Cost-Effectiveness of a Multicomponent Primary Care Intervention for Hypertension.

BACKGROUND: The SingHypertension primary care clinic intervention, which consisted of clinician training in hypertension management, subsidized single-pill combination medications, nurse-delivered motivational conversations and telephone follow-ups, improved blood pressure control and cardiovascular disease (CVD) risk scores relative to usual care among patients with uncontrolled hypertension in Singapore. This study quantified the incremental cost-effectiveness, in terms of incremental cost per unit reduction disability-adjusted life years, of SingHypertension relative to usual care for patients with hypertension from the health system perspective. METHODS AND RESULTS: We developed a Markov model to simulate CVD events and associated outcomes for a hypothetical cohort of patients over a 10-year period. Costs were measured in US dollars, and effectiveness was measured in disability-adjusted life years averted. We present base-case results and conducted deterministic and probabilistic sensitivity analyses. Based on a willingness-to-pay threshold of US $55 500 per DALY averted, SingHypertension was cost-effective for patients with hypertension (incremental cost-effectiveness ratio: US $24 765 per disability-adjusted life year averted) relative to usual care. This result held even if risk reduction was assumed to decline linearly to 0 over 10 years but not sooner than 7 years. Incremental cost-effectiveness ratios were most sensitive to the magnitude of the reduction in CVD risk; at least a 0.13% to 0.16% point reduction in 10-year CVD risk is required for cost-effectiveness. Probabilistic sensitivity analysis indicates that SingHypertension has a 78% chance of being cost-effective at the willingness-to-pay threshold. CONCLUSIONS: SingHypertension represents good value for the money for reducing CVD incidence, morbidity, and mortality and should be considered for wide-scale implementation in Singapore and possibly other countries. REGISTRATION INFORMATION: REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02972619.

Quality of life and its predictors among patients with metastatic cancer in Bangladesh: the APPROACH survey.

BACKGROUND: This study aimed to assess the health-related quality of life (HRQOL) (physical, functional, emotional, social, spiritual) and psychological (anxiety and depression) well-being and their associations with patient characteristics among patients with metastatic cancer in Bangladesh. METHODS: A convenience sample of 386 Bangladeshi patients with stage IV solid cancers was recruited from a palliative care outpatient department and an inpatient palliative center. Dependent variables included the physical, functional, emotional, social, and overall scores of the Functional Assessment of Cancer Therapy-General (FACT-G) scale, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-SP) scale, the anxiety, depression, and overall scores of the Hospital Anxiety and Depression (HADS) scale. Linear regressions examined the association between dependent variables and patient characteristics. RESULTS: A substantial proportion of Bangladeshi patients reported anxiety (59% of outpatients and 55% of inpatients) and depression (60% of outpatients and 73% of inpatients) symptoms. Generally, greater financial difficulty and symptom burden scores were associated with worse health outcomes. Older patients reported poorer functional and spiritual well-being but better anxiety scores. Females reported worse anxiety and depressive symptoms and physical well-being but better spiritual outcomes. CONCLUSIONS: Additional efforts must be directed at improving the HRQOL of patients with metastatic cancer in Bangladesh. Furthermore, assistance should be made more accessible to vulnerable groups, including women, the elderly, and those with financial difficulty.

Cost-effectiveness of alternative first- and second-line treatments for benign prostatic hyperplasia in Singapore.

