Does ChatGPT Accurately Cite Scientific Sources?

BACKGROUND AND PURPOSE:

• ChatGPT performs well when generating new content, but performs poorly when providing scientific references
• Chen and Chen (JAMA Network Open, 2023) quantified ChatGPT’s citation error rate

METHODS:

• Study design
  • The GPT-3.5 and GPT-4 models were used
  • ChatGPT was asked about specific learning health systems topics followed by citation request
    • E.g., “Machine learning can use EHR data. Provide 8 journal articles for stroke risk prediction models using EHR data”
  • Cited journal articles were verified using Google Scholar
    • To determine a reliable error rate, over 300 article references were produced on the LHS topics
  • The error rate between the GPT-4 and GPT-3.5 models was compared using the Fisher exact test
• Primary outcome
  • Error rate in citing scientific articles

RESULTS:

• When asked to provide citations, the error rate was significantly higher for GPT-3.5, compared to GPT-4 (P<0.001), but both had high error rates
  • GPT-3.5: 98.1% (95% CI, 94.7 to 99.6)
  • GPT-4: 20.6% (95% CI, 15.8 to 26.1)
• Narrower topics tended to have more fake articles than broader topics

CONCLUSION:

• GPT-4 could be used to provide citations regarding new learning health systems education and training materials, provided they are verified by humans
• The authors state

When asked why it returned fake references, ChatGPT explained that the training data may be unreliable, or the model may not be able to distinguish between reliable and unreliable sources

Learn More – Primary Sources:

Accuracy of Chatbots in Citing Journal Articles

FDA Finalizes New Mammography Dense Breast Notification Rule

SUMMARY:

The FDA has updated the mammography regulations and now requires that mammography facilities notify patients about the density of their breasts. The amendments incorporate language that specifies how breast density can influence the accuracy of mammography in addition to recommending a discussion with their healthcare professional. The rule goes into effect September 10, 2024. Currently, the ACOG committee opinion states unequivocally that healthcare professionals comply with all laws, although evidence is lacking as to clinical utility and improved outcomes with additional screening and testing.

Summary of Results to be Provided to Patients (FDA Rule)

Non-Dense Breast

Breast tissue can be either dense or not dense

Dense tissue makes it harder to find breast cancer on a mammogram and also raises the risk of developing breast cancer

Your breast tissue is not dense

Talk to your healthcare provider about breast density, risks for breast cancer, and your individual situation

Dense Breast

Breast tissue can be either dense or not dense

Dense tissue makes it harder to find breast cancer on a mammogram and also raises the risk of developing breast cancer

Your breast tissue is dense

In some people with dense tissue, other imaging tests in addition to a mammogram may help find cancers

Talk to your healthcare provider about breast density, risks for breast cancer, and your individual situation

ACOG

• The current ACOG Practice Advisory States

While ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in individuals with dense breasts who are asymptomatic and have no additional risk factors, ACOG recommends that clinicians comply with the new FDA rule and any state laws and federal rules that require disclosure of a patient’s breast density as recorded in a mammogram report

BI-RADS Density Categories (for more on BI-RADS classification, see ‘Related ObG Topics’ Below)

• a. Breasts are almost entirely fatty
  • Prevalence: 10%
  • Mammography considered highly sensitive in this setting (88%)
• b. There are scattered areas of fibroglandular density
  • Prevalence: 43%
  • Still sensitive but decreased from category a (82%)
• c. Breasts are heterogeneously dense
  • Prevalence: 39%
  • Small masses may be obscured
  • Sensitivity drops to 69%
• d. Breasts are extremely dense
  • Prevalence: 8%
  • Significantly lowers sensitivity of mammography (62%)

KEY POINTS:

• Dense breast tissue and screening is more common in younger women
  • Accuracy of mammography for the detection of breast cancer is reduced (less sensitive)
  • In women with heterogeneously and extremely dense breasts, digital mammography appears to be superior to film with respect to efficacy
• Breast cancer risk
  • Dense breast tissue (BI-RADS density categories c and d) is associated with increased breast cancer risk
  • BI-RADS c breast cancer risk: 1.2 relative risk compared to average breast density
  • BI-RADS d breast cancer risk: 2.1 relative risk compared to average breast density
• The FDA also has required reporting language that should be provided to the referring healthcare professional that falls into 4 categories

(A) The breasts are almost entirely fatty

(B) There are scattered areas of fibroglandular density

(C) The breasts are heterogeneously dense, which may obscure small masses

(D) The breasts are extremely dense, which lowers the sensitivity of mammography

Learn More – Primary Sources:

FDA Updates Mammography Regulations to Require Reporting of Breast Density Information and Enhance Facility Oversight (2023)

ACOG Committee Opinion 625: Management of Women With Dense Breasts Diagnosed by Mammography

ACOG Practice Advisory: The U.S. Food and Drug Administration Requires Notification of Breast Density in Mammography Reports

Is Caffeine Consumption Linked to Lower BMI and Risk of Type 2 Diabetes

BACKGROUND AND PURPOSE:

• Coffee consumption has been linked with a lower risk of type 2 diabetes and cardiovascular disease in observational studies
• Larsson et al. (BMJ, 2023) investigate the potential causal effects of long-term plasma caffeine concentrations on adiposity, type 2 diabetes, and major cardiovascular diseases using mendelian randomization to determine causality

METHODS:

• Two sample mendelian randomization study
• Population
  • Primarily European ancestry
  • Participating in cohorts contributing to genome-wide association study consortia
• Exposures
  • Genome-wide association study summary data for associations of two single nucleotide polymorphisms associated with plasma caffeine at the genome-wide significance threshold
    • rs2472297 near the CYP1A2 gene
    • rs4410790 near the AHR gene
• Primary outcomes
  • BMI | Whole body fat mass | Whole body fat-free mass | Type 2 diabetes | Ischemic heart disease | Atrial fibrillation | Heart failure | Stroke

RESULTS:

• 9876 individuals
• Higher genetically predicted plasma caffeine concentrations were associated with lower
  • BMI
    • Beta −0.08 standard deviation (95% CI, −0.10 to −0.06)
    • 1 SD equals about 4.8 kg/m2 in BMI, for every standard deviation increase in plasma caffeine
  • Whole body fat mass
    • Beta −0.06 SD (95% CI, −0.08 to −0.04)
    • 1 SD equals about 9.5 kg | P<0.001
• There was no association with fat-free mass
  • Beta −0.01 SD (95% CI, −0.02 to −0.00)
  • 1 SD equals about 11.5 kg | P=0.17
• Higher genetically predicted plasma caffeine concentrations were associated with a lower risk of type 2 diabetes (two consortia: FinnGen and DIAMANTE)
  • Combined OR 0.81 (95% CI, 0.74 to 0.89) | P<0.001
• Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through BMI reduction
  • 43% (95% CI, 30 to 61)
• There were no strong associations between genetically predicted plasma caffeine concentrations and a risk of any of the studied cardiovascular diseases

CONCLUSION:

• A genetic prediction of lifelong, higher plasma caffeine concentrations was associated with a lower BMI and lower risk of type 2 diabetes
• The authors state

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index reduction 

Learn More – Primary Sources:

Appraisal of the causal effect of plasma caffeine on adiposity, type 2 diabetes, and cardiovascular disease: two sample mendelian randomisation study

Meta-Analysis: Protection Against SARS-CoV-2 From Previous Infection

BACKGROUND AND PURPOSE:

• The COVID-19 Forecasting Team (The Lancet, 2023) systematically synthesized studies to estimate protection from past infection by SARS-CoV-2

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • Cohort studies and test-negative case-control studies
  • Compared risk reduction of COVID-19 among individuals with a past SARS-CoV-2 infection vs those without a previous infection
• Study design
  • Primary outcome was based upon variants and time since infection
  • Bayesian meta-regression was used to estimate the pooled estimates of protection
  • Risk-of-bias assessment was evaluated using quality-assessment tools
• Primary outcome
  • Effectiveness of past infection by outcome against infection, symptomatic disease, and severe disease

RESULTS:

• 65 studies (19 countries)
• Protection from infection and any symptomatic disease was
  • High for ancestral, alpha, beta, and delta variants
  • Lower for the omicron BA.1 variant
    • Against re-infection: 45.3% (95% uncertainty interval (UI), 17.3 to 76.1)
    • Against symptomatic disease: 44.0% (95% UI, 26.5 to 65.0)
• For all variants, protection against re-infection declined over time
  • From ancestral, alpha, and delta variants, this protection declined over time, but remained at 78% for 40 weeks
  • Protection against re-infection by the omicron BA.1 variant declined more rapidly | At 40 weeks: 36.1% (95% UI, 24.4 to 51.3)
• For all variants, mean pooled effectiveness against severe disease was greater than 78%
• Protection against severe disease remained high for all variants
  • Ancestral, alpha, and delta variants at 40 weeks: 90.2% (95% UI, 69.7 to 97.5)
  • Omicron BA.1 at 40 weeks: 88.9% (95% UI, 84.7 to 90.9)

CONCLUSION:

• Protection against re-infection was high and remained high for ancestral SARS-CoV-2 variants
  • For Omicron BA.1, this protection waned more quickly, and was around 36% at 40 weeks
• Protection against severe disease was high for all variants, and remained high for all
• The authors state

Our analysis suggests that the level of protection from past infection by variant and over time is at least equivalent if not greater than that provided by two-dose mRNA vaccines

Learn More – Primary Sources:

Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis

STI Detection Assays: Are Vaginal Swabs Better Than Urine Samples?

