Healthcare utilization and cost burden among women with endometriosis by opioid prescription status in the first year after diagnosis: a retrospective claims database analysis.

Aims: Opioids do not represent standard therapy for endometriosis; however, women with endometriosis are frequently prescribed an opioid to manage related abdominal or pelvic pain. The aim of this study was to evaluate the impact of opioid use on endometriosis-related economic and healthcare burden in the United States.Materials and methods: We performed a retrospective, propensity-matched cohort analysis of the Truven MarketScan Commercial database from 1 January 2011 to 31 December 2016. Eligible women had at least 1 inpatient or 2 outpatient codes for endometriosis and 12 months of continuous enrollment before and after the index date (i.e. first recorded endometriosis diagnosis). The primary analysis examined healthcare costs and utilization for 12 months after the index date in women who filled at least 1 opioid prescription versus those who did not. The secondary analysis examined healthcare costs and utilization by the pattern of opioid use.Results: The primary analysis matched 43,516 women across 2 groups and the secondary analysis matched 13,230 women across 5 groups. In the primary analysis, total 12-month healthcare costs were significantly higher in the opioid group compared to the non-opioid group ($29,236.00 vs. $18,466.00, respectively; p < .001); the same pattern was observed for all healthcare utilization parameters. In the secondary analysis, higher morphine equivalent daily dose and proportion of days covered were associated with the highest healthcare costs and utilization compared to the non-opioid group.Limitations: Retrospective design and inability to confirm whether filled opioid prescriptions were actually taken.Conclusions: Filling an opioid prescription within 1 year after an endometriosis diagnosis was associated with significant excess healthcare burden. Patients prescribed an opioid may experience inadequate symptom management and benefit from the use of disease-specific, non-opioid therapies.

Short communication: the number of HIV major NRTI mutations correlates directly with other antiretroviral-associated mutations and indirectly with replicative capacity and reduced drug susceptibility.

While it is known that selection for specific HIV-1 drug resistance-associated mutations (DRM) occurs following ART failure, the patterns of resistance mutations, reduced susceptibility (RS), and replicative capacity (RC) that appear as the number of major NRTI mutations increases have been less well-studied. These changes were examined as a function of the number of major NRTI mutations using patient-derived HIV samples submitted for resistance testing between 2003-2005 (n = 35,222) that were grouped by number of NRTI-DRMs present. In the absence of NRTI-DRMs, few (3.4%) samples had RS to one or more NRTI, 33.6% to one or more NNRTI, and 12.6% to one or more PI. With one NRTI-DRM, 94% had RS to one or more NRTI, 50% to one or more NNRTI, and 33% to one or more PI. Increases in NRTI-DRMs were accompanied by increased prevalence of NNRTI and PI DRMs and RS. With one NRTI-DRM, the mean number of NRTIs with RS was 1.7, while when five NRTI-DRMs were present, RS to > or =5 NRTIs was observed. PI-DRM and RS increased at a slower rate than NNRTI-DRM and RS. RC declined from a mean of 97.8% for samples without NRTI-DRMs to 68.9% with one NRTI-DRM, possibly due to reduced fitness conferred by K65R or M184I/V, to an RC of 43.9% for samples with seven to eight NRTI-DRMs. The relatively high percent of samples with NNRTI-DRM but without NRTI-DRMs may result from selection following virologic failure, and/or transmission of virus uniquely resistant to NNRTI.

HIV in the brain: RNA levels and patterns of zidovudine resistance.

