Does the North American Society for Pediatric and Adolescent Gynecology Short Curriculum Increase Resident Knowledge in Pediatric and Adolescent Gynecology?

STUDY OBJECTIVE: To determine if the North American Society for Pediatric and Adolescent Gynecology (NASPAG) Short Curriculum improves self-reported knowledge in pediatric and adolescent gynecology (PAG) among obstetrics and gynecology (Ob/Gyn) residents, at programs without PAG-trained faculty. DESIGN: Prospective, cross-sectional exposure to the NASPAG short curriculum with a follow-up questionnaire. SETTING: Ob/Gyn residency training programs without PAG faculty. PARTICIPANTS: Ob/Gyn residents in training from February 2015 to June 2015. INTERVENTIONS: Exposure to the NASPAG Short Curriculum. MAIN OUTCOME MEASURES: Improvement in self-perceived knowledge after completion of curriculum. RESULTS: Two hundred twenty-seven residents met inclusion criteria; 34 completed the study (15% response). Less than 50% of residents reported adequate knowledge in the areas of prepubertal vaginal bleeding, vulvovaginitis, precocious and delayed puberty, Home environment, Education and Employment, Eating, peer-related Activities, Drugs, Sexuality, Suicide/depression, Safety from injury and violence (HEEADSSS) interview, pelvic pain, and bleeding management in teens with developmental delay. After completion of the curriculum, self-reported knowledge improved in 8 of 10 learning objectives, with no significant improvement in bleeding disorders or Müllerian anomalies. There was no association between pretest knowledge and level of residency training, type of residency program, previous exposure to PAG lectures, and previous exposure to patients with PAG complaints. CONCLUSION: Significant deficiencies exist regarding self-reported knowledge of core PAG topics among Ob/Gyn residents at programs without PAG-trained faculty. Use of the NASPAG Short Curriculum by residents without access to PAG-trained faculty resulted in improved self-reported knowledge in PAG.

Diagnosis and treatment of interstitial cystitis in adolescents.

Interstitial cystitis (IC), or painful bladder syndrome, is characterized by irritative voiding symptoms and can be a challenging problem that affects children and adolescents. Diagnosis and management in children and adolescents is challenging because of strict diagnostic criteria and the paucity of investigations focusing on this age group, which often can lead to delayed or missed diagnosis. Clinical features suggestive of IC include bladder pain, urgency, frequency, nocturia, and pressure. Symptoms may wax and wane and often are exacerbated by menstruation, intercourse, dietary triggers, and stress. Diagnosis can be made by history, physical exam findings such as suprapubic tenderness, voiding diaries, and exclusion of other etiologies. Some diagnostic tests such as the potassium sensitivity test and cystoscopy are invasive and often impractical in younger patients. Treatment of IC consists of a multimodal approach that should be tailored to the individual needs of the patient. Therapies for younger patients include oral medication, intravesical therapy, cystoscopy with hydrodistention, and conservative measures such as dietary modification. This review of the literature focuses on diagnosing IC in younger patients and on what treatment modalities are appropriate and effective for this age group.

Incorporation of diffusion-weighted magnetic resonance imaging data into a simple mathematical model of tumor growth.

We build on previous work to show how serial diffusion-weighted MRI (DW-MRI) data can be used to estimate proliferation rates in a rat model of brain cancer. Thirteen rats were inoculated intracranially with 9L tumor cells; eight rats were treated with the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea and five rats were untreated controls. All animals underwent DW-MRI immediately before, one day and three days after treatment. Values of the apparent diffusion coefficient (ADC) were calculated from the DW-MRI data and then used to estimate the number of cells in each voxel and also for whole tumor regions of interest. The data from the first two imaging time points were then used to estimate the proliferation rate of each tumor. The proliferation rates were used to predict the number of tumor cells at day three, and this was correlated with the corresponding experimental data. The voxel-by-voxel analysis yielded Pearson's correlation coefficients ranging from −0.06 to 0.65, whereas the region of interest analysis provided Pearson's and concordance correlation coefficients of 0.88 and 0.80, respectively. Additionally, the ratio of positive to negative proliferation values was used to separate the treated and control animals (p <0.05) at an earlier point than the mean ADC values. These results further illustrate how quantitative measurements of tumor state obtained non-invasively by imaging can be incorporated into mathematical models that predict tumor growth.

Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV outpatient study (HOPS).

PURPOSE: Most HIV-infected persons are now treated as ambulatory patients. Obtaining continually updated data about these patients' changing conditions, therapies, and reimbursement is essential to health care provision and planning. The systematic tracking of patient medical and laboratory information in an ongoing commercial data collection program (The Health Research Network) allows clinicians to better understand health outcomes, practice patterns, and epidemiologic trends for their patients. METHODS: To evaluate trends in conditions and therapies of ambulatory HIV-infected patients, we analyzed such data electronically and prospectively collected in the HIV Outpatient Study (HOPS) from 1992 through 1996 from 1876 patients seen in 11,755 clinic visits to ten HIV clinical practices. RESULTS: Patients were as likely to be diagnosed with Mycobacterium avium complex ([MAC] 5.4 cases per 100 person-years) or wasting syndrome (7.8 cases per 100 person-years), as Pneumocystis carinii pneumonia ([PCP]; 7.6 cases per 100 person-years) or Kaposi sarcoma ([KS]; 6.9 cases per 100 person-years). A nested analysis showed that HIV-infected cigarette smokers were at substantially greater risk of pneumonia (relative hazard [RH] = 2.3), bronchitis (RH = 1.7) and hairy leukoplakia (RH = 1.9) than nonsmokers. By 1996, 35 (56%) of 62 patients with PCP, 9 (30%) of 30 patients with other pneumonias, 28 (90%) of 31 patients with KS, 35 (73%) of 48 patients with MAC, and 24 (63%) of 38 patients with cytomegalovirus retinitis were treated without hospitalization. CONCLUSIONS: The HOPS provides continually updated information on the changing characteristics, conditions, and therapy of ambulatory HIV-infected patients.

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.

BACKGROUND AND METHODS: National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. RESULTS: Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. CONCLUSIONS: The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.

Possible effectiveness of clarithromycin and rifabutin for cryptosporidiosis chemoprophylaxis in HIV disease. HIV Outpatient Study (HOPS) Investigators.

CONTEXT: Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent. OBJECTIVE: To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex. DESIGN: Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992. SETTING: Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities. PATIENTS: A total of 1019 HIV-infected patients with CD4+ cell counts less than 0.075 x 10(9)/L. MAIN OUTCOME MEASURES: Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin. RESULTS: Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard [RH], 0.25 [95% confidence interval (CI), 0.10-0.67]; P=.004). Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 [95% CI, 0.04-0.62]; P=.01). Prophylactic efficacy of either drug was 75% or greater. No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 [95% CI, 0.44-5.04]; P=.46). CONCLUSIONS: Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted.

Decreased exhaled nitric oxide in subjects with HIV infection.

BACKGROUND: Nitric oxide (NO) may be an important component of the host defence against infections. Endogenously produced NO is present in exhaled air and may be representative of respiratory tract production of NO. Since subjects infected with HIV are prone to develop respiratory infections, it was postulated that exhaled NO might be reduced in such individuals. METHODS: The exhaled concentration of NO (nl/l) and minute ventilation (l/min) were measured and exhaled NO release (nl/min/m2) calculated in 36 subjects infected with HIV (20 non-smokers, 16 smokers) and 31 non-smoking subjects with no active medical conditions. RESULTS: Exhaled NO from HIV positive individuals was less than from control subjects of similar age, height, and weight. Cigarette smoking did not account for the decreased exhaled NO in HIV positive individuals as both smoking and non-smoking HIV positive subjects had decreased exhaled NO compared with control subjects. CONCLUSION: Exhaled NO is decreased in subjects infected with the HIV. Since NO functions in host defence against bacterial, viral, and fungal infections, reduced exhaled NO may indicate a mechanism of impaired host defence in HIV infection.

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection. METHODS: A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects, and the CD4 cell response were assessed. RESULTS: After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine only (P=0.24). As compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy than with zidovudine alone. CONCLUSIONS: In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment.

Resource allocation in on-line reading by younger and older adults.

