The clinical pharmacokinetics of the novel antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717)

Summary The pharmacokinetics of the new antifolate CB 3717 were studied in 20 patients during its phase-I clinical evaluation. The drug was administered at doses of 100–550 mg/m² in 1-h and 12-h infusions, resulting in peak plasma concentrations of CB 3717 of 40–200 M. There was a linear relationship between the dose and both CB 3717 AUC and peak plasma levels. Following a 1-h infusion, drug levels in the plasma decayed biphasically (t_1/2=49±9 min, t_1/2=739±209 min). 27%±2% of the dose was excreted in urine in the 24-h period after treatment, suggesting that the major route of elimination was via the bile. Furthermore, the parent compound CB 3717 and its desglutamyl metabolite, CB 3751, were found in a faecal collection although the metabolite was not detected in plasma or urine samples. Plasma protein binding of CB 3717 was extensive (97.6%±0.1%). Significant quantities of CB 3717 penetrated into ascitic fluid but not into cerebrospinal fluid.Residual drug was detected in postmortem kidney tissue from a patient who died of progressive disease 8 days after treatment with 330 mg/m² CB 3717. Thus, dose-limiting renal toxicity (maximum tolerated dose 600 mg/m²) may be due to drug precipitation in the renal tubules. Elevation of liver enzymes, in particular transaminases, occurred frequently as a toxic manifestation of CB 3717 therapy. In 11 patients studied after their first treatment there was a positive correlation between the rise in serum alanine transaminase and peak drug levels (r=0.69, P=0.02)These pharmacokinetic studies have shown that, by analogy with experimental systems, cytotoxic plasma levels of CB 3717 are archieved in man. In addition, they have been valuable in interpreting toxicities observed during phase-I clinical studies.This work was supported by grants from the Medical Research Council and Cancer Research Campaign, U. K.     

Partial interruption of the inferior vena cava using the 2612 filter. Apropos of 35 patients

Partial interruption of inferior vena cava (I.C.V.) forms an integral part of treatment of thromboembolic disease. The most frequently used filter worldwide is currently that of Greenfield, but although its effectiveness and permeability are remarkable it can be the subject of transfixions, sliding movements and migrations. A new model of the authors' own conception is presented which eliminates these faults. The "2612" filter is based on the same concepts, but has added to it 6 lateral flanges soldered to the base of the arms, these applying pressure to the I.V.C. and ensuring its perfect positioning, and 12 hooks (6 turned downwards and 6 upwards) ensuring perfect stability. Results of a multicentre trial in 35 patients, after insertion of the "2612" filter and follow up assessment after 3 months (28 cases) by cavography and in some patients by a scan, showed permeability of 93% and total efficacy. No side effects were reported. This filter appears to represent true progress in the means of interrupting I.V.C., and further studies are contemplated.     

Nutrient Intake in Children 4–13 Years Old in Ibadan,Nigeria

The paucity of adequate data on dietary and nutrient intakes of school-age children is a barrier to addressing malnutrition and associated risks in Nigeria. This study included 955 children aged 4–13 years from Ibadan, Nigeria, using a stratified random sampling design. Information on family socio-demographic characteristics was reported, and child anthropometrics were measured. Dietary intake data were collected using a multi-pass 24 h dietary recall method; 20% of subjects completed a second 24 h recall to estimate usual nutrient intakes. Means and distributions of usual intakes of energy and nutrients as well as prevalence of inadequacy were estimated. Usual energy intake (kcal/day) was 1345 and 1590 for younger (4–8 years) and older (9–13 years) age groups, respectively. The macronutrient intakes of most children did not conform to Adequate Macronutrient Distribution Ranges (AMDRs), which were characterized by a higher proportion of energy from carbohydrates and lower proportion from total fats. Protein intake was largely within the AMDR. Compared to recommendations, over 60% of 4–8-year-old children had inadequate intakes of calcium, copper, iron, folate, and vitamins A, D, and E. There were more micronutrient inadequacies in the older children. This study identifies nutrition gaps and suggests future research and education to improve child nutrition in Nigeria.     

Longitudinal Examination of Prenatal Tobacco Switching Behaviors and Birth Outcomes,Including Electronic Nicotine Delivery System (ENDS) and Dual Use

Maternal and Child Health Journal - In the US, approximately 8% of pregnant women smoke, and 5–11.9% currently use ENDS products. The health effects of ENDS use are debated; however, most...     

Views about integrating smoking cessation treatment within psychological services for patients with common mental illness: A multi‐perspective qualitative study

BackgroundTobacco smoking rates are significantly higher in people with common mental illness compared to those without. Smoking cessation treatment could be offered as part of usual outpatient psychological care, but currently is not.ObjectiveTo understand patient and health care professionals'' views about integrating smoking cessation treatment into outpatient psychological services for common mental illness.DesignQualitative in‐depth interviews, with thematic analysis.ParticipantsEleven Improving Access to Psychological Therapies (IAPT) psychological wellbeing practitioners (PWPs), six IAPT patients, and six stop smoking advisors were recruited from English smoking cessation, and IAPT services.ResultsPatients reported psychological benefits from smoking, and also described smoking as a form of self‐harm. Stop smoking advisors displayed therapeutic pessimism and stigmatizing attitudes towards helping people with mental illness to quit smoking. PWPs have positive attitudes towards smoking cessation treatment for people with common mental illness. PWPs and patients accept evidence that smoking tobacco may harm mental health, and quitting might benefit mental health. PWPs report expertise in helping people with common mental illness to make behavioural changes in the face of mood disturbances and low motivation. PWPs felt confident in offering smoking cessation treatments to patients, but suggested a caseload reduction may be required to deliver smoking cessation support in IAPT.ConclusionsIAPT appears to be a natural environment for smoking cessation treatment. PWPs may need additional training, and a caseload reduction. Integration of smoking cessation treatment into IAPT services should be tested in a pilot and feasibility study.Patient or public contributionService users and members of the public were involved in study design and interpretation of data.     

