Journal : Osteoporosis International (September 2010)
Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate;
Kendler DL, McClung MR, Freemantle N, Lillestol M, Moffett AH, Borenstein J, Satram-Hoang S, Yang YC, Kaur P, Macarios D, Siddhanti S, on behalf of the DAPS Investigators; Osteoporosis International
In this study, 250 women with osteoporosis were randomized to 12 months with subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg once weekly, then crossed over to the other treatment. The primary endpoint, treatment adherence at 12 months, was 76.6% for alendronate and 87.3% for denosumab.
INTRODUCTION: The purpose of this study is to evaluate treatment adherence with subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg once weekly.
METHODS: In this multicenter, randomized, open-label, 2-year, crossover study, 250 postmenopausal women with low bone mineral density received denosumab or alendronate for 12 months, then the other treatment for 12 months. The alendronate bottle had a medication event monitoring system cap to monitor administration dates. Definitions were as follows: compliance, receiving both denosumab doses 6 (±1) months apart or 80-100% of alendronate doses; persistence, receiving both denosumab doses and completing the month 12 visit within the visit window or ≥2 alendronate doses in the final month; adherence, achieving both compliance and persistence. This report includes data from the first 12 months. RESULTS: The primary study endpoint, adherence in the first 12 months, was 76.6% (95/124) for alendronate and 87.3% (110/126) for denosumab. Risk ratios for denosumab compared with alendronate at 12 months were 0.58 (p = 0.043) for non-adherence, 0.48 (p = 0.014) for non-compliance, and 0.54 (p = 0.049) for non-persistence. Subject ratings for treatment necessity, preference, and satisfaction were significantly greater for denosumab and ratings for treatment bother were significantly greater for alendronate. Adverse events were reported by 64.1% of alendronate-treated subjects and 72.0% of denosumab-treated subjects (p = 0.403). The most common adverse events were arthralgia, back pain, pain in extremity, cough, and headache (each in<10% of subjects in each group).
CONCLUSIONS: Significantly greater treatment adherence was observed for subcutaneous administration of denosumab every 6 months than for oral alendronate once weekly.
Journal : Best Practice and Research Clinical Endocrinology & Metabolism, Aug 2010
Metformin treatment for Type 2 diabetes in pregnancy?
Simmons D; Best Practice & Research Clinical Endocrinology & Metabolism 24 (4), 625-34
Metformin lowers blood glucose by reducing hepatic glucose output, increasing insulin sensitivity and enhancing peripheral glucose uptake. Metformin is widely used in women with Type 2 diabetes of child-bearing age, many of whom become pregnant. Studies to date in Type 2 diabetes in pregnancy, gestational diabetes and polycystic ovarian syndrome are reassuring. Metformin is not considered teratogenic.
There is sufficient evidence that metformin is safe used throughout pregnancy, with no worsening of obstetric or perinatal outcomes. Women may benefit from the lesser weight gain. The long-term risks to the offspring remain inadequately researched, with no evidence of harm up to 2 years, and no suggestions of later complications in countries using metformin for many years. Metformin is recommended for use in pregnancies complicated by Type 2 diabetes, but women should be informed of the evidence regarding its associated risks and benefits to enable an informed choice over its use.
Journal: American Journal of Obstetrics & Gynecology
Volume 203, Issue 3 , Pages 192-193, September 2010
Scheduling the first prenatal visit: a missed opportunity : Arnold W. Cohen
As obstetricians we have always stressed the importance of prenatal care. The Centers for Disease Control and Prevention reported that delayed entry into prenatal care was associated with adverse outcomes for the mother and baby. We also know that the earlier in the pregnancy that a patient receives prenatal care, the better the chance for the obstetrics caregiver to establish the gestational age, address the issues that can affect the pregnancy such as preexisting medical diseases or issues related to previous pregnancies, avoidance of teratogenic medications, and modification of lifestyle issues such as smoking, drugs, alcohol, and excessive weight gain. It also allows the provider of care to develop and implement an obstetrics treatment plan best suited to the patient.Prenatal care has always been assumed to start when the pregnant mom is first examined by her obstetrics provider. Unfortunately in many cases, this “start” is after organogenesis has occurred and is too late to avoid adverse outcomes for the mother and fetus.
We know that organogenesis starts 2 weeks after conception. We also know that some medications, diseases like diabetes mellitus, and toxin exposure like cigarette smoke during the first 12 weeks of pregnancy can result in not only an increased risk of miscarriage but also an increased risk of congenital anomalies. For these reasons, it is distressing to see the data reported by Nettleman et al, which indicates that, even in a commercially insured married population, prenatal care is delayed for 25% of pregnant women for >4 weeks. This timeframe is after many organs have formed or interventions that could minimize risk to the fetus should have been initiated. The study also shows that other than information relating to the form of insurance that the patient has, no other information was asked for in >90% of the patients. In fact, only 67% of the office staff asked for the date of the last menstrual period; 14% of the staff asked whether the patient had a previous pregnancy, and <5% of the staff asked about the general well-being, medication use, hypertension, diabetes mellitus, history of pregnancy complications, or smoking. No practice asked the patient about alcohol use.
