For due or overdue cervical cancer screening, direct or opt-in mailing of HPV self-sampling increased screening at 6 mo vs. education.

SOURCE CITATION: Winer RL, Lin J, Anderson ML, et al. Strategies to increase cervical cancer screening with mailed human papillomavirus self-sampling kits: a randomized clinical trial. JAMA. 2023;330:1971-1981. 38015219.

Adding piroxicam to levonorgestrel increased emergency contraception effectiveness.

SOURCE CITATION: Li RHW, Lo SST, Gemzell-Danielsson K, et al. Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial. Lancet. 2023;402:851-858. 37597523.

Use of combined hormonal contraception and stroke: A case-control study of the impact of migraine type and estrogen dose on ischemic stroke risk.

OBJECTIVE: To clarify how factors such as estrogen dose and migraine history (including migraine subtype) impact ischemic stroke risks associated with combined hormonal contraceptive (CHC) use. BACKGROUND: CHC use in those with migraine with aura has been restricted due to concerns about stroke risk. METHODS: We conducted a case-control analysis of stroke risk associated with estrogen dose and migraine history among CHC users in a large tertiary care center. All women aged 18-55 who used a CHC between January 1, 2010, and December 31, 2019, were identified. Those with a stroke diagnosis were identified using ICD codes and confirmed via chart and imaging review. Details of personal and family medical history, stroke evaluation, ethinyl estradiol dosing (EE; ≥30 vs. <30 µg), and demographics were collected. From a random sample of 20,000 CHC users without stroke, a control cohort (n = 635) was identified and matched based on patient characteristics, medical and family histories, as well as stroke risk factors, to assess association between migraine diagnosis, migraine subtype, estrogen dose, and stroke. RESULTS: Of the 203,853 CHC users in our cohort, 127 had confirmed stroke (0.06%; CI 0.05%, 0.07%). In unadjusted analyses, a higher number of patients in the case cohort had a diagnosis of migraine (34/127, 26.8%) compared to controls (109/635, 17.2%; p = 0.011). Stroke risk was higher with ≥30-µg EE doses compared to those using a <30-µg dose (OR, 1.52; CI 1.02, 2.26; p = 0.040). Compared to no migraine, personal history of migraine increased the odds of stroke (OR, 2.00; CI 1.27, 3.17; p = 0.003). Compared to no migraine, stroke risk was not significantly increased in those with migraine with aura, but migraine without aura increased the risk (OR, 2.35; CI 1.32, 4.2; p = 0.004). CONCLUSIONS: Overall stroke risk in our cohort of CHC users was low. When CHCs are used in those with migraine, formulations containing ≤30 µg EE are preferred. Shared decision-making should include discussions about ischemic stroke risks in patients with migraine, even those without aura.

In postmenopausal women, multimodal or US screening for ovarian cancer did not reduce ovarian cancer mortality.

SOURCE CITATION: Menon U, Gentry-Maharaj A, Burnell M, et al. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2021;397:2182-93. 33991479.

In women aged 40 to 48 y, annual mammography vs. usual care reduced breast cancer mortality at 10 but not 23 y.

SOURCE CITATION: Duffy SW, Vulkan D, Cuckle H, et al. Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial. Lancet Oncol. 2020;21:1165-72. 32800099.

Appropriate Use of Point-of-Care Ultrasonography in Patients With Acute Dyspnea in Emergency Department or Inpatient Settings: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of point-of-care ultrasonography (POCUS) in patients with acute dyspnea in emergency department (ED) or inpatient settings to improve the diagnostic, treatment, and health outcomes of those with suspected congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax. METHODS: The ACP Clinical Guidelines Committee based this guideline on a systematic review on the benefits, harms, and diagnostic test accuracy of POCUS; patient values and preferences; and costs of POCUS. The systematic review evaluated health outcomes, diagnostic timeliness, treatment decisions, and test accuracy. The critical health, diagnostic, and treatment outcomes evaluated were in-hospital mortality, time to diagnosis, and time to treatment. The important outcomes evaluated were intensive care unit admissions, correctness of diagnosis, disease-specific outcomes, hospital readmissions, length of hospital stay, and quality of life. The critical test accuracy outcomes included false-positive results for suspected pneumonia, pneumothorax, and pulmonary embolism and false-negative results for suspected congestive heart failure, pneumonia, pneumothorax, and pulmonary embolism. Important test accuracy outcomes included false-positive results for suspected congestive heart failure and false-negative and false-positive results for suspected pleural effusion. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adult patients with acute dyspnea in ED or inpatient settings. RECOMMENDATION: ACP suggests that clinicians may use point-of-care ultrasonography in addition to the standard diagnostic pathway when there is diagnostic uncertainty in patients with acute dyspnea in emergency department or inpatient settings (conditional recommendation; low-certainty evidence).

