Impact of personalized diabetes care on distress and treatment satisfaction in people with breast cancer.

AIMS: In patients with breast cancer (BCa) and diabetes (DM), diabetes distress (DD) and treatment satisfaction (DTS) can influence BCa management and outcomes. We assessed the impact of implementing a personalized diabetes care model in patients with BCa. METHODS: Patients in active treatment or surveillance for BCa with an HbA1c > 53 mmol/mol (7%) or random blood glucose >11.1 mmol/L were included. Participants were offered continuous glucose monitoring (CGM), virtual care and a dedicated diabetes provider for 6 months. Primary outcomes included DD measured by the Diabetes Distress Survey (DDS) and DTS measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Questionnaires were conducted at 0, 3 and 6 months. RESULTS: Thirty-one women were enrolled (median age 61, IQR 49.0-69.0). Compared to baseline, the mean DDS score was lower at both 3 months (2.2 vs. 1.8 [n = 27], p = 0.004, SD = 0.70) and 6 months (2.3 vs. 1.8 [n = 23], p = 0.002, SD = 0.70). The mean DTSQ score was higher at 3 months (baseline: 20.5 vs. 3 months: 28.7 [n = 28], p < 0.001, SD = 9.2) and 6 months (baseline: 20.4 vs. 6 months: 30.0 [n = 26], p < 0.001, SD = 9.7). CONCLUSIONS: Personalized diabetes care models that emphasize remote management and optimize access for those with BCa may lower DD and improve DTS.

Reasons for discontinuation of reversible contraceptive methods by women with epilepsy.

OBJECTIVE: To report the reasons for discontinuation of contraceptive methods by women with epilepsy (WWE). METHODS: These retrospective data come from a web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We determined the frequencies of contraceptive discontinuations and the reasons for discontinuation. We compared risk ratios for rates of discontinuation among contraceptive methods and categories. We used chi-square analysis to test the independence of discontinuation reasons among the various contraceptive methods and categories and when stratified by antiepileptic drug (AED) categories. RESULTS: Nine hundred fifty-nine of 2,393 (40.6%) individual, reversible contraceptive methods were discontinued. One-half (51.8%) of the WWE who discontinued a method discontinued at least two methods. Hormonal contraception was discontinued most often (553/1,091, 50.7%) with a risk ratio of 1.94 (1.54-2.45, p < 0.0001) compared to intrauterine devices (IUDs), the category that was discontinued the least (57/227, 25.1%). Among all individual methods, the contraceptive patch was stopped most often (79.7%) and the progestin-IUD was stopped the least (20.1%). The top three reasons for discontinuation among all methods were reliability concerns (13.9%), menstrual problems (13.5%), and increased seizures (8.6%). There were significant differences among discontinuation rates and reasons when stratified by AED category for hormonal contraception but not for any other contraceptive category. SIGNIFICANCE: Contraception counseling for WWE should consider the special experience profiles that are unique to this special population on systemic hormonal contraception.

Folic acid use by women with epilepsy: Findings of the Epilepsy Birth Control Registry.

