A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults

Background. Invasive Candida infection among nonneutropenic, critically ill adults is a clinical problem that has received increasing attention in recent years. Poor performance of extant diagnostic modalities has promoted risk-based, preemptive prescribing in view of the poor outcomes associated with inadequate or delayed antifungal therapy; this risks unnecessary overtreatment. A rapid, reliable diagnostic test could have a substantial impact on therapeutic practice in this patient population.

Methods. Three TaqMan-based real-time polymerase chain reaction assays were developed that are capable of detecting the main medically important Candida species, categorized according to the likelihood of fluconazole susceptibility. Assay 1 detected Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida dubliniensis. Assays 2 and 3 detected Candida glabrata and Candida krusei, respectively. The clinical performance of these assays, applied to serum, was evaluated in a prospective trial of nonneutropenic adults in a single intensive care unit.

Results. In all, 527 specimens were obtained from 157 participants. All 3 assays were run in parallel for each specimen; they could be completed within 1 working day. Of these, 23 specimens were obtained from 23 participants categorized as having proven Candida infection at the time of sampling. If a single episode of Candida famata candidemia was excluded, the estimated clinical sensitivity, specificity, and positive and negative predictive values of the assays in this trial were 90.9%, 100%, 100% and 99.8%, respectively.

Conclusions. These data suggest that the described assays perform well in this population for enhancing the diagnosis of candidemia. The extent to which they may affect clinical outcomes, prescribing practice, and cost-effectiveness of care remains to be ascertained.

Abstract: Psychometric properties of two self-report clinical competence scales for nursing students.

Abstract: Psychometric properties of two self-report clinical competence scales for nursing students.
Background: It is important to assess the clinical competence of nursing students to gauge their professional development and educational needs. This can be measured by self-assessment tools. Anema and McCoy (2010) contended that the currently available measures need further psychometric testing.
Aim: To test the psychometric properties of Nursing Competencies Questionnaire (NCQ) and Self-Efficacy in Clinical Performance (SECP) clinical competence scales.

Method: A non-randomly selected sample of n=248 2nd year nursing students completed NCQ, SECP and demographic questionnaires (June and September 2013). Mokken Scaling Analysis (MSA) was used to test the structural validity and scale properties, convergent and discriminant validity and reliability were subsequently tested.

Results: The NCQ provided evidence of a unidimensional scale which had strong scale scalability coefficients Hs =0.581; but limited evidence of item rankability HT =0.367. MSA undertaken with the SECP scale identified two potential unidimensional scales the SECP28 and SECP7, each with adequate evidence of good/reasonable scalablity psychometric properties as a summed scale but no/very limited evidence of scale rankability (SECP28: Hs = 0.55, HT=0.211; SECP7: Hs = 0.61, HT=0.049). Analysis of between cohort differences and NCQ/ SECP scale scores produced evidence of convergent and discriminant validity and good internal reliability: NCQ α = 0.93, SECP28 α = 0.96, and SECP7 α=0.89.

Discussion: The NCQ was verified to have evidence of reliability and validity; however, as the SECP findings are new, and the sample small, with reference to Straat and colleagues (2014), the SECP results should be interpreted with caution and verified on a second sample.

Conclusions: Measurement of perceived self-competence could inform the development of nursing competence and could start early in a nursing programme. Further testing of the NCQ and SECP scales with larger samples and from different years is indicated.


References:
Anema, M., G and McCoy, JK. (2010) Competency-Based Nursing Education: Guide to Achieving Outstanding Learner Outcomes. New York: Springer.
Straat, JH., van der Ark, LA and Sijtsma, K. (2014) Minimum Sample Size Requirements for Mokken Scale Analysis Educational and Psychological Measurement 74 (5), 809-822.

Testing the psychometric properties of two self-report clinical competence scales for nursing students.