BACKGROUND AND PURPOSE:

• Vaginal swabs are recommended for detection of chlamydia, gonorrhea, and/or trichomoniasis, but many commercially available kits use urine samples
• Aaron et al. (Ann Fam Med, 2023) assessed the diagnostic sensitivity of commercially available assays for vaginal swabs vs urine specimens from women

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • Studies that evaluated commercially available STI assays
  • Data obtained from the same assay on both a urine specimen and a vaginal swab from the same patient
• Study design
  • Pooled estimates of sensitivity were calculated, as well as odds ratios for any difference in performance
• Primary outcome
  • Sensitivity of tests for detecting chlamydia, gonorrhea, and trichomoniasis

RESULTS:

• 28 articles
  • Comparisons for chlamydia: 30 | Gonorrhea: 16 | Trichomoniasis: 9
• Pooled sensitivity estimates were higher for vaginal swabs for all infections (P<0.001 for all)
  • Chlamydia
    • Vaginal swabs: 94.1% (95% CI, 93.2% to 94.9%) | Urine samples: 86.9% (95% CI, 85.6% to 88.0%) 
    • Odds ratio (OR) that vaginal swabs were more sensitive than urine for detection: 2.69 (95% CI, 2.21 to 3.28); P<.001
  • Gonorrhea
    • Vaginal swabs: 96.5% (95% CI, 94.8% to 97.7%) | Urine samples: 90.7% (95% CI, 88.4% to 92.5%) 
    • OR that vaginal swabs were more sensitive than urine for detection: 3.68 (95% CI, 2.19 to 6.18); P<.001
  • Trichomoniasis
    • Vaginal swabs: 98.0% (95% CI, 97.0% to 98.7%) | Urine samples: 95.1% (95% CI, 93.6% to 96.3%) 
    • The difference in sensitivity was not statistically significant: OR of 2.48 (95% CI, 1.50 to 4.08); P=0.15

CONCLUSION:

• Compared to urine samples, vaginal swabs have superior sensitivity for detecting chlamydia and gonorrhea
• There was a small sample size for trichomoniasis
• The authors state

For female screening, the CDC has recommended vaginal swabs as the optimal specimen type for both CT and NG NAATs since 2014

Our data support and reinforce that recommendation by adding analyses of numerous publications since the evidence for the CDC recommendations was generated

We cannot continue to justify the use of urine except for women for whom collection of a vaginal sample is not acceptable

Learn More – Primary Sources:

Vaginal Swab vs Urine for Detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis: A Meta-Analysis

Does Elinzanetant Improve Sleep and Vasomotor Symptoms Associated with Menopause

BACKGROUND AND PURPOSE:

• Newer nonhormonal medications are being investigated for the treatment of vasomotor symptoms (VMS) and sleep symptoms associated with menopause
• Elinzanetant is a selective NK-1,3 receptor antagonist that may improve sleep and quality of life for women with menopause
• Simon et al. (Menopause, 2023) sought to determine the efficacy and safety of elinzanetant for improving menopause symptoms

METHODS:

• Phase 2b, adaptive, dose-range finding study
• Multicenter, multicountry, double-blind, placebo-controlled
  • 25 sites across the US, UK, and Canada
• Participants
  • Postmenopausal women
  • 40 to 65 years
  • ≥7 moderate-to-severe VMS per day
• Intervention
  • Elinzanetant at 40 mg, 80 mg, 120 mg, or 160 mg once daily
  • Placebo once daily
• Primary outcomes
  • A reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 to 12
• Secondary outcomes
  • Patient-reported assessments of sleep and quality of life

RESULTS:

• 180 participants
• Compared to placebo, elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency
  • 120 mg at week 4: difference in least squares (LS) means −3.93 (SE, 1.02) | P<0.001
  • 120 mg at week 12: difference in LS means −2.95 (SE, 1.15) | P=0.01
  • 160 mg at week 4:  difference in LS means −2.63 (SE, 1.03) | P=0.01
• Elinzanetant 120 mg reduced nighttime awakenings at weeks 1, 2, 4, and 8 (P = 0.006 to P = 0.049), but not at week 12
  • Elinzanetant 160 mg did not improve sleep compared to placebo
• Both 120 mg and 160 mg doses improve quality of life at 4 and 12 weeks
  • 120 mg at week 4: difference in LS means −3.41 (SE, 0.92) | P<0.001
  • 120 mg at week 12: difference in LS means −4.27 (SE, 1.01) | P<0.001
  • 160 mg at week 4: difference in LS means −3.28 (SE, 0.95) | P<0.001
  • 160 mg at week 12: difference in LS means −4.85 (SE, 1.05) | P<0.001
• All doses were well tolerated

CONCLUSION:

• Elinzanetant at 120 mg or 160 mg daily reduced VMS frequency through 4 to 12 weeks vs placebo
• The authors state

…the 120-mg dose offers clinically important efficacy across a range of menopause-related symptoms with the most favorable benefit/risk profile

The efficacy and safety of elinzanetant 120 mg will be further evaluated in a phase 3 program

Learn More – Primary Sources:

Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1)

Cochrane 2023: Is Ultrasonography Plus Mammography Superior to Mammography Alone in Average Risk Women?

BACKGROUND AND PURPOSE:

• Glechner et al. (Cochrane Database of Systematic Reviews, 2023) assessed the comparative effectiveness and safety of mammography in combination with breast ultrasonography vs mammography alone for breast cancer screening for women at average risk of breast cancer

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • Randomized controlled trials and controlled non-randomized studies of women at average risk of breast cancer between the ages of 40 and 75
  • Studies were also included if 80% of the population met the age and breast cancer risk inclusion criteria
• Study design
  • GRADE criteria were used to assess quality of evidence
  • Random-effects meta-analysis was used
• Primary outcome
  • Breast cancer detection
  • Breast cancer mortality

RESULTS:

• 8 studies | 209,207 women
  • Follow-up 1 to 3 years | Dense breasts: 48 to 100% of women in included studies
• None of the studies assessed whether mammography screening in combination with ultrasonography led to lower mortality from breast cancer or all-cause mortality
• Screening with a combination of mammography and ultrasonography detects more breast cancer than mammography alone
  • Additional ultrasonography: 5 detected per 1000
  • Mammography alone: 3 detected per 1000
  • Risk ratio (RR) 1.54 (95% CI, 1.22 to 1.94)
  • 1 trial | High-certainty evidence
• The percentage of invasive tumors was similar between the groups
  • Additional ultrasonography: 69.6%
  • Mammography alone: 73.5%
  • RR 0.95 (95% CI, 0.82 to 1.09)
  • Low-certainty evidence
• Positive lymph node status was detected less frequently in women with invasive cancer who underwent mammography screening and ultrasonography
  • Additional ultrasonography: 18%
  • Mammography alone: 34%
  • RR 0.53 (95% Ci, 0.33 to 0.86)
  • Moderate-certainty evidence
• interval carcinomas occurred less frequently in the group screened by mammography and ultrasonography
  • Additional ultrasonography: 5 per 10,000 women
  • Mammography alone: 10 per 10,000 women
  • RR 0.50 (95% CI, 0.29 to 0.89)
  • High-certainty evidence
• False-negative results were less common when ultrasonography was used in addition to mammography
  • Additional ultrasonography: 9%
  • Mammography alone: 23%
  • RR 0.39 (95% CI, 0.23 to 0.66)
  • Moderate-certainty evidence
• False-positive results were more common in the group with additional ultrasonography
  • RR 1.43 (95% CI, 1.37 to 1.50)
  • High-certainty evidence
• Compared to mammography alone, for every 1000 women participating in screening with a combination of mammography and ultrasonography, 27 more women will have a biopsy
  • RR 2.49 (95% CI, 2.28 to 2.72)
  • High-certainty evidence

Breast Density

• Secondary analysis of J-START trial
  • 19,213 women
  • In women with dense breasts, the combination of mammography and ultrasonography detected 3 more cancer cases per 1000 women screened
    • RR 1.65 (95% CI, 1.0 to 2.72)
    • High-certainty evidence
• Meta-analysis of three cohort studies showed similar findings in women with dense breasts
  • RR 1.78 (95% CI, 1.23 to 2.56)
  • Moderate-certainty evidence
• In women with non-dense breasts, there were more cancer cases detected when adding ultrasound to mammography screening
  • RR 1.93 (95% CI, 1.01 to 3.68)
  • Moderate-certainty evidence
• However, meta-analysis of two cohort studies did not support this finding
  • RR 1.13 (95% CI, 0.85 to 1.49)
  • Low-certainty evidence

CONCLUSION:

• Based on one quality study, adding ultrasonography to mammography results in more screening‐detected breast cancer cases among average risk women
• There were higher false-positives and more biopsies with the addition of ultrasonography
• No studies addressed mortality

The authors state

For women with dense breasts, cohort studies more in line with real‐life clinical practice confirmed this finding, whilst cohort studies for women with non‐dense breasts showed no statistically significant difference between the two screening interventions

Learn More – Primary Sources:

Mammography in combination with breast ultrasonography versus mammography for breast cancer screening in women at average risk

Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial

RCT Results: Does Bariatric-Metabolic Surgery Lead to Better Outcomes in Patients with NASH? 

