the efficiency of the trial. We did this trial for a cost of less than $300,000, and typically it would cost $9 million by using high-quality electronic health data.”

The study also evaluated several secondary outcomes. Recipients of female donor blood had twice the incidence of MRSA infection. In addition, an unadjusted subgroup analysis suggested a 10% lower risk of death among male patients assigned to the female donor group, compared with those assigned to the male donor group.

The risk of death was almost three times higher among patients in the female donor group who received units from donors aged 20-29.9 years (HR, 2.93). “The inconsistency of the point estimates across groups and the multiplicity of analyses increase the risk that those findings were due to chance,” according to the authors.
 

Big data

Commenting on the study, Jeannie Callum, MD, professor and director of transfusion medicine at Queen’s University, Kingston, Ont., said that the use of routinely collected data from the participating hospitals’ electronic medical records was “one of the really great things about this paper.”

This use of Big Data “allows you to do a trial like this with almost 9,000 patients without spending millions and millions of dollars to have people go through charts and record data,” she added.

Dr. Callum also pointed out some of the trial’s limitations. “One of the things that kind of detracts from the study in my mind is that they randomized everybody that was getting a transfusion, but outpatients getting a transfusion have a very low mortality rate. So, you have a group of patients that are never going to have that endpoint being included in the study, and that might’ve diluted the findings.”

About 11.4% of participants received blood from a donor group other than the one to which they had been assigned, and this factor may further dilute the findings, said Dr. Callum. “That’s a difficult thing to avoid.” She noted that a trial in which she is collaborating, called Sex Matters, may answer some of these questions about the use of female versus male donor blood.

The investigators also noted that the findings may not be generalizable to other countries. “Just because we didn’t find something in Canada with our blood production system doesn’t mean that the United States might not find it different, because how they manufacture their red blood cells for transfusion is different than how we do them in Canada,” said Dr. Callum.

Nonetheless, this study shows the potential of using Big Data in medicine. “This is the future of large randomized clinical trials to quickly answer questions,” said Dr. Callum. “In the United States, Canada, and other countries that have these large electronic medical records systems, this kind of trial would be able to be done in other centers.”

The study was funded by the Canadian Institutes of Health Research. Dr. Fergusson and Dr. Callum disclosed no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Physical exercise is associated with a reduction in suicide attempts, new research suggests.

A meta-analysis of 17 randomized controlled trials (RCTs), which included more than 1,000 participants with mental or physical illnesses, showed there was a significant reduction in suicide attempts in participants randomly assigned to receive exercise interventions, compared with inactive controls. However, there were no differences between the exercise and the control groups in suicidal ideation or mortality.

On the other hand, there was also no significant difference in dropout rates between those randomly assigned to exercise versus inactive controls, suggesting that people with mental or physical impairments are able to adhere to exercise regimens.

“A common misconception is that patients, particularly those suffering from mental of physical illness, are not willing or motivated enough to participate in an exercise [regimen], and this has led to primary care providers underprescribing exercise to those with mental or physical illness,” lead author Nicholas Fabiano, MD, a resident in the department of psychiatry at the University of Ottawa, told this news organization.

As a result of the study findings, “we recommend that providers do not have apprehension about prescribing exercise to patients with physical or mental illness. Exercise may be an effective way to reduce suicidal behaviors” in these patients, he said.

The study was published online  in the Journal of Affective Disorders.
 

Physical, mental health strongly linked

Existing literature has “demonstrated a protective effect of physical activity on suicidal ideation in the general population,” but to date there have been no systematic reviews or meta-analyses investigating its impact on suicide-related outcomes in patients with physical or mental illness, the authors write.

“Those with mental or physical illness are at increased risk of suicide, compared to the general population,” Dr. Fabiano commented.

“We often split up ‘mental health’ and ‘physical health’ in medicine; however, I believe that the two are more on a continuum and a holistic term, such as ‘health,’ should be used instead,” he added.

