Peritoneal pharmacokinetics of cefepime in laparotomy patients with inflammatory bowel disease,and dosage considerations for surgical intra-abdominal infections based on pharmacodynamic assessment

This study aimed to examine the peritoneal pharmacokinetics of cefepime and to assess its pharmacodynamic exposure in peritoneal fluid (PF). Cefepime (1 g) was administered to eight patients with inflammatory bowel disease before abdominal surgery. Venous blood and PF samples were obtained at the end of the 0.5-h infusion and at 1, 2, 3, 4, 5, and 6 h thereafter. Drug concentrations in plasma and PF were determined, analyzed pharmacokinetically, and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. Cefepime penetrated well into PF, with a maximum drug concentration in a PF/plasma ratio of 0.59 ± 0.15 (mean ± SD, n = 8), and an area under the concentration-time curve ratio of 0.90 ± 0.10. The probabilities of attaining the bacteriostatic and bactericidal targets (40% and 70% of the time above the MIC, respectively) in PF were ≥85% against Escherichia coli, Klebsiella species, and Enterobacter cloacae with 0.5 g every 12 h, 1 g every 12 h, 1 g every 8 h, and 2 g every 12 h. However, 1 g every 8 h or 2 g every 12 h was required for bacteriostatic and bactericidal probabilities ≥85% against Pseudomonas aeruginosa. These conventional regimens did not achieve a high probability against Bacteroides species. These results should help to give us a better understanding of the peritoneal pharmacokinetics of cefepime while also helping to choose the appropriate dosage to prevent surgical intra-abdominal infections on the basis of the pharmacodynamic assessment.     

N-octyl-O-sulfate chitosan-modified liposomes for delivery of docetaxel: Preparation,characterization, and pharmacokinetics

A N-octyl-O-sulfate chitosan (NOSC) anchored liposome system was developed as the carrier for antitumor drug, docetaxel (DTX). The physicochemical and pharmacokinetic properties of NOSC-modified DTX liposomes (NDLs) were evaluated compared with the conventional DTX liposomes (DLs) and commercial dosage form of DTX, Taxotere^®. The results showed that NDLs had DTX-loading rate of 3.41%, entrapment efficiency of 61.73%, narrow distributed particle size of 147.6 ± 1.9 nm, and high zata potential of −44.2 ± 3.9 mV. The decreased permeability of the liposome bilayer was evaluated by release behavior of calcein (CAL) from the internal phase of NOSC-modified CAL liposomes (NCLs) and enhanced stability of NDLs owed to shielding effect of sulfonic shell from adsorption by BSA. After i.v. administration at the dose of 12 mg/kg, a significant increase in the AUC, MRT, and T_1/2β (P < 0.05) was observed in NDLs group compared with DLs and Taxotere^® group. AUC_0–∞ of NDLs was 6.14 and 1.55 times higher than Taxotere^® and DLs, respectively, and MRT_0–∞ of NDLs was 5.77 and 1.37 times higher than Taxotere^® and DLs, respectively. All these results suggested that anchored liposomes could increase the stability of DTX in vitro and in vivo, as compared with conventional liposomes and Taxotere^®. Therefore, NOSC as a polymeric shell to liposomes was effective to enhance the stability of liposomes containing DTX.     

血清降钙素原和C反应蛋白联合检测指导肺部疾病患者抗菌药物应用的临床意义

目的：探讨血清降钙素原(PCT)与 C 反应蛋白(CRP)联合检测对肺部疾病患者抗菌药物临床应用的指导意义。方法选取2012年10月至2014年10月肺部疾病患者130例,随机分为观察组与对照组,各65例。观察组患者根据血清 PCT 与CRP 水平确定是否选用抗菌药物,对照组患者根据白细胞计数进行确定。比较治疗后两组患者的抗菌药物应用情况、临床治疗效果及患者住院时间等观察指标。结果观察组患者抗菌药物治疗时间[(8.6±0.4)d]少于对照组[(16.2±2.3)d],差异有统计学意义(P <0.05)。治疗后,两组患者白细胞计数、肺功能状态评分、病情加重患者百分比及病死率比较差异均无统计学意义(P >0.05);而与对照组比较,观察组患者住院时间缩短,二重感染率降低,差异均有统计学意义(P <0.05)。结论联合检测PCT 与 CRP 可指导肺部疾病患者合理选择抗菌药物进行治疗,能够有效防止二次感染,提高临床治疗效果。     

Use of ciprofloxacin versus use of aminoglycosides for therapy of complicated urinary tract infection: prospective, randomized clinical and pharmacokinetic study.

