Does Drinking Coffee Help Counteract the Harms of a Sedentary Lifestyle?

BACKGROUND AND PURPOSE:

• Zhou et al. (BMC Public Health, 2024) evaluated the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults

METHODS:

• Prospective cohort study
  • National Health and Nutrition Examination Survey (NHANES) Survey
  • 2007 to 2018
• Participants
  • US adults
• Exposures
  • Daily sitting time
  • Coffee consumption per 24-hour period
• Study design
  • Adjusted hazard ratio (HR) calculated using Cox proportional hazards regression
• Primary outcomes
  • All-cause mortality
  • CVD mortality

RESULTS:

• 10,639 participants
  • Deaths 945 | Deaths from CVD: 284
• Compared to those who sat <4 h/d, sitting more than 8 h/d was associated with higher risks of mortality
  • All-cause mortality: HR 1.46 (95% CI, 1.17 to 1.81)
  • CVD mortality: HR 1.79 (95% CI, 1.21 to 2.66)
• Compared with non-coffee drinkers, people in the highest quartile of coffee consumption had reduced risks of mortality
  • All-cause: HR 0.67 (95% CI, 0.54 to 0.84)
  • CVD mortality: HR 0.46 (95% CI, 0.30 to 0.69)
• Compared to coffee drinkers who sat for <6h/d, sedentary non-coffee drinkers had a higher risk of all-cause mortality while sedentary coffee drinkers did not
  • Sedentary non-coffee drinkers: HR 1.58 (95% CI, 1.25 to 1.99)
  • Sedentary coffee drinkers: HR 1.22 (95% CI, 0.97 to 1.54)

CONCLUSION:

• Risk of all-cause and CVD mortality is higher among individuals leading a sedentary lifestyle, but risk was reduced among coffee drinkers
• The authors state

Notably, the results of a joint analysis of this study identified that that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake

Given that coffee is a complex compound, further research is needed to explore this miracle compound

Learn More – Primary Sources:

Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults

Is Cannabis Use Linked to Worse COVID-19 Outcomes?

BACKGROUND AND PURPOSE:

• Smoking cigarettes is associated with worse COVID-19 outcomes, but it is unclear whether cannabis is also associated with poorer COVID-19 outcomes
• Griffith et al. (JAMA Network Open, 2024) examined adverse COVID-19 outcomes associated with cannabis and tobacco use

METHODS:

• Retrospective cohort study
  • Extracted EHR data
  • Large US midwestern academic medical center    
• Population
  • Patients with COVID-19
• Exposures
  • Current tobacco smoking
  • Current cannabis use
• Study design
  • Multivariable modeling used to calculated odds ratio (OR)
  • Adjustment for
    • Tobacco smoking | Vaccination | Comorbidity | Diagnosis date | Demographic factors
• Primary outcomes
  • Health outcomes of hospitalization
  • ICU admission
  • All-cause mortality following COVID-19 infection

RESULTS:

• 72,501 patients with COVID-19
  • Mean age: 48.9 (SD, 19.3) years | 59.7% female
  • Current smoking: 13.4% | Former smoking: 24.4%
  • Current cannabis use: 9.7%
• For patients with COVID-19, current tobacco smoking was associated with an increased risk of
  • Hospitalization: OR 1.72 (95% CI, 1.62 to 1.82) | P<0.001
  • ICU admission: OR 1.22 (95% CI, 1.10 to 1.34) | P<0.001
  • All-cause mortality: OR 1.37 (95% CI, 1.30 to 1.57) | P<0.001
• Cannabis use was associated with an increased risk of
  • Hospitalization: OR 1.80 (95% CI, 1.68 to 1.93) | P<0.001
  • ICU admission: OR 1.27 (95% CI, 1.14 to 1.41) | P<0.001
• Cannabis use was not associated with all-cause mortality
  • OR 0.97 (95% CI, 0.81 to 1.14) | P=0.69

CONCLUSION:

• Tobacco smoking is linked to an increased risk of poorer COVID-19 outcomes
• Cannabis use also appears to be a risk factor for worse COVID-19 outcomes
• The authors state

Given the recent legalization of recreational marijuana use in more states, including the area served by this academic medical center, further research may aid in guiding interventions, such as substance use prevention and treatment, that would benefit patient outcomes moving forward in the COVID-19 pandemic and the associated heath consequences it will have in our communities

Learn More – Primary Sources:

Cannabis, Tobacco Use, and COVID-19 Outcomes

Do Fish Oil Supplements Impact Cardiovascular Health?

BACKGROUND AND PURPOSE:

• Data on fish oil supplements, and their role in cardiovascular disease, are controversial
• Chen et al. (BMJ Medicine, 2024) examined the effects of fish oil supplements on the clinical course of cardiovascular disease across disease states

METHODS:

• Prospective cohort study
  • UK Biobank study
• Participants
  • Adults aged 40 to 69
• Exposures
  • Fish oil supplements
  • Stage of cardiovascular disease
    • Healthy (primary stage) | Atrial fibrillation (secondary stage) | Major cardiovascular events (tertiary stage) | Death
• Primary outcomes
  • Incident cases of atrial fibrillation | Major adverse cardiovascular events | Death

RESULTS:

