Rapid, high-resolution, non-destructive assessments of metabolic and morphological homogeneity uniquely identify high-grade cervical precancerous lesions.

Purpose: Two-photon microscopy (2PM) is an emerging clinical imaging modality with the potential to non-invasively assess tissue metabolism and morphology in high-resolution. This study aimed to assess the translational potential of 2PM for improved detection of high-grade cervical precancerous lesions. Experimental Design: 2P images attributed to reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and oxidized flavoproteins (FP) were acquired from the full epithelial thickness of freshly excised human cervical tissue biopsies (N = 62). Fifteen biopsies harbored high-grade squamous intraepithelial lesions (HSILs), 14 biopsies harbored low-grade SILs (LSILs), and 33 biopsies were benign. Quadratic discriminant analysis (QDA) leveraged morphological and metabolic functional metrics extracted from these images to predict the presence of HSILs. We performed gene set enrichment analysis (GSEA) using datasets available on the Gene Expression Omnibus (GEO) to validate the presence of metabolic reprogramming in HSILs. Results: Integrating metabolic and morphological 2P-derived metrics from finely sampled, full-thickness epithelia achieved a high 90.8 ± 6.1% sensitivity and 72.3 ± 11.3% specificity of HSIL detection. Notably, sensitivity (91.4 ± 12.0%) and specificity (77.5 ± 12.6%) were maintained when utilizing metrics from only two images at 12- and 72-µm from the tissue surface. Upregulation of glycolysis, fatty acid metabolism, and oxidative phosphorylation in HSIL tissues validated the metabolic reprogramming captured by 2P biomarkers. Conclusion: Label-free 2P images from as few as two epithelial depths enable rapid and robust HSIL detection through the quantitative characterization of metabolic and morphological reprogramming, underscoring the potential of this tool for clinical evaluation of cervical precancers.

Improving the identification of genitourinary syndrome of menopause through the utilization of the Day-to-Day Impact of Vaginal Aging questionnaire.

OBJECTIVE: Genitourinary syndrome of menopause (GSM) affects nearly 50% of postmenopausal women. Yet women fail to recognize GSM as a chronic condition and are reluctant to discuss their vaginal or sexual complaints with a health care provider. This quality improvement project implemented the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire to improve the identification and diagnosis of GSM in women ≥ 45 years of age presenting for an annual wellness examination or a vulvovaginal/genitourinary complaint. METHODS: From October 2019 to February 2020, the DIVA questionnaire was distributed in a large women's health practice setting to women ≥ 45 years of age, for completion before their annual wellness visit or for evaluation of a GSM-related complaint. GSM diagnosis rates during the implementation period were compared with diagnosis rates during a 4-month period immediately preceding the implementation. Data collected during the implementation period were examined to evaluate if GSM diagnosis was more likely in patients who completed the DIVA questionnaire when compared to those women who did not complete the questionnaire. RESULTS: Of the 175 women who met the inclusion criteria, 113 completed the DIVA questionnaire. Completion of the DIVA questionnaire demonstrated a relative percentage increase in GSM diagnosis by 30.7% when compared to the 4-month preimplementation period (10.1% to 13.2%, P = 0.231). This change was not statistically significant. During the implementation period, a statistically significant difference in GSM diagnosis was observed for patients who completed the DIVA questionnaire when compared to those patients who did not complete the questionnaire (37.2% vs 9.7%, P < 0.001). When results were stratified by visit type, women presenting for an annual wellness visit who completed the DIVA questionnaire had a higher GSM diagnosis rate than those who did not complete the questionnaire (37.2% vs 10%, P < 0.001). When results were stratified by menopausal status, GSM diagnosis rates were also more likely for postmenopausal women who completed the DIVA questionnaire when compared to those who did not complete the questionnaire (44.2% vs 8.5%, P < 0.001). CONCLUSIONS: The DIVA questionnaire is a brief, but comprehensive screening tool that can increase GSM identification and treatment, particularly for postmenopausal, and midlife women presenting for an annual wellness visit in a busy women's health practice setting. : Video Summary:http://links.lww.com/MENO/A655.

Video Summary:http://links.lww.com/MENO/A655.

Opioid Prescription and Patient Use After Gynecologic Procedures: A Survey of Patients and Providers.