The efficacy of oral ciprofloxacin was compared with that of parenteral aminoglycoside for therapy of complicated urinary tract infection in a prospective randomized trial. The setting was a chronic-care Veterans Administration facility in which long-term bladder catheterization and resistant bacteria were common. Sixty-five consecutive patients were stratified for presence and type of bladder catheter, the presence of Providencia and Pseudomonas aeruginosa organisms versus other urinary pathogens, and renal dysfunction. A pharmacokinetic study of ciprofloxacin concentrations in serum and urine was performed with selected patients. Urinary catheters were present in 94%. All patients were symptomatic, and 58.5% had fever. Ciprofloxacin, 500 mg every 12 h orally, was compared with parenteral aminoglycoside for 7 to 10 days. Clinical response, defined by resolution of symptoms and fever at 5 to 9 days posttherapy (short-term) and 28 to 30 days posttherapy (long-term), was essentially identical for both treatment groups. Bacteriologic response, defined by sterile urine cultures, showed that ciprofloxacin was significantly more efficacious (P = 0.0005) than aminoglycoside at 5 to 9 days posttherapy. However, by 28 to 30 days, the response rate was essentially identical. Emergence of resistance to the study antibiotic was seen in 62 and 70% of those who did not show a bacteriological response and were receiving ciprofloxacin and aminoglycosides, respectively. Concentrations of ciprofloxacin and aminoglycoside in the urine substantially exceeded the MIC for the urinary pathogens isolated, although these concentrations did not correlate with short-term bacteriologic response for either antibiotic. Ciprofloxacin was efficacious in complicated urinary tract infection compared with the current standard of parenteral aminoglycoside among catheterized patients with relatively resistant bacteria.     

Evaluation of in vitro antibacterial activity of enoxacin: comparison with other orally absorbed antimicrobial agents, proposed disk diffusion test interpretive criteria, and quality control limits

The antibacterial activity of enoxacin was assessed by a standard microdilution susceptibility test method against 6,096 consecutive clinical isolates at four clinical laboratories and compared with that of norfloxacin and cefaclor. Its activity was comparable to that of norfloxacin; both inhibited over 90% of Enterobacteriaceae at 0.5 micrograms/ml. Resistance to enoxacin [minimum inhibitory concentration (MIC) greater than 4 micrograms/ml] was observed in only 18 of 4,076 Enterobacteriaceae (0.5%, 36 of 650 nonfermentative gram-negative bacilli (5.5%), and 6 of 836 staphylococci (0.7%). Relatively poor activity was observed against streptococci. An additional 618 selected clinical isolates were tested with enoxacin and were compared with nine other orally absorbed antimicrobial agents. The greatest activity was observed with enoxacin, norfloxacin, and cotrimoxazole, but some difference were noted with individual species. Results of enoxacin disk diffusion susceptibility testing of 487 isolates were correlated with the MICs, analyzed, and interpretive criteria were determined. With MIC breakpoints of: susceptible = less than or equal to 2.0 micrograms/ml, intermediate = 4.0 micrograms/ml, and resistant = greater than 4.0 micrograms/ml, the corresponding preliminary disk diffusion zone diameter breakpoints for the 10-micrograms enoxacin disk are: susceptible greater than or equal to 18 mm, intermediate 15-17 mm, and resistant less than or equal to 14 mm. Quality control zone diameter limits were determined for three standard QC organisms.     