Appropriate Use of High-Flow Nasal Oxygen in Hospitalized Patients for Initial or Postextubation Management of Acute Respiratory Failure: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of high-flow nasal oxygen (HFNO) in hospitalized patients for initial or postextubation management of acute respiratory failure. It is based on the best available evidence on the benefits and harms of HFNO, taken in the context of costs and patient values and preferences. METHODS: The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of HFNO. The patient-centered health outcomes evaluated included all-cause mortality, hospital length of stay, 30-day hospital readmissions, hospital-acquired pneumonia, days of intubation or reintubation, intensive care unit (ICU) admission and ICU transfers, patient comfort, dyspnea, delirium, barotrauma, compromised nutrition, gastric dysfunction, functional independence at discharge, discharge disposition, and skin breakdown. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adult patients with acute respiratory failure treated in a hospital setting (including emergency departments, hospital wards, intermediate or step-down units, and ICUs). RECOMMENDATION 1A: ACP suggests that clinicians use high-flow nasal oxygen rather than noninvasive ventilation in hospitalized adults for the management of acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use high-flow nasal oxygen rather than conventional oxygen therapy for hospitalized adults with postextubation acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence).

Nonpharmacologic and Pharmacologic Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries in Adults: A Clinical Guideline From the American College of Physicians and American Academy of Family Physicians.

DESCRIPTION: The American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) developed this guideline to provide clinical recommendations on nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults in the outpatient setting. The guidance is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. This guideline does not address noninvasive treatment of low back pain, which is covered by a separate ACP guideline that has also been endorsed by AAFP. METHODS: This guideline is based on a systematic evidence review on the comparative efficacy and safety of nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults in the outpatient setting and a systematic review on the predictors of prolonged opioid use. We evaluated the following clinical outcomes using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system: pain (at ≤2 hours and at 1 to 7 days), physical function, symptom relief, treatment satisfaction, and adverse events. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adults with acute pain from non-low back, musculoskeletal injuries. RECOMMENDATION 1: ACP and AAFP recommend that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with topical nonsteroidal anti-inflammatory drugs (NSAIDs) with or without menthol gel as first-line therapy to reduce or relieve symptoms, including pain; improve physical function; and improve the patient's treatment satisfaction (Grade: strong recommendation; moderate-certainty evidence). RECOMMENDATION 2A: ACP and AAFP suggest that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with oral NSAIDs to reduce or relieve symptoms, including pain, and to improve physical function, or with oral acetaminophen to reduce pain (Grade: conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP and AAFP suggest that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with specific acupressure to reduce pain and improve physical function, or with transcutaneous electrical nerve stimulation to reduce pain (Grade: conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP and AAFP suggest against clinicians treating patients with acute pain from non-low back, musculoskeletal injuries with opioids, including tramadol (Grade: conditional recommendation; low-certainty evidence).

Management of genitourinary syndrome of menopause in female cancer patients: a focus on vaginal hormonal therapy.

Genitourinary syndrome of menopause is a condition describing the hypoestrogenic effects on the female genitals and lower urinary tract leading to symptoms such as vaginal dryness, vulvar and vaginal burning, dyspareunia and dysuria. Genitourinary syndrome of menopause is experienced by over half of postmenopausal women, and is even more pervasive in women with cancer. Due to treatments such as surgery, chemotherapy, radiation, and hormonal therapy, women may experience early menopause resulting in earlier and more severe symptoms. Understanding the scope of this issue in female breast and gynecologic cancer survivors and identifying treatment options for this complex patient population are paramount. Tailored patient treatments include nonhormonal therapies (vaginal moisturizers, lubricants, pelvic floor physical therapy, dilator therapy, counseling), systemic and local hormonal therapies. Consensus recommendations by medical societies and associated evidence are reviewed, with emphasis on safety and efficacy of local vaginal hormonal therapies, and management variations noted depending on cancer type and characteristics. With knowledge and understanding of the unmet need associated with under-recognition and under-treatment of genitourinary syndrome of menopause, providers caring for women with cancer are in a position to improve the quality of life of their patients by providing safe and effective treatments.

HPV Update: Vaccination, Screening, and Associated Disease.

Human papillomavirus (HPV) infection is the causative agent in cervical cancer, and is associated with numerous other genital cancers, including vulvar, vaginal, and anal cancer. Primary prevention with HPV vaccination is safe and efficacious, and a recently approved HPV vaccine will provide even more extensive protection against several oncogenic HPV strains. Screening strategies for HPV are rapidly evolving, reflecting the essential role that HPV infection plays in cervical cancer. This article highlights new evidence regarding the efficacy of the recently approved 9-valent HPV (9vHPV) vaccine and the use of primary high-risk HPV testing in cervical cancer screening. We consider the utility of urinary HPV testing in routine clinical practice and review current guidelines regarding anal HPV screening.

