Processes and outcomes of training on rapid assessment and response methods on injecting drug use and related HIV infection in the Russian Federation

In September 1997, Médecins Sans Frontières-Holland (MSF-H) began a project to provide training and support for HIV/AIDS prevention among injecting drug users (IDUs) in the Russian Federation, focusing on the use of the World Health Organization Rapid Assessment and Response Guide on Injecting Drug Use, and the European Peer Support Manual. As part of the training, participants are asked to carry out a rapid situation assessment (RSA) in their city or region as a major step towards designing and implementing an effective program to prevent HIV transmission among IDUs. This paper focuses on the first four training cycles of the programme (from January 1998 to January 1999), in which 89 health professionals and others from 32 Russian cities took part. A total of 28 rapid situation assessments were completed or almost completed by participants during these four cycles. The paper provides an overview of the methods used and major problems faced by participants undertaking these assessments, as well as summarising the 14 harm reduction programmes which resulted.     

X-linked retinoschisis: novel mutation in the initiation codon of the XLRS1 gene in a large family

PURPOSE: To describe a novel point mutation in the initiation codon of the XLRS1 gene in a large family and the clinical features of males affected with X-linked juvenile retino-schisis. METHODS: Genealogic investigation and mutation screening of the XLRS1 gene were performed for a 4-generation family consisting of 72 members. Affected males were evaluated clinically between 1986 and 2004 with up to 18 years of follow-up. RESULTS: We identified a novel point mutation (1A>T transversion) in the initiation codon of the XLRS1 gene in affected males resulting in an amino acid substitution of methionine to leucine (Met1Leu), therefore abolishing the translation initiation Met codon. CONCLUSION: Identification of the disease-causing mutation in this family with long-term follow-up allows for earlier and more accurate identification of individuals at risk for this inherited progressive macular degeneration, provides for more accurate genetic counseling, and contributes to our understanding of the pathophysiology of this disorder.     

Integrating QOL assessments for clinical and research purposes

QOL questionnaires can be a useful tool for patients, clinicians, and researchers. Although each has a different goal and investment in the data, each of these perspectives can contribute to truly collaborative care in which the needs of the patient are met.     

PAC fixed dose: pharmacokinetics of a 1-hour paclitaxel infusion and comparison to BSA-normalized drug dosing

BACKGROUND: The aim of this study was to determine the pharmacokinetics (PKs) of a 175-mg fixed dose of paclitaxel (PAC) after a 1-h infusion in cancer patients and to compare them with the PK parameters from a study with a dose normalized to the body surface area (BSA) (100 mg/m2). PATIENTS AND METHODS: PAC PKs were studied during the first course of therapy in 13 patients. A fixed dose of 175 mg PAC was administered weekly by a 1-h infusion to patients with advanced cancer. Total PAC in serum was quantified by high-performance liquid chromatography (HPLC). PK parameters were calculated by non-compartmental and model-dependent methods. RESULTS: The mean BSA of 12 patients (1 patient excluded from all analyses because of prolonged infusion duration) was 1.79 m2 (coefficient of variation (CV) 7.8%), the mean dose referred to the individual BSAs was 98.3 mg/m2 (CV 8.3%). The mean area under the curve (AUC) was 6,193 ng/ml x h (CV 46%), the mean plasma clearance (Clp) was 19.7 l/h/m2 (CV 45%), and the volume of distribution at steady state (Vss) was 121.6 l/m2 (CV 52%). The mean residence time (MRT) was 7.6 h (CV 46%), the mean distribution half-life (t1/2 alpha) of PAC(tot) was 0.4 h (CV 62%), and the elimination half-life (t1/2 beta) 10.0 h (CV 42%). Maximum plasma concentration Cmax was 3,161 ng/ml (CV 36%). The mean time above 0.05 microM (42.7 ng/ml) was 19.7 h, and the mean time above 0.1 microM (85.4 ng/ml) was 10.6 h. CONCLUSIONS: In this study, a fixed dose of PAC of 175 mg corresponds to a mean BSA-normalized dose of 98.3 mg/m2 (range 88.8-117.4 mg/m2). A higher variability of PK parameters was observed compared to previously published results of a PK study with BSA-normalized dosing of 100 mg/m2. However, the AUC and the time above threshold concentrations did not depend on the dose. Therefore, a fixed dose of 175 mg weekly could be an option for palliative treatment with PAC and may offer a simple but effective schedule for PAC treatment.     