BACKGROUND: Minimally invasive surgical therapies, such as water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL), are typically second-line options for patients in whom medical management (MM) failed but who are unwilling or unsuitable to undergo invasive transurethral resection of the prostate (TURP). However, the incremental cost-effectiveness of WVTT or PUL as first- or second-line therapy is unknown. We evaluated the incremental cost-effectiveness of alternative first- and second-line treatments for patients with moderate-to-severe benign prostatic hyperplasia (BPH) in Singapore to help policymakers make subsidy decisions based on value for money. METHODS: We considered six stepped-up treatment strategies, beginning with MM, WVTT, PUL or TURP. In each strategy, patients requiring retreatment advance to a more invasive treatment until TURP, which may be undergone twice. A Markov cohort model was used to simulate transitions between BPH severity states and retreatment, accruing costs and quality-adjusted life-years (QALYs) over a lifetime horizon. RESULTS: In moderate patients, strategies beginning with MM had similar cost and effectiveness, and first-line WVTT was incrementally cost-effective to first-line MM (33,307 SGD/QALY). First-line TURP was not incrementally cost-effective to first-line WVTT (159,361 SGD/QALY). For severe patients, WVTT was incrementally cost-effective to MM as a first-line treatment (30,133 SGD/QALY) and to TURP as a second-line treatment following MM (6877 SGD/QALY). TURP was incrementally cost-effective to WVTT as a first-line treatment (48,209 SGD/QALY) in severe patients only. All pathways involving PUL were dominated (higher costs and lower QALYs). CONCLUSION: Based on the common willingness-to-pay threshold of SGD 50,000/QALY, this study demonstrates the cost-effectiveness of WVTT over MM as first-line treatment for patients with moderate or severe BPH, suggesting it represents good value for money and should be considered for subsidy. PUL is not cost-effective as a first- nor second-line treatment. For patients with severe BPH, TURP as first-line is also cost-effective.

Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of the prostate, common among older men. Its symptoms include difficulties with starting and completing urination, incontinence, frequent and urgent need to urinate. Minimally invasive procedures, such as water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL), are typically offered as second-line options to patients for whom medication has failed but who are unwilling or unsuitable to undergo invasive surgery (transurethral resection of the prostate, TURP). However, whether offering these procedures as first-line options represents good value for money (i.e. cost-effectiveness) is an open question. To address this question and inform subsidy decisions in Singapore, we investigated six stepped-up treatment strategies which differ in first- and second-line treatments. For each strategy, we simulated healthcare costs and quality of life for a cohort of moderate and severe BPH patients over their lifetime, considering the possibility of treatment-related adverse effects and multiple rounds of retreatment. The incremental cost of a unit improvement in quality of life for a strategy relative to the next most expensive one was compared against a willingness-to-pay threshold to determine cost-effectiveness. We found that WVTT was cost-effective relative to medication as a first-line treatment for patients with moderate or severe BPH, suggesting it represents good value for money and should be considered for subsidy. PUL was not cost-effective as first- nor second-line treatment. TURP is cost-effective as first-line for severe BPH patients only.

SARS-CoV-2 papain-like protease plays multiple roles in regulating cellular proteins in the endoplasmic reticulum.

Nsp3s are the largest nonstructural proteins of coronaviruses. These transmembrane proteins include papain-like proteases (PLpro) that play essential roles in cleaving viral polyproteins into their mature units. The PLpro of SARS-CoV viruses also have deubiquitinating and deISGylating activities. As Nsp3 is an endoplasmic reticulum (ER)-localized protein, we asked if the deubiquitinating activity of SARS-CoV-2 PLpro affects proteins that are substrates for ER-associated degradation (ERAD). Using full-length Nsp3 as well as a truncated transmembrane form we interrogated, by coexpression, three potential ERAD substrates, all of which play roles in regulating lipid biosynthesis. Transmembrane PLpro increases the level of INSIG-1 and decreases its ubiquitination. However, different effects were seen with SREBP-1 and SREBP-2. Transmembrane PLpro cleaves SREBP-1 at three sites, including two noncanonical sites in the N-terminal half of the protein, resulting in a decrease in precursors of the active transcription factor. Conversely, cleavage of SREBP-2 occurs at a single canonical site that disrupts a C-terminal degron, resulting in increased SREBP-2 levels. When this site is mutated and the degron can no longer be interrupted, SREBP-2 is still stabilized by transmembrane PLpro, which correlates with a decrease in SREBP-2 ubiquitination. All of these observations are dependent on PLpro catalytic activity. Our findings demonstrate that, when anchored to the ER membrane, SARS-CoV-2 Nsp3 PLpro can function as a deubiquitinating enzyme to stabilize ERAD substrates. Additionally, SARS-CoV-2 Nsp3 PLpro can cleave ER-resident proteins, including at sites that could escape analyses based on the established consensus sequence.

