Kelly Ehrlich

Subfornical organ participates in salt appetite.

The effects of subfornical organ (SFO) lesions on salt and water intakes after sodium depletion were studied. Water and salt intakes were measured over 45 hr during a regimen that combined furosemide diuresis and access to low-sodium diet. Water was solely available for 23 hr after diuresis, and water and 0.3 M NaCl solution were available in choice for the next 22 hr. After diuresis, rats with SFO lesions drank significantly less water in 2 hr than controls but achieved equivalent water and sodium balances before salt access 20 hr later. After salt access, rats with SFO lesions drank significantly less saline and water in 2 hr than controls but had similar saline and water intakes over the next 20 hr. Thus, SFO lesions blunted acutely, but not chronically, saline and water intakes to sodium depletion, and the blunted intakes are not explainable by hydrational status.

Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study.

Objective: To evaluate vaginal, endometrial, and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT). Design: This was a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3 and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared. Results: The five groups did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P < 0.05). Abnormal bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups, whereas women in the HT group had a greater risk than those in the placebo group (P < 0.001). Among postmenopausal women, HT significantly decreased follicle-stimulating hormone and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point. Conclusion: Black cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.

Back pain in primary care. Patient characteristics, content of initial visit, and short-term outcomes.

Study Design. Prospective study of patients making primary care visits for back pain. Objective. To examine the content of primary care visits for back pain in patients with little interference of pain with activities at the visit and 1 month later; high interference of pain with activities at the visit but not 1 month later; and high interference of pain with activities, both at the visit and 1 month later. Summary of Background Data. Advice about resumption of activities may be therapeutic for patients with back pain, but little is known about the extent to which primary care providers assess and respond to limitation of activities in patients. Methods. Audiotapes of primary care visits for back pain were coded for content. Patients indicated their goals for the visit and completed measures of pain and the pains interference with activities, just before the visit and 1 month later. Results. In most visits, providers did not assess functional limitations related to pain and did not discuss how to resume normal activities, although this was a highly rated goal for most patients. Providers did not appear to assess or respond to patients differently according to how much pain interfered with their activities. However, in patients with high interference of pain with activities, there was more discussion of limitation of activities and how to return to usual activities among those who improved than there was among those who did not improve during the next month. Conclusions. Although back pain frequently is associated with limitation of activity, pains interference with activities is assessed inconsistently in primary care visits.

Atrial Natriuretic Peptide in the Subfornical Organ Reduces Drinking Induced by Angiotensin or in Response to Water Deprivation

Three experiments tested whether the subfornical organ (SFO) could be a site of action for the antidipsogenic effects of atrial natriuretic peptide (ANP) in rats. Pretreatment with 100, 230, or 500 pmol ANP in the SFO reduced drinking induced by 10 pmol angiotensin II in the SFO. Drinking in response to water deprivation was reduced by ANP in rats having cannulas in or near the SFO, but not in rats having cannulas distant from the SFO or in the ventricles. Finally, ANP had no effect on eating or drinking after food deprivation, suggesting that the rats in the other experiments were not acutely incapacitated. The SFO may mediate the central effects of ANP on drinking induced by angiotensin or in response to water deprivation and could play a similar role in the central effects of ANP on salt appetite, diuresis, vasopressin secretion, and blood pressure.

Effect of temporomandibular disorder pain duration on facial expressions and verbal report of pain.

&NA; This study investigated how specific expressive behaviors (verbal report of pain level and the frequency of emitting specific non‐verbal facial expressions of pain) may change over the course of a chronic pain condition. Based on the concept of chronic pain behaviors, we hypothesized that both verbal and non‐verbal behavior would increase with duration of pain. Thirty‐six women with chronic temporomandibular disorder (TMD) pain (duration over 6 months) were compared with 35 recent onset cases (first episode, duration Symbol= 2 months). Subjects completed questionnaires assessing depression, anxiety, somatization, daily hassles and pain coping strategies. They were videotaped during a resting baseline and 2 painful conditions: experimental cold pressor pain and the clinically relevant pain of palpation of the masticatory muscles and temporomandibular joint; tapes were coded for facial expression using the Facial Action Coding System. Visual analog scale (VAS) ratings of the aversiveness and intensity of ongoing TMD pain were collected at baseline, and similar ratings of cold pressor and clinical examination pain were gathered after the painful stimulus. Recent onset and chronic cases did not differ on self‐report measures of anxiety, depression, somatization or daily stress. Coping strategies were also similar, although chronic cases showed a greater tendency to catastrophize. Self‐report measures of ambient facial pain, as well as the pain of clinical examination and cold pressor stimulation, revealed no significant differences between the 2 groups. In contrast, rates of pain facial expression were significantly higher for chronic cases under all conditions of the experiment, including baseline. The findings suggest that verbal and non‐verbal expressions of pain may be differentially reinforced over the course of a chronic pain condition, such that non‐verbal pain facial expressions become more frequent with time, while verbal reports of pain remain relatively constant. Figure. No caption available

Spreading a Medical Home Redesign: Effects on Emergency Department Use and Hospital Admissions