BACKGROUND AND PURPOSE:

• Observational studies have suggested that non-alcoholic steatohepatitis (NASH) may be significantly improved by bariatric–metabolic surgery
• Verrastro et al. (The Lancet, 2023) compared the efficacy and safety of bariatric-metabolic surgery with lifestyle intervention plus best medical care as a treatment of NASH

METHODS:

• Multicenter, open-label, randomized trial
• Participants
  • 25 to 70 years
  • Obesity, with or without type 2 diabetes
  • Histologically confirmed NASH
• Interventions
  • Lifestyle modification plus best medical care
  • Roux-en-Y gastric bypass
  • Sleeve gastrectomy
• Study design
  • 1:1:1 randomization
  • Obesity: BMI≥30 or 27.5 kg/m2 if Asian descent
  • Hepatopathologists performing biopsies were blinded
  • 80% power, with type I error, set to 0.05 | sample size 77 in each group, with final total of 288 participants to account for 20% attrition rate
• Primary outcome
  • Histological resolution of NASH without worsening of fibrosis at 1-year follow-up

RESULTS:

• Lifestyle modification: 96 patients | Roux-en-Y gastric bypass: 96 | Sleeve gastrectomy: 96
• In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in both surgery groups compared to lifestyle modification (P<0.0001)
  • Lifestyle modification: 16%
  • The Roux-en-Y gastric bypass group: 56%
  • The sleeve gastrectomy group: 57%
• The calculated probability of NASH resolution was also higher in these groups
  • Roux-en-Y gastric bypass group
    • 3.60 times greater (95% CI 2.19 to 5.92) | P<0.0001
  • Sleeve gastrectomy group
    • 3.67 times greater (95% CI, 2.23 to 6.02) | P<0.0001
• In the per protocol analysis, the percentage of participants who met the primary outcome remained higher in the surgery groups (P<0.0001)
  • Lifestyle modification: 19%
  • The Roux-en-Y gastric bypass group: 70%
  • The sleeve gastrectomy group: 70%
• No deaths or life-threatening complications were reported
• Severe adverse events occurred in 6% of bariatric-metabolic surgery participants
  • These individuals did not need re-operations and severe events resolved with medical or endoscopic management

CONCLUSION:

• Treatment of NASH is more effective with bariatric-metabolic surgery than with lifestyle modification and optimized medical therapy
• The authors state

Novel anti-obesity drugs might result in better NASH outcomes than those we observed in the non-surgical group of our study, given their greater weight-loss potential

Future research should compare new anti-obesity drugs with other active drugs or bariatric-metabolic surgery

Learn More – Primary Sources:

Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial

Is the Duration of Proton Pump Inhibitor Use Related to an Increased Dementia Risk?

BACKGROUND AND PURPOSE:

• Northuis et al. (Neurology, 2023) evaluated the associations between current and cumulative PPI use and risk of incident dementia

METHODS:

• Secondary analysis of community-based cohort study
  • Data derived from the Atherosclerosis Risk in Communities (ARIC) Study
• Population
  • Participants in the ARIC study from time of enrollment (1987 to 89) through 2017
• Exposures
  • PPI use
    • Current use at baseline
    • Duration of use prior to baseline: 0 days | 1 day to 2.8 years | 2.8 to 4.4 years | >4.4 years
• Study design
  • ARIC Visit 5 (2011 to 2013) was used as baseline, since this was the first visit in which PPI use was common
  • Cox Proportional Hazards models were used
    • Adjustments: Demographics | Co-morbid conditions | Other medication use
• Primary outcome
  • Incident dementia after visit 5

RESULTS:

• 5,712 dementia-free participants at visit 5
  • Mean age 75.4 (SD, 5.1) years
  • Black: 22% | Female: 58%
  • Median follow-up: 5.5 years
  • Minimum cumulative PPI use: 112 days | Maximum use: 20.3 years
• Incident dementia: 585 cases
• Participants using PPIs at Visit 5 were not at a significantly higher risk of developing dementia during subsequent follow-up than those not using PPIs
  • HR 1.1 (95% CI, 0.9 to 1.3)
• Those who used PPIs for >4.4 cumulative years prior to Visit 5 were at a higher risk of developing dementia during follow-up than those who reported no use
  • HR 1.3 (95% CI, 1.0 to 1.8)
• Associations were not significant for lesser amounts of PPI use

CONCLUSION:

• The use of PPIs for more than 4.4 years was associated with a higher risk of dementia in this population of adults aged 45 and older
• The authors state

Future studies are needed to understand possible pathways between cumulative PPI use and the development of dementia

Learn More – Primary Sources:

Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study

Meta-Analysis: Does Surgery Improve Leg Pain in Individuals with Sciatica?

BACKGROUND AND PURPOSE:

• Treatment for sciatica starts with non-surgical intervention, and can progress to surgical intervention if pain persists
• However, evidence supporting use of surgery in treating sciatica is limited
• Liu et al. (BMJ, 2023) investigated the effectiveness and safety of surgery compared with non-surgical treatment for sciatica

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • Randomized controlled trials
  • Studies that compared any surgical treatment with non-surgical treatment, epidural steroid injections, or placebo or sham surgery
  • Studies in people with sciatica of any duration due to lumbar disc herniation diagnosed by radiological imaging
• Study design
  • Data were pooled using a random effects model
  • Risk of bias was assessed with the Cochrane tool | Certainty of evidence was assessed with GRADE criteria
  • Follow up was intermediate term (≤6 weeks) | Short term (>6 weeks and ≤3 months) | Medium term (>3 and <12 months) | Long term (at 12 months)
  • Pain and disability scores: 100 point scale ranging from 0 (no pain or disability) to 100 (worst pain or disability)
• Primary outcomes
  • Leg pain
  • Disability
• Secondary outcomes
  • Adverse events | Back pain | Quality of life | Satisfaction with treatment

RESULTS:

• 24 trials
  • 12 studies (1711 participants) investigated the effectiveness of discectomy compared with non-surgical treatment or epidural steroid injections
• Very low to low certainty evidence showed that discectomy, compared with non-surgical treatment, reduced leg pain
  • Immediate term: mean difference −12.1 (95% CI, −23.6 to −0.5)
  • Short term: MD −11.7 (95% CI, −18.6 to −4.7))
  • Medium term: MD −6.5 (95% CI, −11.0 to −2.1)
• Negligible effects of discectomy on leg pain were found at long term
  • Long term: MD −2.3 (95% CI, −4.5 to −0.2)
• For disability, small, negligible, or no effects were found
• A similar effect on leg pain was found when comparing discectomy with epidural steroid injections
• For disability, compared to epidural steroid injections, discectomy had
  • A moderate effect was found at short term
  • No effect was observed at medium and long term
• The risk of any adverse events was similar between discectomy and non-surgical treatment
  • RR 1.34 (95% CI, 0.91 to 1.98)

CONCLUSION:

• There is low to very low certainty evidence that discectomy can improve leg pain symptoms in individuals with sciatica, compared to non-surgical treatment
• However, effects waned over time and surgery had a negligible effect on leg pain long term
• The authors state

Discectomy might be an option for people who require rapid leg pain relief and disability improvement, when the benefits outweigh the risks and costs related to surgery

Learn More – Primary Sources:

Surgical versus non-surgical treatment for sciatica: systematic review and meta-analysis of randomised controlled trials

Cochrane Update: Do Cranberry Products Reduce the Risk of UTIs?

BACKGROUND AND PURPOSE:

• Cranberries for prevention of urinary tract infections (UTIs) is thought to be effective because they contain proanthocyanidins (PACs) which inhibit binding of some bacteria to cells lining the bladder
• Williams et al. (Cochrane Database of Systematic Review, 2023) provide an update on the efficacy of cranberries for preventing UTIs

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • Randomized or quasi-randomized controlled trials
  • Studies that compared cranberry products with placebo, no specific treatment, or other intervention (antibiotics, probiotics) for the prevention of UTIs
• Study design
  • Study quality was assessed using the Cochrane risk of bias assessment tool
  • Confidence in the evidence was assessed using GRADE criteria
• Primary outcomes
  • Incidence of symptomatic UTIs
  • Positive culture results
  • Side effects
  • Adherence to therapy

RESULTS:

• 50 total studies (26 new studies added) | 8857 participants
  • The risk of bias was generally low

Cranberry Products vs Placebo or No Treatment

• 45 studies (26 studies included in meta-analysis)
• There is moderate certainty evidence that cranberry products reduced the risk of UTIs
  • Risk ratio (RR) 0.70 (95% CI 0.58 to 0.84) | I2=69% | 6211 participants
• Cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in
  • Women with recurrent UTIs
    • RR 0.74 (95% CI, 0.55 to 0.99) | I2=54%
    • 8 studies | 1555 participants
  • Children
    • RR 0.46 (95% CI, 0.32 to 0.68) | I2=21%
    • 5 studies | 504 participants
  • People with a susceptibility to UTIs due to an intervention
    • RR 0.47 (95% CI, 0.37 to 0.61) | I2=0%
    • 6 studies | 1434 participants
• However, with low-certainty evidence, there may be little or no benefit of cranberry products among
  • Elderly institutionalized men and women
    • RR 0.93 (95% CI, 0.67 to 1.30) | I2=9%
    • 3 studies | 1489 participants
  • Pregnant women
    • RR 1.06 (95% CI, 0.75 to 1.50) | I2=3%
    • 3 studies | 765 participants
  • Adults with neuromuscular bladder dysfunction with incomplete bladder emptying
    • RR 0.97 (95% CI, 0.78 to 1.19) | I2=0%
    • 3 studies | 464 participants
• The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving placebo or no specific treatment
  • RR 1.33 (95% CI, 1.00 to 1.77) | I2=0%
  • Moderate certainty evidence | 10 studies | 2166 participants

Cranberry Products vs Antibiotics

• 6 studies
• Compared to antibiotics, cranberry products may make little or no difference to the risk of
  • Symptomatic, culture-verified UTIs
    • RR 1.03 (95% CI, 0.80 to 1.33) | I2=0%
    • 2 studies | 385 participants
  • Clinical symptoms without culture
    • RR 1.30 (95% CI, 0.79 to 2.14) | I2=68%
    • 2 studies | 336 participants

Cranberry Products vs Probiotics

• 3 studies
• Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs
  • RR 0.39 (95% CI, 0.27 to 0.56) | I2=0%
  • 3 studies | 215 participants

Cranberry Tablets vs Juice

• 1 study
• It is unclear whether efficacy differs between cranberry juice and tablets as the certainty of the evidence was very low

Different Doses of PACs

• 2 studies
• It is unclear whether efficacy differs between different doses of PACs as the certainty of the evidence was very low
• No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs

CONCLUSION:

• Cranberry products reduce the risk of UTIs in women with recurrent UTIs, children, and those at risk due to a procedure
• The use of cranberry products is not supported in the elderly, pregnant women, or adults with neuromuscular bladder dysfunction

Learn More – Primary Sources:

Cranberries for preventing urinary tract infections

Cochrane Review: Is Obesity an Independent Risk Factor for COVID-19 Severity?

