Use of the Levonorgestrel Intrauterine System to Treat Heavy Menstrual Bleeding in Adolescents and Young Adults with Inherited Bleeding Disorders and Ehlers-Danlos Syndrome.

STUDY OBJECTIVE: To report on the rate of amenorrhea among adolescents and young adults with a bleeding diathesis after insertion of the 52-mg levonorgestrel intrauterine system (LNG-IUS) DESIGN: Retrospective chart review SETTING: Tertiary care, multidisciplinary Gynecology-Hematology clinic or Adolescent Gynecology clinic PARTICIPANTS: The cohort included 35 females aged 12-25 years presenting from January 2010 to January 2020 with heavy menstrual bleeding, 23 with an inherited blood disorder, and 12 with Ehlers-Danlos syndrome INTERVENTIONS: The 52-mg LNG-IUS MAIN OUTCOME MEASURES: Primary outcome was bleeding profile after LNG-IUS insertion. Secondary outcomes included rates of amenorrhea, intrauterine device (IUD) expulsion, IUD discontinuation, and unplanned pregnancy. RESULTS: Mean age at menarche was 11.6 years, with mean age at insertion of 16.9 (range 11-23). Most participants were white (n = 26, 74.3%). Von Willebrand disease was present in 16 patients (45.7%) and Ehlers-Danlos syndrome in 12 (34.3%). Most (91.4%) had tried at least 1 hormonal regimen prior to LNG-IUS. Most participants (81.8%) reported improvement in bleeding, with 60.6% reporting spotting or amenorrhea. LNG-IUS expulsion occurred in 3 participants (9.1%) within the first 21 days, despite hemostatic agents at time of insertion. Mean continuation was 5.08 years (95% CI, 4.24-5.92), with 79% likelihood that participants kept their IUD in place for at least 2.5 years, and some up to 6 years. CONCLUSION: The 52-mg LNG-IUS is an effective treatment option for adolescents and young adults with heavy menstrual bleeding and a bleeding diathesis, with high rates of amenorrhea. Rates of IUD expulsion appeared higher during the first 30 days, but long-term continuation remained high.

Standardization of State Definitions for Neonatal Abstinence Syndrome Surveillance and the Opioid Crisis.

Rates of neonatal abstinence syndrome (NAS) have increased fivefold in the past decade. To address this expanding and complex issue, state public health agencies have addressed the opioid crisis affecting newborns in diverse ways, leading to a variety of methods to quantify the burden of NAS.In an effort to understand this variability, we summarized clinical case and surveillance definitions used across jurisdictions in the United States. We confirmed that the rapid progression of the nation's opioid crisis resulted in heterogeneous processes for identifying NAS. Current clinical case definitions use different combinations of clinician-observed signs of withdrawal and evidence of perinatal substance exposure. Similarly, there is discordance in diagnosis codes used in surveillance definitions. This variability makes it difficult to produce comparable estimates across jurisdictions, which are needed to effectively guide public health strategies and interventions.Although standardization is complicated, consistent NAS definitions would increase comparability of NAS estimates across the nation and would better guide prevention and treatment efforts for women and their infants.

Recruitment and Baseline Characteristics of Participants in the Lifestyle Improvement Through Food and Exercise (LIFE) Study.

African Americans experience poorer diabetes outcomes than non-Hispanic Whites. Few clinical trials of diabetes self-management interventions specifically target African Americans, perhaps due to well-documented barriers to recruitment in this population. This paper describes strategies used to successfully recruit 211 low-income African Americans from community clinics of a large, urban public hospital system to a randomized clinical trial of an 18-month diabetes self-management intervention. Diabetes-related physiological, psychosocial, and behavioral characteristics of the sample are reported. The sample was 77% female, mean age = 55, mean A1C = 8.5%, 39% low health literacy, 28.4% moderate/severe depression, and 48.3% low adherence. Participants ate a high-fat diet with low vegetable consumption. Relative to males, females had higher BMI, depression, and stress, and better glycemic control, less physical activity, and less alcohol consumption. Males consumed more daily calories, but females consumed a greater proportion of carbohydrates. Gender-specific diabetes self-management strategies may be warranted in this population.