• Healthy starting population: 415,737
  • Median follow-up 11.9 years
  • Progressed to
    • Atrial fibrillation: 18,367 | Major cardiovascular events: 22,636 | Death: 22,140
• For healthy participants, fish oil was associated with a greater incidence of atrial fibrillation and stroke
  • Atrial fibrillation: Hazard Ratio HR) 1.13 (95% CI, 1.10 to 1.17)
  • Stroke: HR 1.05 (95% CI, 1.00 to 1.11)
• For patients with a diagnosis of cardiovascular disease, regular use of fish oil was beneficial in reducing transitions from
  • Atrial fibrillation to major cardiovascular events: HR 0.92 (95% CI, 0.87 to 0.98)
  • Atrial fibrillation to myocardial infarction: HR 0.85 (95% CI, 0.76 to 0.96)
  • Heart failure to death: HR 0.91 (95% CI, 0.84 to 0.99)

CONCLUSION:

• In the general healthy population, regular use of fish oil supplements may increase the risk of atrial fibrillation and stroke
• For those with cardiovascular disease, fish oil supplements may be beneficial at reducing the risk of transitioning to worse cardiovascular states
• The authors state

When we divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction), we found associations that could suggest a mildly harmful effect between regular use of fish oil supplements and transitions from a healthy cardiovascular state to stroke, whereas potential beneficial associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to myocardial infarction, atrial fibrillation to death, and heart failure to death

Learn More – Primary Sources:

Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study

Meta-Analysis: What are the “Red Flag” Signs of Early Onset Colorectal Cancer?

BACKGROUND AND PURPOSE:

• Rate of early-onset colorectal cancer (EOCRC; defined as diagnosis <50 years) is increasing
• Demb et al. (JAMA Network Open, 2024) sought to determine the frequency of presenting red flag signs and symptoms among individuals with EOCRC

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • Patients <50 years diagnosed with nonhereditary CRC
  • Reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis 
• Study design
  • Quality of the included studies and risk of bias was measured
  • Data on frequency of signs and symptoms were pooled using a random-effects model
• Primary outcomes
  • Pooled proportions of signs and symptoms in patients with EOCRC
  • Estimates for association of signs and symptoms with EOCRC risk
  • Time from sign or symptom presentation to EOCRC diagnosis

RESULTS:

• 81 studies | 24,908,126 patients <50
• Most common presenting signs and symptoms (78 studies)
  • Hematochezia: pooled prevalence 45% (95% CI, 40 to 50)
  • Abdominal pain: pooled prevalence 40% (95% CI, 35 to 45)
  • Altered bowel habits: pooled prevalence 27% (95% CI, 22 to 33)
• The signs and symptoms with the greatest association with EOCRC likelihood were
  • Hematochezia: estimate range 5.2 to 54.0
  • Abdominal pain: estimate range 1.3 to 6.0
  • Anemia: estimate range 2.1 to 10.8
• Time from signs and symptoms presentation to EOCRC diagnosis
  • Mean 6.4 (range 1.8 to 13.7) months | 23 studies
  • Median 4 (range 2.0 to 8.7) months | 16 studies

CONCLUSION:

• For patients with early onset colorectal cancer, the most common signs and symptoms were hematochezia and abdominal pain (nearly half of all patients) and altered bowel habits (over a quarter of all patients)
• Hematochezia was associated with the highest risk of EOCRC
• Delays in diagnosis were common, and were generally on the order of 4 to 6 months
• The authors state

These findings and the increasing risk of CRC in individuals younger than 50 years highlight the urgent need to educate clinicians and patients about these signs and symptoms to ensure that diagnostic workup and resolution are not delayed

Adapting current clinical practice to identify and address these signs and symptoms through careful clinical triage and follow-up could help limit morbidity and mortality associated with EOCRC

Learn More – Primary Sources:

Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis

What is the Most Trusted Source of Health Information in the US?

BACKGROUND AND PURPOSE:

• Suran and Bucher (JAMA, 2024) review important survey data that ascertained where individuals in the US get their news and the which health information sources they trust

METHODS:

• Survey of a nationally representative sample of Black, Hispanic and White US adults

RESULTS:

• Trust in health professionals was high, and crossed party lines
  • 95% of both Republicans and Democrats reported that they trusted their personal physicians to provide accurate recommendations on health issues
• Trust in the government was lower, but still relatively high, but varied more across party lines
  • Trust in CDC
    • Republicans: 49% | Democrats: 87%
  • Trust in state and local public health officials
    • Republicans: 58% | Democrats: 74%
• The vast majority (96%) of respondents reported hearing at least one of the 10 false claims presented by the survey
  • e.g. that the MMR vaccine causes autism
• While knowledge of misinformation was high, the percentage of people that believed false claims was generally lower: 14 to 35%
• Most respondents (74%) were concerned about the spread of false health claims
  • Desire for Congress and President Joe Biden to do more: 68 to 78%
  • Desire for US news media to do more: 70%
• Social media use was high, but most people reported not trusting the health information on platforms
  • Users who visited Facebook weekly: 63% | Users who trust health claims on Facebook: 5%
• Use of local and national news media was also high, and respondents reported a greater trust in health information from these sources
  • Local news watchers: 62%
  • Watchers who have “a lot” of trust in health claims on local news: 37%

CONCLUSION:

• Most adults are aware that there are a lot of false health claims circulating on social media, and through society in general
• Despite many respondents having heard these claims, far fewer actually believe them
• The most trusted source for health information was respondent’s personal physician

Learn More – Primary Sources:

False Health Claims Abound, but Physicians Are Still the Most Trusted Source for Health Information

KFF Health Misinformation Tracking Poll Pilot

RCT Follow-Up: How Long Do the Benefits of Early Glycemic Control Last for Those with Diabetes?

