Infections in baricitinib clinical trials for patients with active rheumatoid arthritis.

Objectives: To evaluate the incidence of infection in patients with active rheumatoid arthritis (RA) treated with baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor.

Methods: Infections are summarised from an integrated database (8 phase 3/2/1b clinical trials and 1 long-term extension (LTE)) with data to 1 April 2017. The 'all-bari-RA' analysis set included patients who received any baricitinib dose.

Effects of results-based financing of maternal and child health services on patient satisfaction in Afghanistan.

Objective: To examine the impact of a results-based financing programme on patient satisfaction in Afghanistan.

Methods: We analysed data collected from over 3000 patients from a stratified sample of 112 health facilities (56 results-based financing and 56 non-results-based financing) in 11 out of the 34 provinces of Afghanistan over a three-year period. The 112 facilities were part of 442 primary care facilities that were stratified on facility type and randomly assigned to the results-based financing (intervention) and non-results-based financing (control) groups in the 11 provinces.

Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment.

Objective: Baricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA). We evaluated baricitinib's safety profile through 288 weeks (up to September 1, 2016) with an integrated database [8 phase III/II/Ib trials, 1 longterm extension (LTE)].

Methods: The "all-bari-RA" group included patients who received any baricitinib dose.

Mothering at a Distance: what incarcerated mothers value about a parenting programme.

Background: Children with incarcerated mothers experience adverse health, social and emotional circumstances, and are a particularly vulnerable group. Mothers in custody face significant challenges in parenting their children.

Aims: The study aimed to identify participants' views on impact of a parenting support programme for incarcerated mothers in NSW Australia.

Longitudinal change in coronary heart disease risk factors in older runners.

Background: it is currently not clear how coronary heart disease (CHD) risk factors change over time in chronic exercisers. Therefore, the purpose of this study is to describe the longitudinal change in CHD risk factors in chronically endurance-trained men and women, and to determine the exercise and nutritional factors associated with those respective changes.

Methods And Results: ninety-one middle-aged runners (56 male, 35 female) were tested on two occasions approximately 10 years apart (aged 50.

Clinical safety of the selective PKC-beta inhibitor, ruboxistaurin.

The aim of this manuscript is to report the safety profile of patients treated with ruboxistaurin mesylate (RBX; LY333531), a selective protein kinase C-beta (PKC-beta) inhibitor, for up to 4 years. Data from patients with diabetes (1396 RBX 32 mg/day; 1408 placebo) were combined from 11 placebo-controlled, double-masked studies. The proportion of patients who reported one or more serious adverse events was greater in the placebo group than in the RBX-treated group (23.

2,3,4,5-tetrahydro- and 2,3,4,5,11,11a-hexahydro-1H-[1,4]diazepino[1,7-a]indoles: new templates for 5-HT(2C) agonists.

The design and synthesis of the novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole 5 is described. This azepinoindole has excellent affinity for 5-HT(2C) (K(i) 4.8 nM) and modest selectivity over 5-HT(2A) ( approximately 4-fold).

Longitudinal analysis of lactate threshold in male and female master athletes.

Purpose: The lack of relationship between lactate threshold (LT) and running performance in older runners, and the increase in LT with age, has not been previously studied in a longitudinal design. We evaluated the cross-sectional and longitudinal changes in LT with age and compared the changes in LT with changes in performance variables.

Methods: Fifty-one male and 23 female runners (39-77 yr) performed two graded treadmill exercise tests with minute-by-minute venous blood lactate analysis, separated by 5.

Functional selectivity of dopamine receptor agonists. I. Selective activation of postsynaptic dopamine D2 receptors linked to adenylate cyclase.

Dihydrexidine (DHX), the first high-affinity D(1) dopamine receptor full agonist, is only 10-fold selective for D(1) versus D(2) receptors, having D(2) affinity similar to the prototypical agonist quinpirole. The D(2) functional properties of DHX and its more D(2) selective analog N-n-propyl-dihydrexidine (PrDHX) were explored in rat brain and pituitary. DHX and PrDHX had binding characteristics to D(2) receptors in rat striatum typical of D(2) agonists, binding to both high- and low-affinity sites and being sensitive to guanine-nucleotides.

Relationship between physiological loss, performance decrement, and age in master athletes.

Background: The use of master athletes to describe an idealized rate of physiological loss associated with aging is quite common. The results of such studies suggest that older athletes may be able to reduce the rate of decline in functional loss. The findings of such studies have been questioned due to their limited sample size and the age range and gender of their subjects.

Maximal aerobic power, lactate threshold, and running performance in master athletes.

Purpose: This study sought to determine how lactate threshold (LT) is related to running performance in older male and female runners, if LT changes significantly with age, and if gender alters the relationship between LT and performance in older runners.

Methods: Subjects were 168 master runners (111 men, 57 women) selected from a longitudinal study, who ran at least 10 miles x wk(-1) for 5 yr or more. VO2max was measured on a treadmill and body composition by hydrostatic weighing.

Reboxetine: a pharmacologically potent, selective, and specific norepinephrine reuptake inhibitor.