Group III and IV muscle afferents: role on central motor drive and clinical implications.

The present review is focused on neural mechanisms responsible of group III and IV muscle afferent actions on central motor drive during physical exercise in both healthy and pathological populations. It seems that these mechanisms contribute to improve muscle performance by regulating the peripheral fatigue development and by avoiding excessive muscle impairments. Therefore, a great deal of attention is paid to their influences on motor unit activation during fatiguing exercise both in human and animal models. Recent evidence indicated that these afferents from a given active muscle could contribute to regulate the motor activity of the homonymous as well as surrounding skeletal muscles by acting at both spinal and supraspinal levels. In addition, given that the recovery of the sensory feedback plays a key role in the improvement of motor function following numerous neuromuscular traumas, the role of these afferents in preclinical and clinical situations is also explored in animal and human models. It is supposed that studying the motor and autonomic functions of group III and IV afferents might help healthcare professionals in the future to find appropriate treatments and rehabilitation programs.

Application of a Mixed Methods Approach to Identify Community-Level Solutions to Decrease Racial Disparities in Infant Mortality.

Objectives: This study aimed to identify community-level actions to decrease racial disparities in infant mortality (IM). Design: Six urban multidisciplinary teams generated ideas for decreasing racial disparities in IM using a mixed methods concept mapping approach. Participants rated each idea as to its necessity and action potential and grouped ideas by theme. A cluster analysis produced a series of visual representations, showing relationships between the identified actions and the clustering of actions into themes. Multidimensional scaling techniques were used to produce analyses describing the necessity of and action potential for implementing the proposed ideas. Participants identified actions communities could take to decrease racial disparities in IM and suggested applications of the knowledge gained from the mapping process. Results: Participants produced a total of 128 actions, within 11 thematic clusters, for decreasing racial disparities in IM. The thematic clusters contained a range of elements designed to promote knowledge and understanding of the relationship between health and racism; improve educational systems and community opportunities; facilitate community-driven health promotion, marketing, and research; improve health services for women; address physical and social environments that impact community health; prioritize resource allocation of community-based services; institutionalize strategies that promote equity across all systems; and create and support legislation and policies that address social determinants of health. Correlation coefficients of the clusters ranged from 0.17 to 0.90. Average necessity ratings ranged from 2.17 to 3.73; average action potential ratings ranged from 1.64 to 3.61. Conclusion: Findings suggest that thematic clusters with high action potential usually represented ongoing community activities or actions communities could easily initiate. Community size, existing programs, partnerships, policies, and influential advocates were among the factors cited affecting feasibility of implementation. Clusters with lower action potential require broader, longer term, policy, institutional or system-wide changes, and significant resources. High necessity clusters often contained actions perceived as essential for change, but sometimes outside of a community's control. Participants identified a number of practical actions that were considered to hold potential for individual, community, and institutional changes which could result in decreasing racial disparities in IM.

Successful isolated intestinal transplantation in sensitized recipients with the use of virtual crossmatching.