This study points out the “missed opportunities” that occur in medicine and that the system of providing prenatal care is flawed. The first encounter with the patient (ie, scheduling of an appointment) is handled as a “nonevent” when in actuality it should be used as an effective educational and triaging opportunity. Multiparous women with no medical problems could be given an appointment at the convenience of the office, but first-time pregnant women and those with medical or lifestyle issues should be effectively triaged and given appointments without delay. It is clear that obstetrics care is initiated at the convenience of the provider's office as opposed to the individual needs of the pregnant patient. This opportunity to “triage” patients when they call for their first prenatal appointment has the potential to improve prenatal care significantly and decrease some very important morbidities.
Imagine an office that trained the front office to ask the following simple questions when the patient called for her obstetrics appointment:
These questions would take approximately 60 seconds to ask but could result in the ability to triage patients effectively. Those women who need to be seen right away could be accommodated, and those women who could be seen in 3, 4, or 6 weeks could wait, as appropriate. It would allow the obstetrician/midwife to provide the care to patients who are in most need of early evaluation and treatment in pregnancy appropriately and delay appointments for patients who are routine.
If this approach to care based on individual need rather than who calls first were adopted, as well as adopting scheduling of prenatal care visits for routine patients that results in fewer visits, providers could actually provide better care for those who need it and decrease the number of traditional visits offered to those who do not have any risk factors. The traditional prenatal care schedule for low risk patients (ie, 8, 12, 16, 20, 24, 28, 30, 32, 34, 36, 37, 38, 39, and 40 weeks) has been shown to not be necessary for low-risk women.The scheduling of visits at 8, 12, 16, 24, 28, 32, 36, 38, and 40 weeks for a Kaiser Permanente group compared with the traditional scheduling of prenatal visits resulted in no differences in perinatal outcome and the use of diagnostic prenatal testing or the use of other medical services. “Group” prenatal care has also been studied and has been shown to be another method that results in equal or improved perinatal outcomes with less physician involvement.
By instituting individualized prenatal care first appointments and using reduced scheduled appointments or group prenatal care for low-risk patients, obstetrics care providers could use their time and efforts more effectively to improve prenatal care, rather than just provide prenatal care. Nettleman et al have shown that we have opportunities to significantly improve the provision of early prenatal care. By combining this information with the adoption of other proven methods of providing prenatal care to the low-risk population, I believe we can establish a win for the patient and a win for the obstetrics providers. To do this though, we each must ask ourselves what the barriers are in my practice to the implementation of this type of care and find ways to overcome them.
American Journal of Obstetrics & Gynecology
Volume 203, Issue 3 , Pages 194-200, September 2010
Von Willebrand disease and pregnancy: a practical approach for the diagnosis and treatment
Von Willebrand disease is caused by either a quantitative or qualitative defect in von Willebrand factor (VWF). Patients may have extensive mucosal bleeding (because of platelet dysfunction) and prolonged bleeding after surgery (because of factor VIII deficiency). Up to 6 different subtypes of the disease have been described, and diagnosis is based on clinical suspicion and laboratory confirmation. Accurate diagnosis is of paramount importance because therapy will vary according to the subtype. Bleeding complications during pregnancy are more frequent when levels of the von Willebrand ristocetin cofactor assay and factor VIII levels are <50 IU/dL. In such cases, therapy before any invasive procedure or delivery must be instituted. The mainstays of therapy are desmopressin and plasma concentrates that contain von Willebrand factor. Delayed postpartum hemorrhage may occur, despite adequate prophylaxis. Frequent monitoring and continued prophylaxis and/or treatment are recommended for at least 2 weeks after delivery.
American Journal of Obstetrics & Gynecology: September 2010
Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass
We sought to compare the Risk of Malignancy Index (RMI) to the Risk of Ovarian Malignancy Algorithm (ROMA) to predict epithelial ovarian cancer (EOC) in women with a pelvic mass.
In all, 457 women with imaging results from ultrasound, computed tomography, magnetic resonance imaging, and serum HE4 and CA125 determined prior to surgery for pelvic mass were evaluable. RMI values were determined using CA125, imaging score, and menopausal status. ROMA values were determined using HE4, CA125, and menopausal status.
At a set specificity of 75%, ROMA had a sensitivity of 94.3% and RMI had a sensitivity of 84.6% for distinguishing benign status from EOC (P = .0029). In patients with stage I and II disease, ROMA achieved a sensitivity of 85.3% compared with 64.7% for RMI (P < .0001).
The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value achieves a significantly higher sensitivity for identifying women with EOC than does RMI.
Renee Heffron, Deborah Donnell, Helen Rees, Connie Celum, Nelly Mugo, EdwinWere, Guyde Bruyn, Edith Nakku-Joloba, Kenneth Ngure, James Kiarie, Robert W Coombs, Jared M Baeten, for the Partners in Prevention HSV/HIV Transmission Study Team*
Background Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1 infected women to their male partners.
Methods in this prospective study, we followed up 3970 heterosexual HIV-1 – serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modeling to assess the effect of contraceptive use on HIV-1 risk.
Finding Among 1314 couples in which the HIV-1 seronegative partner was female (median follow-up 18-0 (IQR 12.6-24.2 months), rates of HIV-1 acquisition were 6.61 per 100 person-years in women who used hormonal contraception and 3.78 per 100 person-years in those who did not (adjusted hazard ratio 1.98, 95% CI 18.7 [IQR 12.8-24.2] months), rates of HIV-1 transmission from women to men were 2.61 per 100 person years in couples in which women used hormonal contraception and 1.51 per 100 person years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1.97, 95% CI 1.12-3.45, p=0.02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression.
Interpretation Women should be counseled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception especially injectable methods and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1.