Pharmacokinetics and safety of antimicrobial agents during pregnancy

The use of antimicrobial agents during pregnancy poses unique concerns because of both potential toxicity and special pharmacokinetic considerations that have important therapeutic implications for both mother and fetus. Various physiologic adaptations occur with advancing gestation, including marked increases in maternal intravascular volume, glomerular filtration, and hepatic and metabolic activities; thinning and maturation of the fetomaternal membrane; and increases in transplacental diffusion capacity. The net result is that maternal antimicrobial concentrations tend to be 10%-50% lower in late pregnancy and the immediate postpartum period than in the nonpregnant state. Placental transfer of antimicrobial agents and their excretion in amniotic fluid or breast milk are similarly affected by hemodynamic changes, membrane transport characteristics, and maturation or metabolic activity of the specific organs involved. Review of the literature suggests that, although the need for caution in the use of antimicrobial agents during pregnancy has been well emphasized, firm data on the pharmacokinetics, efficacy, and optimal use of these drugs in this situation are extremely sparse and urgently needed. However, recommendations regarding the use of specific antibacterial, antifungal, antiviral, and antiparasitic agents against selected infections during pregnancy can be made.     

The association between HLA genes and radiological erosions in Malaysian patients with rheumatoid arthritis

Objective: To assess the relationship between the HLA-DRB1 genes with disease severity as assessed by radiological erosions in Malaysian patients with rheumatoid arthritis (RA).

Methods: In this cross-sectional study, we studied 61 RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1 genotyping was performed by sequence specific primer (SSP)—PCR. Radiological grading and erosive score of the hands and wrists was calculated according to the Larsen–Dale method. Demographic data and treatment given to the patients were obtained from their case records.

Results: Fifty-six females and five males were studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE) in 31%. The median delay in starting DMARDs was 24 months. The presence of rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated with a worse erosive score. Patients who possessed the SE had a higher erosive scores, compared to those who did not (p = 0.05). Concurrently, a delay in starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348). However, after adjustment for the delay in starting DMARD, SE was no longer significantly associated with the erosive score.

Conclusions: In these patients, the delay in starting DMARDs had a greater influence on the erosive score than SE alone. Whilst we cannot discount the contribution of the SE presence, we would advocate early usage of DMARDs in every RA patient to reduce joint erosions and future disability.     

Reliability of Lateral Cephalometric Radiographs in the Assessment of the Upper Airway in Children: A Retrospective study

ObjectivesTo test the reliability of Lateral cephalometric radiographs (LCRs) for use in the assessment of the upper airway, hyoid bone, soft palate, and tongue.Materials and MethodsThe records of 57 healthy Chinese children from a nonhospital population (mean age = 12.6 years, SD = 0.5, 28 males and 29 females) who received two consecutive LCRs in the natural head posture were retrospectively analyzed. Fifteen linear, angular, and area measurements were used to describe the airway, hyoid bone, soft palate, and tongue. The reliability between the two LCRs was assessed with the intraclass correlation coefficient (ICC) and F-test. Errors were estimated with the Dahlberg and Bland-Altman method, and intra- and inter-assessor agreements were determined.ResultsMeasurements of upper airway and hyoid bone had excellent method reliability, intra-assessor reliability, and inter-assessor reliability (ICC > 0.8). However, the method reliability and the inter-assessor reliability for soft palate and tongue was less favorable (ICC from 0.60 to 0.96). Soft palate area and thickness were the most critical parameters. Intra-assessor reliability was greater than both method reliability and inter-assessor reliability (which were similar).ConclusionsThe measurement of upper airway morphology, defined as the intramural space, and of the hyoid bone position were highly reliable on LCRs of children. However, the limited reliability in the assessment of tongue and soft palate area may compromise the diagnostic application of LCRs to these structures.     

Early Changes in Liver Distribution Following Implementation of Share 35

In June 2013, a change to the liver waitlist priority algorithm was implemented. Under Share 35, regional candidates with MELD ≥ 35 receive higher priority than local candidates with MELD < 35. We compared liver distribution and mortality in the first 12 months of Share 35 to an equivalent time period before. Under Share 35, new listings with MELD ≥ 35 increased slightly from 752 (9.2% of listings) to 820 (9.7%, p = 0.3), but the proportion of deceased‐donor liver transplants (DDLTs) allocated to recipients with MELD ≥ 35 increased from 23.1% to 30.1% (p < 0.001). The proportion of regional shares increased from 18.9% to 30.4% (p < 0.001). Sharing of exports was less clustered among a handful of centers (Gini coefficient decreased from 0.49 to 0.34), but there was no evidence of change in CIT (p = 0.8). Total adult DDLT volume increased from 4133 to 4369, and adjusted odds of discard decreased by 14% (p = 0.03). Waitlist mortality decreased by 30% among patients with baseline MELD > 30 (SHR = 0.70, p < 0.001) with no change for patients with lower baseline MELD (p = 0.9). Posttransplant length‐of‐stay (p = 0.2) and posttransplant mortality (p = 0.9) remained unchanged. In the first 12 months, Share 35 was associated with more transplants, fewer discards, and lower waitlist mortality, but not at the expense of CIT or early posttransplant outcomes.