BACKGROUND AND PURPOSE:

• The 20-year UK Prospective Diabetes Study (UKPDS) found that individuals who underwent an intensive glycemic control strategy with sulfonylurea or insulin therapy or metformin therapy had better outcomes than those who controlled glycemic levels through diet alone
  • A 10-year follow-up highlighted the long-term benefits of intensive therapy
• Adler et al. (The Lancet, 2024) determined whether the benefits of intensive glycemic control would wane after another 14 years of follow-up

METHODS:

• Extended follow-up of randomized controlled trial
• Participants
  • Individuals with diabetes
• Original intervention (over 20 year period)
  • Intensive glycemic control (sulfonylurea or insulin, or metformin if BMI >27 kg/m2)
  • Conventional glycemic control (primarily diet)
• Study design
  • This study reports on an additional 14 years of follow-up after the initial 10-year post-trial monitoring period
  • Kaplan–Meier time-to-event and log-rank analyses were used
• Primary outcomes
  • Aggregate clinical outcomes
    • Any diabetes-related endpoint | Diabetes-related death | Death from any cause | Myocardial infarction | Stroke | Peripheral vascular disease | Microvascular disease

RESULTS:

• 1489 participants (of 3277 individuals surviving at the start of the initial 10-year follow-up)
  • Mean age at baseline: 50.2 (SD, 8.0) years | Mean age in 2021: 79.9 (IQR, 12.3 to 26.8)
  • Female: 41.3%
• For up to 24 years after trial end, the glycemic and metformin legacy effects showed no sign of waning
• Those allocated to early intensive glycemic control with sulfonylurea or insulin therapy had overall lower risks of
  • Death from any cause: Relative Risk (RR) 0.90 (95% CI, 0.83 to 0.98) | P=0.015
  • Myocardial infarction: RR 0.83 (95% CI, 0.74 to 0.94) | P=0.002
  • Microvascular disease: RR 0.76 (95% CI, 0.64 to 0.89) | P<0.0001
• Early intensive glycemic control with metformin therapy led to overall risk reductions for
  • Death from any cause: RR 0.80 (95% CI, 0.68 to 0.95) | P=0.010
  • Myocardial infarction: RR 0.69 (95% CI, 0.54 to 0.88) | P=0.003
• There were no significant differences in risk of stroke or peripheral vascular disease during or after the trial
  • There was no risk reduction for microvascular disease with metformin therapy

CONCLUSION:

• For patients with type 2 diabetes, early intensive glycemic control confers near life-long risk reduction in all-cause mortality, microvascular complications and myocardial infarction
• The authors state

The legacy benefits from early intensive glycaemic control with sulfonylurea or insulin led to overall relative risk reductions from baseline of 10% for death, 17% for myocardial infarction, and 26% for microvascular complications

Early intensive glycaemic control with metformin led to numerically larger overall relative risk reductions than with sulfonylurea or insulin, from baseline of 20% for death and 31% for myocardial infarction

Achieving near-normal glycaemia immediately after type 2 diabetes is diagnosed appears to be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible

Learn More – Primary Sources:

Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)

Cochrane Review: Does Zinc Prevent or Shorten Colds?

BACKGROUND AND PURPOSE:

• Zinc supplements are commonly taken to prevent or shorten colds, but evidence to support this practice is generally lacking
• Nault et al. (Cochrane Database of Systematic Reviews, 2024) assessed the effectiveness and safety of zinc for the prevention and treatment of the common cold

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • RCTs
  • Studies that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI) in children or adults
• Study design
  • Risk of bias was assessed with the Cochrane risk of bias tool
  • Certainty of evidence was assessed using GRADE Criteria
• Primary outcomes
  • Proportion of participants developing colds
  • Duration of cold | Measured in days from start to resolution of the cold
  • Adverse events potentially due to zinc supplements
    • e.g., unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhea
  • Adverse events considered to be potential complications of the common cold
    • e.g. respiratory bacterial infections

RESULTS:

• 15 prevention studies | 19 treatment studies | 8526 participants
  • On adults: 22 studies | On children: 12 studies
• Most studies evaluated the effectiveness of zinc administered as lozenges
  • Zinc gluconate doses: range 45 and 276 mg/day
  • Time period: range 4.5 and 21 days
• Other forms of zinc administration: Capsules | Dissolved powders | Tablets | Syrups | Intranasal sprays
• Most studies were at unclear or high risk of bias in at least one domain

Prevention of Colds

• There may be little or no reduction in the risk of developing a cold with zinc compared to placebo
  • Risk ratio (RR) 0.93 (95% CI, 0.85 to 1.01)
  • I2=20% | 9 studies | 1449 participants | Low-certainty evidence
• There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow‐up
  • Mean difference (MD) –0.90 (95% CI –1.93 to 0.12)
  • I2 =96% | 2 studies | 1284 participants | Low‐certainty evidence
• If a cold does occur despite use of zinc
  • There is probably little or no difference in the duration of colds in days
    • MD –0.63 (95% CI –1.29 to 0.04)
    • I2 =77% | 3 studies | 740 participants | Moderate‐certainty evidence
  • There may be little or no difference in global symptom severity
    • Standardized mean difference 0.04 (95% CI, –0.35 to 0.43)
    • I2 =0% | 2 studies | 101 participants | Low‐certainty evidence