BACKGROUND AND PURPOSE:

• Tadayon Najafabadi et al. (Cochrane Database of Systematic Reviews, 2023) assess whether obesity as an independent prognostic factor for COVID-19 severity and mortality

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • Case-control, case-series, prospective and retrospective cohort studies, secondary analyses of RCTs
  • Studies that evaluated associations between obesity and COVID-19 adverse outcomes
  • Studies needed to adjust for at least one factor other than obesity to be eligible
• Study design
  • Obesity classes
    • No obesity: BMI 18.5 to 24.9 kg/m2
    • Class I: BMI 30 to 35 kg/m2
    • Class II: BMI 35 to 40 kg/m2
    • Class III: BMI 40 kg/m2 and above
  • Random-effects meta-analyses were used to generate pooled estimated of association
    • Meta-analyses for each obesity class were conducted separately for the main comparison
    • Meta-analysis of unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI) was also performed
  • Risk of bias was assessed
  • Certainty of evidence was determined using GRADE criteria
• Primary outcome
  • COVID-19-related mortality and other severe adverse outcomes

RESULTS:

• 149 studies included in meta-analysis
• Compared to patients without obesity, patients with obesity class I or II were not at increased odds of mortality
  • Class I
    • OR 1.04 (95% CI, 0.94 to 1.16)High certainty evidence | 15 studies | 335,209 participants
  • Class II
    • OR 1.16, 95% CI, 0.99 to 1.36
    • High certainty | 11 studies | 317,925 participants
• Class III obesity may be at increased risk of COVID-19-related mortality
  • Class III
    • OR 1.67 (95% CI, 1.39 to 2.00)
    • Low certainty | 19 studies | 354,967 participants
• There was increased odds of mechanical ventilation with higher classes of obesity
  • Class I
    • OR 1.38 (95% CI, 1.20 to 1.59)
• • • Moderate certainty | 10 studies | 187,895 participants
    Class II
    • OR 1.67 (95% CI, 1.42 to 1.96)
• • • High certainty | 6 studies | 171,149 participants
  • Class III
    • OR 2.17 (95% CI, 1.59 to 2.97)
    • High certainty | 12 studies | 174,520 participants
• There was no dose-response relationship across increasing obesity classifications for ICU admission and hospitalization

CONCLUSION:

• Class III obesity may increase the risk of mortality related to COVID-19
• All classes of obesity appear to be associated with increased odds of mechanical ventilation in a dose-dependent manner

Learn More – Primary Sources:

Obesity as an independent risk factor for COVID‐19 severity and mortality

Are Uterine Cancer Rates Rising More Rapidly for Women of Hispanic Ethnicity? 

BACKGROUND AND PURPOSE:

• Liao et al. (Gynecologic Oncology, 2023) determined the rate of uterine cancer among Hispanic women

METHODS:

• Retrospective cohort study
  • Data derived from the United States Cancer Statistics (USCS) database and the Behavioral Risk Factors Surveillance System (BRFSS) survey from 2001 to 2018
• Population
  • ≥18 years
• Diagnosed with uterine cancer in the Exposures
  • Age: Divided into 5 to 10 year age groups
  • Ethnicity: Hispanic women and non-Hispanic White women
• Study design
  • Reproductive age definition: <50 years
  • Young reproductive age: 18 to 40 years
  • Obesity-related cancers: Classified according to the CDC
  • The average annual percent change (AAPC) calculated using joinpoint regression
• Primary outcomes
  • Incidence rates of overall uterine cancers and obesity-related uterine cancers
  • AAPC of uterine cancers

RESULTS:

• 843,116 patients with uterine cancer
  • In reproductive age women: 12.7% of cases
• In 2018, Hispanic women aged 35 to 39 years had the highest incidence of uterine cancer among young reproductive-age women
  • Hispanic women: 13.9 per 100,000
  • Non-Hispanic White women: 9.3 per 100,000
• The incidence of new uterine cancers increased annually for women aged 25 to 39 in both groups with Hispanic women experiencing a higher AAPC
  • Hispanic women: AAPC 4.0 to 4.5%
  • Non-Hispanic White women: AAPC 1.5 to 2.3%
• Hispanic women aged 35 to 39 living in the West specifically had higher incidences of uterine cancer and AAPCs
  • Incidence
    • Hispanic women: 14.93 per 100,000
    • Non-Hispanic White women: 6.61 per 100,000
  • AAPCs
    • Hispanic women: 5.24%
    • Non-Hispanic White women: 1.48%
• By the year 2026, the incidence of uterine cancer in 35 to 39 year old Hispanic women in the West will be three times that of White women
  • Hispanic women: estimated 22.4 per 100,000
  • Non-Hispanic White women: estimated 7.4 per 100,000
• In the BRFSS survey, Hispanic women aged 35 to 44 years reported an obesity rate of 30.1% in 2018
  • The rate of obesity in Hispanic women rose by 1.4% annually from 2001 to 2018

CONCLUSION:

• The overall incidence of uterine cancer continues to grow for women in the US with Hispanic women experiencing particularly high increases in incidence each year
• The authors state

The incidence of uterine cancer is rising rapidly in young reproductive-age Hispanic women compared to White women

These results may have public health implications towards the prevention and early detection of uterine cancer in this high-risk population 

Learn More – Primary Sources:

The rising rates of uterine cancer in Hispanic women of reproductive age in the United States (444)

For Rare Medullary Thyroid Cancer, Consider MEN2

SUMMARY:  

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant condition involving predisposition to distinct types of endocrine tumors. Associated tumors may develop at any age, but typically occur in early adulthood.  

Symptoms and Tumor Risks 

• Medullary thyroid carcinoma (MTC) or its precursor C-cell hyperplasia  
  • nearly 100% by age 35 
• Three clinical subtypes are distinguished based on additional features 
  • MEN2A 
    • Pheochromocytoma (typically adrenal): 50% 
    • Parathyroid adenoma or hyperplasia: 20% to 30% 
  • MEN2B 
    • Pheochromocytoma: 50% 
    • Marfanoid habitus (tall with long thin limbs) 
    • Mucosal neuromas  
    • Diffuse ganglioneuromatosis of the GI tract: 40% 
  • Familial Medullary Thyroid Cancer (FMTC) 
    • Typically later age of onset 

Genetics  

• Caused by pathogenic variants in the RET gene 
  • Specific variants can be used to predict subtype or associated clinical features 
• Autosomal dominant 
  • 5% of MEN2A are de novo 
  • 50% of MEN2B are de novo 

Diagnosis 

• MEN2 should be suspected in: 
  • Any individual with MTC 
  • Families with MEN2-related tumors in multiple close relatives 
  • Individuals with marfanoid features and mucosal neuromas (MEN2B) 
• Targeted genetic testing for the familial RET variant is appropriate when a close family member has been diagnosed with MEN2  

Management  

• Referral to cancer genetics and endocrinology for counseling and management 
• Treatment and surveillance generally include  
  • Prophylactic thyroidectomy OR annual measurement of plasma calcitonin (indicates presence of MTC or C-cell hyperplasia) 
  • Biochemical screening for pheochromocytomas and hyperparathyroidism  
    • plasma catecholamines and metanephrines 
    • serum calcium and parathyroid hormone 
• Genetic testing is appropriate for at-risk children | Prophylactic surgery and surveillance may be recommended as early as the first year of life, depending on the specific genetic variant 

Note: Because prompt medical interventions can prevent severe morbidity and mortality, MEN2 is on the ACMG list of secondary findings | In summary, the ACMG document on reporting such findings makes the following recommendations 

• In the course of genetic testing for research or clinical care, the laboratory may identify variants in genes unrelated to the initial indication for testing, but nevertheless may have important health implications 
• Results of such secondary findings should be communicated to the individuals who may benefit from this knowledge 
• An individual can ‘opt out’ of receiving secondary findings 

KEY POINTS: 

• Consider MEN2 and referral to genetics for patients who present with medullary thyroid carcinoma, pheochromocytoma, parathyroid adenoma, or diffuse intestinal ganglioneuromatosis 
• Management includes prophylactic thyroidectomy and regular surveillance for biomarkers associated with pheochromocytoma and hyperparathyroidism 

Learn More – Primary Sources:  

ACMG and NSGC Joint Practice Guidelines: Referral Indications for Cancer Predisposition Assessment

GeneReviews – Multiple Endocrine Neoplasia type 2

NCCN Guidelines: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic

ACOG Committee Opinion 793: Hereditary cancer syndromes and risk assessment.  

Locate a Genetic Counselor or Genetics Services:   

Genetic Services Locator-ACMG 

Genetic Services Locator-NSGC   

Genetic Services Locator-CAGC   

RCT Results: Does Spironolactone Improve Acne for Women?