Energy-sparing systems for use in medicine: Past,present and future solutions

Summary. Implantable devices for medical use like permanent pacemakers, defibrillators and fluid pumps depend on energy provided by batteries. Unfortunately, the battery usually determines the duration of life of these devices, while technical problems occur infrequently. Replacement due to battery exhaustion requires surgical procedures and accounts for up to one-third of all pacemakers sold. Attempts to provide unlimited power support using radio transmission, nuclear energy, etc., did not gain clinical acceptance. We therefore evaluated the potential role of a microgenerator (designed for use in wrist watches) to recharge pacemaker batteries. We used the EPSON-SEIKO Caliber 5M22 that uses a ‘Gold-Cap’ for energy storage. The mass of the actuator is 1.6 g and an angle of >10° is needed to overcome friction. Output at a rotor frequency of 200 Hz is 1.8 mW. To measure the power provided, various experiments were made with the microgenerator taped to the chest of a normal person working in an office. A typical wearing experiment over a working day resulted in 0.9 to 6.1 μW. By taking a bridge rectifier into account, 12.2μW were delivered. The demands of a pacemaker are 34.3μW. Thus, this commercially available, yet not optimized microgenerator provides already approximately one-third of the power requirements of a pacemaker, making a ‘lifetime warranty’ for implanted devices a possibility for the future.     

'Lavender retirement': a questionnaire survey of lesbian, gay and bisexual people's accommodation plans for old age

A global increase in older people will also mean an increase in the numbers of lesbian, gay and bisexual people requiring residential support. All health practitioners working with older people need to be aware of the existence of older lesbian, gay and bisexual people in order to provide health care that is appropriate. This study describes lesbian, gay and bisexual people's accommodation plans for old age through a cross-sectional quantitative survey design. Participants were recruited through mainstream and lesbian, gay and bisexual media and venues. A total of 2269 participants completed the 133-item survey. When asked about what accommodation plans they had for their older years lesbian, gay and bisexual people identified that they were least likely to choose living in a retirement community/facility. However, if unable to live independently the majority of respondents identified they would prefer to live in a retirement facility that specifically catered for people who did not identify as heterosexual. This study has found that the residential support sector needs to be prepared to provide a health service that is person-centred, free from discriminatory practices and meets the needs of all health consumers regardless of sexual orientation.     

The human rhinovirus: human‐pathological impact,mechanisms of antirhinoviral agents,and strategies for their discovery

As the major etiological agent of the common cold, human rhinoviruses (HRV) cause millions of lost working and school days annually. Moreover, clinical studies proved an association between harmless upper respiratory tract infections and more severe diseases e.g. sinusitis, asthma, and chronic obstructive pulmonary disease. Both the medicinal and socio‐economic impact of HRV infections and the lack of antiviral drugs substantiate the need for intensive antiviral research. A common structural feature of the approximately 100 HRV serotypes is the icosahedrally shaped capsid formed by 60 identical copies of viral capsid proteins VP1‐4. The capsid protects the single‐stranded, positive sense RNA genome of about 7,400 bases in length. Both structural as well as nonstructural proteins produced during the viral life cycle have been identified as potential targets for blocking viral replication at the step of attachment, entry, uncoating, RNA and protein synthesis by synthetic or natural compounds. Moreover, interferon and phytoceuticals were shown to protect host cells. Most of the known inhibitors of HRV replication were discovered as a result of empirical or semi‐empirical screening in cell culture. Structure–activity relationship studies are used for hit optimization and lead structure discovery. The increasing structural insight and molecular understanding of viral proteins on the one hand and the advent of innovative computer‐assisted technologies on the other hand have facilitated a rationalized access for the discovery of small chemical entities with antirhinoviral (anti‐HRV) activity. This review will (i) summarize existing structural knowledge about HRV, (ii) focus on mechanisms of anti‐HRV agents from synthetic and natural origin, and (iii) demonstrate strategies for efficient lead structure discovery. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 42–92, 2010     

A behavioral approach to adolescent cannabis use: Accounting for nondeliberative,developmental, and temperamental factors