Used for Cold Treatment

• There may be a reduction in the mean duration of the cold in days
  • MD –2.37 (95% CI, –4.21 to –0.53)
  • I2 =97% | 8 studies | 972 participants | Low‐certainty evidence
• It is uncertain whether there is a reduction in the risk of
  • Having an ongoing cold at the end of follow‐up
    • RR 0.52 (95% CI, 0.21 to 1.27)
    • I2 =65% | 5 studies | 357 participants | Very low‐certainty evidence
  • Global symptom severity
    • SMD ‐0.03 (95% CI, –0.56 to 0.50)
    • I2 =78% | 2 studies | 261 participants | Very low‐certainty evidence

Adverse events

• 31 studies | 2422 participants
• It is uncertain whether there is a
  • Difference in the risk of adverse events with zinc used for cold prevention
    • RR 1.11 (95% CI, 0.84 to 1.47)
    • I2 =0% | 7 studies | 1517 participants | Very low‐certainty evidence
  • Increase in the risk of serious adverse events
    • RR 1.67 (95% CI, 0.78 to 3.57)
    • I2 =0% | 3 studies | 1563 participants | Low‐certainty evidence
• There is probably an increase in the risk of non‐serious adverse events when zinc is used for cold treatment
  • RR 1.34 (95% CI, 1.15 to 1.55)
  • I2 =44% | 2084 participants | 16 studies | Moderate‐certainty evidence
• No treatment study provided information on serious adverse events
• No study provided clear information about adverse events considered to be potential complications of the common cold

CONCLUSION:

• Zinc supplements may have little to no effect on common cold prevention, but may reduce the duration of ongoing colds
• The authors state

Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold

Learn More – Primary Sources:

Zinc for prevention and treatment of the common cold

RCT Results: What is the Best Strategy for Smoking Cessation Following Not Achieving Abstinence After a First Attempt?

BACKGROUND AND PURPOSE:

• Cinciripini et al. (JAMA Netw Open, 2024) determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT)

METHODS:

• Double-blind, placebo-controlled, sequential multiple assignment randomized trial
• Participants
  • 18 to 75 years
  • Smoked 5 or more cigarettes per day with an expired CO of ≥6 ppm
• Interventions
  • Initial randomization
    • Varenicline for 6 weeks, 2 mg/d
    • CNRT for 6 weeks, 21 mg patch + 2 mg lozenge
  • Rerandomization for those who were nonabstainers after 6 weeks
    • Continue for 6 weeks
    • Switch to other treatment option for 6 weeks
    • Increase medication dose for 6 weeks
      • ≥3mg/d varenicline | 42 mg patch + lozenges
• Study design
  • All participants received brief weekly counseling
• Primary outcomes
  • Biochemically verified 7-day point prevalence abstinence at the end of treatment at 12 weeks

RESULTS:

• 490 participants
  • Female: 43% | Non-Hispanic White: 58%
  • Mean age: 48.1 years
• After first phase
  • CNRT group
    • Abstinent: 54 participants | Nonabstinent: 191
    • Rerandomized: 151
  • Varenicline:
    • Abstinent: 88 | Nonabstinent: 157
    • Rerandomized: 122
• The end-of-treatment abstinence rate for phase 1 nonabstainers
  • Initial CNRT
    • Continued: 8% (95% credible interval [CrI], 6 to 10)
    • Increased dosage: 14% (95% CrI, 10 to 18)
    • Switched to varenicline: 14% (95% CrI, 10 to 18)
    • Absolute risk difference 6% (95% CrI, 6 to 11)
    • >99% posterior probability that either strategy conferred benefit over continuing the initial dosage
  • Initial varenicline
    • Continued: 3% (95% CrI, 1% to 4%)
    • Increased dosage: 20% (95% CrI, 16 to 26)
    • Switched to CNRT: 0% (95% CrI, 0 to 0)
    • Absolute risk difference 18% (95% CrI, 13% to 24%)
    • >99% posterior probability of increasing the varenicline dosage conferring benefit
• At 6 months, only increased dosages of the CNRT and varenicline provided benefit over continuation of the initial treatment dosages

CONCLUSION:

• For those who attempted to quit smoking using varenicline but did not achieve abstinence after the first attempt, increasing the dosage was more helpful than continuing at the initial dosage
• For those who used CNRT to quit, both increasing the CNRT dosage, or switching to varenicline, were more helpful than continuing at the same dosage
• The authors state

For individuals who do not achieve abstinence after treatment with varenicline, increasing the dosage enhances abstinence relative to continuing at the initial dosage, whereas for those who don’t achieve abstinence with CNRT, a dosage increase or switching to varenicline are viable rescue strategies, with continuous abstinence results favoring a dosage increase

Learn More – Primary Sources:

Smoking Cessation After Initial Treatment Failure With Varenicline or Nicotine Replacement: A Randomized Clinical Trial

Is Olive Oil Consumption Linked to Reduced Dementia-Related Mortality?

