Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case–Control Study

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case–control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09–90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08–10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04–339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63–456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.     

The Effects of Bariatric Procedures on Bowel Habit

Background

Bariatric procedures are increasingly being used to combat the rising obesity epidemic. The aim of this study was to assess the effect of these interventions on bowel habit.

Methods

We recruited obese adults listed for a bariatric procedure. Demographic data, medical history, medications and anthropometric measurements were recorded. Bowel habit was characterized using a 7-day Bristol Stool Form Scale (BSFS) diary. A validated food frequency questionnaire (FFQ) was used to assess diet.

Results

Twenty-six patients were assessed pre-operatively and at a median of 6.4 months post-operatively. Nineteen had a Roux-en-Y gastric bypass (RYGB), five had a sleeve gastrectomy (SG) and two had an intra-gastric balloon (IGB) with median percentage excess weight loss (% EWL) of 67.9, 52.4 and 31.3 %, respectively. Dietary fibre intake decreased from 24.4 (±12.1) g/day pre-operatively to 17.5 (±7.3) g/day post-operatively (P?=?0.008). Frequency of bowel motions decreased from 8.6 (±3.5) to 5.7 (±3.5) motions/week (P?=?0.001). Mean usual BSFS score decreased (towards firmer stool) from 4.1 (±1.3) pre-operatively to 3.1 (±1.9) post-operatively (P?=?0.016). Constipation increased from 8 to 27 %, but this did not reach statistical significance (P?=?0.125).

Conclusions

Constipation is a common problem after bariatric surgery. The decrease in bowel motion frequency and change towards firmer stools suggest prolonged intestinal transit time after bariatric procedures. Reduction in dietary fibre intake is likely to be a contributory factor.

     

Postoperative Analgesia Due to Sustained-Release Buprenorphine,Sustained-Release Meloxicam,and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus)

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day–1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity–but not thermal hypersensitivity–on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR—but not Melox-SR or CG—effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.Abbreviations: Bup HCl, buprenorphine HCl; Bup-SR, sustained-release buprenorphine; CG, carprofen gel; Melox-SR, sustained-release meloxicamPostoperative analgesia is a vital aspect of laboratory animal medicine. Investigators have a responsibility to follow an effective and safe pain management protocol for research animals that have undergone surgical procedures. Pain and distress are serious animal welfare concerns that directly affect animal physiology and can result in altered research data.^1,17,30 Continued refinement of pre-, intra-, and postoperative pain management in rodents is necessary to improve animal wellbeing, obtain high-quality research data, and ensure compliance with standards set forth by the Guide for the Care and Use of Laboratory Animals.²¹Many classes of analgesics are available to veterinary practitioners, but in the laboratory setting, the options tend to be simpler and typically involve 1 of 2 drug classes, opioids and NSAID. Buprenorphine HCl (Bup HCl), a partial μ-opioid receptor agonist, has long been the ‘gold standard’ for postoperative analgesia in laboratory animals due to the drug''s prolonged plasma half-life and effective analgesic properties.^15,28 Buprenorphine effectively controls mild to moderate postoperative pain in rodents for 6 to 12 h.¹⁶ Because many rodent surgical procedures might cause pain for at least 48 h, researchers must handle these animals at least twice daily during this time period to readminister buprenorphine. Repeated dosing requires frequent handling of surgically manipulated animals, resulting in handling-associated stress.¹ In addition, handling an animal frequently likely is disruptive to its cagemates and potentially to animals in the same room. Because of their analgesic and antiinflammatory properties, NSAID are often used either in conjunction with or as an alternative to opioids to control pain in laboratory animals.^11,33 Meloxicam and carprofen are 2 NSAID that preferentially inhibit cyclooxygenase 2 and thus prostaglandin synthesis.^10,11 Although generally considered safe, reported side effects of NSAID include gastrointestinal ulceration, altered platelet function, and renal dysfunction.¹¹Novel formulations of opioid and NSAID analgesics have recently been introduced to the veterinary market and include sustained-release injectables,^2,5,14,22 gel-based oral compounds,^6,19 and transdermal patches.^13,18,25,37 Our group previously demonstrated the effectiveness of sustained-release buprenorphine (Bup-SR) in controlling mild to moderate incisional pain in rats.⁷ Another study found that Bup-SR successfully controlled orthopedic surgical pain in rats.¹⁴ These alternative formulations show great potential in decreasing the stress associated with frequent handling and dosing requirements. Many of these products are still considered new in the veterinary market, and few evidence-based recommendations for their use in laboratory animal species are available. The main goal of the current study was to refine postoperative analgesia by using longer-lasting or gel-formulation products. To this end, we investigated whether Bup-SR, sustained-release meloxicam (Melox-SR), or carprofen gel (CG) provided postoperative analgesia in the rat plantar incisional model according to results of behavioral testing. We hypothesized that Bup-SR, Melox-SR, and CG would provide effective postoperative analgesia as evidenced by reduced pain responses in this model.     

Junior staffing changes and the temporal ecology of adverse incidents in acute psychiatric wards

AIM: This paper reports an examination of the relationship between adverse incident rates, the arrival of new junior staff on wards, and days of the week on acute psychiatric wards. BACKGROUND: Incidents of violence, absconding and self-harm in acute inpatient services pose risks to patients and staff. Previous research suggests that the arrival of inexperienced new staff may trigger more adverse incidents. Findings on the relationship between incidents and the weekly routine are inconsistent. METHOD: A retrospective analysis was conducted of formally reported incident rates, records of nursing student allocations and junior doctor rotation patterns, using Poisson Regression. Variance between days of the week was explored using contingency table analysis. The data covered 30 months on 17 psychiatric wards, and were collected in 2002-2004. FINDINGS: The arrival of new and inexperienced staff on the wards was not associated with increases in adverse incident rates. Most types of incidents were less frequent at weekends and midweek. Incident rates were unchanged on ward-round days, but increased rates were found on the days before and after ward rounds. CONCLUSION: Increased patient tension is associated with raised incident rates. It may be possible to reduce incident rates by moderating stimulation in the environment and by mobilizing support for patients during critical periods.     