Background: It is important to assess the clinical competence of nursing students to gauge their educational needs. Competence can be measured by self-assessment tools; however, Anema and McCoy (2010) contend that currently available measures should be further psychometrically tested.
Aim: To test the psychometric properties of Nursing Competencies Questionnaire (NCQ) and Self-Efficacy in Clinical Performance (SECP) clinical competence scales.
Method: A non-randomly selected sample of n=248 2nd year nursing students completed NCQ, SECP and demographic questionnaires (June and September 2013). Mokken Scaling Analysis (MSA) was used to investigate structural validity and scale properties; convergent and discriminant validity and reliability were also tested for each scale.
Results: MSA analysis identified that the NCQ is a unidimensional scale with strong scale scalability coefficients Hs =0.581; but limited item rankability HT =0.367. The SECP scale MSA suggested that the scale could be potentially split into two unidimensional scales (SECP28 and SECP7), each with good/reasonable scalablity psychometric properties as summed scales but negligible/very limited scale rankability (SECP28: Hs = 0.55, HT=0.211; SECP7: Hs = 0.61, HT=0.049). Analysis of between cohort differences and NCQ/SECP scores produced evidence of discriminant and convergent validity; good internal reliability was also found: NCQ α = 0.93, SECP28 α = 0.96 and SECP7 α=0.89.

Discussion: In line with previous research further evidence of the NCQ’s reliability and validity was demonstrated. However, as the SECP findings are new and the sample small with reference to Straat and colleagues (2014), the SECP results should be interpreted with caution and verified on a second sample.
Conclusions: Measurement of perceived self-competence could start early in a nursing programme to support students’ development of clinical competence. Further testing of the SECP scale with larger nursing student samples from different programme years is indicated.

References:
Anema, M., G and McCoy, JK. (2010) Competency-Based Nursing Education: Guide to Achieving Outstanding Learner Outcomes. New York: Springer.
Straat, JH., van der Ark, LA and Sijtsma, K. (2014) Minimum Sample Size Requirements for Mokken Scale Analysis Educational and Psychological Measurement 74 (5), 809-822.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

Physicochemical characterization and preliminary in vivo efficacy of bioadhesive, semisolid formulations containing flurbiprofen for the treatment of gingivitis

In this study, the physicochemical properties and preliminary in vivo clinical performance of formulations containing hydroxyethylcellulose (HEC; 3, 5, 10% w/w, poly(vinylpyrrolidone) (PVP; 3, 5% w/w), polycarbophil (PC; 1, 3, 5% w/w), and flurbiprofen (5% w/w) were examined. Flurbiprofen release into PBS pH 7.4 was performed at 37 degrees C. The mechanical properties (hardness, compressibility, adhesiveness, initial stress) and syringeability of formulations were determined using a texture analyzer in texture profile analysis (TPA) and compression modes, respectively. In general, the time required for release of 10 and 30% of the original mass of flurbiprofen (t(10%), t(30%)) increased as the concentration of each polymeric component increased. However, in the presence of either 5 or 10% HEC and 5% PC, increased PVP concentration decreased both t(10%), t(30%) due to excessive swelling land disintegration) of these formulations. Increased concentrations of HEC, PVP, and PC significantly increased formulation hardness, compressibility, work of syringe expression, and initial stress due to the effects of these polymers on formulation viscoelasticity. Similarly, increased concentrations of PC (primarily), HEC, and PVP increased formulation adhesiveness-due to the known bioadhesive properties of these polymers. Clinical efficacies of formulations containing 3% HEC, 3% PVP, 3% PC, and either 0% (control) of 5% (test) flurbiprofen, selected to offer optimal drug release and mechanical properties, were evaluated and clinically compared in an experimental gingivitis model. The test (flurbiprofen-containing) formulation significantly reduced gingival inflammation, as evaluated using the gingival index, and the gingival crevicular fluid volume, whereas, these clinical parameters were generally increased in volunteers who had received the control formulation. There were no observed differences in the plaque indices of the two subject groups, confirming that the observed differences in gingival inflammation could not be accredited to differences in plaque accummulation. This study has shown both the applicability of the in vitro methods used, particularly TPA, for the rational selection of formulations for clinical evaluation and, additionally, the clinical benefits of the topical application of a bioadhesive semisolid flurbiprofen-containing formulation for the treatment of experimental gingivitis.

Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers

This study examined the mechanical/textural, viscoeiastic and mucoadhesive properties of a range of aqueous gels composed of either hydroxyethylcellulose (HEC) or sodium carboxymethylcellulose (Na CMC). The mechanical/textural properties of each formulation were determined using texture profile analysis. The viscoelastic properties of each formulation were examined over a defined frequency range (0.01-1.0 Hz) using oscillatory rheometry in conjunction with stainless steel parallel plate geometry. The mucoadhesive properties of the gels were evaluated by measuring the tensile force required to overcome the gel/mucin adhesive interaction. Both gel hardness and compressibility, properties that affect the ease of product removal from a container and spreadability, increased as a function of increasing polymer concentrations. This is attributed to the effects of HEC and Na CMC on gel viscosity. Gel adhesiveness, a property related to bioadhesion, also increased as a function of polymer concentration and is attributed to the reported adhesive nature of these polymers. Increasing frequency of oscillation increased the storage and loss moduli yet decreased bath the dynamic viscosity of each gel type and also the loss tangent of HEC (but not Na CMC) gels. Therefore, following exposure to the range of oscillatory stresses that may be expected in vivo, HEC gels will be more susceptible than Na CMC gels to alterations in these rheological properties. Consequently, it would be expected that the clinical performance of HEC gels will be modified to a greater extent than Na CMC gels. In general, HEC gels exhibited a greater elastic nature than Na CMC gels over the frequency range employed for oscillation The storage and loss moduli and dynamic viscosity of both gel types increased, yet the loss tangent of both gel types decreased as a function of increasing polymer concentration. Gel mucoadhesive strength was dependent on both the time of contact of the formulation with mucin and also on polymer concentration. In conclusion, this study has characterised a number of gels containing either HEC or Na CMC in terms of their mechanical/textural, viscoelastic and mucoadhesive properties. Due to its relevance to the clinical performance, it is suggested that the information derived from these methods may be usefully combined to provide a more rational basis for the selection of polymers and their formulation as topical drug delivery systems. (C) 1997 Elsevier Science B.V.

Hydrogel-forming microneedle arrays exhibit antimicrobial properties:potential for enhanced patient safety

We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture were greater than 105 cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 104 microorganisms penetrated into the viable tissue and 106 cfu of Candida albicans and Staphylococcus epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard.

Design of binary polymeric systems containing ɩ-carrageenan and hydroxypropylcellulose for use in cataract surgery.

This study describes the design and characterisation of the rheological and mechanical properties of binary polymeric systems composed of 2-Hydroxypropylcellulose and ɩ-carrageenan, designed as ophthalmic viscoelastic devices (OVDs). Platforms were characterised using dilute solution, flow and oscillatory rheometry and texture profile analysis. Rheological synergy between the two polymers was observed both in the dilute and gel states. All platforms exhibited pseudoplastic flow. Increasing polymer concentrations significantly decreased the loss tangent and rate index yet increased the storage and loss moduli, consistency, gel hardness, compressibility and adhesiveness, the latter being related to the in-vivo retention properties of the platforms. Binary polymeric platforms exhibited unique physicochemical properties, properties that could not be engineered using mono-polymeric platforms. Using characterisation methods that provide information relevant to their clinical performance, low-cost binary platforms (3% hydroxypropylcellulose and either 1% or 2% ɩ-carrageenan) were identified that exhibited rheological, textural and viscoelastic properties advantageous for use as OVDs.

A 'before and after' study of nursing students' self-assessed competence in identifying the needs of older patients in hospital using an educational workbook.

Background: A core component of nurse education is clinical practice in order to support the development of clinical skills and competence. Assessment and measurement of the clinical competence of nursing students is important to gauge their professional development and educational needs.

Aim: To evaluate the impact of an Older Persons’ Assessment Educational Workbook (OPAEW) and explore second year nursing students’ competence and their opinions and use of the workbook.

Methods: A ‘before and after’ pre-experimental design was undertaken with n=6 second year nursing students. Outcome measures were the Nursing Competencies Questionnaire and the Self-efficacy in Clinical Performance Scale. Content analysis of workbooks and a survey (n=5) of opinions regarding the workbook was undertaken.