BACKGROUND AND PURPOSE:

• Spironolactone is often prescribed off-label for the treatment of acne, and may be useful in reducing antibiotic use in this setting
• Santer et al. (BMJ, 2023) assessed the effectiveness of oral spironolactone for acne vulgaris in adult women

METHODS:

• Pragmatic, multicenter, phase 3, double blind, randomized controlled trial
  • Spironolactone for women with acne vulgaris (SAFA) trial
  • England and Wales
• Participants
  • Women ≥18 years
  • Facial acne for ≥6 months
  • Appropriate to use oral antibiotics for acne treatment
• Interventions
  • Spironolactone
    • 50 mg/day until week 6, increasing to 100 mg/day until week 24
  • Placebo
• Study design
  • Acne-Specific Quality of Life (Acne-QoL) scores range from 0 to 30
    • Higher scores indicate improved QoL
• Primary outcomes
  • Acne-QoL symptom subscale score at week 12
• Secondary outcomes
  • Acne-QoL at week 24
  • Participant self-assessed improvement
  • Investigator’s global assessment (IGA) for treatment success
  • Adverse reactions

RESULTS:

• Spironolactone: 176 women | Placebo: 166 women
  • Mean age 29.2 years | Ethnicities other than White: 7%
  • Mild acne: 46% | Moderate acne: 40% | Severe acne: 13%
• Mean Acne-QoL symptom scores
  • Baseline
    • Spironolactone: 13.2 (SD, 4.9)
    • Placebo: 12.9 (SD, 4.5)
  • Week 12
    • Spironolactone: 19.2 (SD, 6.1)
    • Placebo: 17.8 (SD)
    • Difference 1.27 (95% CI 0.07 to 2.46)
  • Week 24
    • Spironolactone: 21.2 (SD, 5.9)
    • Placebo: 17.4 (SD, 5.8)
    • Difference 3.45 (95% CI, 2.16 to 4.75)
• More participants in the spironolactone group reported acne improvement
  • There was no significant difference at week 12
    • Spironolactone: 72% | Placebo: 68%
    • OR 1.16 (95% CI, 0.70 to 1.91)
  • There was a significant difference at week 24
    • Spironolactone: 82% | Placebo: 63%
    • OR 2.72 (95% CI, 1.50 to 4.93)
• Treatment success (IGA classified) at week 12 was greater in the spironolactone group
  • Spironolactone: 19% | Placebo: 6%
  • OR 5.18 (95% CI, 2.18 to 12.28)
• Adverse reactions were slightly more common in the spironolactone group
  • More headaches were reported (20% vs 12% | P=0.02)
• There were no serious adverse reactions

CONCLUSION:

• Compared to placebo, spironolactone improved acne symptoms at week 24
  • There was no difference from the placebo group at week 12
• That authors state

The findings from this trial show the effectiveness, safety, and tolerability of spironolactone in women with acne

Adopting a combined approach using oral spironolactone and topical agents has the potential to reduce the long term prescribing of oral antibiotics and therefore to reduce the likelihood of emerging bacterial resistance

Treatment courses of spironolactone over three months are likely of greater benefit than shorter treatment duration 

Learn More – Primary Sources:

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial

Improvement in Cognitive Function in Older Adults Following Exercise

BACKGROUND AND PURPOSE:

• Aging is associated with a loss in functional connectivity (FC) between brain regions important for
  • Higher-order cognitive processes (region: FPN)
  • Introspection and self-generated thoughts (region: DMN)
  • Sensory information integration (region: SAL)
• Won et al. (Journal of Alzheimer’s Disease Reports, 2023) investigated the effects of exercise on within- and between-network functional connectivity of the DMN, FPN, and SAL in older adults with intact cognition (CN) and older adults diagnosed with mild cognitive impairment (MCI)

METHODS:

• Prospective intervention trial
  • Older adults recruited from in-person informational sessions at retirement communities and community recreation centers
• Participants
  • 60 to 88 years
• Intervention
  • Before and after implementation of an exercise intervention
    • 12-week walking program
• Study design
  • A resting state functional magnetic resonance imaging (fMRI) was performed after the 12-week exercise program
  • Changes in network connectivity and cognitive function after exercise were assessed using linear regression
• Primary outcomes
  • Measures of cognitive function
    • Controlled Oral Word Association Test (COWAT)
    • Rey Auditory Verbal Learning Test (RAVLT)
    • Narrative memory test (logical memory; LM)
  • Changes in within and between network connectivity

RESULTS:

• Intact cognition: 17 | Mild cognitive impairment: 16
• 78.0 (SD, 7.0) years
• The 12-week walking program led to a significant improvement in cardiorespiratory fitness among participants (P=0.005)
• Following exercise, all measures of cognitive function also increased
  • COWAT (P=0.041)
  • RAVLT (P=0.035)
  • LM (P=0.014)
• There were also significant increases in network connectivity following exercise
  • Within network connectivity
    • In the DMNW | SALW
  • Between network connectivity
    • Between the DMN-FPNB | DMN-SALB | FPN-SALB

CONCLUSION:

• Exercise training may improve cognition and memory performance by increasing between and within brain network connectivity in older adults both with normal cognition and with mild cognitive impairment
• The authors state

These findings suggest regular participation in simple aerobic exercise like moderate intensity walking may induce neuroplastic effects even in the face of Alzheimer’s disease-related neurodegenerative processes that have resulted in a diagnosis of MCI

Learn More – Primary Sources:

Large-Scale Network Connectivity and Cognitive Function Changes After Exercise Training in Older Adults with Intact Cognition and Mild Cognitive Impairment

Does Sjögren’s Syndrome Increase the Risk of Adverse Pregnancy Outcomes?

BACKGROUND AND PURPOSE:

• Sjögren’s syndrome is an autoimmune disorder affecting lacrimal and salivary glands, resulting in dry eyes and mouth, and may be associated with other autoimmune disorders (e.g., SLE)
• De Frémont et al. (The Lancet Rheumatology, 2023) described adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren’s syndrome

METHODS:

• Multicenter, prospective, cohort study
  • French registry
  • GR2 cohort (Groupe de Recherche sur la Grossesse et les Maladies Rares)
• Participants
  • Ongoing pregnancy at 12 weeks
  • Matched controls from the general population
• Exposures
  • Diagnosed primary Sjögren’s syndrome
• Study design
  • The GR2 cohort was used to assess outcomes and risk factors for flares
  • Matched controls used to assess outcomes vs patients without Sjögren’s syndrome
  • Flares defined using European Alliance of Associations for Rheumatology (EULAR) Disease Activity Index (ESSDAI) scores
• Primary outcomes
  • Factors associated with primary Sjögren’s syndrome flare
    • ≥3-point increase in ESSDAI score
  • Factors associated with adverse pregnancy outcomes
    • Fetal or neonatal death | Placental insufficiency leading to a preterm delivery | Small-for-gestational-age
  • Pregnancy | Delivery | Birth outcome rates

RESULTS:

• 96 women with primary Sjögren’s syndrome | 106 pregnancies
  • Median age at pregnancy: 33 (IQR, 31 to 36) years
  • White women: 83% | Black women: 17%
  • Previous systemic activity (ESSDAI score of ≥1): 90%
  • Systemic activity at inclusion: 45%
• Incidence of primary Sjögren’s syndrome flares in pregnancy: 13%
  • No baseline parameters were associated with these flares
• Incidence of adverse pregnancy outcomes: 7%
• Among pregnancies in women with data for antiphospholipid antibodies, antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (P=0.023)
  • Adverse outcomes: 50% of 4 pregnancies
  • No adverse outcomes: 4% of 51 pregnancies
• In the matched controlled study, there was no significant difference in adverse pregnancy outcomes in women with primary Sjögren’s syndrome vs matched controls
  • Primary Sjögren’s syndrome: 9%
  • Controls: 7%
  • Odds ratio 1.31 (95% CI, 0.53 to 2.98) | P=0.52

CONCLUSION:

• Among women with primary Sjögren’s syndrome, pregnancy prognoses were generally good, and the odds of adverse outcomes were no higher than in the general population
• Women with antiphospholipid antibodies may be at higher risk, and should be monitored more closely

Learn More – Primary Sources:

Pregnancy outcomes in women with primary Sjögren’s syndrome: an analysis of data from the multicentre, prospective, GR2 study

What Percentage of Breast Cancers May Be Overdiagnosed in Older Women?

BACKGROUND AND PURPOSE:

• Richman et al. (Annals of Internal Medicine, 2023) estimated the overdiagnosis rate associated with breast cancer screening among older women by age

METHODS:

• Retrospective cohort study
  • Data derived from SEER Medicare registry
• Population
  • Women ≥70 years
  • Recently received breast cancer screening
  • No breast cancer at baseline
• Exposures
  • Screening continuation in the next interval
  • Exit from screening
• Study design
  • Analyses used competing risk models, and were stratified by age
• Primary outcomes
  • Breast cancer diagnoses for up to 15 years of follow-up
  • Breast cancer deaths for the same period

RESULTS:

• 54,635 women
• For women aged 70 to 74, the rate of potential overdiagnosis was 31%
  • Cumulative incidence of breast cancer
    • Screened: 6.1 cases per 100 women (95% CI, 5.7 to 6.4)
    • Unscreened: 4.2 cases per 100 women (95% CI, 3.5 to 5.0)
• For women aged 75 to 84, the rate of potential overdiagnosis was 47%
  • Cumulative incidence of breast cancer for women aged 75 to 84
    • Screened: 4.9 cases per 100 women (95% CI, 4.6 to 5.2)
    • Unscreened: 2.6 per 100 women (95% CI, 2.2 to 3.0)
• For women 85 and older, the rate of potential overdiagnosis was 54%
  • Cumulative incidence of breast cancer for women aged 85 and older
    • Screened: 2.8 per 100 women (95% CI, 2.3 to 3.4)
    • Unscreened: 1.3 per 100 women (95% CI, 0.9 to 1.9)
• There was no significant reduction in breast cancer-specific death associated with screening
• Absolute risk for overdiagnosis did not differ regardless of age group
  • Range: 1.5 to 2.3 cases per 100 women screened

CONCLUSION:

• Women 70 years and older who continue breast cancer screening face a risk of overdiagnosis
• This increased risk became more marked with increasing age
• The authors state

The relative risk for overdiagnosis increases with age and is highest for the oldest women or those with lowest life expectancy

Overdiagnosis should be explicitly considered when making screening decisions, along with considering possible benefits of screening

Learn More – Primary Sources:

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States

How Does Current Breast Cancer Prognosis Compare to the 1990s?