OBJECTIVE: To examine the association between HIV RNA levels, patterns of antiretroviral resistance, and neurologic status. METHODS: Autopsy samples from 13 HIV-infected subjects were examined for HIV-1 viral RNA (vRNA), and viral reverse transcriptase (RT) genotype was determined. All subjects had been clinically characterized using standard instruments before death. RESULTS: The median HIV-1 vRNA level in brain samples from subjects with moderate dementia was 7.79 log(10) copies/g (range 5.56 to 9.75 log(10) copies/g) compared with 5.44 log(10) copies/g (range 3.51 to 9.32 log(10) copies/g) for mildly demented subjects and 4.87 log(10) copies/g (3.51 to 6.86 log(10) copies/g) for those obtained from nondemented individuals. There were differences between subjects with moderate dementia and nondemented subjects (p = 0.0002) and between subjects with moderate and mild dementia (p = 0.0128). No significant differences among the groups were observed for vRNA levels in peripheral tissues. Some demented subjects had relatively low levels of HIV-1 vRNA, and paradoxically some nondemented subjects had high vRNA brain levels. Little subject effect in vRNA was noted in peripheral regions, but high regional variation in vRNA was noted within the brain. Patterns of the major zidovudine (ZDV) RT mutations in brain and peripheral tissues were concordant in most subjects. Subjects with longer duration of exposure to ZDV tended to have lower brain vRNA levels and a greater number of RT mutations than those with limited to no exposure. CONCLUSIONS: The presence and severity of HIV dementia correlates with the levels of productive HIV replication within the brain. Other pathophysiologic events (including macrophage activation) probably also contribute to neurologic dysfunction.

A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection.

Mycophenolic acid (MPA) increases the activity of both abacavir (ABC) and didanosine (ddI) in vitro against wild-type and multinucleoside-resistant HIV. We treated 7 patients with diagnosed AIDS who did not respond to eight or more antiretroviral therapies in an open label pilot study with mycophenolate mofetil (MMF), ABC, ddI, amprenavir (APV), and ritonavir (RTV), with or without efavirenz (EFV). Therapy was well tolerated despite the patients' advanced disease states. No significant decline in lymphocyte or other blood counts was observed. Median HIV RNA was 5.26 log10 copies/ml at entry, 4.53 log10 copies/ml at 4 weeks, and 5.13 log10 copies/ml at 16 weeks. Median CD4+ count was 34 cells/microl at entry and 39 cells/microl at 16 weeks of therapy. CD4+ counts increased further in five study subjects on extended therapy to 25 weeks (median 27 cells/microl at entry, 66 cells/microl at close), despite loss of virologic suppression in 4 of 5 cases. MPA can induce apoptosis in lymphocytes in vitro. However despite viral rebound, cell surface markers of apoptosis and activation declined in total CD3+ cells and CD3+/CD4+ cells twofold to fourfold in 4 of 5 adherent study subjects at 16 weeks, reaching levels comparable with those found in seronegative donors. Although low-dose MMF appears safe in late-stage HIV disease, this study did not demonstrate virologic efficacy. Higher doses of MMF may be more effective. With careful monitoring of toxicities and pharmacokinetics, MMF deserves further testing in HIV therapy.

Gross anatomy course content and teaching methodology in allied health: clinicians' experiences and recommendations.

The purpose of this study was to sample the experiences and recommendations of clinicians in allied health fields about gross anatomy courses. The objective was to determine if practicing clinicians recommended a course in gross anatomy, and, if so, their recommendations for course content and teaching methodology. Questionnaires were mailed to a random selection of occupational therapists (OTs), physician assistants (PAs), and physical therapists (PTs) licensed in the state of Texas. In addition to demographics, the survey asked 14 questions regarding the experiences and recommendations in seven areas of interest about gross anatomy courses. The responding sample appeared to be representative of the target population. A course in human gross anatomy during professional school was recommended by 96% of OTs, and 100% of PAs and PTs. The single most recommended teaching method was student dissection of human cadavers. Although significant differences were found regarding primary course orientation, a majority favored some form of combined systems and regional oriented courses. A majority of clinicians in each field recommended a gross anatomy course at the beginning of professional training. Specific recommendations were given for content of systems and regional oriented gross anatomy courses. We recommend that the gross anatomy course content and teaching methodologies in allied health areas be responsive to the specific needs of each clinical specialty.

Deletions in the beta3-beta4 hairpin loop of HIV-1 reverse transcriptase are observed in HIV-1 isolated from subjects during long-term antiretroviral therapy.