Most behavioral models examine adolescent health risk behaviors using a reflective, deliberate social–psychological framework. In this study, adolescent cannabis use is investigated via an expanded social–psychological model of behavioral decision-making: the Theory of Planned Behavior (TPB). The aim was to examine the contribution of nondeliberative (impulsivity), developmental (perceived parenting styles), and temperamental (moral norms, mental health, delinquency) factors in adolescent cannabis use. A longitudinal questionnaire with baseline and follow-up measurement (14-day interval) was used. Participants were Sixth Form College students (n = 199) aged 16–18 (mean age = 16.44, SD = ?0.55). At baseline (T1), demographics, TPB variables, and additional socio-psychological variables were measured. Fourteen days later (T2) self-reported cannabis use was measured. Logistic regression analyses indicated that the impulsivity subcomponent of lack of premeditation and moral norms predicted self-reported cannabis use behavior. Perceived parental rejection predicted cannabis use intentions. Adolescent cannabis use can be better understood through the expanding of behavioral models to account for nondeliberative, developmental, and temperamental factors. Drug education interventions should aim at developing self-instruction training programs teaching adolescents effortful thinking while family-based interventions should focus on encouraging open parent–adolescent communication which has shown to influence adolescents’ cannabis use.     

Acetylcholine receptors from normal human muscle: concentration, purification, and use in radioreceptor assays for autoantibodies

We measured the concentration of acetylcholine receptor (AChR) in various normal human muscles, obtained at autopsy, in order to find a more reliable and convenient source than the amputated leg muscle from diabetic patients for the isolation of AChR. We found that human calf muscle contains the highest concentration of AChR, approaching the concentration of receptor required for the radioreceptor assay for autoantibodies in myasthenia gravis (MG). Because the amount of contaminant proteins in the receptor preparations affect the sensitivity and precision of the assay, various chromatographic techniques were tested to improve the purity of the receptor preparation. We found that both G-100 Sephadex and DEAE Sephacel chromatographies were effective in removing contaminant proteins. DEAE Sephacel chromatography is particularly useful because the procedure provides higher recovery of receptor. Against the same pool of autoantibodies from patients with MG, AChRs from diabetic and normal leg muscle exhibit similar affinities. We conclude that AChR from normal human calf muscle can be used in radioreceptor assays for measuring autoantibodies in patients with myasthenia gravis.     

Last three days of life in the hospital: a comparison of symptoms,signs and treatments in the young old and the oldest old patients using the Resident Assessment Instrument for Palliative Care

Background. Knowledge concerning the provision of end of life care to the oldest old hospitalised patients is deficient. Aims and objectives. To analyse whether there were differences in registered nurses’ documentation of the young old vs. the oldest old patients according to symptoms, clinical signs and treatment in the last 3 days of life. Design. Data were collected retrospectively in a cross‐sectional comparative study at a hospital between autumn 2007 and spring 2009. Methods. The study included 190 patients: 101 (65–84 years) and 89 (85+). Data were extracted from the patients’ electronic records using the Resident Assessment Instrument for Palliative Care (RAI‐PC). Results. Falls (OR = 4.01, 95% CI 1.47–10.90) and peripheral oedema (OR = 2.74, 95% CI 1.06–7.11) were significantly more frequent documented in the oldest old patients compared with the young old patients. Delirium was recorded in 15.3% of all patients. Conclusion. With the exception of more falls and peripheral oedema in the oldest old patients, this study showed no differences in symptoms and treatment between the young old and the oldest old patients. Delirium was poorly documented compared to other studies. Implications for practice. The oldest old patients have a higher risk of falls in the final phase of life, and fall prevention should be considered.     

Electronic health records: use, barriers and satisfaction among physicians who care for black and Hispanic patients

Objectives  Electronic health records (EHRs) are a promising tool to improve the quality of health care, although it remains unclear who will benefit from this new technology. Given that a small group of providers care for most racial/ethnic minorities, we sought to determine whether minority-serving providers adopt EHR systems at comparable rates to other providers.
Methods  We used survey data from stratified random sample of all medical practices in Massachusetts in 2005. We determined rates of EHR adoption, perceived barriers to adoption, and satisfaction with EHR systems.
Results  Physicians who reported patient panels of more than 40% black or Hispanic had comparable levels of EHR adoption than other physicians (27.9% and 21.8%, respectively, P  = 0.46). Physicians from minority-serving practices identified financial and other barriers to implementing EHR systems at similar rates, although these physicians were less likely to be concerned with privacy and security concerns of EHRs (47.1% vs. 64.4%, P  = 0.01). Finally, physicians from high-minority practices had similar perceptions about the positive impact of EHRs on quality (73.7% vs. 76.6%, P  = 0.43) and costs (46.9% vs. 51.5%, P  = 0.17) of care.
Conclusions  In a state with a diverse minority population, we found no evidence that minority-serving providers had lower EHR adoption rates, faced different barriers to adoption or were less satisfied with EHRs. Given the importance of ensuring that minority-serving providers have equal access to EHR systems, we failed to find evidence of a new digital divide.     