Pap smear recommendations in older women, does the data support stopping?

PURPOSE OF REVIEW: To review the recommendations for cervical cancer screening in older women and to determine the evidence upon which the current and emerging recommendations are based on. To evaluate the possible consequences of stopping cervical cancer screening in older women. RECENT FINDINGS: Recommendations are to space cervical cancer screening intervals for women aged 21-65 and stop in women older than 65. Cervical cancer incidence and mortality burden are significant in women over the age of 65. Human papillomavirus (HPV) vaccination rates are poor in older women. Advanced cervical cancer rates are increasing, including adenocarcinoma rates. Vulvar carcinoma rates are also increasing, and gynecological care and exams are less frequent when women are not getting routine pap testing. SUMMARY: The current review shows that there is limited evidence on which to base the recommendation to stop screening. There is confusion among patients and physicians, and other healthcare providers over who to screen and when, and this is exacerbating the already known difficulty accessing healthcare among racial and ethnic minorities, underinsured, and rural populations, but rates of cancer are also rising most rapidly in white women. Recommendations to space or stop screening are often based on the perceived psychological distress of women undergoing testing and the cost of population screening.

Complex vulvar and vaginal disease in menopause.

PURPOSE OF REVIEW: Menopause is a time of vulvar and vaginal changes that are physiologic and are often symptomatic. These changes can impact up to 50% of women in menopause. There are also several vulvar dermatoses that are more common after menopause and should be recognized early to allow for symptomatic treatment. Some of these conditions can lead to squamous cell carcinoma over time, and early recognition and appropriate treatment reduce this risk. Treatment for women with symptomatic vulvar and vaginal conditions is important for maintaining the quality of life. RECENT FINDINGS: There are multiple review articles, small case series, and small comparative trials, but definitive trials are unavailable for most of these conditions. SUMMARY: Current research on pathophysiology and treatment is limited to all of these conditions, and more focus on these life-altering conditions is warranted.

Testosterone Therapy in Women: A Clinical Challenge.

The physiology of testosterone as a normal female hormone in reproductive years and beyond is poorly taught and understood. This has led to unregulated and dangerous prescribing practices by physicians and other health care professionals. There are data for safe use, and as women's health care practitioners, we owe it to our patients to follow these guidelines and practices, as well as advocate for more research and safer, regulated products to prescribe.

Menopause: A Global Perspective and Clinical Guide for Practice.

Perimenopause and menopause are a time of great transition for women-physically, mentally, and emotionally. Symptoms of the menopause transition and beyond impact women worldwide. Unfortunately, physician knowledge and comfort with addressing menopausal concerns vary greatly, limiting the support physicians provide to women in need. This review aims to increase physician understanding of the epidemiology, physiology, symptomology, and treatment options available for perimenopausal and menopausal women. Our goal is to empower physicians to educate and treat their patients to reduce the negative impact of perimenopausal changes and enhance overall well-being for women.

What Is New in Insights and Strategies in Postpartum Hemorrhage?: Best Articles From the Past Year.

This month we focus on current research in postpartum hemorrhage. Dr. Dunsmoor-Su discusses five recent publications, which are concluded with a "bottom line" that is a take-home message. A complete reference for each can be found in on this page along with direct links to abstracts.

What Is New in Labor Management?: Best Articles From the Past Year.

This month, we focus on current research in labor management. Dr. Dunsmoor-Su discusses five recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.

Cost-benefit analysis of indirect antiglobulin screening in Rh(D)-negative women at 28 weeks of gestation.