OBJECTIVES: To examine the effect of in-frame deletions in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on plasma viremia and phenotypic resistance to antiretroviral drugs. STUDY DESIGN/METHODS: Plasma HIV-1 RNA was isolated from 168 antiretroviral therapy-experienced subjects for quantification of plasma viremia, RT sequence analysis, and phenotypic resistance assays. RESULTS: Four patients were found to harbor HIV-1 strains possessing in-frame, 3-nucleotide deletions at RT codons 67, 69, and 70. In these subjects, phenotypic resistance and high plasma viremia were observed only in a background of multiple resistance mutations. A recombinant virus engineered with an in-frame deletion of RT codon 67 did not have increased resistance to nucleoside reverse transcriptase inhibitors (NRTIs). CONCLUSIONS: Selection for deletions within the beta3-beta4 hairpin loop of the HIV-1 RT is an uncommon event most likely to occur in subjects with long-term antiretroviral experience. The codon 67 deletion does not appear to cause increased phenotypic resistance or increased viremia in the absence of concomitant RT mutations.

Phenotypic testing predicts virological response in successive protease inhibitor-based regimens.

OBJECTIVE: To evaluate the importance of the number of active drugs, as determined by phenotypic resistance testing, in achieving virological response in successive salvage regimens. DESIGN: Phenotypic study of 57 plasma samples corresponding to 24 patients who had sequentially received three protease inhibitor-containing regimens. Phenotypic susceptibility to a drug (active drug) was defined as less than a four-fold-increase in the IC50 in comparison with the wild type. MAIN OUTCOME MEASURE: Virological response according to the number of active drugs (three versus two or fewer), HIV load, length of antiretroviral exposure, and line of protease inhibitor-based therapy (first, second and third regimen). RESULTS: Before the first protease inhibitor-based therapy, the median time on antiretroviral treatment was 42 months, and before the second and third protease inhibitor-salvage regimens it was 10 and 8 months, respectively. The number of patients receiving three active drugs simultaneously was 24, 35 and 31% in each line of therapy. At week 12, a close correlation was found between the presence of three active drugs in the antiretroviral regimen and the rate of virological response, in comparison with those patients receiving two or fewer active drugs [76 versus 45%, relative risk (RR), 1.7; 95% confidence interval (CI) 1.1-2.6; P = 0.028]. In a multivariate analysis, the use of two or fewer active drugs was an independent predictor of lack of response, regardless of HIV load, length of previous antiretroviral exposure and line of salvage therapy (RR, 4.5; 95%CI, 1.1-18.3; P = 0.03). Of note, a higher rate of response was observed in patients receiving the first protease inhibitor-containing regimen in comparison with those in subsequent protease inhibitor-based salvage regimens (83 versus 50 versus 28%, P < 0.01), even when only those patients receiving three active drugs were included (100 versus 71 versus 60%). CONCLUSIONS: This data confirm the usefulness of phenotypic testing in guiding antiretroviral therapy in heavily pretreated patients. The number of active drugs and the line of salvage therapy are independent predictors of virological response, regardless of HIV load and the length of antiretroviral exposure.

The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan.

To assess the relation between resistance to antiretroviral drugs for treatment of HIV-1 infection and virological response to therapy, results from 12 different studies were re-analysed according to a standard data analysis plan. These studies included nine clinical trials and three observational cohorts. The primary end-point in our analyses was virological failure by week 24. Baseline factors that were investigated as predictors of virological failure were plasma HIV-1 RNA, the number and type of new antiretroviral drugs in the regimen, and viral susceptibility to the drugs in the regimen, determined by genotyping or phenotyping methods. These analyses confirmed the importance of both genotypic and phenotypic drug resistance as predictors of virological failure, whether these factors were analysed separately or adjusted for other baseline confounding factors. In most of the re-analysed studies, the odds of virological failure were reduced by about twofold for each additional drug in the regimen to which the patient's virus was sensitive by genotyping methods, and by about two- to threefold for each additional drug that was sensitive by phenotyping.