PURPOSE: To determine the prevalence and predictors of folic acid (FA) use by women with epilepsy (WWE) at risk of unintended pregnancy. METHODS: These retrospective data come from the Epilepsy Birth Control Registry (EBCR) web-based survey of 1144 WWE in the community, 18-47years, who provided demographic, epilepsy, AED, contraception, pregnancy, healthcare visits and FA data. We report prevalence and predictors of FA use in relation to risk of pregnancy (not at risk, at risk, seeking pregnancy, pregnant), demographics, seizure types and AED and contraception categories. RESULTS: 368 (47.6%) of the 773 WWE at risk of unintended pregnancy in the EBCR took FA supplement. Being at risk was a significant predictor in comparison to WWE not at risk (OR=1.464 [1.103-1.944], p=0.008). In comparison to WWE at risk, FA use trended greater for WWE actively seeking pregnancy (29/47, 61.7% v 368/773, 47.6%; p=0.0605) and was greater for pregnant WWE (17/19, 89.5% v 368/773, 47.6%; p=0.0007). Demographic predictors for WWE at risk were race (p=0.003), education (p=0.012) and income (0.043) with significantly greater FA use by Caucasians than minorities and direct correlations between FA use and levels of education and household income. Seizure type, AED use, category and dosage, polytherapy and contraceptive category were not predictors. A healthcare provider visit during the year prior to the survey was not a predictor. Prevalence of FA use was similar following visits with gynecologists - 51.7%, neurologists - 48.7% and primary care - 48.6%. FA supplementation by prescription was greater for WWE at risk on AED versus no AED (190/355, 53.5% v 3/13, 23.1%; p=0.045). CONCLUSION: Low prevalence of preconception FA use may reflect a need for more education. In addition, further research is needed to provide definitive evidence that FA reduces congenital malformations in the offspring of WWE.

Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry.

OBJECTIVE: To report the contraceptive practices of women with epilepsy (WWE) in the community, predictors of highly effective contraception use, and reasons WWE provide for the selection of a particular method. METHODS: These cross-sectional data come from the Epilepsy Birth Control Registry (EBCR) web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We report demographic, epilepsy, and antiepileptic drug (AED) characteristics as well as contraceptive use. We determined the frequency of use of highly effective contraception use, that is, methods with failure rate <10%/year, and conducted binary logistic regression analysis to determine predictors of highly effective contraception use. We report frequencies of WWE who consult various health care providers regarding the selection of a method and the reasons cited for selection. RESULTS: Of the 796 WWE at risk of unintended pregnancy, 69.7% use what is generally considered to be highly effective contraception (hormonal, intrauterine device [IUD], tubal, vasectomy). Efficacy in WWE, especially for the 46.6% who use hormonal contraception, remains to be proven. Significant predictors of highly effective contraception use are insurance (insured 71.6% vs. noninsured 56.0%), race/ethnicity (Caucasian 71.3% vs. minority 51.0%), and age (38-47, 77.5%; 28-37, 71.8%; 18-27, 67.0%). Of the 87.2% who have a neurologist, only 25.4% consult them regarding selection of a method, although AED interaction is cited as the top reason for selection. SIGNIFICANCE: The EBCR web-based survey is the first large-scale study of the contraceptive practices of WWE in the community. The findings suggest a need for the development of evidence-based guidelines that address the efficacy and safety of contraceptive methods in this special population, and for greater discourse between neurologists and WWE regarding contraception.

Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry.

PURPOSE: The aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category. METHODS: Retrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories. RESULTS: More women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (p<0.0001). The risk ratio for seizure increase on hormonal (18.7%) versus nonhormonal contraception (4.2%) was 4.47 (p<0.0001). The risk ratio for seizure decrease on hormonal (9.5%) versus nonhormonal contraception (5.5%) was 1.71, p<0.0001. On hormonal contraception, the risk ratio for seizure increase was greater than for decrease (1.98, p<0.0001). In comparison to combined pills, both hormonal patch and progestin-only pills had greater risk ratios for seizure increase. Depomedroxyprogesterone was the only hormonal method with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (p<0.001). On hormonal contraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio=2.53, p=0.0002). CONCLUSION: The findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category.

Distribution of seizures across the menstrual cycle in women with epilepsy.