BACKGROUND AND PURPOSE:

• Tessier et al. (JAMA Network Open, 2024) examined the association of olive oil intake with the subsequent risk of dementia-related death and assessed the joint association with diet quality and substitution for other fats

METHODS:

• Prospective cohort study
  • Nurses’ Health Study (NHS; 1990 to 2018)
  • Health Professionals Follow-Up Study (HPFS; 1990 to 2018)
• Participants
  • Women and men who were free of cardiovascular disease and cancer at baseline
• Exposures
  • Olive oil intake, assessed every 4 years using a food frequency questionnaire
    • Never, or <1x per month
    • >0 to ≤4.5 g/d
    • >4.5 to <7 g/d
    • >7 g /d
  • Diet quality
    • Assessed with the Alternative Healthy Eating Index and Mediterranean Diet score
• Study design
  • Multivariable Cox proportional hazards regressions were used to estimate hazard ratio (HR)
  • Adjusted for confounders: Genetic | Sociodemographic | Lifestyle factors
• Primary outcome
  • Dementia-related mortality

RESULTS:

• 92,383 participants
  • Women: 65.6%
  • Mean age: 56.4 (SD, 8.0) years
  • 28 years of follow-up (2,183,095 person-years)
• Dementia-related deaths: 4751
  • Individuals who were homozygous for the apolipoprotein ε4 (APOE ε4) allele were 5 to 9 times more likely to die with dementia
• Compared with never or rarely consuming olive oil, consuming at least 7 g/d of olive oil was associated with a lower risk of dementia-related death
  • Overall: Adjusted pooled HR 0.72 (95% CI, 0.64 to 0.81)
  • Women: Adjusted pooled HR 0.67 (95% CI, 0.59 to 0.77) 
  • Men: adjusted pooled HR 0.87 (95% CI, 0.69 to 1.09)
• Results were consistent after adjustment for APOE ε4
• There was no interaction by diet quality score
• In modeled substitution analyses, replacing 5 g/d of margarine and mayonnaise with the equivalent amount of olive oil was associated with lower risk of dementia mortality
  • Margarine: 8% (95% CI, 4 to 12)
  • Mayonnaise: 14% (95% CI, 7 to 20)
• Substitutions for other vegetable oils or butter were not significant

CONCLUSION:

• A higher intake of olive oil was associated with a reduced risk of dementia-related mortality regardless of diet quality
• The authors state

This study found that in US adults, particularly women, consuming more olive oil was associated with lower risk of dementia-related mortality, regardless of diet quality

These findings extend the current dietary recommendations of choosing olive oil and other vegetable oils to the context of cognitive health and related mortality

Learn More – Primary Sources:

Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death

What Health Outcomes are Associated with Hormone Therapy Use Beyond Age 65?

BACKGROUND AND PURPOSE:

• Baik et al. (Menopause, 2024) assessed the use of menopausal hormone therapy (HT) beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths

METHODS:

• Retrospective cohort study
  • CMS provided access to 100% claims data for Medicare Parts A (hospital), B (medical insurance), C (Medicare Advantage) and D (drug benefits)
• Population
  • Women who were Medicare enrollees at age 65 during Part D benefits (2007 to 2020)
• Exposures
  • HT type
    • Estrogen: estradiol (E2) | Conjugated estrogen (CEE) | ethinyl estradiol (EE)
    • Progestogen: progesterone (natural) | Progestin (synthetic)
  • Routes: Oral | Transdermal | Vaginal | Injectable
  • Dose
• Study design
  • Only included enrollees with ≥6 months follow-up
  • Cox regression analyses were used, adjusted for time-varying characteristics of the women
• Primary outcome
  • All-cause mortality | Cancer | Cardiovascular disease | Dementia

RESULTS:

• 10 million women
• Compared with never use or discontinuation of HT >65 years, the use of estrogen monotherapy >65 years was associated with significant risk reductions in
  • Mortality: Adjusted hazard ratio (aHR) 0.81 (95% CI, 0.79 to 0.82)
  • Breast cancer: aHR 0.84 (95% CI, 0.83 to 0.86)
  • Lung cancer: aHR 0.87 (95% CI, 0.84 to 0.90)
  • Colorectal cancer: aHR 0.88 (95% CI, 0.84 to 0.91)
  • Congestive heart failure: aHR 0.95 (95% CI, 0.94 to 0.96)
  • VTE: aHR 0.97 (95% CI, 0.96 to 0.98)
  • Atrial fibrillation: aHR 0.96 (95% CI, 0.95 to 0.98)
  • Acute myocardial infarction: aHR 0.89 (95% CI, 0.87 to 0.92)
  • Dementia: aHR 0.98 (95% CI, 0.97 to 1.00)
• Combo-therapy with either progestin or progesterone was associated with increased risk of breast cancer
  • E+progestin: aHR 1.10 (95% CI, 1.06 to 1.15)
  • E+progesterone: aHR 1.19 (95% CI, 1.14 to 1.24)
• Combo-therapy with progestin exhibited significant risk reductions in
  • Endometrial cancer: aHR 0.55 (95% CI, 0.50 to 0.60)
  • Ovarian cancer: aHR 0.79 (95% CI, 0.71 to 0.89)
  • Ischemic heart disease: aHR 0.95 (95% CI, 0.93 to 0.97)
  • Congestive heart failure: aHR 0.95 (95% CI, 0.91 to 0.98)
  • VTE: aHR 0.95 (95% CI, 0.91 to 0.99)
• Combo-therapy with progesterone exhibited risk reduction only in congestive heart failure
  • aHR 0.96 (95% CI, 0.92 to 1.00)

CONCLUSION:

• Health implications of using hormone therapy beyond age 65 vary based on the type of HT, route of administration, and dose
• Benefits accrue to estrogen monotherapy, appropriate for women without an intact uterus
• It appears that risk for breast cancer is most reduced with lower doses, vaginal or transdermal administration and use of estradiol
• The authors state

Our study suggests the possibility of important health benefits with use of menopausal HT beyond age 65 years

…low dose of transdermal and vaginal EPT (especially E+ progestin) can mitigate the risk of breast cancer 

Learn More – Primary Sources:

Use of menopausal hormone therapy beyond age 65 years and its effects on women’s health outcomes by types, routes, and doses

Does a Single PSA Screening Test Reduce the Long-Term Risk of Prostate Cancer Specific Mortality?