BACKGROUND AND PURPOSE:

• Taylor et al. (BMJ, 2023) described long-term breast cancer mortality among women with a past vs more recent diagnosis of breast cancer

METHODS:

• Population based observational cohort study
  • Data from the UK National Cancer Registration and Analysis Service
• Population
  • All women registered with early invasive breast cancer in England from 1993 to 2015
• Primary outcomes
  • Annual breast cancer mortality rates and cumulative risks by time since diagnosis
  • Calendar period of diagnosis
  • Characteristics of patients and tumors

RESULTS:

• Women registered: 512,447
• For women with a diagnosis made within each of the 5-year calendar periods starting in 1993
  • The crude annual breast cancer mortality rate was highest during the five years after diagnosis and then declined
• For any given time since diagnosis
  • Crude annual breast cancer mortality rates and risks decreased with increasing calendar period
  • Crude five-year breast cancer mortality risk
    • Diagnosis made during 1993 to 1999: 14.4% (95% CI, 14.2 to 14.6)
    • Diagnosis made during 2010 to 2015: 4.9% (95% CI, 4.8 to 5.0)
  • Adjusted annual breast cancer mortality rates also decreased with increasing calendar period in nearly all patient groups
• There was considerable variability in risk of death from breast cancer among those recently diagnosed
  • <3% for 62.8%
  • ≥20% in 4.6% of women

CONCLUSION:

• For women with early-stage breast cancer, prognoses have improved substantially since 1993
• The authors state

Since the 1990s, the five year risk of death from breast cancer has decreased from 14.4% to 4.9% overall, with reductions seen in nearly all patient groups

Learn More – Primary Sources:

Breast cancer mortality in 500 000 women with early invasive breast cancer in England, 1993-2015: population based observational cohort study

How Useful is ChatGPT at Evaluating Public Health Queries for Patients?

BACKGROUND AND PURPOSE:

• Ayers et al. (JAMA Netw Open, 2023) evaluated ChatGPT responses to public health questions from the non-professional community

METHODS:

• Cross-sectional study
• Questions
  • 23 questions in 4 categories
    • Addiction | Interpersonal violence | Mental health | Physical Health
  • Questions used a common help-seeking structure
• Response evaluation criteria (performed by two authors, independently)
  • Was the question responded to?
  • Was the response evidence-based?
  • Did the response refer the user to an appropriate resource?
• Study design
  • Interrater reliability was measured
  • The percentage corresponding to each outcome (overall and among categories) was calculated
  • The number of words in ChatGPT responses and its reading level were assessed using the Automated Readability Index

RESULTS:

• Median ChatGPT response length: 225 (IQR, 183 to 274) words
• Mode reading level: 9^th grade to 16^th grade
• ChatGPT recognized and responded to all 23 questions in 4 public health domains
  • Responses determined to be evidence based: 91% (95% CI, 71 to 98)
  • Responses that made referrals to specific resources: 22% (95% CI, 8 to 44)
    • Addiction: 2 of 14 queries
    • Interpersonal violence: 2 of 3 queries
    • Mental health: 1 of 3 queries
    • Physical health: 0 of 3 queries

CONCLUSION:

• The advice ChatGPT provided to public health queries was generally evidence-based but infrequently provided referrals to specific resources
• The authors state

Limitations of this study include relying on an abridged sample of questions whose standardized language may not reflect how the public would seek help (ie, asking follow-up questions)

Additionally, ChatGPT responses are probabilistic and in constant stages of refinement; hence, they may vary across users and over time

Learn More – Primary Sources:

Evaluating Artificial Intelligence Responses to Public Health Questions

RCT Results: Does Metformin Reduce the Risk of Long COVID?

BACKGROUND AND PURPOSE:

• Bramante et al. (The Lancet Infectious Diseases, 2023) examined whether treatment with metformin, ivermectin, or fluvoxamine reduced the risk of long COVID

METHODS:

• Randomized, phase 3 trial
  • 6 sites in the US
  • Trial’s original primary outcome was severe COVID-19 by day 14 (data published separately)
• Participants
  • 30 to 85 years
  • Overweight or obese
  • COVID-19 symptoms <7 days
  • Positive COVID test within 3 days before enrollment
  • Pregnant women were not excluded
  • Exclusions: Low risk of severe COVID-19 (Normal BMI and <30 years)
• Interventions
  • Metformin plus ivermectin
  • Metformin plus fluvoxamine
  • Metformin plus placebo
  • Ivermectin plus placebo
  • Fluvoxamine plus placebo
  • Placebo plus placebo
• Study design
  • Participants were randomly assigned to an intervention group (1:1:1:1:1:1)
  • Trial was blinded
• Primary outcome
  • Long COVID diagnosed by a medical provider

RESULTS:

• 1126 participants were assigned, received a dose of study treatments, and consented to long-term follow-up at day 180
  • Metformin: 564 | Placebo: 562
  • Female: 56.1% (Pregnant: 7.0%)
  • Median age: 45 (IQR, 37 to 54) years
  • Median BMI: 29.8 (IQR, 27.0 to 34.2) kg/m2
• Long COVID diagnoses by day 300: 8.3%
• The incidence of long COVID was reduced in the metformin group vs placebo
  • Metformin: cumulative incidence 6.3% (95% CI, 4.2 to 8.2)
  • Placebo: Cumulative incidence 10.4% (95% CI, 7.8 to 12.9)
  • HR 0.59 (95% CI, 0.39 to 0.89) | P=0.012
• The beneficial effect of metformin was consistent across prespecified subgroups
• When metformin was started within 3 days of symptom onset, the HR of long COVID was even lower
  • Hazard Ratio (HR) 0.37 (95% CI, 0.15 to 0.95)
• Compared to placebo, there was no effect on cumulative incidence of long COVID with
  • Ivermectin: HR 0.99 (95% CI, 0.59 to 1.64)
  • Fluvoxamine: HR 1.36 (95% CI, 0.78 to 2.34)

CONCLUSION:

• In this population of adults with overweight or obesity, metformin reduced the incidence of long COVID compared to placebo (note: pregnant women were not excluded)
• The authors state

In conclusion, early outpatient COVID-19 treatment with metformin decreased the subsequent risk of long COVID by 41.3% during 10-month follow-up

This finding is consistent with the 42.3% reduction in health-care utilisation for severe COVID-19 with metformin in the first 14 days of the trial 

Learn More – Primary Sources:

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial

RCT Results: Does Daily Low-Dose Aspirin Increase Incidence of Anemia?

BACKGROUND AND PURPOSE:

• McQuilten et al. (Ann Intern Med, 2023) investigated the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations

METHODS:

• Post hoc analysis of an RCT
  • ASPREE (ASPirin in Reducing Events in the Elderly) trial
• Participants
  • Community-dwelling ≥70 years or ≥65 years for Black and Hispanic persons
• Intervention
  • 100 mg of aspirin daily
  • Placebo
• Primary outcomes
  • Anemia incidence
  • Hemoglobin concentrations (measured annually)
  • Ferritin concentrations (measured at 3 years after assignment)

RESULTS:

• 19,114 individuals
• Anemia incidence was higher in the aspirin group
  • Placebo: 42.9 events per 1000 person-years | Aspirin: 51.2 events
  • Hazard ratio (HR) 1.20 (95% CI, 1.12 to 1.29)
• Both groups experienced declines in hemoglobin concentrations with steeper decline in the aspirin group
  • Placebo: 3.6 g/L per 5 years
  • Aspirin: 0.6 (95% CI, 0.3 to 1.0) g/L per 5 years
• Subgroup analysis: Aspirin group had
  • Greater prevalence of ferritin levels <45 µg/L at year 3
    • Placebo: 9.8% | Aspirin: 13%
  • Greater overall decline in ferritin
    • Aspirin: 11.5% (95% CI, 9.3 to 13.7)
• Similar results found in the absence of major bleeding

CONCLUSION:

• Even in the absence of major bleeding, daily aspirin led to increased incidence of anemia and reduced ferritin levels in healthy older adults
• The authors state

Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding

Periodic monitoring of hemoglobin should be considered in older persons on aspirin 

Learn More – Primary Sources:

Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly: A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial

Does Menopausal Hormone Therapy Contribute to Dementia Risk?