The purpose of this study was to determine whether seizure frequency and cycle days with seizure occurrence vary across the menstrual cycle. The subjects were the first 100 women with intractable focal onset seizures, 13-45 years old, who completed the baseline phase of the National Institutes of Health (NIH) Progesterone Trial. Each subject recorded seizures and menses during a 3-month baseline phase. Data consisted of (1) seizure numbers for each cycle day and (2) cycle days with seizure occurrence. Statistical comparisons of seizure frequency and days with seizures were performed using generalized estimating equation one-way analysis of variance (ANOVA) and logistic regression followed by pairwise multiple comparisons of days based on the least square means. Seizure numbers and cycle days with seizure occurrence varied across the menstrual cycle. There was an approximately twofold difference between the highest (day 1) and lowest (day -8) values for both seizure frequency and days with occurrence. The demonstration of variation in seizure frequency and cycle days with seizure occurrence across the menstrual cycle, as well as identification of specific days that have substantially higher or lower frequencies than other days, supports the existence of catamenial epilepsy.

Variation of seizure frequency with ovulatory status of menstrual cycles.

PURPOSE: To determine if seizure frequency differs between anovulatory and ovulatory cycles. METHODS: The data came from the 3-month baseline phase of an investigation of progesterone therapy for intractable focal onset seizures. Of 462 women who enrolled, 281 completed the 3-month baseline phase and 92 had both anovulatory and ovulatory cycles during the baseline phase. Midluteal progesterone levels ≥5 ng/ml were used to designate cycles as ovulatory. Among the 92 women, average daily seizure frequency (ADSF) for all seizures combined and each type of seizure considered separately (secondary generalized tonic-clonic seizures - 2°GTCS, complex partial seizures - CPS, simple partial seizures - SPS) were compared between anovulatory and ovulatory cycles using paired t-tests. A relationship between the proportional differences in ADSF and estradiol/progesterone (EP) serum level ratios between anovulatory and ovulatory cycles was determined using bivariate correlational analysis. KEY FINDINGS: ADSF was 29.5% greater for 2°GTCS during anovulatory than during ovulatory cycles. ADSF did not differ significantly for CPS or SPS or for all seizures combined. Proportional differences in anovulatory/ovulatory 2°GTCS ADSF ratios correlated significantly with differences in anovulatory/ovulatory EP ratios. Among the 281 women, the three seizure types did not differ in ovulatory rates, but EP ratios were greater for cycles with 2°GTCS than partial seizures only. SIGNIFICANCE: Seizure frequency is significantly greater for 2°GTCS, but not CPS or SPS, during anovulatory cycles than ovulatory cycles. Because the proportional increases in 2°GTCS frequency during anovulatory cycles correlate with the proportional increases in EP level ratios, these findings support a possible role for reproductive steroids in 2°GTCS occurrence.

Premenstrual dysphoric disorder in women with epilepsy: relationships to potential epileptic, antiepileptic drug, and reproductive endocrine factors.

The purpose of this prospective observational investigation was to determine whether the frequency of premenstrual dysphoric disorder (PMDD) and the severity of PMDD symptoms differ between women with epilepsy and controls without epilepsy and whether there exists a relationship between the severity of PMDD symptoms and some epileptic, antiepileptic drug, and reproductive endocrine features. The results suggest that epilepsy, antiepileptic drug levels, ovulatory status, and hormone levels and ratios may all influence PMDD in women with epilepsy. PMDD severity scores may be greater in people with right-sided than in those with left-sided epilepsy, and in people with temporal than in those with nontemporal epileptic foci. PMDD severity scores may be greater with anovulatory cycles, and scores may correlate negatively with midluteal serum progesterone levels and positively with midluteal estradiol/progesterone ratios. Mood score may vary with particular antiepileptic drugs, favoring carbamazepine and lamotrigine over levetiracetam. PMDD severity scores may correlate directly with carbamazepine levels, whereas they correlate inversely with lamotrigine levels.

A comparison of anastrozole and testosterone versus placebo and testosterone for treatment of sexual dysfunction in men with epilepsy and hypogonadism.