BACKGROUND AND PURPOSE:

• The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) found that while a single PSA screening test increased the number of prostate cancers, the test had no effect on prostate cancer mortality 10 years post-screening
• Martin et al. (JAMA Network Open, 2024) sought to determine whether a single PSA screening test reduced prostate cancer mortality 15 years post-screening

METHODS:

• Secondary analysis of CAP randomized trial
  • 8 hospitals across England and Wales
• Participants
  • Men aged 50 to 69
• Intervention
  • Invitation to a single PSA screening test, with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher
  • Standard care
• Pre-specified secondary outcomes
  • Prostate cancer–specific mortality | All-cause mortality
  • Prostate cancer stage | Gleason grade at diagnosis

RESULTS:

• 415,357 men
  • Mean age 59.0 (SD, 5.6) years
• 15-year cumulative risk of prostate cancer
  • Screening: 7.08% (95% CI, 6.95 to 7.21)
  • Control: 6.94% (95% CI, 6.82 to 7.06)
• There was a slight but significant decrease in the number of deaths in the screening group
  • Screening: 0.69% (95% CI, 0.65 to 0.73)
  • Control: 0.78% (95% CI, 0.73 to 0.82)
  • Rate ratio (RR) 0.92 (95% CI, 0.85 to 0.99 | P=0.03
• Compared with the control, the PSA screening intervention increased detection of
  • Low-grade disease (Gleason score [GS] ≤6)
    • Screening: 2.2% | Control: 1.6% | P<0.001
  • Localized (T1/T2) disease
    • Screening: 3.6% | Control: 3.1% | P<0.001
• PSA screening had no effect on the detection rate of intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors
• There was no significant difference in all-cause deaths between the groups
  • Screening: 23.2% (95% CI, 23.0 to 23.4)
  • Control: 23.3% (95% CI, 23.1 to 23.5)
  • RR 0.97 (95% CI, 0.94 to 1.01) | P=0.11

CONCLUSION:

• A single PSA screening test modestly decreased the rate of prostate cancer specific mortality after 15 years of follow up
• There was no significant difference in all-cause mortality
• The authors state

In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years

However, the absolute reduction in deaths was small

Learn More – Primary Sources:

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial

RCT Results: Does Paxlovid Reduce Time to COVID-19 Symptom Alleviation in Groups Other Than Unvaccinated with High Risk for Severe Disease?

BACKGROUND AND PURPOSE:

• Paxlovid (nirmatrelvir with ritonavir) is an effective antiviral treatment for unvaccinated adults with COVID-19 at risk for severe disease
• Effectiveness in other groups remain unclear
• Hammond et al. (NEJM, 2024) evaluated the efficacy and safety of nirmatrelvir–ritonavir among vaccinated adults at risk for severe COVID-19 as well as unvaccinated individuals at standard risk

METHODS:

• Phase 2 to 3 double-blind, randomized, placebo-controlled trial
• Participants
  • Adults with confirmed COVID-19 with symptom onset within the past 5 days who were
    • ≥1 risk factor severe disease: Fully vaccinated against COVID-19 or
    • 0 risk factors for severe disease: Never vaccinated or not vaccinated within the previous year
• Interventions
  • Nirmatrelvir–ritonavir every 12 hours for 5 days
  • Placebo
• Study design
  • Participants logged the presence and severity of prespecified COVID-19 signs and symptoms daily from day 1 through day 28
• Primary outcome
  • Time to sustained alleviation of all targeted COVID-19 signs and symptoms
• Secondary outcome
  • COVID-19–related hospitalization and death from any cause through day 28

RESULTS:

• Nirmatrelvir–ritonavir: 654 participants | Placebo: 634 participants
• There was no significant difference in median time to sustained alleviation of all targeted signs and symptoms of COVID-19
  • Nirmatrelvir–ritonavir: 12 days | Placebo: 13 days | P=0.60
• Hospitalizations for COVID-19 or death from any cause
  • Nirmatrelvir–ritonavir: 0.8% | Placebo: 1.6%
  • Difference −0.8 percentage points (95% CI, −2.0 to 0.4)
• The percentages of participants with adverse events were similar in the two groups
  • Nirmatrelvir–ritonavir: 25.8% | Placebo: 24.1%
• In the nirmatrelvir–ritonavir group, the most commonly reported treatment-related adverse events were
  • Dysgeusia: 5.8%
  • Diarrhea: 2.1%

CONCLUSION:

• Paxlovid did not alter the time to sustained symptom alleviation in adult participants with Covid-19 who were at standard or high risk for severe disease
• The authors state

Nirmatrelvir–ritonavir was not associated with a significantly shorter time to sustained alleviation of Covid-19 symptoms than placebo, and the usefulness of nirmatrelvir–ritonavir in patients who are not at high risk for severe Covid-19 has not been established

Learn More – Primary Sources:

Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19

RCT Results: Does Apple Cider Vinegar Improve Weight Loss Metrics in Adults with Overweight and Obesity?