PURPOSE The patient-centered medical home (PCMH) is being rapidly deployed in many settings to strengthen US primary care, improve quality, and control costs; however, evidence supporting this transformation is still lacking. We describe the Group Health experience in attempting to replicate the effects on health care use seen in a PCMH prototype clinic via a systemwide spread using Lean as the change strategy. METHODS We used an interrupted time series analysis with a patient-month unit of analysis over a 4-year period that included baseline, implementation, and stabilization periods for 412,943 patients. To account for secular trends across these periods, we compared changes in use of face-to-face primary care visits, emergency department visits, and inpatient admissions with those of a nonequivalent comparison group of patients served by community network practices. RESULTS After accounting for secular trends among network patients, patients empaneled to the PCMH clinics had 5.1% and 6.7% declines in primary care office visits in early and later stabilization years, respectively, after the implementation year. This trend was accompanied by a 123% increase in the use of secure electronic message threads and a 20% increase in telephone encounters. Declines were also seen in emergency department visits at 1 and 2 years (13.7% and 18.5%) compared with what would be expected based on secular trends in network practices. No statistically significant changes were found for hospital admissions. CONCLUSIONS The Group Health experience shows it is possible to reduce emergency department use with PCMH transformation across a diverse set of clinics using a clear change strategy (Lean) and sufficient resources and supports.

Complex hyperplasia with and without atypia: clinical outcomes and implications of progestin therapy.

OBJECTIVE: Limited data exist to inform clinicians and patients as to the likelihood of long-term endometrial hyperplasia response to progestin therapy, especially for atypical hyperplasia. We evaluated women with complex and atypical endometrial hyperplasia, comparing those prescribed progestin with those not prescribed progestin. METHODS: This retrospective cohort study was conducted in 1985–2005 among women aged 18–88 years at an integrated health plan in Washington State. Women were ineligible if they achieved an outcome (endometrial carcinoma, hysterectomy, or both) within 8 weeks of hyperplasia diagnosis. Exposure was progestin use for at least 14 days by duration and recency. Outcomes included rate of 1) endometrial carcinoma, 2) hysterectomy, or 3) both. Analyses performed included Kaplan-Meier, incident rate ratios, and Cox proportional hazard ratios. RESULTS: One thousand four hundred forty-three eligible women were identified. One thousand two hundred one had complex (n=164 no progestin) and 242 had atypical (n=62 no progestin) hyperplasia. During follow-up, a median of 5.3 years (range 8 weeks to 20.8 years), 71 women were diagnosed with endometrial carcinoma (35 complex, 36 atypia) and 323 underwent hysterectomy (216 complex, 107 atypia). Among women with complex and atypical hyperplasia, rates of endometrial carcinoma among progestin users were 3.6 and 20.5 per 1,000 woman-years, respectively (compared with women who did not use progestin, 10.8 and 101.4). Among women with complex and atypical hyperplasia, rates of hysterectomy among progestin users were 23.3 and 61.4 per 1,000 woman-years, respectively (compared with women who did not use progestin, 55.1 and 297.3). CONCLUSION: Endometrial carcinoma risk is diminished approximately threefold to fivefold in women diagnosed with complex or atypical endometrial hyperplasia and dispensed progestin; hysterectomy risk is also decreased. LEVEL OF EVIDENCE: II

Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer.

Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS). The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE) and the Women’s Health Initiative (WHI). We detected clonal mosaicism in 169 individuals (1.4%) and large clonal mosaic events (>2 mb) in 117 (1.0%) individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia), the carriers had a 5.5-fold increased risk (95% CI: 3.3–9.3; p-value = 7.5×10−11) of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9–41.6; p-value = 7.3×10−14). Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications.

Enhancing the Power of Genetic Association Studies through the Use of Silver Standard Cases Derived from Electronic Medical Records

The feasibility of using imperfectly phenotyped “silver standard” samples identified from electronic medical record diagnoses is considered in genetic association studies when these samples might be combined with an existing set of samples phenotyped with a gold standard technique. An analytic expression is derived for the power of a chi-square test of independence using either research-quality case/control samples alone, or augmented with silver standard data. The subset of the parameter space where inclusion of silver standard samples increases statistical power is identified. A case study of dementia subjects identified from electronic medical records from the Electronic Medical Records and Genomics (eMERGE) network, combined with subjects from two studies specifically targeting dementia, verifies these results.

Hormone therapy discontinuation: physician practices after the Women's Health Initiative.

Objective:No guidelines or randomized trials address best practices for hormone therapy (HT) discontinuation. Methods:We conducted a survey study to explore HT discontinuation practices at Group Health and Harvard Vanguard, large integrated health systems in the Northwest and Northeast United States, focusing on differences between specialties and study site. Results:The response rate to the written questionnaire (mailed between December 2005 and May 2006) was 78.5% (736/928); this article reports the results for 483 eligible physicians. To discontinue oral HT, most physicians (91%) advised tapering, not immediate cessation (8%), and most (60%) suggested decreasing both dose and days per week. Almost 60% of physicians reported no experience with tapering patches. Harvard Vanguard physicians were more likely than Group Health physicians to encourage discontinuing HT and less likely to recommend resuming HT when a womans symptoms returned after discontinuing HT. Physicians were most strongly influenced by their own experience (48%), advice from colleagues (25%), and the womans preference (19%) when choosing a discontinuation strategy; only 2% relied on research evidence. Physicians endorsed various approaches to manage symptoms after HT discontinuation, most often behavioral changes (44%) and increased exercise (37%), and these approaches were more often endorsed by Harvard Vanguard physicians and obstetrician/gynecologists than Group Health physicians or family practitioners or internists. Conclusions:Two health plans in the Northwestern and Northeastern United States have no standard protocol for HT discontinuation. Physicians customized approaches, influenced by their location, colleagues, and specialty. Research is needed to guide approaches to HT discontinuation.