Management of access to branded psychotropic medications in private health plans

BACKGROUND: In the past decade, health insurers have increased their reliance on cost control policies such as prior authorization and 3-tier formularies. Little is known about how these policies are being applied to psychotropic medications, many of which have low rates of patient adherence. OBJECTIVE: This study reports on plans' cost-sharing tier placement and authorization policies for 12 brand only psychotropic medications in 3 classes: antidepressants, anti-psychotics, and medications for attention deficit/hyperactivity disorder (ADFID). METHODS: Data were from a nationally representative survey of private health plans regarding mental health and substance-abuse services in 2003; 368 plans responded (83% response rate). Results were weighted and represent national estimates of health-plan characteristics. RESULTS: The majority of insurance products provided unrestricted placement on Tier 2 (medium copayment) for at least 2 brand-only antidepressants and at least 2 brand-only antipsychotics. This approach allows clinicians some limited leeway in initial medication selection. However, most patients who did not respond to the Tier-2 options typically faced a substantial escalation in copayment (Tier 3), possibly leading to premature medication discontinuation. For ADHI)5 the options were considerably more limited, with 22.1% of products applying some restriction to all 3 medications and only 15.9% of products leaving all 3 medications unrestricted. Plans with specialty contracts for mental health were considerably more likely to use Tier 3 (highest copayment) as their only restriction approach. CONCLUSIONS: Based on the results of this analysis,private plans were managing psychotropic costs using copayment incentives rather than administrative controls. This approach was less intrusive for clinicians, but resulting higher copayments could worsen already high rates of nonadherence; future research should examine this issue.     

Suspension culture of separated follicles consisting of differentiated thyroid epithelial cells

We have prepared thyroid follicles in suspension culture to use as a model system in vitro for investigation of some properties of the thyroid gland. The follicles were free of endothelial cells, fibroblasts, and other nonepithelial cells. They were prepared by collagenase treatment of minced rat thyroid glands followed by differential filtration of the suspension through nylon meshes. Small clusters of principal thyroid epithelial cells were separated from large fragments and single cells. They were cultured in dilute suspension in Coon's modified F-12 medium in dishes coated with agarose to avoid having the cells attach to the dishes. By culture day 3, most of the clusters formed closed follicles containing a periodic acid-Schiff-positive colloid but without a basal lamina. Follicle walls contained an occasional C cell. The epithelium resembled that in the thyroid of a recently hypophysectomized rat, with normal polarity and organelle complement normal with respect to position and abundance, with basally located lysosomes, no pseudopods, and no colloid droplets. The cells were responsive to thyroid-stimulating hormone (thyrotropin) and to dibutyryl cyclic AMP. Thyroid-stimulating hormone at 10 munits/ml resulted in apical migration of lysosomes and formation of pseudopods and colloid droplets within 30 min; longer exposure resulted in depletion of luminal colloid. The results indicate that the suspended follicles resemble follicles in vivo with respect to morphology and responsiveness to thyroid-stimulating hormone in the absence of other cell types.     

Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5

Hyperphosphorylation of microtubule-associated proteins such as tau and neurofilament may underlie the cytoskeletal abnormalities and neuronal death seen in several neurodegenerative diseases including Alzheimer's disease. One potential mechanism of microtubule-associated protein hyperphosphorylation is augmented activity of protein kinases known to associate with microtubules, such as cdk5 or GSK3beta. Here we show that tau and neurofilament are hyperphosphorylated in transgenic mice that overexpress human p25, an activator of cdk5. The p25 transgenic mice display silver-positive neurons using the Bielschowsky stain. Disturbances in neuronal cytoskeletal organization are apparent at the ultrastructural level. These changes are localized predominantly to the amygdala, thalamus/hypothalamus, and cortex. The p25 transgenic mice display increased spontaneous locomotor activity and differences from control in the elevated plus-maze test. The overexpression of an activator of cdk5 in transgenic mice results in increased cdk5 activity that is sufficient to produce hyperphosphorylation of tau and neurofilament as well as cytoskeletal disruptions reminiscent of Alzheimer's disease and other neurodegenerative diseases.     

A refined protocol for coding nursing home residents' comments during satisfaction interviews

OBJECTIVE: This study's objective was to refine a method for coding nursing home (NH) residents' comments about their perceptions of care into unmet needs specific to the manner and frequency of care delivery. METHODS: NH residents (N=69) were interviewed with both closed-ended (i.e., forced-choice) and open-ended (i.e., residents' own words) questions about their perceptions of care across eight care domains. Unmet needs included comments indicating that residents desired a change in staff- and non-staff-related care. Staff-related unmet needs were further coded into unmet emotional support (i.e., emotional support or manner of care delivery) and instrumental (i.e., instrumental support or frequency of care) needs. RESULT: Of 66 residents who commented, 66% expressed at least one unmet need across eight care domains. Among these 44 residents, 52% and 84% had unmet emotional support and instrumental support needs, respectively (kappa=68 and.92). An additional 18% expressed both unmet emotional support and instrumental support needs. DISCUSSION:The refined method offers a systematic way to code residents' comments about their care into unmet needs related to the manner and frequency of care delivery. The findings have direct implications for the identification of care areas in need of improvement from the resident's perspective and the evaluation of improvement efforts.