He noted that mental and physical health are “inexorably intertwined” and those with physical illness are more prone to developing mental illness, whereas those with mental illness are more likely to suffer from a variety of other medical conditions. “Therefore, when treating those with mental illness, it is also imperative that we bolster one’s physical health through easily accessible activities such as exercise,” he said.

The goal of the study was to determine whether individuals with “any mental, physical, clinical, or subclinical condition” might benefit from exercise, particularly in relation to suicide-related outcomes. They searched multiple databases from inception to June 2022 to identify RCTs investigating exercise and suicidal ideation in participants with physical or mental conditions.

Of 673 studies, 17 met the inclusion criteria (total of 1,021 participants). Participants’ mean age was 42.7 years, 82% were female, and 54% were randomly assigned to an exercise intervention.

Most studies (82%) focused on clinical versus subclinical outcomes. Depression was the most commonly included condition (59%). Aerobic exercise (53%) was the most common form of exercise used in the active study groups. This was followed by mind-body exercise and strength training (53%, 17.6%, and 17.6%, respectively). The mean follow-up time was 10 weeks.
 

Reduced impulsivity

The researchers found a difference in post-intervention suicidal ideation when they compared exercise participants to all control and inactive control participants (standardized mean difference, –1.09; 95% confidence interval, –3.08 to 0.90; P = .20, k = 5). However, the difference was not statistically significant.

Similarly, there was no significant difference (P = .60) in suicidal ideation incidence for subgroup analyses that stratified data among participants with depression, sickle cell disease, and suicidality.

All-cause discontinuation also did not significantly differ between participants who were randomly assigned to exercise interventions versus all controls or inactive controls (odds ratio, 0.85; 95% CI, 0.38-1.94; P = .86, k = 12 and OR, 0.81; 95% CI, 0.25-2.68; P = .70). All-cause discontinuation also did not differ between participants randomized to exercise versus active controls (OR, 0.94; 95% CI, 0.38-2.32; P = .79, k = 3).

Likewise, there were nonsignificant differences between participants who underwent aerobic exercise and strength training (P = .20).

However, there were some nonsignificant differences when comparing participants with depression and stress who received the exercise intervention versus controls (P = .46).

There was a significant reduction in suicide attempts in individuals who participated in exercise interventions versus inactive controls (OR, 0.23; 95% CI, 0.09-0.67; P = .04, k = 2). On the other hand, there was no significant difference in mortality (P = .70).

Most of the studies (82%) were “at high risk of bias,” the authors note. In addition, the analysis was limited because the included studies were “few, underpowered, and heterogeneous.”

Dr. Fabiano hypothesized that the lack of effect on suicidal ideation or mortality is “likely due to the limited sample size.” As additional RCTs are conducted, Dr. Fabiano expects to see decreases in both suicidal ideation and suicide attempts.

The findings may “be explained by the ideation-to-action framework, which suggests that the development of suicidal ideation and the progression to suicide attempts are distinct processes with different influential factors,” he said.

Increased levels of exercise have been “shown to reduce emotional impulsivity and, as it has been shown that most suicide attempts are characterized by impulsivity and low lethality, we hypothesize that regular exercise serves as a protective factor against suicide attempts,” he said.
 

Not useful?

Commenting on the study, Fabien Legrand, PhD, a lecturer in clinical psychology, University of Reims Champagne-Ardenne, Reims, France, said that the impact of physical activity is of “particular interest” to him because it is closely linked to his research activity, where he has “been exploring the antidepressant effects of exercise for more than 15 years.”

A small pilot study conducted by Dr. Legrand and colleagues found rigorous physical activity to be helpful in reducing hopelessness in psychiatric patients, compared with controls. “This result is of particular relevance for suicidal patients, since it has long been documented that hopelessness is one of the main triggers of suicide ideation and suicide attempts,” he said.

Initially, Dr. Legrand “warmly welcomed” the current review and meta-analysis on the exercise and suicide. However, he felt that the paper fell short in accomplishing its intended goal. “After a thorough reading of the paper, I don’t think that the information provided can be used in any way,” he stated.