We evaluated virtual crossmatching (VXM) for organ allocation and immunologic risk reduction in sensitized isolated intestinal transplantation recipients. All isolated intestine transplants performed at our institution from 2008 to 2011 were included in this study. Allograft allocation in sensitized recipients was based on the results of a VXM, in which the donor-specific antibody (DSA) was prospectively evaluated with the use of single-antigen assays. A total of 42 isolated intestine transplants (13 pediatric and 29 adult) were performed during this time period, with a median follow-up of 20 months (6-40 months). A sensitized (PRA ≥ 20%) group (n = 15) was compared to a control (PRA < 20%) group (n = 27) to evaluate the efficacy of VXM. With the use of VXM, 80% (12/15) of the sensitized patients were transplanted with a negative or weakly positive flow-cytometry crossmatch and 86.7% (13/15) with zero or only low-titer (≤ 1:16) DSA. Outcomes were comparable between sensitized and control recipients, including 1-year freedom from rejection (53.3% and 66.7% respectively, p = 0.367), 1-year patient survival (73.3% and 88.9% respectively, p = 0.197) and 1-year graft survival (66.7% and 85.2% respectively, p = 0.167). In conclusion, a VXM strategy to optimize organ allocation enables sensitized patients to successfully undergo isolated intestinal transplantation with acceptable short-term outcomes.

Recovery pattern of motor reflex after a single bout of neuromuscular electrical stimulation session.

We aimed at determining the recovery pattern of neural properties of soleus muscle after a single bout of neuromuscular electrical stimulation (NMES) session. Thirteen subjects performed an NMES exercise (75 Hz, 40 contractions, 6.25 s per contraction). Maximal voluntary contraction (MVC), H-reflex at rest and during voluntary contraction fixed at 60% of MVC (respectively, H(max) and H(sup) ) and volitional (V) wave were measured before and during the recovery period following this exercise [i.e., immediately after, 2 h (H2), 2 days (D2) and 7 days (D7)]. MVC exhibited an immediate and a delayed declines at 2 days (respectively, -29.8±4.6%, P<0.001; -13.0±3.4%, P<0.05). Likewise, V/M(sup) was decreased immediately and 2 days after NMES session (respectively, -43.3±11.6%, P<0.05; 35.3±6.6%, P<0.05). The delayed decrements in MVC and V-wave occurred concomitantly with muscle soreness peak (P<0.001). It could be concluded that motor command alterations after an NMES resistance session contributed to the immediate and also to the delayed decreases in MVC without affecting resting and active H-reflex excitability. These results suggested that spinal circuitry function of larger motoneurons was inhibited by NMES (as indicated by the depressed V-wave responses) contrary to the smaller one (indicated by the unchanged H-reflex responses).

Liver transplantation in the management of hepatic epithelioid hemangioendothelioma: a single-center experience and review of the literature.

Hepatic epitheliod hemangioendothelioma (HEHE) is a rare tumor of vascular origin with unpredictable malignant potential. We describe our experience with four biopsy-proven HEHE cases that were considered for orthotopic liver transplant (OLT). Three patients had preserved hepatic function and despite extensive disease burden did not develop disease progression while awaiting OLT. We were able to utilize the review process allowed by United Network of Organ Sharing to obtain additional priority for OLT for these patients. This led to expedited organ allocation and excellent post-OLT outcomes.

Behavioral treatment of insomnia: a proposal for a stepped-care approach to promote public health.

Chronic insomnia is a highly prevalent condition that has psychological and medical consequences for those who suffer from it and financial consequences for both the individual and society. In spite of the fact that nonpharmacologic treatment methods have been developed and shown to be as or more effective than medication for chronic insomnia, these methods remain greatly underutilized due to an absence of properly trained therapists and a general failure in dissemination. A stepped-care model implemented in a primary-care setting offers a public health solution to the problem of treatment accessibility and delivery of behavioral treatments for insomnia. Such a model would provide graduated levels of cognitive behavioral intervention, with corresponding increases in intensity and cost, including self-help, manualized group treatment, brief individual treatment, and finally, individualized behavioral treatment provided by a specialist. To provide such a systematic approach, future research would need to confirm several aspects of the model, and a cadre of professionals would need to be trained to administer manualized care in both group and individualized formats.

Impact of hospital policies on breastfeeding outcomes.