Hyposexuality is commonly associated with low bioavailable testosterone (BAT) and relative estradiol elevation in men with epilepsy. This prospective, randomized, double-blind trial compared the effects of depotestosterone+the aromatase inhibitor anastrozole (T-A) versus depotestosterone+placebo (T-P) on sexual function, hormone levels, mood, and seizure frequency in men with epilepsy. Forty men with focal epilepsy, hyposexuality, and hypogonadism were randomized 1:1 to two groups (T-A or T-P) for a 3-month treatment trial of depotestosterone+either anastrozole or matching placebo. Outcomes included both efficacy and safety measures. Normalization of sexual function (S-score) occurred with greater frequency in the T-A (72.2%) than in the T-P (47.4%) group, but the difference was not statistically significant. T-A resulted in significantly lower estradiol levels and S-scores correlated inversely with estradiol levels at baseline and during treatment. Beck Depression Inventory II (BDI-II) scores improved significantly in both groups and changes in S-score correlated inversely with changes in BDI-II score. Changes in seizure frequency correlated with changes in BDI-II score. Seizure frequency decreased with both treatments and showed significant correlations with estradiol levels. Triglyceride levels increased with T-P and decreased with T-A. The difference in triglyceride changes between the two treatments was significant and correlated with changes in estradiol levels. Significant correlations between estradiol levels and S-scores, as well as seizure outcomes and triglyceride levels, suggest further study regarding a potential role for anastrozole in the treatment of men with epilepsy who have hyposexuality and hypogonadism.

Circalunar and ultralunar periodicities in women with partial seizures.

PURPOSE: Little consensus exists for the definition of catamenial epilepsy. Few studies have evaluated the periodicity of seizures to test the hypothesis that seizures in women have periodic patterns of occurrence independent of a priori hormonal considerations. In the present study, we determined seizure periodicity according to a "menstrual clock" provided by a common phase marker of the onset of menses. METHODS: Seizure and menstrual diaries of approximately 3 months duration were obtained from women enrolled in a trial of hormonal therapy for localization-related epilepsy. Midluteal progesterone levels identified ovulatory (>or=5 ng/ml, OC) from anovulatory cycles (AC). Individual cycles were normalized to a common phase and period (day 0 = menses onset, intervening days = 28 bins). Periodicity of combined data was estimated with cosinor-nonlinear least squares analysis. Best-fit rhythms were estimated with 95% confidence limits. RESULTS: 100 patients provided 3344 seizures within 293 cycles (77% OC, 20% AC, indeterminate 3%). OC seizures displayed a circalunar rhythm with peak phase of occurrence at onset of menses. AC seizures also featured a circalunar rhythm that peaked at menses onset but also had ultralunar rhythms of approximately 14 and approximately 9 days. DISCUSSION: Seizures in women with epilepsy occur in circalunar rhythms. OC and AC seizures differ in seizure timing with the latter occurring in ultralunar rhythms in addition to the predominant circalunar rhythm. This finding supports the existence of catamenial epilepsy and differences in patterns of seizure occurrence between OC and AC.

Design and Clinical Evaluation of a Novel Low-Glucose Prediction Algorithm with Mini-Dose Stable Glucagon Delivery in Post-Bariatric Hypoglycemia.

BACKGROUND: Postbariatric hypoglycemia (PBH) is a complication of bariatric surgery with limited therapeutic options. We developed an event-based system to predict and detect hypoglycemia based on continuous glucose monitor (CGM) data and recommend delivery of minidose liquid glucagon. METHODS: We performed an iterative development clinical study employing a novel glucagon delivery system: a Dexcom CGM connected to a Windows tablet running a hypoglycemia prediction algorithm and an Omnipod pump filled with an investigational stable liquid glucagon formulation. Meal tolerance testing was performed in seven participants with PBH and history of neuroglycopenia. Glucagon was administered when hypoglycemia was predicted. Primary outcome measures included the safety and feasibility of this system to predict and prevent severe hypoglycemia. Secondary outcomes included hypoglycemia prediction by the prediction algorithm, minimization of time below hypoglycemia threshold using glucagon, and prevention of rebound hyperglycemia. RESULTS: The hypoglycemia prediction algorithm alerted for impending hypoglycemia in the postmeal state, prompting delivery of glucagon (150 µg). After observations of initial incomplete efficacy to prevent hypoglycemia in the first two participants, system modifications were implemented: addition of PBH-specific detection algorithm, increased glucagon dose (300 µg), and a second glucagon dose if needed. These modifications, together with rescue carbohydrates provided to some participants, contributed to progressive improvements in glucose time above the hypoglycemia threshold (75 mg/dL). CONCLUSIONS: Preliminary results indicate that our event-based automatic monitoring algorithm successfully predicted likely hypoglycemia. Minidose glucagon therapy was well tolerated, without prolonged or severe hypoglycemia, and without rebound hyperglycemia.

Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes.

Context: Plasma betaine correlates with insulin sensitivity in humans. Betaine supplementation improves metabolic effects in mice fed a high-fat diet. Objective: To assess metabolic effects of oral betaine in obese participants with prediabetes. Design: A 12-week, parallel arm, randomized, double-masked, placebo-controlled trial. Setting: University-affiliated hospital. Participants and Interventions: Persons with obesity and prediabetes (N = 27) were randomly assigned to receive betaine 3300 mg orally twice daily for 10 days, then 4950 mg twice daily for 12 weeks, or placebo. Main Outcome Measures: Changes from baseline in insulin sensitivity, glycemia, hepatic fat, and endothelial function. Results: There was a 16.5-fold increase in plasma dimethylglycine [dimethylglycine (DMG); P < 0.0001] levels, but modest 1.3- and 1.5-fold increases in downstream serine and methionine levels, respectively, in the betaine vs placebo arm. Betaine tended to reduce fasting glucose levels (P = 0.08 vs placebo) but had no other effect on glycemia. Insulin area under curve after oral glucose was reduced for betaine treatment compared with placebo (P = 0.038). Insulin sensitivity, assessed by euglycemic hyperinsulinemic clamp, was not improved. Serum total cholesterol levels increased after betaine treatment compared with placebo (P = 0.032). There were no differences in change in intrahepatic triglyceride or endothelial function between groups. Conclusion: DMG accumulation supports DMG dehydrogenase as rate limiting for betaine metabolism in persons with prediabetes. Betaine had little metabolic effect. Additional studies may elucidate mechanisms contributing to differences between preclinical and human responses to betaine, and whether supplementation of metabolites downstream of DMG improves metabolism.

Predictors of unintended pregnancy in women with epilepsy.

OBJECTIVE: To determine whether rates of unintended pregnancy in women with epilepsy (WWE) vary by contraceptive category and when stratified by antiepileptic drug (AED) category. METHODS: These retrospective data come from the Epilepsy Birth Control Registry (EBCR) web-based survey of 1,144 WWE in the community, 18-47 years of age, who provided demographic, epilepsy, AED, contraceptive, and pregnancy data. Participants indicated whether pregnancies were intended or unintended, as well as the type of contraceptive and AED used at conception. We report failure rates relative to the frequency of use of each contraceptive category in the EBCR. RESULTS: Most WWE (78.9%) reported having at least one unintended pregnancy; 65.0% of their pregnancies were unintended. Unintended pregnancy was more common among younger, racial minority, and Hispanic WWE. Among reversible contraceptive categories, the intrauterine device had the lowest failure rate. Failure rates varied greatly on systemic hormonal contraception (HC), depending on whether oral or nonoral forms were used and especially in relation to the category of AED with which HC was combined. Oral forms had greater failure rate than nonoral forms. HC combined with enzyme-inducing AEDs had a substantially greater failure rate than HC combined with no AED or any other AED category and in comparison to barrier plus any AED category. Other AED-HC combinations, in contrast, carried lower risks than barrier. CONCLUSIONS: Unintended pregnancy is common among WWE and may vary by contraceptive category and AED stratification. In view of the important consequences of unintended pregnancy on pregnancy outcomes, these retrospective findings warrant further prospective investigation.