BACKGROUND AND PURPOSE:

• Alternative remedies for weight-loss are popular, but their evidence for their efficacy is often lacking
  • Apple cider vinegar (ACV) has shown benefit in animal studies and some small-scale studies in humans
• Abou-Khalil et al. (BMJ Nutrition Prevention and Health, 2024) investigated the effects of ACV consumption on weight, blood glucose, triglyceride and cholesterol levels

METHODS:

• Randomized controlled trial
  • Lebanese population
• Participants
  • Overweight and obese adolescents and adults  12 to 25 years
    • BMI: Between 27 and 34 kg/m2
  • No chronic diseases
  • No intake of medications
• Intervention
  • ACV (5% acetic acid diluted in 250 ml of water)
    • 5 mL | 10 mL | 15 mL over 12 weeks
  • Placebo
• Study design
  • ACV taken in the morning on an empty stomach
  • Lactic acid was used to give placebo a similar acidic taste
  • Measurements were taken at 0, 4, 8 and 12 weeks
• Primary outcomes
  • Anthropometric parameters
  • Fasting blood glucose
  • Triglyceride and cholesterol levels

RESULTS:

• 120 participants
• No change in diet diary and physical activity throughout the study
• Consuming 5 mL, 10 mL or 15 mL of ACV resulted in significant decreases in body weight and BMI by week 12 (P<0.05)
  • Body weight at week 12
    • 15 mL ACV: 70.2 kg (SD, 25.0)
    • Placebo: 78.8 kg (SD, 28.6)
  • BMI at week 12
    • 15 mL ACV: 27.2 (SD, 2.9)
    • Placebo: 30.6 (SD, 3.2)
• Serum glucose, triglyceride and cholesterol levels all decreased significantly with ACV by week 12 (P<0.05)
• There were no significant adverse effects

CONCLUSION:

• Consuming ACV (either 5, 10 or 15 mL) daily led to improved anthropometric and metabolic parameters for adults and adolescents with overweight and obesity 
• The authors state

Biological action of acetate may be mediated by binding to the G-protein coupled receptors (GPRs), including GPR43 and GPR41

These receptors are expressed in various insulin-sensitive tissues, such as adipose tissue, skeletal muscle, liver, and pancreatic beta cells, but also in the small intestine and colon

Learn More – Primary Sources:

Apple cider vinegar for weight management in Lebanese adolescents and young adults with overweight and obesity: a randomised, double-blind, placebo-controlled study

Rising Incidence of Cervical Cancer in the US

BACKGROUND AND PURPOSE:

• Cervical cancer cases have historically declined in the US following introduction of cytological testing
• Amboree et al. (International Journal of Cancer, 2024) evaluated trends in hysterectomy-corrected cervical cancer incidence and mortality rates by county-level income and race/ethnicity

METHODS:

• Analysis of Surveillance, Epidemiology, and End Results-22 (SEER-22) dataset for 2000 to 2019
• Exposures
  • County-level income (First quartile: $19,330 to $38,820 | Fourth quartile: $52,260 to $123,450)
  • Race/ethnicity
  • Stage at diagnosis
• Primary outcomes
  • Age-standardized incidence rates for cervical cancer and related mortality

RESULTS:

• Following a period of decline, hysterectomy-corrected cervical cancer incidence increased for non-Hispanic White women in low-income counties
  • 1.0% per year (95% CI, 0.1 to 4.5)
• There was a significant increase in distant-stage cancer for this group
  • 4.4% per year (95% CI, 1.7 to 7.5)
• There were also recent non-significant increases in cervical cancer mortality for
  • Non-Hispanic Black women in low-income counties
    • 2.9% per year (95% CI, –2.3 to 18.2)
  • Hispanic women in low-income counties
    • 1.5% per year (95% CI, –0.6 to 4.1)

CONCLUSION:

• Cervical cancer rates among women in low-income counties in the US are increasing
  • There is a particular increase in distant-stage cancer
• The authors suggest that these results indicate disruptions in the screening to cancer care pipeline

Future research to further comprehend these trends and continued enhancements in prevention are crucial to combat rising cervical cancer incidence and mortality in low-income counties in the United States

Learn More – Primary Sources:

Recent trends in cervical cancer incidence, stage at diagnosis, and mortality according to county-level income in the United States, 2000–2019

How Satisfied are Physicians with Electronic Health Information Interoperability?

BACKGROUND AND PURPOSE:

• Healthcare IT interoperability should allow for the seamless exchange electronic information to improve patient care and related efforts
• Everson et al. (JAMA Netw Open, 2024) assessed PCP perspectives on the state of interoperability

METHODS:

• Cross-sectional survey
  • Data derived from the American Board of Family Medicine certification process
  • Includes completion of the Continuous Certification Questionnaire (CCQ)
• Participants
  • Family medicine physicians in the US
• Study design
  • 18 items on the CCQ assessed experience accessing and using various information from outside organizations
• Primary outcome
  • Satisfaction with interoperability

RESULTS:

• 2088 physicians
  • Women: 50%
  • Practiced in hospitals or health system–owned practices: 35%
  • Practiced in independently owned practices: 27%
• Satisfaction with ability to electronically access all 10 types of information from outside organizations
  • Very satisfied: 11%
  • At least somewhat satisfied: 70%
• Ease of use of information from outside organizations
  • Very easy: 23%
  • At least somewhat easy: 65%
• Reported information from different EHR developers’ products was very easy to use: 8%
• Reported information from the same EHR developers’ product was very easy to use: 38%

CONCLUSION:

• Family medicine physicians reported only modest satisfaction with healthcare EHR interoperability
• Truly improving interoperability will likely require diverse policy and strategies
• The authors state

Findings revealed that satisfaction varied across multiple dimensions—by physician, by the EHR from which the data originated, and by the type of information—and that physicians frequently experienced both missing information and too much information

Learn More – Primary Sources:

Primary Care Physicians’ Satisfaction With Interoperable Health Information Technology

Are Plant-Based Diets Associated with a Higher Risk of Hip Fracture Among Postmenopausal Women?