OBJECTIVE: The objective of this study was to explore the association between the Ten Steps of the Baby Friendly Hospital Initiative (BFHI) of the World Health Organization (Geneva, Switzerland) and breastfeeding at 2 days and 2 weeks. METHODS: A 65-question institutional survey assessing compliance with the Ten Steps was used to determine an overall breastfeeding Support Score for each of Oregon's 57 birthing hospitals. Hospital breastfeeding outcomes were obtained from the newborn metabolic screening forms. RESULTS: Hospitals' overall breastfeeding Support Scores ranged from 49.4 to 98.2 out of a possible total score of 100. Hospital compliance with individual Steps ranged from 5.3% for Step 2 (staff training) to 93% for Step 4 (helping with breastfeeding initiation) and Step 8 (encouraging feeding on demand). After controlling for institutional differences (by multivariate linear regression) we found that increases in overall hospital breastfeeding Support Scores were associated with increases in breastfeeding percentage at 2 days (p = 0.021) and at 2 weeks postpartum (p = 0.011). In analyzing each Step individually, however, only the presence of a written hospital policy was independently associated with breastfeeding percent (p = 0.028). CONCLUSIONS: This institutional-level evaluation corroborates previous findings demonstrating that increased implementation of the Ten Steps is associated with increased breastfeeding. Further, it suggests that hospitals with comprehensive breastfeeding policies are likely to have better breastfeeding support services and better breastfeeding outcomes. Hospitals may consider using these results to prioritize breastfeeding support services through development of hospital breastfeeding policies and to utilize institutional surveys as a component of breastfeeding quality improvement initiatives.

Marketing infant formula through hospitals: the impact of commercial hospital discharge packs on breastfeeding.

OBJECTIVES: Commercial hospital discharge packs are commonly given to new mothers at the time of newborn hospital discharge. We evaluated the relationship between exclusive breastfeeding and the receipt of commercial hospital discharge packs in a population-based sample of Oregon women who initiated breastfeeding before newborn hospital discharge. METHODS: We analyzed data from the 2000 and 2001 Oregon Pregnancy Risk Assessment Monitoring System (PRAMS), a population-based survey of postpartum women (n=3895; unweighted response rate=71.6%). RESULTS: Among women who had initiated breastfeeding, 66.8% reported having received commercial hospital discharge packs. We found that women who received these packs were more likely to exclusively breastfeed for fewer than 10 weeks than were women who had not received the packs (multivariate adjusted odds ratio=1.39; 95% confidence interval=1.05, 1.84). CONCLUSIONS: Commercial hospital discharge packs are one of several factors that influence breastfeeding duration and exclusivity. The distribution of these packs to new mothers at hospitals is part of a longstanding marketing campaign by infant formula manufacturers and implies hospital and staff endorsement of infant formula. Commercial hospital discharge pack distribution should be reconsidered in light of its negative impact on exclusive breastfeeding.

Unintended childbearing and knowledge of emergency contraception in a population-based survey of postpartum women.

OBJECTIVES: We examined the relationship between unintended childbearing and knowledge of emergency contraception. METHODS: The Oregon Pregnancy Risk Assessment Monitoring System (PRAMS) is a population-based survey of postpartum women. We analyzed data from the 2001 PRAMS survey using logistic regression to assess the relationship between unintended childbearing and emergency contraception while controlling for maternal characteristics such as age, race/ethnicity, education, marital status, family income, and insurance coverage before pregnancy. RESULTS: In 2001, 1,795 women completed the PRAMS survey (78.1% weighted response proportion). Of the women who completed the survey, 38.2% reported that their birth was unintended and 25.3% reported that they did not know about emergency contraception before pregnancy. Unintended childbearing was associated with a lack of knowledge of emergency contraception (OR 1.43, 95% CI 1.00, 2.05) after controlling for marital status and age. CONCLUSIONS: Women in Oregon who were not aware of emergency contraception before pregnancy were more likely to have had an unintended birth when their marital status and age were taken into account. Unintended birth was more likely among women who were young, unmarried, lower income, and uninsured. Given that emergency contraception is now available over-the-counter in the US to women who are 18 years of age or older, age- and culturally-appropriate public health messages should be developed to expand women's awareness of, dispel myths around, and encourage appropriate use of emergency contraception as a tool to help prevent unintended pregnancy and birth.