The added benefit of local Patanol therapy when combined with systemic Claritin for the inhibition of ocular itching in the conjunctival antigen challenge model.

BACKGROUND: Allergic conjunctivitis very often occurs simultaneously with rhinitis in seasonal allergy sufferers. While systemic anti-allergic and antihistaminic agents are effective against many signs and symptoms of allergy, they may not adequately control ocular signs and symptoms in patients with multiple target organ hypersensitivity. Patanol (olopatadine hydrochloride 0.1% ophthalmic solution, Alcon Laboratories, Inc., Fort Worth, TX), a new effective anti-allergic mast cell stabilizer with antihistaminic properties, is approved for the prevention of ocular itching due to allergic conjunctivitis. OBJECTIVE: To determine whether Patanol in combination with the systemic antihistamine Claritin (loratadine, Schering, Kenilworth, NJ) reduces the ocular itching associated with allergic conjunctivitis more effectively than Claritin alone. A topical ocular antigen challenge induced the allergic conjunctivitis in 15 subjects. METHODS: This was a randomized, double-masked study in which the contralateral eye served as the control. On Visit 1, an allergen dose which elicited response scores > 2 for ocular itching was identified. Itching was graded by the subject using a 0 to 4 point scale. At Visit 2, the threshold allergen concentration was confirmed. At Visit 3, the onset of action challenge, in addition to Claritin (10 mg tablet), each subject received Patanol in one eye and placebo in the fellow eye in a randomized, double-masked fashion. Allergen was instilled one hour after dosing, and ocular itching was graded at 3, 7, 10 and 20 minutes after challenge. At Visit 4, the duration of action challenge, the same drug regimen was followed as in Visit 3. However, allergen challenge was performed eight hours after dosing, and itching graded after 3, 7, 10 and 20 minutes. RESULTS: Patient eyes treated with Patanol were significantly less itchy than those treated with systemic Claritin alone at critical time points 3, 7, and 10 minutes after the onset of action challenge (p < 0.05), and at 3 and 7 minutes after the duration of action challenge (p < 0.05). CONCLUSION: The addition of topical Patanol to systemic Claritin therapy significantly reduced ocular itching associated with allergic conjunctivitis compared to treatment with Claritin alone. These findings prove the added benefit of local Patanol therapy in the treatment of ocular allergic symptoms in patients receiving systemic antihistamines for concomitant systemic allergies.

A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma.

BACKGROUND: Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few. OBJECTIVE: We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma. METHODS: Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards. RESULTS: Fluticasone propionate treatment resulted in significantly (P

A dose-ranging study to evaluate the safety and efficacy of abacavir alone or in combination with zidovudine and lamivudine in antiretroviral treatment-naive subjects.