Triangulation for the assessment of clinical nursing skills: A review of theory, use and methodology

Aim

To review the use and usefulness of the methodological strategy of triangulation in the assessment of skill in nursing curricula.

Design

Systematic search of the literature relevant to the definition and assessment of skill, reliability and validity of assessment methods and triangulation of assessment strategies.

Data sources

One hundred and twenty papers from nursing, medical, educational and social scientific databases, relevant websites and relevant books were reviewed. Forty papers were included based on their relevance to the theory and methodology of clinical skills assessment of health care professionals, particularly nurses. Papers concerning vocational skills assessment and the assessment of skill in school children were excluded.

Results

There is a current imperative within the field of health care professional education to assess clinical skills and to quantify this assessment. However, clinical skill, as it relates to cognition, is poorly defined concept and may be viewed as a quality of the practitioner and, as such, is difficult to quantify. Very many methods of assessing clinical skill have been documented and there are inherent issues in ensuring both reliability and validity of these assessment strategies for clinical skill. This has led commentators to suggest that the process of triangulation should be employed.

Conclusions

The paper fundamentally questions whether the concept of triangulation can be applied to skills assessment without dependable measures of reliability and validity of the tools of assessment and concludes that the process of applying multiple modes of assessment should not be confused with the process of triangulation.     

Pilates for people with multiple sclerosis who use a wheelchair: feasibility,efficacy and participant experiences

Abstract

Purpose: This mixed methods study aimed to explore the feasibility, efficacy and the participants’ experiences of a Pilates programme for people with Multiple Sclerosis (pwMS) who use a wheelchair. Method: Fifteen pwMS took part in the 12-week Pilates programme. At baseline and after 6 and 12 weeks of the programme, sitting stability, measured as maximum progression of the Centre of Pressure when leaning sideways (COPmax), posture, pain on a Visual Analogue Scale, function, fatigue and the impact of MS (MSIS29) were assessed. Ten participants took part in two focus groups within six weeks of the completion of the programme. Results: Significant improvements at the 12-week assessment were found in COPmax (p?=?0.046), sitting posture (p?=?0.004), pain in the shoulders (p?=?0.005) and back (p?=?0.005) and MSIS29 (p?=?0.006). The majority of participants described various physical, functional, psychological and social benefits from participation that reflected increased confidence in activities of daily living. Enjoyment of the classes was expressed by all, and most wished to continue participation. Conclusions: Pilates appears to be efficacious in improving sitting stability and posture and decreasing pain and was also well tolerated by wheelchair users with MS. Further mixed methods studies are warranted.

• Implications for Rehabilitation

• Group-based core stability exercise or Pilates for people with MS who use wheelchair is a feasible and safe way of exercising for this patient group.

• Pilates exercises for people moderately to severely affected by MS resulted in a decrease in back and shoulder pain and improvement in sitting balance.

• Future appropriately powered randomised controlled studies into Pilates for people with MS reliant on wheelchair are warranted.

     

Outcome measures in physiotherapy management of patients with stroke: a survey into self‐reported use,and barriers to and facilitators for use

Objective . To investigate physiotherapists' self‐reported use of outcome measures as recommended in the Dutch Clinical Practice Guideline on Physiotherapy Management of Patients with Stroke (CPGPS) and to assess perceived barriers to and facilitators for the use of outcome measures in everyday practice. Method . A 41‐item survey, including the barriers and facilitators questionnaire (BFQ), was sent by post to 400 physiotherapists in each of the following settings in the Netherlands: acute care hospitals (ACH; n = 100), rehabilitation centres (RC; n = 100), nursing homes (NH; n = 100) and private physiotherapy practices (PPP; n = 100). Results . One hundred and eighty‐nine physiotherapists returned the survey (47%; ACH, n = 57; RC, n = 67; NH, n = 26 and PPP, n = 39) and the surveys of 167 physiotherapists involved in stroke settings were analysed. These physiotherapists reported regularly using three (median; range 0–7) of the seven recommended outcome measures, with those working in RC or ACH reporting a significantly higher use than their colleagues in PPP (4 vs. 0 and 3 vs. 0; p < 0.001 and p = 0.02, respectively). The BFQ revealed that there were setting‐specific facilitators, such as ‘a positive attitude towards outcome measures’ (as mentioned by 93% of the physiotherapists) and ‘acquaintance with outcome measures’ (90%), and barriers such as ‘changing routines’ (32%), ‘time investment’ (29%) and ‘financial compensation’ (21%). Conclusion . Despite an almost uniformly positive attitude, physiotherapists infrequently use the outcome measures recommended in the CPGPS. Robust setting‐specific tailored implementation strategies based on the reported barriers and facilitators are needed. Copyright © 2008 John Wiley & Sons, Ltd.     