BACKGROUND AND PURPOSE:

• Pourhadi et al. (BMJ, 2023) assessed the association between use of menopausal hormone therapy and dementia

METHODS:

• Nationwide, nested case-control study
  • Danish national registries
• Participants
  • Danish women | 50 to 60 years on January 1, 2000
  • No history of dementia or contraindications for hormone therapy
  • Exclusion: Prior hysterectomy and bilateral oophorectomy
• Exposures
  • Menopausal hormone therapy
• Study design
  • Cases: Patients with dementia
  • Controls: Age-matched patients
• Primary outcome
  • All-cause dementia defined as
    • First-time diagnosis or
    • First-time use of dementia specific medication

RESULTS:

• Cases: 5589 | Controls: 55,890
• Estrogen-progestogen therapy was associated with increased rate for all-cause dementia
  • Hazard ratio (HR) 1.24 (95% CI, 1.17 to 1.33)
• Increasing durations of use yielded higher hazard ratios
  • ≤1 year of use: HR 1.21 (95% CI, 1.09 to 1.35)
  • >12 years of use: HR 1.74 (95% CI, 1.45 to 2.10)
• Estrogen-progestogen therapy was positively associated with development of dementia for both
  • Continuous regimens: HR 1.31 (95% CI, 1.18 to 1.46)
  • Cyclic regimens: HR 1.24 (95% CI, 1.13 to 1.35)
• Associations persisted in women who received treatment at ≤55 years
  • HR 1.24 (95% CI, 1.11 to 1.40)
• Findings persisted when restricted to
  • Late onset dementia (≥65 years): HR 1.21 (95% CI, 1.12 to 1.30)
  • Alzheimer’s disease: HR 1.22 (95% CI, 1.07 to 1.39)

CONCLUSION:

• Menopausal hormone therapy was associated with an increased risk of all-cause dementia, late onset dementia and Alzheimer’s disease
  • Risk persisted even in women who received hormone therapy at 55 years of age or younger
• Authors acknowledge that study is associative and not causative
  • Can not determine if actual effect of hormone therapy on dementia risk or underlying predisposition among women who need hormone therapy

Accompanying Editorial

• An accompanying editorial recognizes study strengths, including use of the entire population of Denmark
• The editorial provides multiple examples of confounding, including the possibility that women who have subjective cognitive changes and sleep disturbance during transition may be more likely to seek out hormone therapy
• RCTs that focused on younger women (50 to 55 years) did not show a negative impact
• The authors of the editorial conclude that

… the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk

These findings cannot inform shared decision making about use of hormone therapy for menopausal symptoms 

Learn More – Primary Sources:

Menopausal hormone therapy and dementia: nationwide, nested case-control study

RCT Results: Once-Weekly vs Once-Daily Insulin for Type 2 Diabetes

BACKGROUND AND PURPOSE:

• Rosenstock et al. (NEJM, 2023) investigated the efficacy and long-term safety of once-weekly insulin icodec vs once-daily insulin glargine U100 in persons with type 2 diabetes

METHODS:

• Randomized, open-label phase 3a trial
  • 52-week main phase | 26-week extension phase | 5-week follow-up
• Participants
  • ≥18 years  Type 2 diabetes: Glycated hemoglobin level, 7 to 11%
  • Not previously received insulin
• Interventions
  • Once-weekly insulin icodec (700 U per milliliter)
  • Once-daily insulin glargine U100 (100 U per milliliter)
• Study design
  • 1:1 randomization
  • Medication given subQ
  • Starting dose
    • Icodec: 70 U per week
    • Glargine U100: 10 U per day
  • Treat-to-target trial
    • Insulin doses adjusted to target prebreakfast self-measured blood glucose target of 80 to 130 mg per deciliter (4.4 to 7.2 mmol per liter)
  • Hypoglycemic episodes (from baseline to weeks 52 and 83) were recorded
• Primary outcome
  • Change in the glycated hemoglobin level from baseline to week 52
• Secondary outcome
  • Percentage of time spent in the glycemic range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) in weeks 48 to 52

RESULTS:

• Once-weekly: 492 participants | Once-daily: 492 participants
  • Baseline characteristics were similar between the 2 groups
• Mean reduction in the glycated hemoglobin level at 52 weeks was greater with icodec
  • Icodec: 8.50% to 6.93% | Mean change −1.55 percentage points
  • Glargine U100: 8.44% to 7.12% | Mean change −1.35 percentage points
  • Estimated between-group difference: −0.19 (95% CI, −0.36 to −0.03) percentage points
  • Noninferiority: P<0.001 | Superiority of icodec: P=0.02
• Percentage of time spent in the glycemic range of 70 to 180 mg per deciliter was significantly higher with icodec
  • Icodec: 71.9% | Glargine U100: 66.9%
  • Estimated between-group difference: 4.27 (95% CI, 1.92 to 6.62) percentage points
  • Superiority: P<0.001
• Rates of combined clinically significant or severe hypoglycemia similar between the groups
  • At week 52
    • Icodec: 0.30 events per person-year of exposure
    • Glargine U100: 0.16 events
    • Estimated rate ratio (RR) 1.64 (95% CI, 0.98 to 2.75)
  • At week 83
    • Icodec: 0.30 events per person-year of exposure
    • Glargine U100: 0.16 events
    • Estimated RR 1.63 (95% CI, 1.02 to 2.61)
• Safety
  • There were no new safety signals detected
  • Incidences of adverse events were similar between the two groups

CONCLUSION:

• For patients with type 2 diabetes, better glycemic control was achieved with once-weekly insulin icodec compared to once-daily insulin glargine U100

Learn More – Primary Sources:

Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin

RCT Results: Is Intermittent Fasting Better Than Calorie Restriction for Long-Term Weight Loss?

BACKGROUND AND PURPOSE:

• Time-restricted eating (TRE), also called intermittent fasting, without calorie counting has become a popular weight loss method
• Lin et al. (Ann Intern Med, 2023) studied whether TRE is more effective for weight control and cardiometabolic risk reduction vs calorie restriction (CR) or control

METHODS:

• Randomized controlled trial
• Participants
  • Between 18 and 65 years
  • BMI between 30 and 50 kg/m2
• Intervention
  • 8-hour TRE
    • Eating between noon and 8:00 p.m. only, without calorie counting
  • CR
    • 25% energy restriction daily
  • Control
    • Eating over a period of 10 or more hours per day
• Study design
  • 1:1:1 randomization
  • Participants were not blinded
  • Physical habits unchanged
  • This study took place over 12 months
    • TRE and CR interventions: 6-month weight loss phase and 6-month maintenance phase
• Primary outcome
  • Change in body weight at 12 months
  • Change in metabolic markers at 12 months
  • Change in energy intake at 12 months

RESULTS:

• 77 participants
  • Mean age: 40 (SD, 11) years
  • Black: 33% | Hispanic: 46%
• Mean reduction in energy intake
  • TRE: −425 (SD, 531) kcal/d
  • CR: −405 (SD, 712) kcal/d
• Compared with the control group, weight loss by month 12 was higher with both intervention groups
  • TRE group
    • Absolute weight loss: −4.61 kg (95% CI, −7.37 to −1.85) | P≤0.01
    • Weight loss as a percentage of baseline body weight: −4.87% (95% CI, −7.61 to −2.13)
  • CR group
    • Absolute weight loss: −5.42 kg (95% CI, −9.13 to −1.71) | P≤0.01
    • Weight loss as a percentage of baseline body weight: −5.30% (95% CI, −9.06 to −1.54)
• There was no significant difference in weight loss at 12 months between the TRE and CR groups
  • Absolute weight loss: 0.81 kg (95% CI, −3.07 to 4.69) | P=0.68
  • Weight loss as a percentage of baseline body weight: 0.43% (95% CI, −3.48 to 4.34)

CONCLUSION:

• Both CR and TRE improves weight loss compared to control
• There was no difference in weight loss between the CR and TRE groups
• The authors state

TRE is effective for weight loss when compared with controls eating over a period of 10 or more hours but not more effective than daily CR in a racially diverse population

Future studies are needed to confirm our findings

Learn More – Primary Sources:

Time-Restricted Eating Without Calorie Counting for Weight Loss in a Racially Diverse Population: A Randomized Controlled Trial

How Often Does Low-Dose CT Lung Screening Uncover Other Significant Abnormalities?

BACKGROUND AND PURPOSE:

• Low-dose computed tomography (LDCT) lung screening reduces lung cancer mortality, but may reveal significant abnormalities that are not associated with lung cancer
• Gareen et al. (JAMA Intern Med, 2023) describe significant incidental findings (SIFs) reported in the LDCT arm of the National Lung Screening Trial

METHODS:

• Retrospective case series study
• Population
  • Participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT
• Study design
  • Data were collected from 2002 to 2009 at 33 US medical centers
  • Participants were scheduled to undergo 3 screenings during the course of the trial
• Primary outcomes
  • SIFs, defined as either a
    • Final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer
    • Positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm

RESULTS:

• 26,455 participants | 75,126 LDCT screening examinations
  • Mean age: 61.4 (SD, 5.0) years
  • Women: 41.0%
  • Black: 4.5% | Hispanic/Latino: 1.8% | White: 91.2%
• Incidence of SIFs: 33.8% of participants
  • Incidence of SIFs considered reportable: 89.1%
• There was a higher incidence of reportable SIFs among those with a positive screen result for lung cancer, compared to those with a negative screen result
  • Positive screen result: 94.1% | Negative screen result: 81.8%
• The most common SIFs reported
  • Emphysema: 43.0% of SIFs reported
  • Coronary artery calcium: 12.2% of SIFs reported
  • Masses or suspicious lesions: 7.4% of SIFs reported
• Masses reported occurred in the
  • Kidney: 3.2%
  • Liver: 2.1%
  • Adrenal: 1.3%
  • Breast: 0.8%

CONCLUSION:

• SIFs were common with LDCT screening
  • Most SIFs were considered reportable and would likely require follow-up
• The authors state

In this case series study, slightly more than one-third of all NLST LDCT screening participants had a SIF detected

… the discovery of these SIFs can potentially present an opportunity for early detection of non–lung cancer conditions in a high-risk population

Learn More – Primary Sources:

Significant Incidental Findings in the National Lung Screening Trial

SURMOUNT-2 RCT Results: Does Tirzepatide Treatment Improve Weight Loss for Individuals with Obesity and Type 2 Diabetes?