BACKGROUND AND PURPOSE:

• Previous studies have identified a higher risk of fractures associated with plant-based diets although there is limited data regarding the quality of these diets
• Sotos-Prieto et al. (Jama Network Open, 2024) examined the association between the quality of plant-based diets and hip fracture risk among postmenopausal women

METHODS:

• Retrospective cohort study
  • US Nurses’ Health Study
  • Between 1984 to 2014
• Population
  • Postmenopausal women
• Exposures
  • Quality of plant-based diet
• Study design
  • Diet was assessed every 4 years using a validated questionnaire
  • Diet quality was assessed using 2 established indices
    • Healthful Plant-Based Diet Index (hPDI)
      • Positive scores given to healthy plant foods (e.g. whole grains, fruits, vegetables, nuts, legumes, etc.)
      • Negative scores given to less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, and sweets or desserts) and animal foods
    • Unhealthful Plant-Based Diet Index (uPDI)
      • Positive scores given to less healthy plant foods
      • Negative scores given to healthy plant and animal foods
  • Quintile scores of 18 food groups were summed
    • Range for both indices: 18 to 90 (highest adherence)
  • Cox proportional hazards regression with time-varying covariates used to compute hazard ratios (HR)
• Primary outcome
  • Hip fractures

RESULTS:

• 70,285 participants
  • Mean age 54.92 (SD, 4.48) years | White: 100%
• For long-term diet adherence, neither quality measure was associated with hip fracture risk
  • hPDI (higher scores = more healthy)
    • HR (highest vs lowest quintile) 0.97 (95% CI, 0.83 to 1.14)
  • uPDI (higher scores = less healthy)
    • HR 1.02 (95% CI, 0.87 to 1.20)
• However, for recent intake (baseline diet) higher hPDI was associated with a lower risk of hip fracture, and higher uPDI was associated with a higher risk (P_trend=0.008)
  • hPDI
    • HR (highest vs lowest quintile) 0.79 (95% CI, 0.68 to 0.92)
  • uPDI
    • HR 1.28 (95% CI, 1.09 to 1.51)

CONCLUSION:

• Long-term adherence to a healthy plant-based diet by postmenopausal women was not associated with any changes in risk of hip fracture, compared to an unhealthy plant-based diet
• The authors state

The results of this cohort study indicated that long-term adherence to a plant-based diet was not associated with hip fracture risk. Future research should clarify whether the results for recent dietary intake are associated with the relatively short-term effects of these dietary patterns, reverse causality, or both

Learn More – Primary Sources:

Plant-Based Diets and Risk of Hip Fracture in Postmenopausal Women

Does Long-Term Calcium/Vitamin D Supplementation Improve All-Cause Mortality Among Postmenopausal Women?

BACKGROUND AND PURPOSE:

• Thomson et al. (Annals of Internal Medicine, 2024) evaluated long-term health outcomes related to calcium and vitamin D (CaD) intake among postmenopausal women

METHODS:

• Post hoc analysis of long-term, postintervention follow-up of an RCT
  • Women’s Health Initiative 7-year CaD trial
• Participants
  • Postmenopausal women
  • No history of breast or colorectal cancer
• Intervention
  • 1000 mg of calcium carbonate (400 mg of elemental calcium) with 400 IU of vitamin D3 daily
  • Placebo
• Study design
  • Analyses stratified based on prerandomization supplement use 
• Primary outcome
  • Incidence of colorectal, invasive breast, and total cancer
  • Disease-specific and all-cause mortality
  • Total cardiovascular disease (CVD)
  • Hip fracture by randomization assignment

RESULTS:

• 36,282 women
  • Median cumulative follow-up: 22.3 years
• CaD supplementation was associated with a
  • 7% reduction in cancer mortality
    • Hazard ratio (HR) 0.93 (95% CI, 0.87 to 0.99)
  • 6% increase in CVD mortality
    • HR 1.06 (95% CI, 1.01 to 1.12)
• There was no overall effect on other measures
  • E.g., all-cause mortality: HR 1.00 (95% CI, 0.97 to 1.03)
• Estimates for cancer incidence varied widely when stratified by whether participants reported supplement use before randomization
• Estimates on mortality generally did not vary
• Analyses of hip fracture outcomes were limited due to samples size

CONCLUSION:

• After 20 years of follow-up, CaD supplementation among postmenopausal women was associated with a slight reduction in cancer mortality and a slight increase in CVD mortality
• Long-term, all-cause mortality was not impacted by CaD supplementation
• The authors state

Given the study design, we could not disentangle the added benefit or harms of supplementation with CaD in combination versus vitamin D alone, a topic worthy of future study

Learn More – Primary Sources:

Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women: Postintervention Follow-up of a Randomized Clinical Trial