Reduced Plasmodium vivax erythrocyte infection in PNG Duffy-negative heterozygotes.

BACKGROUND: Erythrocyte Duffy blood group negativity reaches fixation in African populations where Plasmodium vivax (Pv) is uncommon. While it is known that Duffy-negative individuals are highly resistant to Pv erythrocyte infection, little is known regarding Pv susceptibility among heterozygous carriers of a Duffy-negative allele (+/-). Our limited knowledge of the selective advantages or disadvantages associated with this genotype constrains our understanding of the effect that interventions against Pv may have on the health of people living in malaria-endemic regions. METHODS AND FINDINGS: We conducted cross-sectional malaria prevalence surveys in Papua New Guinea (PNG), where we have previously identified a new Duffy-negative allele among individuals living in a region endemic for all four human malaria parasite species. We evaluated infection status by conventional blood smear light microscopy and semi-quantitative PCR-based strategies. Analysis of a longitudinal cohort constructed from our surveys showed that Duffy heterozygous (+/-) individuals were protected from Pv erythrocyte infection compared to those homozygous for wild-type alleles (+/+) (log-rank tests: LM, p = 0.049; PCR, p = 0.065). Evaluation of Pv parasitemia, determined by semi-quantitative PCR-based methods, was significantly lower in Duffy +/- vs. +/+ individuals (Mann-Whitney U: p = 0.023). Overall, we observed no association between susceptibility to P. falciparum erythrocyte infection and Duffy genotype. CONCLUSIONS: Our findings provide the first evidence that Duffy-negative heterozygosity reduces erythrocyte susceptibility to Pv infection. As this reduction was not associated with greater susceptibility to Pf malaria, our in vivo observations provide evidence that Pv-targeted control measures can be developed safely.

A Phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease.

BACKGROUND: As a potential disease-modifying treatment for Alzheimer disease (AD), 3-amino-1-propanesulfonic acid (3APS) is a compound that binds to amyloid beta (Abeta), a toxic protein known to aggregate, leading to amyloid plaque deposition in the brain. METHODS: We assessed the safety, tolerability, and pharmacokinetic/pharmacodynamic effect of 3APS in a randomized, double-blind, placebo-controlled Phase II study in which 58 subjects with mild-to-moderate AD were randomly assigned to receive placebo or 3APS 50, 100, or 150 mg BID for 3 months. At the end of the double-blind phase, 42 of these subjects entered an open-label phase in which they received 3APS 150 mg BID for 17 months. Assessments included plasma and CSF 3APS concentrations, CSF levels of Abeta (Abeta(40) and Abeta(42)), and total tau, as well as cognitive (Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination) and clinical (Clinical Dementia Rating scale-Sum of Boxes) measures. RESULTS: 3APS had no significant impact on vital signs or laboratory test values. The most frequent side effects were nausea, vomiting, and diarrhea, which were intermittent and mild to moderate in severity. Seven 3APS-treated subjects discontinued because of side effects (all causalities) over the course of the study, and there were no 3APS-related serious adverse events. 3APS crossed the blood-brain barrier, and dose-dependently reduced CSF Abeta(42) levels after 3 months of treatment. There were no psychometric score differences between groups over the 3-month double-blind period. CONCLUSION: Long-term administration of 3-amino-1-propanesulfonic acid is safe, tolerated and reduces CSF Abeta(42) levels in patients with mild-to-moderate Alzheimer disease.

Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis.