Younger and older adults read a series of expository passages for immediate recall by self-pacing the presentation sector-by-sector on a computer screen. Regression analysis of sector reading times (RT) was used to estimate the time allocated by individuals to word-level (i.e., syllable length and mean word frequency), text-level (i.e., number of propositions, number of new concepts introduced, and total Yngve depth), and discourse-level (i.e., serial position) features. Age differences were found in the pattern of reading time allocation that engendered high levels of recall. Specifically, younger adults who achieved high recall were more responsive to word frequency and the introduction of new concepts. By contrast, high recall among the old was related to a greater degree of on-line contextual facilitation (i.e., a steeper serial position effect). These data suggest that there is an age difference in how the allocation of resources at encoding optimizes subsequent memory performance.

Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors.

The majority of human immunodeficiency virus (HIV)-seropositive patients develop bone marrow abnormalities associated with hematopoietic malfunction during the progression of disease. One important manifestation of HIV-associated hematopoietic dysfunction is that after myelosuppression, bone marrow recovery, a process known to be mediated in part by the production of stromal cell-derived hematopoietic growth factors, is impaired. We sought to test the hypothesis that bone marrow stromal cells are infected by HIV-1 in vivo and that production of certain stromal cell-derived hematopoietic growth factors is deficient as a consequence. In this report, we demonstrate that bone marrow microvascular endothelial cells (MVEC), a key element of the stroma, are the predominant cells infected by HIV (5% to 20%) in bone marrow stromal cultures obtained from 11 consecutive HIV-seropositive patients. Although HIV-infected stromal cultures enriched for MVEC constitutively express normal levels of interleukin (IL)-4, IL-6, granulocyte (G)-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and Steel factor, IL-1 alpha-induced release of IL-6 and G-CSF is significantly reduced in these cultures. These observations suggest that HIV infection of bone marrow MVEC reduces the capacity of hematopoietic stroma to respond to regulatory signals that normally augment blood cell production during periods of increased demand.

Disseminated acanthamoeba infection in patients with AIDS: case reports and review.

Acanthamoeba infection has been described as an opportunistic infection in persons with AIDS. We report two cases of patients with AIDS and acanthamoeba infection and review the manifestations of this protozoan infection in patients infected with human immunodeficiency virus. The diagnosis of this infection requires a high index of suspicion because the clinical and histologic manifestations may be confused with those of disseminated fungal or algal disease. Clinicians and laboratory personnel should be aware of this potentially fatal condition so that appropriate diagnostic studies can be performed and treatment can be urgently administered. Early initiation of therapy may alter the clinical outcome of the disease.

Predicting the effect of the Oregon Health Plan on Medicaid coverage for outpatients with HIV.

The Oregon Health Plan, which took effect in February 1994, extends Medicaid eligibility but limits coverage to conditions and treatments above a certain threshold on a prioritized list. Retrospective analysis was conducted on records of visits to two Oregon human immunodeficiency virus (HIV) outpatient clinics in 1991 and 1992 to determine Medicaid coverage if the plan had been operational. Of 1129 patients, 21.1% were Medicaid-eligible; an additional 56.5% would have been eligible under the Oregon plan. Only 5.0% to 6.8% of these patients' visits were for conditions listed below the plan's coverage threshold; almost none of these were for HIV-specific conditions.

Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome.

Latent 2', 5'-oligoadenylate (2-5A) synthetase activity, bioactive 2-5A and RNase L activity were measured in extracts of peripheral blood mononuclear cells (PMBC) before and during a randomized, multicenter, placebo-controlled, double-blind study of poly(I)-poly(C12U) in individuals with chronic fatigue syndrome (CFS) as defined by the Centers for Disease Control and Prevention. The mean values for bioactive 2-5A and RNase L activity were significantly elevated at baseline compared to controls (p < .0001 and p = .001, respectively). In individuals that presented with elevated RNase L activity at baseline, therapy with poly(I)-poly(C12U) resulted in a significant decrease in both bioactive 2-5A and RNase L activity (p = .09 and p = .005, respectively). Decrease in RNase L activity in individuals treated with poly(I)-poly(C12U) correlated with cognitive improvement (p = .007). Poly(I)-poly(C12U) therapy resulted in a significant decrease in bioactive 2-5A and RNase L activity in agreement with clinical and neuropsychological improvements (Strayer DR, et al., Clin. Infectious Dis. 18:588-595, 1994). The results described show that poly(I)-poly(C12U) is a biologically active drug in CFS.