OBJECTIVE: To compare antiretroviral efficacy, safety and tolerance of three dosing regimens of the novel nucleoside reverse transcriptase inhibitor, abacavir (1592U89) over 24 weeks and its efficacy in open-label combination with zidovudine and lamivudine. DESIGN: Sixty HIV-1-infected antiretroviral therapy naive subjects (entry criteria; CD4+ cell count > or = 100 cells/mm(3), plasma HIV-1 RNA > or = 30 000 copies/ml), randomized into 20 subjects per cohort received 100, 300 or 600 mg abacavir twice daily. Subjects successfully completing 24 weeks' randomized therapy could switch to open label therapy (abacavir, zidovudine, lamivudine at 300, 300 and 150 mg twice daily, respectively) for a further 24 weeks of studly, as could subjects meeting one or more switch criteria. METHODS: Subjects were assessed for antiretroviral activity by measuring changes in plasma HIV-1 RNA load and CD4+ cell counts. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. RESULTS: At week 4, subjects receiving 300 or 600 mg abacavir twice daily had greater reductions in plasma HIV-1 RNA (median changes -1.55 and -1.61 log10) copies/ml, respectively); differences (P = 0.007 and P < or = 0.001, respectively) than subjects receiving 100 mg abacavir twice daily (median change, -0.63 log10 copies/ml). Differences between the 300 and 600 mg twice daily groups were not clinically or statistically significant. At 24 weeks, analysis showed a median change in plasma HIV-1 RNA of -0.70 and -1.30 log10 copies/ml in the 300 and 600 mg twice daily groups, respectively. During the open label phase in which zidovudine/lamivudine was added to 300 mg abacavir twice daily, a further median reduction in plasma HIV-1 RNA of 1.74 log10 copies/ml was seen. At 48 weeks pooled data from all abacavir-treated subjects showed a sustained reduction in plasma HIV-1 RNA of 2.8 log10) copies/ml; 65% and 43% of subjects had < or = 400 and < or = 50 HIV-1 RNA copies/ml, respectively, and a further median increase of 111 CD4+ cells/mm3 were seen. Abacavir was generally well tolerated with few clinically significant adverse events. Two subjects (3.3%) developed hypersensitivity reactions to abacavir. There were no differences between the groups with regard to serious adverse events. CONCLUSIONS: In terms of antiretroviral therapy naive subjects, treatment with 300 or 600 mg abacavir twice daily was statistically superior to a 100 mg twice daily dose at 4 weeks. Combinations therapy containing abacavir-zidovudine-lamivudine was a highly effective antiretroviral regimen, resulting in substantial reductions in plasma HIV-1 RNA which may be comparable to combinations containing protease inhibitors. Abacavir was generally tolerated.

Expressions of accuracy in the evaluation of biomedical instrumentation.

This review discusses and compares the most common and appropriate expressions and representations of accuracy in the evaluation of biomedical instrumentation. Instruments used to measure blood pressure illustrate the various expressions of accuracy in common use. Accuracy of biomedical instruments can be defined as a measure of system error. In system error there is a consistent, systematic bias inherent in the method or instrument being tested. Two cases or conditions in which accuracy may be determined were identified and analyzed: 1) static or single-target conditions, and 2) dynamic or continuum-of-target conditions. Expressions of accuracy tested included the mean difference/standard deviation (MD/SD) method and the regression analysis (RA) method. In the static, single-target cases examined, the MD/SD method proved acceptable. In the dynamic, continuum-of-targets cases examined, the RA method proved the most accurate and useful expression of instrumental accuracy. The MD/SD method could be significantly misleading in these dynamic target cases. Since the majority of biomedical instruments are used in dynamic or continuum-of-targets situations, RA is, generally, the method of choice.

Can concomitant restriction be detected in adult men with airflow obstruction?

A reduction in lung volume is used to diagnose physiologic restriction in the pulmonary function tests of patients with lung disease. Airflow obstruction is commonly associated with hyperinflation of static lung volume. Because restriction and obstruction exert opposite effects on lung volumes, we questioned whether the lack of hyperinflation of static lung volumes could indicate the presence of concomitant restriction in patients with airflow obstructive ventilatory defects. To assess this, we evaluated by pulmonary function tests and chest roentgenograms of 58 patients with airflow obstruction (group 1), 18 of whom then sustained various types of resection for lung cancer (group 2) as a type of superimposed restriction. We selected 80 percent of predicted as the lower limit of "normal" frequently used by clinical pulmonary function laboratories. Despite a statistically significant decrease in total lung capacity (p less than 0.05) for the postpneumonectomy patients, when the static lung volume measurements of the patients with resection were evaluated, no one lung volume showed a consistent reduction sufficient to detect the superimposed restriction in all these patients. Using 80 percent of predicted as "normal," 61 percent of our patients with airflow obstruction and superimposed restriction would have been missed. We conclude that it is clinically difficult, based on only static lung volume measurements alone, to detect restriction superimposed on the hyperinflation of airflow obstruction unless these lung volumes are reduced to below accepted "normal" limits.