Assistive devices and community-based services among 85-year-old community-dwelling elderly in The Netherlands: Ownership,use,and need for intervention

Objective.?To assess the home-situation of the oldest old regarding the ownership, use, and need for intervention of assistive devices and community-based services.

Methods.?A research nurse and an occupational therapist, who evaluated the current situation regarding ownership and use of assistive devices, visited a representative group of 147 Dutch community-dwelling 85-year-olds in their own homes. Furthermore, the occupational therapist assessed whether an intervention was indicated. Assistance in purchasing devices, information, and instruction were provided when necessary.

Results.?94% of the subjects owned one or more assistive devices, with a mean of 4.5 (SD 2.7) assistive devices. Most frequently owned were grab rails. Of the total number of 591 assistive devices, 74 (13%) were not in use. In 66 of the 147 (45%) subjects at least one intervention was indicated. A total number of 23 subjects received information and instruction on mobility-related issues, while 17 subjects received information and instruction on personal care-related issues. Moreover, for 19 subjects an application procedure was started for a total of 25 assistive devices and five community-based services in the mobility category while for 19 subjects an application procedure was started for a total of 31 devices and four services in the personal care category.

Conclusions.?Based on detailed information from occupational therapists, the home situation of community-dwelling elderly regarding the presence and use of assistive devices and community-based services is not optimal.     

Current perspectives on the treatment of venous thromboembolism: need for effective, safe and convenient new antithrombotic drugs

Treatment of venous thromboembolism (VTE) has evolved significantly over the last decade. Low-molecular-weight heparins have largely replaced unfractionated heparin in the treatment of deep-vein thrombosis (DVT) but the majority of patients with pulmonary embolism (PE) continue to be treated with unfractionated heparin. Fondaparinux is the first synthetic selective inhibitor of factor Xa. It has recently been proved to be more effective than, and as safe as, a low-molecular-weight heparin for the prevention of VTE after major orthopaedic surgery. The two large randomised MATISSE trials demonstrated that fondaparinux was at least as effective and as safe as previous reference heparin therapies in the treatment of VTE. Fondaparinux should further simplify the treatment of this frequent disease since a single once-daily fixed dosage regimen may effectively and safely treat both DVT and PE, an important point especially considering the frequent though clinically silent concomitance of these two thrombotic events.     

Current status of mechanical circulatory support for treatment of advanced end-stage heart failure: successes,shortcomings and needs

Introduction: Heart failure (HF) remains a major global burden in terms of morbidity and mortality. Despite advances in pharmacological and resynchronization device therapy, many patients worsen to end-stage HF. Although the gold-standard treatment for such patients is heart transplantation, there will always be a shortage of donor hearts.

Areas covered: A left ventricular assist device (LVAD) is a valuable option for these patients as a bridge measure (to recovery, to candidacy for transplant, or to transplant itself) or as destination therapy. This review describes the current indications for and complications of the most commonly implanted LVADs. In addition, we review the potential and promising new LVADs, including the HeartMate 3, MVAD, and other LVADs. Studies investigating each were identified through a combination of online database and direct extraction of studies cited in previously identified articles.

Expert commentary: The goal of LVADs has been to fill the gap between patients with end-stage HF who would likely not benefit from heart transplantation and those who could benefit from a donor heart. As of now, the use of LVADs has been limited to patients with end-stage HF, but next-generation LVAD therapy may improve both survival and quality of life in less sick patients.