STUDY OBJECTIVE: To describe opioid distribution and patient use after gynecologic procedures. DESIGN: Survey study (Canadian Task Force classification III). SETTING: An urban academic tertiary care hospital. SUBJECTS: Ninety-six gynecologists in the Boston area, and 147 patients who underwent a benign hysterectomy between January 2015 and April 2016. INTERVENTIONS: Survey study of physicians and patients composed of 2 parts: (1) a physician survey on opioid prescribing practices after gynecologic procedures and (2) a patient survey on opioid consumption after hysterectomy. Physicians were contacted via e-mail to participate in an online survey. Eligible patients were contacted via telephone and asked to participate in a telephone survey. MEASUREMENTS AND MAIN RESULTS: Fifty-one physicians responded to an online survey and prescribed a mean of 27.1 tablets (range, 5-30) of oxycodone (5 mg) or hydromorphone (2 mg) after abdominal hysterectomy (AH), a mean of 22.6 tablets (range, 5-30) after laparoscopic hysterectomy (LH), and a mean of 16.8 tablets (range 5-30) after vaginal hysterectomy (VH). Physicians prescribed more opioids for AH compared with LH, with a mean difference of 4.5 tablets (standard deviation, 4.7; p < .01), and AH compared with VH, with a mean difference of 6.8 tablets (standard deviation, 5.8; p < .01), which were both statistically significant. In addition, 40.0% of physicians prescribe opioids after a hysteroscopy and 19.2% after a dilation and curettage. Fifty-six patients participated in the telephone survey: 64.6% of patients used less than half of the opioids prescribed and 16.1% used none. For AH, patients reported being prescribed a mean of 25.7 tablets and using a mean of 8.7 tablets (range, 0-60; 33.9% used). For LH or VH, patients reported being prescribed a mean of 24.2 tablets and using a mean of 10.0 tablets (range, 0-30; 41.4% used). Opioid consumption was not significantly different for AH compared with LH or VH (p = .613 for AH to LH, p = .279 for AH to VH). CONCLUSIONS: With respect to the physician survey, we conclude there is a wide range of opioid prescription practices and patient opioid consumption after gynecologic surgery. The patient survey revealed that physicians prescribe fewer opioid tablets after a minimally invasive approach to hysterectomy versus open hysterectomy. However, most patients use less than half of prescribed opioids, and a fraction did not use any opioids at all.

Transition of care to an adult provider.

PURPOSE OF REVIEW: The transition from adolescence to young adulthood can be a difficult and overwhelming time. Many adult care providers are unaware of the issues facing adolescents and young adults. Often the focus is on older patients and their problems. Internists, family practitioners and obstetricians and Gynecologists (OBGYNs) typically care for these patients. Often, young adults view their obstetrician and gynecologist as their primary care physician, so reviewing the issues facing this age group is important. RECENT FINDINGS: Lifestyle habits begun in childhood frequently continue throughout life. Adolescence and young adulthood are times when change in these habits may be easier to enforce. Reviewing nutrition, exercise, risky behaviors, preventive health objectives, sexuality and mental health are of utmost importance in the transition of care from a pediatric to an adult provider. SUMMARY: The transition from adolescence to young adulthood can be difficult for patients. Knowledge of these issues is crucial to the adult provider caring for these patients. Although visits frequently are short in duration, using screening tools and checklists filled out by the patient prior to the visit may be beneficial.

See, Test & Treat: A 5-Year Experience of Pathologists Driving Cervical and Breast Cancer Screening to Underserved and Underinsured Populations.

CONTEXT: - See, Test & Treat is a pathologist-driven program to provide cervical and breast cancer screening to underserved and underinsured patient populations. This program is largely funded by the CAP Foundation (College of American Pathologists, Northfield, Illinois) and is a collaborative effort among several medical specialties united to address gaps in the current health care system. OBJECTIVE: - To provide an outline for administering a See, Test & Treat program, using an academic medical center as a model for providing care and collating the results of 5 years of data on the See, Test & Treat program's findings. DESIGN: - Sources include data from patients seen at Tufts Medical Center (Boston, Massachusetts) who presented to the See, Test & Treat program and institutional data between 2010 and 2014 detailing the outline of how to organize and operationalize a volunteer cancer-screening program. RESULTS: - During the 5-year course of the program, 203 women were provided free cervical and breast cancer screening. Of the 169 patients who obtained Papanicolaou screening, 36 (21.3%) had abnormal Papanicolaou tests. In addition, 16 of 130 patients (12.3%) who underwent mammography had abnormal findings. CONCLUSIONS: - In general, women from ethnic populations have barriers that prevent them from participating in cancer screening. However, the CAP Foundation's See, Test & Treat program is designed to reduce those barriers for these women by providing care that addresses cultural, financial, and practical issues. Although screening programs are helpful in identifying those who need further treatment, obtaining further treatment for these patients continues to be a challenge.