OBJECTIVE: To estimate the potential economic benefit of reduced indirect antiglobulin screening for Rh(D)-negative pregnant women. METHODS: A chart review of all Rh(D)-negative mothers delivering at the University of Washington from 2002 to 2012 was conducted to determine the rate of gestational seroconversion to anti-D antibodies before 28 weeks of gestation. A decision tree was constructed to estimate the economic effects of eliminating the indirect antiglobulin screen at 28 weeks of gestation and instead immunizing all Rh(D)-negative, anti-D antibody-negative women with anti-D immune globulin at that time. A theoretical cohort of 100,000 women was modeled. Probabilities and costs were derived from published literature, chart review, and expert opinion. Univariate sensitivity analyses followed by a Monte Carlo analysis examined assumptions and uncertainties in our model across entire distributions. RESULTS: The seroconversion rate of development of anti-D antibodies before 28 weeks of gestation in the cohort analyzed was 0.099% (2/2,029 women). From a societal perspective, the expected cost savings from implementing the reduced indirect antiglobulin screening strategy, per 100,000 women, ranged from $6 to $7.7 million. The overall cost savings for implementing this strategy in the United States for 1 year ranged from $34.7 to $35.6 million. This strategy remained cost-beneficial when varying our parameters (eg, anti-D immune globulin, antibody test cost) to their logical extremes. The Monte Carlo analysis verified the cost savings of our strategy. CONCLUSION: The updated seroconversion rate and our model suggest that eliminating the 28-week antibody screen would be cost-beneficial from a societal perspective while posing minimal potential harm to the recipients.

Evidence-based selection of candidates for the levonorgestrel intrauterine device (IUD).

BACKGROUND: Recent evidence-based guidelines expanded the definition of appropriate candidates for the levonorgestrel-releasing intrauterine system (LNG-IUS). We investigated correlates of evidence-based selection of candidates for the LNG-IUS by physicians who offer insertion. METHODS: We conducted a mixed-mode (online and mail) survey of practicing family physicians and obstetrician-gynecologists in Seattle. RESULTS: A total of 269 physicians responded to the survey (44% response rate). Of the 217 respondents who inserted intrauterine devices, half or fewer routinely recommended the LNG-IUS to women who are nulliparous, younger than 20 years old, or have a history of sexually transmitted infections (STIs). In multivariable analyses, training/resident status was positively associated with recommending the LNG-IUS to women <20 years old (adjusted odds ratio [aOR], 3.6; 95% confidence interval [CI], 1.6-8.0) and women with history of STI (aOR, 3.7; 95% CI, 1.6-8.4). Perceived risk of infection or infertility was negatively associated with recommending the LNG-IUS to nulliparous women (aOR, 0.2; 95% CI, 0.1-0.5) and women with a history of STI (aOR, 0.3; 95% CI, 0.1-0.8). CONCLUSIONS: Many family physicians and obstetrician-gynecologists who insert the LNG-IUS are overly restrictive in selecting candidates, although those who train residents are more likely to follow evidence-based guidelines. Interventions that address negative bias and perceptions of risks, in addition to improving knowledge, are needed to promote wider use of the LNG-IUS.

Correlation between spontaneous preterm birth and mid-trimester maternal serum estriol.

OBJECTIVE: Elevated third trimester salivary estriol levels have been associated with preterm birth. We evaluated whether maternal estriol concentrations from second trimester serum correlated with preterm delivery. METHODS: A retrospective cohort study of 7767 patients evaluated with second trimester aneuploidy screening. Unconjugated serum estriol was measured by immunoassay, expressed as multiples of the median (MoM) for gestational age and evaluated for association with preterm (<37 week) birth. RESULTS: Elevated maternal serum estriol was significantly associated with preterm birth (1.15 MoM versus 1.03 MoM for delivery at term, OR 1.69 CI 1.41 to 2.02). 9.95% of spontaneously laboring patients <34 weeks had estriol MoM > 2, as opposed to 6.23% of >34 week deliveries (p = 0.031). There was a direct correlation between level of estriol concentrations and gestational age at time of delivery. CONCLUSIONS: Elevated second trimester maternal serum unconjugated estriol is independently associated with a higher rate of spontaneous preterm birth.

Bakri balloon effectiveness for postpartum hemorrhage: a "real world experience".