In Papua New Guinea (PNG), complex patterns of malaria commonly include single and mixed infections of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale. Here, we assess recent epidemiologic characteristics of Plasmodium blood-stage infections in the Wosera region through four cross-sectional surveys (August 2001 to June 2003). Whereas previous studies performed here have relied on blood smear/light microscopy (LM) for diagnosing Plasmodium species infections, we introduce a newly developed, post-polymerase chain reaction (PCR), semi-quantitative, ligase detection reaction-fluorescent microsphere assay (LDR-FMA). A direct comparison of the two methods for > 1,100 samples showed that diagnosis was concordant for > 80% of the analyses performed for P. falciparum (PF), P. vivax (PV), and P. malariae (PM). Greater sensitivity of the LDR-FMA accounted for 75% of the discordance between diagnoses. Based on LM, the prevalence of blood-stage PF, PV, and PM infections was found to be markedly reduced compared with an early 1990s survey. In addition, there were significant shifts in age distribution of infections, with PV becoming the most common parasite in children < 4 years of age. Consistent with previous studies, prevalence of all Plasmodium species infections increased significantly in samples analyzed by the PCR-based LDR-FMA. This increase was most pronounced for PM, PO, and mixed infections and in adolescent (10-19 years) and adult age groups, suggesting that LM may lead to under-reported prevalence of less common Plasmodium species, infection complexity, and a skewed distribution of infections towards younger age groups. This study shows that the application of LDR-FMA diagnosis in large epidemiologic studies or malaria control interventions is feasible and may contribute novel insights regarding the epidemiology of malaria.

Diagnosing infection levels of four human malaria parasite species by a polymerase chain reaction/ligase detection reaction fluorescent microsphere-based assay.

Improving strategies for diagnosing infection by the four human Plasmodium species parasites is important as field-based epidemiologic and clinical studies focused on malaria become more ambitious. Expectations for malaria diagnostic assays include rapid processing with minimal expertise, very high specificity and sensitivity, and quantitative evaluation of parasitemia to be delivered at a very low cost. Toward fulfilling many of these expectations, we have developed a post-polymerase chain reaction (PCR)/ligase detection reaction-fluorescent microsphere assay (LDR-FMA). This assay, which uses Luminex FlexMAP microspheres, provides simultaneous, semi-quantitative detection of infection by all four human malaria parasite species at a sensitivity and specificity equal to other PCR-based assays. In blinded studies using P. falciparum-infected blood from in vitro cultures, we identified infected and uninfected samples with 100% concordance. Additionally, in analyses of P. falciparum in vitro cultures and P. vivax-infected monkeys, comparisons between parasitemia and LDR-FMA signal intensity showed very strong positive correlations (r > 0.95). Application of this multiplex Plasmodium species LDR-FMA diagnostic assay will increase the speed, accuracy, and reliability of diagnosing human Plasmodium species infections in epidemiologic studies of complex malaria-endemic settings.

Why do we need to know more about mixed Plasmodium species infections in humans?

Four Plasmodium species cause malaria in humans. Most malaria-endemic regions feature mixed infections involving two or more of these species. Factors contributing to heterogeneous parasite species and disease distribution include differences in genetic polymorphisms underlying parasite drug resistance and host susceptibility, mosquito vector ecology and transmission seasonality. It is suggested that unknown factors limit mixed Plasmodium species infections, and that mixed-species infections protect against severe Plasmodium falciparum malaria. Careful examination of methods used to detect these parasites and interpretation of individual- and population-based data are necessary to understand the influence of mixed Plasmodium species infections on malarial disease. This should ensure that deployment of future antimalarial vaccines and drugs will be conducted in a safe and timely manner.

Development of a multiplex PCR-ligase detection reaction assay for diagnosis of infection by the four parasite species causing malaria in humans.