Growth and distribution of selected allied health professional groups, United States, 1970-1980.

The growth and geographical distribution of selected allied health professional groups were compared with medicine, dentistry, and nursing for the periods 1970 to 1980 using data from the US census (1970 to 1980) and AMA Physician Masterfile. GINI indexes of health professionals concentration were computed as global measures to evaluate changes in the pattern of locational choice. All allied health professional groups reflected large percentage increases ranging from 25% to 432% in supply of practitioners from 1970 to 1980, with a median percentage increase of 71.9%, and compared well with medicine and dentistry. These allied health supply increases were generally related to better distributional outcomes among the general population and physicians, although several allied health groups became less evenly distributed during this decade. These gains were realized during a decade when less federal support was available for the allied health professions compared with medicine, dentistry, and nursing.

A comparison of inhaled albuterol and cromolyn in the prophylaxis of exercise-induced bronchospasm.

Inhaled albuterol and cromolyn by spinhaler have both been shown to be effective in the treatment of exercise-induced bronchospasm. Eighty subjects with exercise-induced bronchospasm participated in a randomized parallel group study comparing albuterol (180 microgram) and cromolyn (20 mg) administered 15 minutes prior to a standardized treadmill challenge. The cromolyn group was restudied after 2 and 4 weeks of 4 times/day cromolyn therapy. The albuterol group was also studied at 2 and 4 weeks, but they only used their inhaler as needed between study visits. The mean maximum FEV1 drop post-exercise in the albuterol group improved from 33% (screening visit) to 6% (treatment day 1). The cromolyn group showed significantly less (P less than .01) improvement than the albuterol group (31% drop at the screening visit to 14% drop at treatment day 1). When 2 or 4 weeks of continuous cromolyn therapy was given in addition to a dosage 15 minutes prior to exercise, there was no significant difference compared with acute cromolyn administration alone. In summary, acute administration of albuterol was better prophylaxis for exercise-induced bronchospasm than acute or chronic cromolyn treatment.

Professional performance of physician's assistants: a comparison of physician's assistant and physician ratings.

Physician's assistant educational programs have used surveys of their graduates as one method of evaluating educational objectives and curricula. A concern is the validity of physician's assistant self-ratings as measures of job performance. Ratings by supervising physicians have been suggested as more valid measures. In the present study ratings of physician's assistants and their supervising physicians were compared. Physician's assistants and their supervising physicians were interviewed using an interview instrument developed to cover the performance of the physician's assistant in the major activities of primary care practice. While the physicians and physician's assistants disagreed on several measures, in all cases the ratings of the physician's assistants were more conservative. Thus, the physician's assistants did not show any tendency to inflate ratings of their own performance.

Admissions procedures of educational programs for the specialist in blood bank technology.

A national survey of specialists in blood bank technology educational programs was performed to describe current admissions procedures. Programs generally were AABB approved for and accepted either two or four students annually from 10 to 14 complete applications which result from 25 to 50 inquiries. The program selection criteria usually included an evaluation of overall GPA, science GPA, prior blood bank experience, three professional references, and a non-standardized interview with the medical director, educational coordinator, and other faculty or staff. Admissions procedures were characterized by an admissions committee of four members differentially weighting the various selection criteria that often were not quantified through the use of a point value system. Programs reported that their admissions procedures were not quantified through the use of a point value system. Programs reported to their admissions procedures were objective enough and resulted in students of adequate quality, even though their procedures could be improved, possibly with more specific AABB guidelines.

Predicting academic performance in medical technology: a university-based program in retrospect.

In a study of the relative contribution of two achievement measures and five aptitude measures in determining three measures of academic performance, an achievement measure in combination with an aptitude measure provided the most efficient explanations. Stepwise multiple regressions were performed on data from 112 medical technology graduates to determine that science grade point average (GPA) and Nelson-Denny Combination sub-score significantly predicted professional GPA. Additionally, science GPA and the Otis Test score explained the variations in both certification examination performance and comprehensive examination performance.