The HIV wasting syndrome: a review.

The HIV wasting syndrome and other HIV-associated weight loss is a major problem in HIV-infected patients. The available data strongly suggest that wasting is associated with decreased survival. It may also further impair immune function. A variety of etiologies probably contribute to this wasting, including hypermetabolism, alterations in metabolism, lessened oral intake, malabsorption, cytokine effects, and endocrine dysfunction. The relative contributions of each of these etiologies to wasting probably varies considerably from patient to patient. Successful treatment calls for identification of possible etiologies of wasting in the individual patient with AIDS. Further treatment may include treating underlying conditions and controlling such symptoms as diarrhea, nausea, or fever. Nutritional support, including both parenteral and enteral nutrition, has shown some promise of efficacy, and a variety of drugs appears to be helpful. Future treatment to reverse wasting may include the use of several of these agents in combination. Currently, there is much that clinicians can do to evaluate and treat the HIV wasting syndrome, with significant potential benefits to their patients.

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a physically debilitating illness associated with immunologic abnormalities, viral reactivation, and impairment of cognition. In a randomized, multicenter, placebo-controlled, double-blind study of 92 patients meeting the CFS case definition of the Centers for Disease Control and Prevention, the response of several laboratory and clinical variables to an antiviral and immunomodulatory drug, poly(I).poly(C12U), was determined. Measures of clinical response included Karnofsky performance score, a cognition scale derived from a self-administered instrument assessing symptomatology (SCL-90-R), an activities of daily living scale, and exercise treadmill performance. After 24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both global performance and perceived cognition than did patients receiving placebo. In particular, patients given poly(I).poly(C12U) had increased Karnofsky performance scores (P < .03), exhibited a greater ability to do work during exercise treadmill testing (P = .01), displayed an enhanced capacity to perform the activities of daily living (P < .04), had a reduced cognitive deficit (P = .05), and required less use of other medications (P < .05).

Endocrine function in the HIV wasting syndrome.

We compared endocrine function in patients with the HIV wasting syndrome with other HIV-positive patients without wasting to determine associations between endocrine dysfunction and wasting. Sixty-six HIV-seropositive patients were evaluated by thyroid, gonadal, and adrenal function tests. Fourteen of these patients met the clinical definition of wasting. Total and free testosterone levels were significantly lower in patients with wasting compared with patients without wasting with both similar and higher mean CD4 counts. Prolactin levels were significantly higher, and cortisol levels were higher with borderline significance in patients with wasting compared with patients with similar CD4 counts without wasting. These findings suggest that endocrine function in the HIV wasting syndrome differs from that of HIV-infected patients without wasting, which may have implications about the pathogenesis and treatment of the HIV wasting syndrome.

Micronutrient concentrations in the HIV wasting syndrome.

OBJECTIVE: We measured micronutrient values in patients with the HIV wasting syndrome and in other HIV-seropositive patients to determine whether specific micronutrient deficiencies were associated with the wasting syndrome. METHODS: Serum from 47 HIV-seropositive patients was evaluated for concentrations of vitamin A, B6, B12, C, D, E, folate, the mineral zinc, carotene and glutathione. Comparisons were made between groups stratified by CD4 cell count and wasting/non-wasting status. RESULTS: Mean serum levels were significantly lower for vitamin A (P = 0.04), folate (P = 0.04) and carotene (P = 0.06) in patients with the HIV wasting syndrome than in non-wasting patients with comparable CD4 cell counts. Values of vitamins A, B6, C, D, carotene and glutathione were below the normal range in over 10% of HIV-seropositive patients in this study. CONCLUSION: Decreased micronutrient concentrations are common in HIV-infected patients and occur more frequently in patients with the wasting syndrome. Clinicians may wish to evaluate HIV-seropositive patients with wasting for individual micronutrient deficiencies, although they should note that particular deficiencies may be only part of the larger picture of malabsorption and undernutrition.