The diagnosis of infections caused by Plasmodium species is critical for understanding the nature of malarial disease, treatment efficacy, malaria control, and public health. The demands of field-based epidemiological studies of malaria will require faster and more sensitive diagnostic methods as new antimalarial drugs and vaccines are explored. We have developed a multiplex PCR-ligase detection reaction (LDR) assay that allows the simultaneous diagnosis of infection by all four parasite species causing malaria in humans. This assay exhibits sensitivity and specificity equal to those of other PCR-based assays, identifying all four human malaria parasite species at levels of parasitemias equal to 1 parasitized erythrocyte/microl of blood. The multiplex PCR-LDR assay goes beyond other PCR-based assays by reducing technical procedures and by detecting intraindividual differences in species-specific levels of parasitemia. Application of the multiplex PCR-LDR assay will provide the sensitivity and specificity expected of PCR-based diagnostic assays and will contribute new insight regarding relationships between the human malaria parasite species and the human host in future epidemiological studies.

Stereoselective in vitro degradation pattern of mivacurium in human plasma.

BACKGROUND: Mivacurium is a mixture of three isomers, two of which are rapidly broken down in vivo by plasma cholinesterases. This study investigates the stereospecificity of mivacurium in vitro degradation to determine if it accounts for its in vivo behaviour. METHODS: The in vitro rate of degradation of each isomer of mivacurium and the in vitro rate of formation of their primary (monoesters and alcohols) and secondary (alcohols) metabolites were examined using human plasma from six healthy volunteers. The in vitro rate of degradation of the monoester metabolites was also assessed. All these determinations were made using a stereospecific high-performance liquid chromatography assay. RESULTS: The in vitro rate of disappearance of the two active isomers of mivacurium was very rapid, with mean values for the trans trans and cis trans isomers of 0.803 and 0.921 min(-1) respectively. These values are twofold faster than published in vivo data. The in vitro rate of disappearance was much slower for the cis cis isomer, with a mean value of 0.0106 min(-1). The cis trans isomer was converted exclusively to cis monoester and trans alcohol, while only metabolites in the trans and cis configuration were found for the trans trans and cis cis isomers respectively. Mean in vitro rates of disappearance for the trans and cis monoester were 0.00750 and 0.000633 min(-1) respectively. CONCLUSIONS: The in vitro rates of hydrolysis of the active isomers of mivacurium confirm that plasma cholinesterases play a major role in their in vivo degradation, but that in vivo elimination is slowed by extravascular distribution. Mivacurium hydrolysis is stereoselective, the ester group in the trans configuration being more accessible to enzymatic attack. This stereoselective pattern, along with the relatively slow breakdown of the cis cis isomer, sheds light on the in vivo disposition of the cis alcohol metabolite.

A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C.

Interferon (IFN) therapy has been associated with the development of Major Depressive Disorder (MDD) when given to patients with hepatitis C (HCV). The incidence, time course, risk factors, and treatment of IFN-induced MDD are poorly understood. The objectives of the present study were to determine the incidence of IFN-induced MDD, as well as to determine the efficacy of open-label antidepressant treatment, in particular selective serotonin reuptake inhibitors (SSRIs) for IFN-induced MDD. Thirty-nine HCV patients on IFN therapy were monitored weekly using the Beck Depression Inventory (BDI). Those who became depressed were treated with citalopram, a SSRI antidepressant. Main outcome measures included the incidence of IFN-induced MDD, as well as response rates to antidepressants in those patients who developed IFN-induced MDD. Our results showed that 13 of 39 patients (33%) developed IFN-induced MDD. There were no differences in age, gender, past history of MDD, or substance use between those who became depressed and those who did not. However, there were significantly fewer African American patients in the depressed group. Patients who developed IFN-induced MDD were on IFN therapy for an average of 12.1 weeks prior to the development of MDD. Eleven of 13 patients (85%) were responsive to antidepressant treatment. We conclude that IFN-induced MDD is common in HCV patients. Health care providers should follow IFN-treated HCV patients for the development of MDD, particularly between the 2nd and 5th months of IFN therapy. SSRIs, in particular citalopram, are an effective treatment for IFN-induced depression in HCV patients.