Etoposide pharmacokinetics in children treated for acute myeloid leukemia

We studied the pharmacokinetics of etoposide in 45 children treated for newly diagnosed acute myeloid leukemia. Etoposide, 100 mg/m body surface area/24 h, was administered by 96-h continuous intravenous infusion. Concomitantly, the children received cytarabine 200 mg/m/24 h by intravenous infusion and 6-thioguanine 100 mg/m twice daily orally. Median total body clearance in children 0.5-1.8 (n=4) and 2.3-17.7 years old (n=36) without Down's syndrome was 17.1 and 17.6 ml/min/m, respectively (P=0.96). Five children with Down's syndrome had a median clearance of 13.6 ml/min/m (P=0.067 compared with non-Down's syndrome children). Eighteen of the children received a second identical treatment course 3-4 weeks later; there was a significant correlation between individual clearance values (rho=0.56; P=0.017). We found no significant correlation between etoposide pharmacokinetics and the remission rate or the relapse rate. In conclusion, our findings indicate that special dose-calculation guidelines for infants above 3 months old are not substantiated by age-dependent pharmacokinetics of etoposide. Down's syndrome children might be candidates for dose reduction if our data are confirmed in larger numbers of patients. Low course-to-course variability indicates that pharmacokinetically guided dosing of etoposide might be clinically relevant, if larger studies can demonstrate that this approach decreases toxicity or increases response rates.     

Doxorubicin pharmacokinetics is correlated to the effect of induction therapy in children with acute myeloid leukemia

We studied the pharmacokinetics of doxorubicin in 41 children treated for newly diagnosed acute myeloid leukemia. Doxorubicin, 75 mg/m2 body surface area, was administered by constant i.v. infusion over 8 h. Four children with Down's syndrome (DS), 1.2-2.3 years old, had a median total body clearance of 523 ml/min/m2. The median clearance in non-DS children, 0.6-1.8 years old (n = 4) and 2.5-17.7 years old (n = 33), was 446 and 538 ml/min/m2, respectively. Patients who went into complete remission (CR) after induction therapy had a significantly higher median plasma concentration of doxorubicin than those who did not, 249 compared with 180 ng/ml, respectively (P = 0.036; analysis restricted to non-DS patients). Doxorubicin plasma concentration was an independent factor for CR, both in univariate (P = 0.031) and multivariate analysis including sex, age and white blood cell count at diagnosis (P = 0.021). Patients who reached CR had a significantly lower doxorubicin clearance than those who did not, 513 and 657 ml/min/m2, respectively (P = 0.017). In conclusion, doxorubicin plasma concentration and total body clearance during up-front treatment were correlated to the effect of induction therapy. Prospective studies should be performed to confirm the concentration-effect relationship and explore the possibility of therapeutic monitoring.     

Quality of life of caregivers of patients with advanced-stage cancer

There has been much research documenting the impact of having a loved one diagnosed with advanced cancer, but little is known about how to reduce care-giver burden. In this randomized controlled trial, the authors examined the potential relationship of an advanced cancer patient's participation in an 8-session, structured, multidisciplinary intervention on the care-giver's burden and quality of life (QOL). Although the patients randomly assigned to the intervention (n = 54) demonstrated improved QOL compared to the control condition (n = 49) participants (P < .05), there was no evidence that improving the patient's QOL made an impact on the caregiver's level of burden or the care-giver's QOL. Further investigation is warranted in this area, including interventions specifically designed and targeted to both reduce caregiver burden and to improve caregiver QOL.     

Provision of contraceptive and related services by publicly funded family planning clinics, 2003

CONTEXT: In addition to contraceptive services, publicly funded family planning clinics provide low-income women with a range of reproductive diagnostic, treatment and educational services. Nationally representative information about the scope of services available from clinics is needed to formulate policy and programmatic recommendations. METHODS: In 2003, more than 1,000 U.S. clinics responded to an eight-page survey on service availability and clinic policies. Differences in the proportions of clinics reporting each service or policy were examined by clinic type and receipt of Title X funding. RESULTS: Nearly all clinics offer pills, injectables and condoms; 75% offer the patch; and 80% offer emergency contraception. Most clinics (73%) typically use a conventional Pap smear for initial cervical cancer screenings; 27% use liquid-based Pap tests. For follow-up, 68% of clinics use liquid-based or other advanced testing. Virtually all clinics screen at least some clients for chlamydia; Planned Parenthood and Title X-funded clinics, more than others, tend to focus screening efforts on sexually active women aged 25 and younger. Single-dose treatments are provided by 58% of clinics. Nine in 10 clinics offer HIV testing on-site, most of them to any client who requests it. Services targeted to specific populations include counseling about abstinence for minors (91%); non-reproductive health services for men (36%); and availability of staff such as translators (81%) and bilingual administrative (59%) or clinical personnel (57%) for non-English-speaking clients. CONCLUSIONS: More public funding is imperative for clinics to keep up with the demands of new technologies and a diverse client base.