BACKGROUND AND PURPOSE:

• Tirzepatide is a once-weekly injectable insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist
  • Demonstrated weight loss in non-diabetic patients (SURMOUNT-1)
• Garvey et al. (The Lancet, 2023) assessed the efficacy and safety of tirzepatide for weight management in people with obesity and type 2 diabetes

METHODS:

• Phase 3, double-blind, randomized, placebo-controlled trial
  • SURMOUNT-2 trial, 7 countries
• Participants
  • BMI ≥27 kg/m2
  • Glycated hemoglobin (HbA1c) 7 to 10% (53 to 86 mmol/mol)
• Interventions
  • Once-weekly, subcutaneous tirzepatide (10 mg or 15 mg) for 72 weeks
  • Placebo
• Study design
  • Intention-to-treat
• Primary outcomes
  • The percent change in bodyweight from baseline
  • Bodyweight reduction of 5% or higher

RESULTS:

• Tirzepatide 10 mg: 312 participants | Tirzepatide 15 mg: 311 | Placebo: 315
  • Mean age: 54.2 (SD, 10.6) years | Female: 51%
  • White: 76% | Hispanic/Latino: 60%
• Baseline characteristics
  • Mean bodyweight: 100.7 (SD, 21.1) kg
  • BMI: 36.1 (SD, 6.6) kg/m2
  • HbA1c: 8.02% (SD, 0.89) | 64.1 (SD, 9.7) mmol/mol
• Least-squares mean change in bodyweight at week 72
  • Tirzepatide 10 mg: –12.8%
  • Tirzepatide 15 mg: –14.7%
  • Placebo: –3.2%
• There was a significant reduction in body weight over 72 weeks with tirzepatide (P<0.0001)
  • Tirzepatide 10 mg vs placebo: –9.6% percentage points (95% CI, –11.1 to –8.1)
  • Tirzepatide 15 mg vs placebo: –11.6% percentage points (95% CI, –13.0 to –10.1)
• More participants treated with tirzepatide vs placebo met bodyweight reduction thresholds of 5% or higher
  • Tirzepatide 10 mg: 79%
  • Tirzepatide 15 mg: 83%
  • Placebo: 32%
• Mean HbA1c improved with tirzepatide vs placebo over 72 weeks
  • Tirzepatide 10 mg: 6.0%
  • Tirzepatide 15 mg: 5.9%
  • Placebo: 7.5%
• The most frequent adverse events with tirzepatide were
  • Nausea | Diarrhea | Vomiting
• Most adverse events were mild to moderate, and few events led to treatment discontinuation (<5%)
• Serious adverse events: 7% of participants
  • There were 2 deaths in the tirzepatide 10 mg group
  • Neither related to study treatment

CONCLUSION:

• For adults with obesity and type 2 diabetes, tirzepatide 10 mg or 15 mg for 72 weeks provided statistically and clinically significant weight reduction compared to placebo
• The authors state

In conclusion, in adults with a BMI of 27 kg/m2 or higher and type 2 diabetes, once-weekly treatment with tirzepatide demonstrated substantial, clinically meaningful bodyweight reductions of up to 15%, with weight reductions of 20% or higher reached by up to nearly one-third of tirzepatide-treated participants

Learn More – Primary Sources:

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

SARS-CoV-2 Vaccines Do Not Cause Female Sterility

BACKGROUND AND PURPOSE:

• Some people on social media have claimed that there is an alleged similarity between syncytin-1 and the SARS-CoV-2 spike protein which, through immune cross-reactivity, could lead to female sterility
• Morris (F&S Reports, 2021) used frozen embryo transfer to compare the implantation rates between SARS-CoV-2 seropositive vs seronegative women

METHODS:

• Cohort study
• Participants
  • Women undergoing frozen embryo transfer (FET)
• Exposures
  • Seropositive due to vaccination (Pfizer or Moderna)
  • Seropositive due to natural infection
  • Seronegative
• Study design
  • Levels of SARS-CoV-2 IgG were determined from serum samples obtained prior to FET
  • All transfers used a single expanded blastocyst in a hormone-prepared uterus
  • Transfer was performed under transabdominal ultrasound guidance
• Primary outcomes
  • Embryo implantation rates
    • Serum hCG level of >5 mIU/mL obtained 8 days after transfer, followed by a rising level two to three days later
  • Sustained implantation rates
    • Presence of ultrasound visualized fetal heart tones at two time points at least one week apart

RESULTS:

• 148 patients
  • Seropositive: 37.8%
    • Due to vaccination: 64.8%
    • Due to natural infection: 35.2%
  • Baseline characteristics were similar between exposure groups, except for higher mean BMI in the post-infection group than the vaccinated group and the nonreactive group (P = 0.005)
• There was no difference in embryo implantation rates between the groups (P=0.99)
  • Vaccine seropositive: 80.0%
  • Infection seropositive: 73.7%
  • Seronegative: 73.9%
• There was also no difference in sustained implantation rates between the groups (P=0.99)
  • Vaccine seropositive: 65.7%
  • Infection seropositive: 47.4%
  • Seronegative: 52.3%

CONCLUSION:

• SARS-CoV-2 seropositivity, whether from vaccination or infection, does not prevent embryo implantation or early pregnancy development
• Claims that SARS-CoV-2 spike protein may induce cross-reactivity with syncytin-1 appear unfounded
• The authors state

Physicians and public health personnel can counsel women of reproductive age that neither previous illness with COVID-19 nor antibodies produced from vaccination to COVID-19 will cause sterility

Learn More – Primary Sources:

SARS-CoV-2 spike protein seropositivity from vaccination or infection does not cause sterility

Meta-Analysis: Which Anticoagulant Treatments Are Best for Preventing Venous Thromboembolism in Hospital?

BACKGROUND AND PURPOSE:

• Eck et al. (BMJ, 2022) assessed the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism (VTE) in hospitalized patients who are acutely ill

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • RCTs
  • Studies that investigated the prevention of VTE among acutely ill adult patients in the hospital
  • Eligible studies compared
    • Low or intermediate dose low-molecular-weight heparin (LMWH) | Low or intermediate dose unfractionated heparin | Direct oral anticoagulants (DOACs) | Pentasaccharides | Placebo | No intervention
• Study design
  • Random effects, Bayesian network meta-analyses were used to assess primary outcomes
  • The quality of evidence was graded using the Confidence in Network Meta-Analysis framework
• Primary outcomes
  • All-cause mortality
  • Symptomatic VTE
  • Major bleeding
  • Serious adverse events at or closest time to 90 days

RESULTS:

• 44 RCTs | 90,095 participants
  • Evidence was low to moderate quality
• None of the interventions assessed reduced all-cause mortality compared with placebo
• Some interventions were most likely to reduce symptomatic VTE
  • Pentasaccharides
    • OR 0.32 (95% credible interval [CrI], 0.08 to 1.07)
  • Intermediate dose LMWH
    • OR 0.66 (95% CrI, 0.46 to 0.93)
  • DOACs
    • OR 0.68 (95% CrI, 0.33 to 1.34)
  • Intermediate dose unfractionated heparin
    • OR 0.71 (95% CrI, 0.43 to 1.19)
• Two interventions were most likely to increase major bleeding
  • Intermediate dose unfractionated heparin
    • OR 2.63 (95% CrI, 1.00 to 6.21)
  • DOACs
    • OR 2.31 (95% CrI, 0.82 to 6.47)
  • Low to moderate quality evidence
• No conclusive differences were found between interventions regarding serious adverse events
  • Very low to low quality evidence
• When compared with no intervention rather than placebo, all active interventions performed
  • More favorably regarding risk for
    • VTE
    • Mortality
  • Less favorably regarding risk for major bleeding
• The results were robust in prespecified sensitivity andsubgroup analyses

CONCLUSION:

• For prevention of VTE among acutely ill patients, LMWH maximized benefit while limiting major bleeding risk vs other interventions
• Interventions with the least favorable outcomes included
  • Unfractionated heparin, especially intermediate dose
  • DOACs
• The authors state

Our results support the National Institute for Health and Care Excellence and the American Society of Hematology guidelines on thrombosis prophylaxis in their recommendations on the use of low-molecular-weight heparins or pentasaccharides

Learn More – Primary Sources:

Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis

Do Proton Pump Inhibitors Increase the Risk for CVD in Patients with Type 2 Diabetes?

BACKGROUND AND PURPOSE:

• Proton pump inhibitors (PPIs), used for treating gastric-acid related diseases, have been linked with cardiovascular disease (CVD)
  • How PPI use affects type 2 diabetes (T2D) patients, who are more likely to use PPIs and more likely to develop CVD, is unclear
• Geng et al. (Journal of Clinical Endocrinology & Metabolism, 2022) evaluate the associations of PPI use with risks of CVD and all-cause mortality in patients with T2D

METHODS:

• Secondary analysis of prospective cohort study
• Population
  • Patients in the UK Biobank with preexisting T2D
• Exposure
  • PPI use
• Primary outcomes
  • Coronary artery disease (CAD)
  • Myocardial infarction (MI)
  • Heart failure (HF)
  • Stroke
  • All-cause mortality

RESULTS:

• 19,229 adults with T2D
  • Median follow up: 10.9 to 11.2 years
• PPI use was significantly associated with higher risks of
  • CAD: HR 1.27 (95% CI, 1.15 to 1.40)
  • MI: HR 1.34 (95% CI, 1.18 to 1.52)
  • HF: HR 1.35 (95% CI, 1.16 to 1.57)
  • All-cause mortality: HR 1.30 (95% CI, 1.16 to 1.45)
• The results were consistent in the subgroup analyses stratified by factors including
  • Indications of PPI | Antidiabetic medication use | Antiplatelet drug use
• Analyses in a 1:1 propensity score-matched cohort of PPI users vs nonusers yielded similar results

CONCLUSION:

• PPI use among patients with T2D is associated with an increased risk of CVD events, compared to non-use
• The authors state

The benefits and risks of PPI use should be carefully balanced among patients with T2D, and monitoring of adverse CVD events during PPI therapy should be enhanced

Learn More – Primary Sources:

Proton Pump Inhibitor Use and Risks of Cardiovascular Disease and Mortality in Patients with Type 2 Diabetes