Background: Reboxetine is a potent antidepressant, with efficacy comparable to that of imipramine, desipramine, and fluoxetine, and has improved side-effect profile. The basis of its efficacy and improved tolerability is sought through studies of reboxetine in a number of pharmacological models of depression.

Methods: Pharmacological selectivity for uptake systems was defined by uptake and binding assays for the three monoamine uptake sites.

The inability of hormone replacement therapy or chronic running to maintain bone mass in master athletes.

Background: Previous studies have demonstrated equivocal findings on the effect of chronic running on bone mass in post-menopausal women. The purpose of this study was to determine the effect of chronic running alone and in conjunction with hormone replacement therapy (HRT) on bone mineral density (BMD) in postmenopausal women.

Methods: Forty-three women [15 premenopausal 48.

Excitation of type II anterior caudate neurons by stimulation of dopamine D3 receptors.

Previous studies have demonstrated that both direct- and indirect-acting dopamine (DA) receptor agonists excite type II neurons in the anterior caudate (CN) by stimulation of DA receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes). In the present study, pramipexole, a D3-preferring DA agonist effective in treating Parkinson's disease, excited type II anterior CN neurons. As with other direct-acting agonists, excitation of the CN neurons occurred only at doses above those that silenced DA neurons in the substantia nigra pars compacta (SNPC).

Synthesis and biological activities of (R)-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine and its metabolites.

The imidazoquinoline (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine [(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and oxidation to (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(1H) -one [(R)-6], intermediate metabolites, where N-demethylation to the imidazoquinoline (R)-4 and where oxidation to the imidazoquinolinone (R)-5 has taken place, are also observed in these incubates. A cross-species study on the metabolism of (R)-3 in vitro has shown large variations in the extent of metabolism from species to species.

Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor-preferring agonist: comparison to other dopamine receptor agonists.

Pramipexole, an amino-benzathiazole [(S)-4,5,6,7-tetrahydro-N-6-propyl-2, 6-benzothiazolediamine dihydrochloride monohydrate] direct-acting dopamine receptor agonist effective in treating Parkinson's disease, bound selectively and with high affinity to dopamine D2-like receptors, with highest affinity at dopamine D3 receptors. Ergot dopamine receptor agonists (bromocriptine, lisuride, pergolide) bound to both dopamine and non-dopamine receptors. Although all agonists depressed dopamine neuron firing, only pramipexole and quinpirole completely silenced firing when administered in slowly-accumulating doses.

Excitation of type II caudate neurons by systemic administration of dopamine agonists.

Using chloral hydrate anesthetized rats, dopamine (DA) agonists were evaluated for their systemic effects on firing rates of DA neurons in rat substantia nigra pars compacta (SNPC) and postsynaptic type II neurons in the anterior caudate nucleus (CN), the major projection area for SNPC DA neurons. Intravenous injections of the indirect DA agonist D-amphetamine, but not L-amphetamine, excited spontaneously active CN neurons by a haloperidol-sensitive mechanism. Doses to achieve CN excitation were similar to those required to inhibit SNPC firing.

Sensitive and specific radioimmunoassay for fialuridine: initial assessment of pharmacokinetics after single oral doses to healthy volunteers.

Fialuridine (FIAU) is a halogen-substituted analog of thymidine that was undergoing clinical investigation as a drug for the treatment of chronic hepatitis B viral infection. However, clinical trials of FIAU were terminated after adverse events occurred following chronic oral administration. Prior to the termination of clinical trials, a sensitive assay was needed for the measurement of FIAU because of the anticipated low dose administered to patients.

Loracarbef (LY163892) versus cefaclor and norfloxacin in the treatment of uncomplicated pyelonephritis.

Optimal therapy for pyelonephritis requires the immediate administration of an effective broad-spectrum antibiotic. Because conventional oral antibiotics such as the sulfonamides and the aminopenicillins are limited by the development of resistant bacteria associated with this common disease, the therapeutic effectiveness of a new oral carbacephem antibiotic was investigated. Two double-blind, randomized clinical trials of loracarbef (LY163892) were conducted.

Efficacy and safety of loracarbef in the treatment of pneumonia.

The treatment of bacterial pneumonia requires an agent with activity against a wide range of bacterial pathogens, including pathogens that produce beta-lactamase. Loracarbef, a member of the carbacephem class of antibiotics, was tested in a series of clinical trials for its efficacy and safety in the treatment of lobar and bronchial bacterial pneumonia. Successful clinical responses were achieved in 97.

Loracarbef (LY163892) versus amoxicillin/clavulanate in bronchopneumonia and lobar pneumonia.

In a single-blind study, 134 patients with bronchopneumonia or lobar pneumonia were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for 10 to 14 days. Treatment efficacy was evaluated in 38 patients treated with loracarbef and in 39 treated with amoxicillin/clavulanate in whom pre-treatment positive cultures of pathogens susceptibile to the study drugs were isolated. Streptococcus pneumoniae and Haemophilus influenzae were cultured as single pathogens in 40.