INTRODUCTION: The Bakri balloon has been advocated for management of obstetric hemorrhage, based on several small studies (2-16 patients) where it was over 90% effective. OBJECTIVE: To estimate the effectiveness of the Bakri balloon for treating postpartum hemorrhage (PPH) in clinical practice at academic institutions. METHODS: This is a retrospective cohort study evaluating efficacy of Bakri balloon use in 35 women with PPH, performed as a chart review. Charts were reviewed to determine if balloon placement was deemed a "success" or "failure", as well as to abstract relevant demographic and clinical factors. Failure was defined as need for another form of hemorrhage control. RESULTS: Success rate was 67.57%. Bakri failure was associated with Cesarean section (67% versus 16%, p = 0.031) and predelivery Pitocin (67% versus 28%, p = 0.003) and had more ICU admissions (58% versus 4%, p = 0.0003), transfusions (5.4 red blood cell units versus 1.6, p = 0.007) and hospital days (5.65 versus 3.75, p = 0.011). Reasons for failure were continued bleeding or balloon extrusion. CONCLUSION: Our results suggest that the Bakri balloon is useful for treating PPH but not as effective as previously published. When balloon use is effective, however, the maternal morbidity is significantly decreased.

Abnormal second-trimester serum analytes are more predictive of preterm preeclampsia.

OBJECTIVE: We sought to determine the association of abnormal second-trimester serum analytes with early preterm preeclampsia. STUDY DESIGN: We conducted a retrospective study of 7767 subjects undergoing second-trimester serum aneuploidy screening. Values of maternal serum α-fetoprotein (AFP), ß-human chorionic gonadotropin (hCG), and inhibin (INH) were calculated as multiples of the median (MoM) and evaluated by gestational age at delivery and occurrence of preeclampsia. RESULTS: Of 459 (6.5%) cases of preeclampsia, 65 (14%) delivered <34 weeks and 394 (86%) delivered >34 weeks. Elevated AFP, hCG, and INH >2 MoM were associated with preeclampsia, and the odds ratio was higher for the development of preeclampsia <34 weeks than >34 weeks (odds ratio, 8.04 vs 2.91 for AFP, 3.6 vs 2 for hCG, and 4.17 vs 3.08 for INH, P < .001 for all). The higher the MoM for each analyte the greater the likelihood of preeclampsia. CONCLUSION: Elevated AFP, hCG, and INH levels >2 MoM are associated with developing early preeclampsia, and the more elevated they are, the higher the likelihood.

Pelvic exenteration in the age of modern chemoradiation.

BACKGROUND: To examine outcomes after pelvic exenteration in women treated with modern chemoradiation and surgical techniques. METHODS: All patients at our institution with a diagnosis of gynecologic malignancy who underwent pelvic exenteration after treatment with chemoradiation between 1/90 and 6/08 were evaluated with a retrospective chart review. RESULTS: 44 women were identified, of whom 29 (66%) had cervical, 6 (14%) had uterine, 5 (11%) had vaginal, and 4 (9%) had vulvar cancer. The majority of patients (82%) were initially treated with external beam whole-pelvic radiation with concurrent cisplatin. 38 patients (86%) underwent exenteration for a central pelvic recurrence, and the remaining 6 patients (14%) for radiation necrosis. The most common surgical complication was transfusion requirement in 36 patients (82%), followed by wound infection in 15 (34%), small bowel obstruction in 8 (18%), and sepsis in 6 (14%). The median time spent in the ICU post-operatively was 2 days. One patient (2%) died during her post-operative hospital stay. The mean EBL overall was 2497 cc and the mean operative time was 544 min. Use of electrothermal bipolar coagulation, which was used in 64% of the exenterations, significantly reduced blood loss (3679 cc vs. 1836 cc, p=0.014). After exenteration, 21 patients (48%) were diagnosed with a recurrence of cancer, and the mean progression free survival was 31 months. Patients who received exenteration less than 2 years after their initial chemoradiation had a significantly shorter overall survival time (8 months vs. 33 months, p=0.016). CONCLUSIONS: Approximately 50% of women develop recurrence following exenterations done after chemoradiation. Survival is significantly longer in patients who necessitate exenteration greater than 2 years out from initial treatment. Electrothermal bipolar coagulation appears to significantly reduce blood loss during these surgeries.