Variation in Self-Perceived Fecundity among Young Adult U.S. Women

BackgroundIndividuals’ perceptions of their fecundity, or biological ability to bear children, have important implications for health behaviors, including infertility help-seeking and contraceptive use. Little research has examined these perceptions among U.S. women.MethodsThis cross-sectional study examines perceptions of one's own fecundity among U.S. women aged 24 to 32 who participated in the 2009–2011 rounds of the National Longitudinal Survey of Youth (1997) cohort. Analyses were limited to 3,088 women who indicated that they or their partners never received a doctor's diagnosis regarding fertility difficulties.ResultsOf the women in the sample, 67% perceived their hypothetical chances of becoming pregnant as very likely; the remainder perceived their chances as somewhat likely (13%), not as likely (15%), or provided a “don't know” response (6%). Twenty-six percent of Black women and 19% of Latina women perceived themselves as not very likely to become pregnant, compared with only 12% among non-Black/non-Latina women (p < .001). Only 6% of women with a college degree perceived their chances of becoming pregnant as not very likely, compared with 36% among women without a high school degree (p < .001). Racial/ethnic and educational differences persisted in fully adjusted models. Other factors associated with fecundity self-perceptions include partnership status, parity, fertility expectations, sexual activity, prolonged exposure to unprotected intercourse for at least 6 and/or 12 months without becoming pregnant, and self-rated health.ConclusionsFindings indicate that self-perceived fecundity differs systematically by demographic and other characteristics. This phenomenon should be investigated further to understand how it may influence disparities in health behaviors and outcomes.     

Treatment of infants with ureteropelvic junction obstruction: findings from the PURSUIT network

International Urology and Nephrology - Studies based on administrative databases show that infant pyeloplasty is associated with minority race/ethnicity but lack clinical data that may influence...     

A Web-Based Interactive Patient-Provider Software Platform Does Not Increase Patient Satisfaction or Decrease Hospital Resource Utilization in Total Knee and Hip Arthroplasty Patients in a Single Large Hospital System

BackgroundWeb-based platforms used to enhance patient-provider communication are being explored to improve patient satisfaction and care delivery, and decrease cost. This study tested a web-based interactive patient-provider software platform (IPSP), JointCOACH, which enabled patient communication with their care team and preparatory/recovery guidance. The aims of this study are to compare (1) patient satisfaction and (2) healthcare resource utilization by patients who underwent total knee and hip replacements and added IPSP to standard of care (SOC).MethodsThis study is a prospective, randomized clinical trial at a single large academic healthcare system. Between May 2018 and March 2020, 399 patients undergoing elective total hip or knee arthroplasty were randomized to SOC arm (n = 204) or SOC + IPSP arm (n = 195). Patient demographics, surgical details, and comorbidities were collected. Patient satisfaction was assessed using Visual Analog Scale and the Picker Patient Experience-15. Healthcare utilization was measured using length of stay, emergency department and office visits, office calls, readmissions, and reoperations at 30 and 90 days after surgery.ResultsNo difference was found in length of stay between SOC and SOC + IPSP. No differences were found in 30-day or 90-day satisfaction or in healthcare resource utilization (P > .05) including number of office and emergency department visits, phone calls, and readmissions.ConclusionStatistical differences were not found in satisfaction and healthcare utilization with the addition of IPSP to SOC. IPSP can be used to reinforce patient education and communication between the patient and provider, and should be evaluated as an element of virtual care rather than supplementing traditional in-office follow-up.Clinicaltrials.govMore information on this study can be found at clinicaltrials.gov NCT03499028.     

Health Service Use and Quality of Life Recovery 12 Months Following Major Osteoporotic Fracture: Latent Class Analyses of the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS)

Major osteoporotic fractures (MOFs) are associated with a rapid decline in health-related quality of life (HRQoL); however, there is limited knowledge about which healthcare services positively affect HRQoL postfracture. This study aimed to identify specific combinations of health service use associated with recovery of HRQoL 12 months post-MOF. The analyses included 4126 adults aged ≥50 years with an MOF (1657 hip, 1354 distal forearm, 681 vertebrae, 434 humerus) participating in the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS), a multinational observational study (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, United Kingdom, and United States). HRQoL at prefracture and 12 months postfracture was measured using the EuroQoL questionnaire (EQ-5D-3L). Health service use data were collected via participant interviews and medical record reviews including in-hospital care; outpatient care; community services; and medication use. Data analyses involved two stages: (i) latent class analyses to identify different combinations of health service use (“classes”); and (ii) logistic regression to assess effects of classes on HRQoL recovery. Analyses were repeated excluding hip fractures (non-hip MOFs). Overall, 2057 MOF participants (49.9%) recovered to their prefracture HRQoL at 12-month follow-up; this proportion was higher for non-hip MOFs (n = 1439; 58.3%). Several distinct classes were identified across countries (range, 2–5 classes). Classes that were associated with increased odds of HRQoL recovery were characterized by a combination of hospital presentations without admission; outpatient department visits; allied health visits; vitamin D/calcium supplementation; and/or non-opioid analgesic use. Similar classes were observed for non-hip MOFs. Understanding country-specific healthcare service pathways that influence greater recovery of HRQoL, particularly services that are uncommon in some countries and routine in others, could improve postfracture care on a global scale. © 2020 American Society for Bone and Mineral Research (ASBMR).