Bone, Breath, Heart, Guts: Eight Essential Papers in Primary Care

Roxanne Nelson, RN, BSN

May 04, 2022

From stubborn high blood pressure to diverticulitis, two deputy editors of the Annals of Internal Medicine reviewed eight recently published articles they feel will influence practice.

1. Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults: A Retrospective Observational Study

Roughly 1 in 3 adults with hypertension have inadequate blood pressure control, and clinicians have two options for intensifying treatment: "The dose of the current drug regimen can be maximized, or a new drug can be added," said Deputy Editor Christina C. Wee, MD, MPH.

Data from randomized controlled trials suggest treatment with lower doses of combination therapy may be more effective, with fewer side effects — although the best strategy in older adults remains unclear.

To answer that question, researchers conducted a large-scale, population-based, retrospective cohort study, and observational data were used to emulate a target trial with two groups: new medication and maximizing dose.

The cohort comprised people aged 65 years or older with hypertension and was limited to those with a systolic blood pressure of 130 mm Hg or higher. Two intensification approaches were used: (1) adding a new medication, defined as a total dose increase with a new medication; and (2) maximizing dose, defined as a total dose increase without new medication.

A total of 178,562 patients were included in the study, and 45,575 (25.5%) had intensification by adding a new medication and 132,987 (74.5%) by maximizing dose.

"Both produced systolic blood pressure reduction with a slight advantage in the 'add a new medication' group," Wee said. "That group reduced their systolic blood pressure by over 4.5 points as compared to 3.8 points in the maximized [dose] group."

At 12 months the results were similar, but only 50% of patients in the new medication group were able to sustain that strategy compared with two thirds of patients who had their dose increased.

"This suggests that in older adults, adding a new antihypertensive medication versus maximizing dosing of existing regimen is less common, only minimally more effective, and less sustainable," Wee said. "Maximizing dose of antihypertensive medication is a reasonable approach [and] may be easier to sustain."

2. Cost-Effectiveness of Screening Mammography Beyond Age 75 Years: A Cost-Effectiveness Analysis

The US Preventive Services Task Force recommends biennial screening mammograms through the age of 74 years, and a meta-analysis of randomized controlled trials suggests mortality is reduced among women with at least a 10-year life expectancy, Wee said.

However, whether screening beyond age 75 years is cost-effective, especially among women with comorbidities, is unclear.

To address that question, researchers estimated benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden, using data from the Surveillance, Epidemiology, and End Results program and the Breast Cancer Surveillance Consortium.

The results showed that extending annual mammography beyond age 75 years was not cost-effective, but biennial mammography was. "It was cost-effective to age 80 regardless of baseline comorbidity score, but it averted only small, absolute numbers of breast cancer deaths — especially for women with comorbidities," Wee said. "It was not cost-effective beyond age 80."

3. Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race: A Prospective Cohort Study

Estimated glomerular filtration rate (eGFR) is associated with end-stage kidney disease (ESKD) and is used to make dialysis and transplant decisions. "However, the accuracy of using eGFR alone has been questioned and, previously, some eGFR equations included a correction for race and this has been quite controversial," Wee said. "And just last year, the Chronic Kidney Disease Epidemiology Collaboration released their new equations, removing the adjustment for race."

The study authors posed two questions:

  1. How well does eGFR alone predict risk of ESKD compared to Kidney Function Risk Equation (KFRE)?  

  2. Does using different eGFR equations affect performance of either eGFR alone or KFRE in predicting the risk of ESKD?

During a maximum 16 years of follow-up, 856 participants (N = 3873) developed end-stage kidney disease. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of end-stage kidney disease compared with eGFR alone.

"KFRE score better predicted 2-year risk of ESKD than eGFR alone regardless of eGFR equations used," Wee said. "Correcting eGFR equations for race did not improve performance and validates recent guidelines."

4. Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy: A Propensity Score-Matched Cohort Study

The study looked at the comparative risks of drug holidays after long-term (≥ 3 years) risedronate vs alendronate therapy in a cohort of individuals aged 66 years or older. The primary outcome was hip fracture within 3 years after a 120-day ascertainment period.

The cohort included 25,077 propensity score-matched pairs (81% female) with a mean age of 81 years. Hip fracture rates were higher among risedronate than alendronate drug holidays, although this association was attenuated when any fracture was included as the outcome.

Overall, risedronate treatment before a drug holiday was associated with an 18% greater risk of hip fractures than alendronate, and this relative increase translated to a small absolute increase of 0.6%.

"These differences primarily manifested after 24 months, but given these small differences, I'm not sure if we need to change our current management strategy," Wee said. "But further study is warranted."

5. The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults: A Response-Adaptive, Randomized Clinical Trial

This study assessed the effects of four doses of vitamin D3 supplements on the risk of falls.

The cohort included 688 participants, aged 70 years and older, with an elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L. The intervention was 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day.

"Their results showed that supplementation at doses of 1000 IU/day or higher did not prevent falls compared with 200 IU/day," Deputy Editor Stephanie Chang, MD, MPH, said. "Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/day or higher."

6. Postdiagnosis Smoking Cessation and Reduced Risk for Lung Cancer Progression and Mortality: A Prospective Cohort Study

This study sought to determine if quitting smoking after a diagnosis of lung cancer reduced the risk for disease progression and mortality. Researchers prospectively analyzed patients with non-small cell lung cancer (NSCLC) who were recruited between 2007 and 2016 and followed annually through 2020. The cohort comprised 517 current smokers who were diagnosed with early-stage (IA-IIIA) NSCLC.

The adjusted median overall survival time was 21.6 months higher among patients who quit smoking vs those who continued smoking, and a higher 5-year overall and progression-free survival were observed among patients who quit than those who continued smoking. After adjusting for confounders, smoking cessation remained associated with a lower risk for all-cause mortality, cancer-specific mortality, and disease progression.

7. Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events

This study sought to determine if alcohol consumption heightened the risk for an episode of atrial fibrillation (AF). The cohort included 100 individuals with paroxysmal AF who were fitted with a continuous electrocardiogram monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded and finger-stick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events.

PEth testing correlated with the number of real-time recorded drinks and with the transdermal alcohol sensor. Consuming one alcoholic drink was associated with a twofold increased risk of AF over the next 4 hours. The risk rose threefold with the consumption of two drinks.

"There is evidence of dose response relationship with higher risk with more drinks," Chang said. "Even one drink may predispose to an acute episode of AF in those so predisposed."

8. Evaluation and Management After Acute Left-Sided Colonic Diverticulitis: A Systematic Review

Management of uncomplicated diverticulitis is usually conservative and includes bowel rest and fluids. However, uncertainty remains about the role of hospitalization and antibiotics, Chang said. The new review included 51 studies looking at colonoscopy, nonsurgical treatments, and elective surgery for patients with diverticulitis.

It was unclear if patients with recent acute diverticulitis are at increased risk for colorectal cancer, although those with complicated diverticulitis do appear to be at a higher risk of the disease. Treatment with mesalamine was shown to be ineffective in preventing recurrence, and other nonsurgical treatments lacked adequate evidence.

As for surgery, elective procedures reduce recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most.

"The ACP recommends initial management without antibiotics," said Chang, adding that other questions need to be addressed, such as inpatient vs outpatient management and elective surgery after an acute episode.

Wee and Chang have disclosed no relevant financial relationships.

American College of Physicians (ACP-IM) Internal Medicine Meeting 2022: Recent Articles That Should Influence Practice. Presented April 29, 2022.

Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.

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