Episiotomy practice in a community hospital setting.

OBJECTIVE: Episiotomy practice in the United States has changed dramatically over the past 20 years, and recent studies have questioned the utility of routine episiotomy. Our objective was to evaluate current episiotomy practice in a community hospital. STUDY DESIGN: We reviewed vaginal deliveries at a community hospital from January 1, 2004, to December 31, 2005. Maternal,fetal, labor and provider data were collected. Data were analyzed with t test, chi2 and logistic regression. RESULTS: A total of 2,959 deliveries by 17 practitioners were evaluated. The episiotomy rate increased for younger patients, with estimated fetal weight > 4,000 g, when presentation was not occiput anterior and with decreasing parity. Provider characteristics, such as a greater number of years in practice or when the delivering physician was not the outpatient physician, increased episiotomy rates. The overall episiotomy rate declined from 20.6% to 17.7% during the study; however, this did not reach statistical significance, and some practitioners had unchanged or increased rates. CONCLUSION: Practitioner characteristics were the strongest predictors of episiotomy. Overall, the rate at this community hospital was within published recommendations, but wide variations in practice (range, 2-43%) suggest that education needs to target community physicians remote from training to ensure that all women receive optimal, evidence-based delivery care.

Impact of sociodemographic and hospital factors on attempts at vaginal birth after cesarean delivery.

OBJECTIVE: To estimate the clinical and nonclinical factors associated with whether a patient attempts a trial of labor after previous cesarean delivery or elects to have a repeat cesarean delivery. METHODS: We conducted a retrospective, cohort study comparing all women with previous low transverse cesarean delivery who attempted a trial of labor with those who elected to have a repeat cesarean delivery. Data from 17 hospital sites for the period 1995-1998 were included, for a total of 15,172 patients. Bivariate, site-adjusted, and multivariable logistic regression analyses were used. RESULTS: Odds of trial of labor by hospital were not uniform in the unadjusted or adjusted analyses. The odds of trial of labor decreased significantly with increasing age, gravidity, and number of previous cesarean deliveries. Medicaid patients had higher odds of trial of labor than did privately insured patients (odds ratio [OR] 1.37 [95% confidence interval (CI) 1.20, 1.55]). Patients with nonrecurrent indication for previous cesarean delivery had generally higher odds of trial of labor than did those with a recurrent indication. Black women were more likely to attempt trial of labor than were white women (OR 2.17 [95% CI 1.83, 2.56] for those with a nonrecurrent indication). CONCLUSION: Clinical and nonclinical factors influence rates of attempted vaginal birth after cesarean delivery.

Effect of endometriosis on in vitro fertilization.

OBJECTIVE: To investigate the IVF outcome for patients with endometriosis. DESIGN: Meta-analysis. SETTING: Academic research center. PATIENT(S): A MEDLINE search and review of the literature were performed. Patients were classified by level of endometriosis, and controls were classified according to the indication for IVF. INTERVENTION(S): Bivariate analysis and multivariate logistic regression was used to estimate overall effect and control for confounding. MAIN OUTCOME MEASURE(S): Pregnancy rates, fertilization rate, implantation rates, and numbers of oocytes retrieved. RESULT(S): Twenty-two published studies were included in the overall analysis. The chance of achieving pregnancy was significantly lower for endometriosis patients (odds ratio, 0.56; 95% confidence interval, 0.44-0.70) when compared with tubal factor controls. Multivariate analysis also demonstrated a decrease in fertilization and implantation rates, and a significant decrease in the number of oocytes retrieved for endometriosis patients. Pregnancy rates for women with severe endometriosis were significantly lower than for women with mild disease (odds ratio, 0.60; 95% confidence interval, 0.42-0.87). CONCLUSION(S): Patients with endometriosis-associated infertility undergoing IVF respond with significantly decreased levels of all markers of reproductive process, resulting in a pregnancy rate that is almost one half that of women with other indications for IVF. These data suggest that the effect of endometriosis is not exclusively on the receptivity of the endometrium but also on the development of the oocyte and embryo.