J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial.

AIM: In patients with coronary artery disease (CAD), a J-curve relationship has been reported between blood pressure (BP) and future cardiovascular events. However, this is controversial. The purpose of the study was to determine the relationship between on-treatment BP and cardiovascular outcomes in patients with CAD. METHODS AND RESULTS: We evaluated 10 001 patients with CAD and a low-density lipoprotein (LDL) cholesterol level <130 mg/dL, randomized to atorvastatin 80 vs. 10 mg, enrolled in the TNT trial. The post-baseline, time-dependent BPs [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were categorized into 10 mmHg increments. The primary outcome was a composite of death from coronary disease, non-fatal myocardial infarction (MI), resuscitated cardiac arrest, and fatal or non-fatal stroke. Among the 10 001 patients, 982 (9.82%) experienced a primary outcome at 4.9 years (median) of follow-up. The relationship between SBP or DBP and primary outcome followed a J-curve with increased event rates above and below the reference BP range, both unadjusted and adjusted (for baseline covariates, treatment effect, and LDL levels). A time-dependent, non-linear, multivariate Cox proportional hazard model identified a nadir of 146.3/81.4 mmHg where the event rate was lowest. A similar non-linear relationship with a higher risk of events at lower pressures was found for most of the secondary outcomes of all-cause mortality, cardiovascular mortality, non-fatal MI, or angina. However, for the outcome of stroke, lower was better for SBP. CONCLUSION: In patients with CAD, a low BP (<110-120/<60-70 mmHg) portends an increased risk of future cardiovascular events (except stroke).

Intensive lipid lowering with atorvastatin in patients with coronary artery disease, diabetes, and chronic kidney disease.

OBJECTIVE: To investigate the effect of intensive lipid lowering with high-dose atorvastatin on the incidence of major cardiovascular events compared with low-dose atorvastatin in patients with coronary artery disease and type 2 diabetes, with and without chronic kidney disease (CKD). PATIENTS AND METHODS: Following 8 weeks' open-label therapy with atorvastatin (10 mg/d), 10,001 patients with coronary artery disease were randomized to receive double-blind therapy with either 80 mg/d or 10 mg/d of atorvastatin between July 1, 1998, and December 31, 1999. Of 1501 patients with diabetes, renal data were available for 1431. Patients with CKD were defined as having a baseline estimated glomerular filtration rate (eGFR) below 60 mL/min per 1.73 m2, using the Modification of Diet in Renal Disease equation. RESULTS: After a median follow-up of 4.8 years, 95 (17.4%) of 546 patients with diabetes and CKD experienced a major cardiovascular event vs 119 (13.4%) of 885 patients with diabetes and normal eGFRs (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.00-1.72; P<.05). Compared with 10 mg of atorvastatin, 80 mg of atorvastatin reduced the relative risk of major cardiovascular events by 35% in patients with diabetes and CKD (20.9% [57/273] vs 13.9% [38/273]; HR, 0.65; 95% CI, 0.43-0.98; P=.04) and by 10% in patients with diabetes and normal eGFR (14.1% [62/441] vs 12.8% [57/444]; HR, 0.90; 95% CI, 0.63-1.29; P=.56). The absolute risk reduction in patients with diabetes and CKD was substantial, yielding a number needed to treat of 14 to prevent 1 major cardiovascular event over 4.8 years. Both treatments were well tolerated. CONCLUSION: Patients with diabetes, stable coronary artery disease, and mild to moderate CKD experience marked reduction in cardiovascular events with intensive lipid lowering, in contrast to previous observations in patients with diabetes and end-stage renal disease. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00327691.

Amlodipine/atorvastatin: the first cross risk factor polypill for the prevention and treatment of cardiovascular disease.

In 2002, the World Health Organization estimated that over 58% of cardiovascular disease in North America is due to 'both blood pressure and cholesterol higher than optimal'. Unfortunately, less than a third of patients with both conditions are identified, and fewer than one in ten reach the treatment goals for both factors. Adherence to treatment is notably improved when therapy is initiated simultaneously. Combination therapy of amlodipine besylate (Norvasc, Pfizer Ltd) with atorvastatin calcium (Lipitor, Pfizer Ltd), marketed as Caduet (Pfizer Ltd) is the first dual-therapy compound designed to treat hypertension and/or angina and dyslipidemia concurrently with a single daily pill in the full range of dosing combinations. Amlodipine/atorvastatin retains the safety and efficacy of its parent compounds whilst simplifying the management of these comorbid conditions, in what may be considered the first version of a polypill.