Findings: Pre and post test results for the study (n=5) were tested to determine if there was a relationship between changes in the NCQ and SECP repeated measures and use of an OPAEW. Testing identified evidence of a statistically significant difference for both SECP measures (SECP28 p=0.043; SECP7 p=0.042), with no clear statistical evidence of a difference for the NCQ (p=0.08). A weak negative association (NCQ ρ=-0.600 p=0.285; SECP28 ρ=-0.300 p=0.624; SECP7 ρ=-0.205 p=0.741), was found indicating that those participants who scored the lowest scores at the start of the study, benefited most from the workbook.

Content analysis of the OPAEW (n=5) found that 3 of the 5 participants completed all components of the workbook, with a mean of 1051 words used (SD 281.8). Through the survey (n=5) students reported the workbook as a useful guide when undertaking a patient assessment.

Conclusions: The OPAEW showed potential as an intervention to support the development of nursing students’ competence in older person assessment skills.

A 'before and after' study of nursing students' self-assessed competence in identifying the needs of older patients in hospital using an educational workbook.

Background: A core component of nurse education is clinical practice in order to support the development of clinical skills and competence. Assessment and measurement of the clinical competence of nursing students is important to gauge their professional development and educational needs.

Aim: To evaluate the impact of an Older Persons’ Assessment Educational Workbook (OPAEW) and explore second year nursing students’ competence and their opinions and use of the workbook.

Methods: A ‘before and after’ pre-experimental design was undertaken with n=6 second year nursing students. Outcome measures were the Nursing Competencies Questionnaire and the Self-efficacy in Clinical Performance Scale. Content analysis of workbooks and a survey (n=5) of opinions regarding the workbook was undertaken.

Findings: Pre and post test results for the study (n=5) were tested to determine if there was a relationship between changes in the NCQ and SECP repeated measures and use of an OPAEW. Testing identified evidence of a statistically significant difference for both SECP measures (SECP28 p=0.043; SECP7 p=0.042), with no clear statistical evidence of a difference for the NCQ (p=0.08). A weak negative association (NCQ ρ=-0.600 p=0.285; SECP28 ρ=-0.300 p=0.624; SECP7 ρ=-0.205 p=0.741), was found indicating that those participants who scored the lowest scores at the start of the study, benefited most from the workbook.

Content analysis of the OPAEW (n=5) found that 3 of the 5 participants completed all components of the workbook, with a mean of 1051 words used (SD 281.8). Through the survey (n=5) students reported the workbook as a useful guide when undertaking a patient assessment.

Conclusions: The OPAEW showed potential as an intervention to support the development of nursing students’ competence in older person assessment skills.

Examination of surface properties and in vitro biological performance of amorphous diamond-like carbon-coated polyurethane

Despite the emerging use of diamond-like carbon (DLC) as a coating for medical devices, few studies have examined the resistance of DLC coatings onto medical polymers to both microbial adherence and encrustation. In this study, amorphous DLC of a range of refractive indexes (1.7-1.9) and thicknesses (100-600 nm) was deposited onto polyurethane, a model polymer, and the resistance to microbial adherence (Escherichia coli; clinical isolate) and encrustation examined using in vitro models. In comparison to the native polymer, the advancing and receding contact angles of DLC-coated polyurethane were lower, indicating greater hydrophilic properties. No relationship was observed between refractive index, thickness, and advancing contact angle, as determined using multiple correlation analysis. The resistances of the various DLC-coated polyurethane films to encrustation and microbial adherence were significantly greater than that to polyurethane; however, there were individual differences between the resistances of the various DLC coatings. In general, increasing the refractive index of the coatings (100 nm thickness) decreased the resistance of the films to both hydroxyapatite and struvite encrustation and to microbial adherence. Films of lower thicknesses (100 and 200 nm; of defined refractive index, 1.8), exhibited the greatest resistance to encrustation and to microbial adherence. In conclusion, this study has uniquely illustrated both the microbial antiadherence properties and resistance to urinary encrustation of DLC-coated polyurethane. The resistances to encrustation and microbial adherence were substantial, and in light of this, it is suggested that DLC coatings of low thickness and refractive index show particular promise as coatings of polymeric medical devices. (c) 2006 Wiley Periodicals, Inc.