“The paper’s title – ‘Effects of Physical Exercise on Suicidal Ideation and Behavior’ – does not do justice to its content, since 9 of the included 17 RCTs did not measure changes in suicidal ideation and/or suicidal behavior following participation in an exercise program,” noted Dr. Legrand, who was not involved with authorship or the current analysis.

The study was funded by the University of Ottawa department of psychiatry. Dr. Fabiano declares no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Legrand declares no relevant financial relationships.

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

Key clinical point: Polatuzumab vedotin (Pola)-rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with other novel regimens prolongs progression-free survival (PFS) in patients with previously untreated activated B-cell (ABC)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Pola-R-CHP prolonged PFS in patients with ABC-type DLBCL compared with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)+bortezomib (hazard ratio [HR] 0.52; P  =  .02); R-CHOP+ibrutinib (HR 0.43; P  =  .001), R-CHOP+lenalidomide (HR 0.51; P  =  .009), obinutuzumab-CHOP (HR 0.46; P  =  .008), R-CHOP (HR 0.40; P < .001), and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P  =  .07). Pola-R-CHP had no PFS benefit in patients with germinal center B-cell (GCB)-type DLBCL.

Study details: This was a network meta-analysis of 12 randomized controlled trials involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received Pola-R-CHP or other regimens.

Disclosures: This study did not report the funding source. The authors declared no conflicts of interest.

Source: Sheng Z et al. Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC‑type diffuse large B‑cell lymphoma: A network meta‑analysis of 20 RCTs. Ann Hematol. 2023;102:1011-1017 (Mar 22). Doi: 10.1007/s00277-023-05161-1

Key clinical point: Polatuzumab vedotin (Pola)-rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with other novel regimens prolongs progression-free survival (PFS) in patients with previously untreated activated B-cell (ABC)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Pola-R-CHP prolonged PFS in patients with ABC-type DLBCL compared with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)+bortezomib (hazard ratio [HR] 0.52; P  =  .02); R-CHOP+ibrutinib (HR 0.43; P  =  .001), R-CHOP+lenalidomide (HR 0.51; P  =  .009), obinutuzumab-CHOP (HR 0.46; P  =  .008), R-CHOP (HR 0.40; P < .001), and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P  =  .07). Pola-R-CHP had no PFS benefit in patients with germinal center B-cell (GCB)-type DLBCL.

Study details: This was a network meta-analysis of 12 randomized controlled trials involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received Pola-R-CHP or other regimens.

Disclosures: This study did not report the funding source. The authors declared no conflicts of interest.

Source: Sheng Z et al. Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC‑type diffuse large B‑cell lymphoma: A network meta‑analysis of 20 RCTs. Ann Hematol. 2023;102:1011-1017 (Mar 22). Doi: 10.1007/s00277-023-05161-1

Key clinical point: Polatuzumab vedotin (Pola)-rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with other novel regimens prolongs progression-free survival (PFS) in patients with previously untreated activated B-cell (ABC)-type diffuse large B-cell lymphoma (DLBCL).

Major finding: Pola-R-CHP prolonged PFS in patients with ABC-type DLBCL compared with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)+bortezomib (hazard ratio [HR] 0.52; P  =  .02); R-CHOP+ibrutinib (HR 0.43; P  =  .001), R-CHOP+lenalidomide (HR 0.51; P  =  .009), obinutuzumab-CHOP (HR 0.46; P  =  .008), R-CHOP (HR 0.40; P < .001), and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P  =  .07). Pola-R-CHP had no PFS benefit in patients with germinal center B-cell (GCB)-type DLBCL.

Study details: This was a network meta-analysis of 12 randomized controlled trials involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received Pola-R-CHP or other regimens.

Disclosures: This study did not report the funding source. The authors declared no conflicts of interest.

Source: Sheng Z et al. Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC‑type diffuse large B‑cell lymphoma: A network meta‑analysis of 20 RCTs. Ann Hematol. 2023;102:1011-1017 (Mar 22). Doi: 10.1007/s00277-023-05161-1