Effect of Targeting Inflammation With Salsalate: The TINSAL-CVD Randomized Clinical Trial on Progression of Coronary Plaque in Overweight and Obese Patients Using Statins.

IMPORTANCE: Inflammation may contribute to pathological associations among obesity, diabetes mellitus, and cardiovascular disease. OBJECTIVE: To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque. DESIGN, SETTING, AND PARTICIPANTS: In the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial participants were randomly assigned between September 23, 2008, and July 5, 2012, to 30 months of salsalate or placebo in addition to standard, guideline-based therapies. Randomization was computerized and centrally allocated, with patients, health care professionals, and researchers masked to treatment assignment. Participants were overweight and obese statin-using patients with established, stable coronary heart disease. INTERVENTIONS: Salsalate (3.5 g/d) or placebo orally over 30 months. MAIN OUTCOMES AND MEASURES: The primary outcome was progression of noncalcified coronary artery plaque assessed by multidetector computed tomographic angiography. Secondary outcomes were other measures of safety and efficacy. RESULTS: Two hundred fifty-seven participants were randomized to salsalate (n = 129) or placebo (n = 128). Their mean (SD) age was 60.8 (7.0) years, and 94.0% (236 of 251) were male. One hundred ninety participants (89 in the salsalate group and 101 in the placebo group) completed the study. Compared with baseline, there was no increase in noncalcified plaque volume in the placebo-treated patients and no difference in change between the salsalate and placebo groups (mean difference, -1 mm3; 95% CI, -11 to 9 mm3; P = .87). Salsalate treatment decreased total white blood cell, lymphocyte, monocyte, and neutrophil counts and increased adiponectin levels without change in C-reactive protein levels. Fasting glucose, triglycerides, uric acid, and bilirubin levels were decreased in the salsalate group compared with the placebo group, while hemoglobin levels were increased. Urinary albumin levels increased, with tinnitus and atrial arrhythmias more common, in the salsalate group compared with the placebo group. CONCLUSIONS AND RELEVANCE: Salsalate when added to current therapies that include a statin does not reduce progression of noncalcified coronary plaque volume assessed by multidetector computed tomographic angiography in statin-using patients with established, stable coronary heart disease. The absence of progression of noncalcified plaque volume in the placebo group may limit interpretation of the trial results. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00624923.

Sexual hormones and epilepsy: threat and opportunities.

PURPOSE OF REVIEW: This article reviews recent developments in our knowledge of the reciprocal interactions between epilepsy and sex hormones and how these interactions may play a role in the pathophysiology and treatment of both. RECENT FINDINGS: Community studies confirm that menstrual disorders are overrepresented among women with epilepsy, especially among women with high seizure frequency and in those on valproate or polytherapy. Reproductive function is not affected in women with epilepsy who discontinued antiepileptic drug therapy during pubertal maturation. While valproate has been implicated as having particularly notable disruptive effects on reproductive function in women with epilepsy (polycystic ovaries and hyperandrogenemia), this was not evident in non-epileptic primates. The role of epilepsy itself is evident from a study that showed that the laterality of unilateral temporolimbic discharges is associated with predictable directional changes in hormonal secretion at all levels of the reproductive neuroendocrine axis. Epilepsy in men is associated with reduced levels of sexual function, bioactive testosterone and sperm. Various antiepileptic drugs may differ in this regard. SUMMARY: Epilepsy and antiepileptic drugs can alter sex hormone levels to promote the development of reproductive endocrine disorders in both women and men. Reproductive endocrine disorders may adversely affect both reproductive function and seizure control. Treatment of epilepsy and selection of antiepileptic drugs may be important to reproductive health in women and men with epilepsy. Sex steroids and their metabolites may also provide treatment for seizures.