In the clinic. Perimenopause.

This issue provides a clinical overview of Perimenopause focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.

Nonhormone therapies for vasomotor symptom management.

Vasomotor symptoms (VMS) are associated with adverse health consequences and can cause significant morbidity for postmenopausal women. Although hormone therapy remains the gold standard of VMS treatment in menopausal women, some women have contraindications to or may choose not to take hormone therapy. This article provides an up-to-date overview of the current evidence-based nonhormone therapies available for managing VMS. Evidence supporting various treatment options is reviewed, including lifestyle interventions, mind-body therapies, procedures, pharmacologic agents, and emerging therapies, such as neurokinin-receptor antagonists. The efficacy, safety, and clinical use of these treatments are detailed, offering insights for clinicians to make informed decisions in menopausal VMS management.

Use of exogenous hormones in those at increased risk for breast cancer: contraceptive and menopausal hormones in gene carriers and other high-risk patients.

IMPORTANCE AND OBJECTIVE: Addressing the hormonal needs of individuals at increased risk of breast cancer (BC) can be a challenge. Observational, prospective, and case-control data support the safety of hormonal contraception in women, often with the added benefits of ovarian and endometrial cancer risk reduction. The majority of data on menopausal hormone therapy (HT) in the highest-risk patients comes from studies of patients with pathogenic variants in BRCA1 and BRCA2 who undergo early surgical menopause. The benefits of risk-reducing salpingo-oophorectomy are not minimized by HT, whereas its use mitigates accelerated osteoporosis and cardiovascular disease. In other patients at increased risk, such as with family history, studies have shown little risk with significant benefit. METHODS: We review evidence to help women's health practitioners aid patients in making choices. The paper is divided into four parts: 1, contraception in the very high-risk patient (ie, with a highly penetrant BC predisposition gene); 2, contraception in other patients at increased risk; 3, menopausal HT in the gene carrier; and 4, HT in other high-risk patients. DISCUSSION AND CONCLUSION: Women at increased risk for BC both early and later in life should be offered reassurance around the use of premenopausal and postmenopausal hormone therapies. The absolute risks associated with these therapies are low, even in the very high-risk patient, and the benefits are often substantial. Shared decision making is key in presenting options, and knowledge of the data in this area is fundamental to these discussions.

Update on current contraceptive options: A case-based discussion of efficacy, eligibility, and use.

With high rates of unintended pregnancy in the United States, it is crucial for clinicians to be well-informed about the full spectrum of contraceptive options to improve reproductive autonomy. We review new contraceptive options including a nonhormonal intravaginal gel, hormonal contraceptives in the form of new pills, patches, and vaginal rings, and combined hormonal contraceptives that contain new estrogens as alternatives to ethinyl estradiol. We review updated prescribing methods for several established hormonal contraceptives such as depot medroxyprogesterone acetate, which is now available for subcutaneous self-injection. Additional choices of available contraceptive methods have important clinical implications that may remove unnecessary barriers to contraceptive use.

Effect of contraceptive hormonal therapy on mammographic breast density: A longitudinal cohort study.

PURPOSE: Evaluate the longitudinal relationship between mammographic density and hormonal contraceptive use in late reproductive-aged women. METHODS: Patients aged 35-50 years old who underwent 5 or more screening mammograms within a 7.5-year period between 2004 and 2019 in a single urban tertiary care center were randomly selected. Patients were categorized into four cohorts based on hormonal contraceptive exposure during a 2-year lead-in period and a 7.5-year study period: 1) never exposed, 2) always exposed, 3) interval hormonal contraceptive start, and 4) interval hormonal contraceptive stop. The primary outcome was difference in BI-RADS breast density category between initial and final mammograms. RESULTS: Of the 708 patients included, long-term use of combined oral contraceptives or a levonorgestrel intrauterine device were not associated with an increase in breast density category over the 7.5-year study period, compared to those with no hormonal contraceptive exposure. Initiation of combined oral contraceptives was associated with an increase in breast density category (ß = 0.31, P = 0.045); however, no difference in initial density category was noted between those exposed and those never exposed to combined oral contraceptives during the 2-year lead-in period, and discontinuation was not associated with a decrease in breast density category when compared to those with continuous exposure. CONCLUSION(S): Long-term use of combined oral contraceptives or a levonorgestrel intrauterine device was not associated with an increase in BI-RADS breast density category. Initiation of a combined oral contraceptive was associated with an increase in breast density category, although this may be a transient effect.