Topically Applied Therapies for the Treatment of Skin Disease: Past, Present, and Future.

The purpose of this review is to summarize essential biological, pharmaceutical, and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin and routes of drug absorption and their limitations is provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory diseases, microbial infections, skin cancers, and genetic skin diseases. The complexity of topical product development through to large-scale manufacturing along with recommended risk mitigation approaches are then highlighted. As such topical treatments are applied externally, patient preferences along with the challenges they invoke are then described, and finally the future of this field of drug delivery is discussed, with an emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of the skin and its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient population's preferences, limitations, and the future with regard to new skin diseases and topical medicine approaches.

Implementation of Body Worn Camera: Practical and Ethical Considerations.

Body-worn cameras are increasingly being used as a violence prevention tool in inpatient mental health wards. However, there remains a limited understanding of this technology from an implementation perspective, such as protocols and best practice guidance if cameras are to be used in these settings. This study explores the perspectives of patients, mental health staff, and senior management to understand the practical and ethical issues related to the implementation of body-worn cameras. Semi-structured interviews (n = 64) with 24 patients, 25 staff from acute wards, six Mental Health Nursing Directors, and 9 community-based patients were conducted. Interviews were analysed using reflexive thematic analysis. Ethical approval was granted by the Health Research Authority. Findings from this study show that the implementation of BWC in healthcare settings requires careful consideration. The perspectives of patients and staff demonstrate the complex reality of implementation alongside the consideration of practical and ethical issues around implementation that are essential to ensures that wards recognise the need to assess their capacity to use the cameras in a way that is fair and consistent for all involved. The findings further highlight wider questions around power and autonomy in mental health care.

Exploring the use of body-worn cameras in acute mental health wards: A qualitative interview study with mental health patients and staff.

BACKGROUND: Body-worn cameras are increasingly being used as a violence prevention tool in inpatient mental health wards. However, there is a dearth of research on their use in these settings, particularly when it comes to patient perspectives. OBJECTIVE: This study aimed to explore the perspectives of patients, mental health staff, and senior management on body-worn cameras to identify the possible impacts of this technology in inpatient mental health settings. DESIGN: This was an exploratory qualitative study. SETTING: We undertook interviews online and in-person on a number of acute inpatient wards across five mental health hospitals in England. Participants were recruited in-person, online via social media, and through professional networks. PARTICIPANTS: This study recruited 24 patients from acute wards, 25 staff from acute wards, six Mental Health Nursing Directors, and nine community-based patients. METHODS: Semi-structured interviews were conducted online and in-person. Interviews were analysed using reflexive thematic analysis. Ethical approval was granted by the Health Research Authority. RESULTS: The subjective nature of how violence and aggression is defined shapes how staff and patients view the prospect of using body-worn cameras. Both staff and patients cited issues resulting from an underlying culture of mistrust in inpatient settings that leave staff and patients feeling unsafe. Body worn cameras may intensify power dynamics and undermine therapeutic relationships. Participants felt that engaging existing interventions and addressing systemic causes of violence and aggression should take priority over introducing body-worn cameras. CONCLUSIONS: There is no indication that staff or patients believe body-worn cameras will deter violence and aggression on inpatient mental health wards. They may serve as a tool for safeguarding and staff training, but there are still unexplored ethical concerns about their use and a lack of evidence to support use of this technology to deter violence in NHS mental health settings. TWEETABLE ABSTRACT: Mental health patients & staff have complex perspectives on controversial body-worn camera technology @thekeiranwilson @unafoye @maddych4dwick @gbrennancafc @cityalan.

Lot verification practices in Ontario clinical chemistry laboratories - Results of a patterns-of-practice survey.

Objectives: Verifying new reagent or calibrator lots is crucial for maintaining consistent test performance. The Institute for Quality Management in Healthcare (IQMH) conducted a patterns-of-practice survey and follow-up case study to collect information on lot verification practices in Ontario. Methods: The survey had 17 multiple-choice questions and was distributed to 183 licensed laboratories. Participants provided information on materials used and approval/rejection criteria for their lot verification procedures for eight classes of testing systems. The case study provided a set of lot comparison data and was distributed to 132 laboratories. Responses were reviewed by IQMH scientific committees. Results: Of the 175 laboratories that responded regarding reagent lot verifications, 74% verified all tests, 11% some, and 15% none. Of the 171 laboratories that responded regarding calibrator lot verifications, 39% verified all calibrators, 4% some, and 57% none. Reasons for not performing verifications ranged from difficulty performing parallel testing to high reagent cost. For automated chemistry assays and immunoassays, 23% of laboratories did not include patient-derived materials in reagent lot verifications and 42% included five to six patient materials; 58% of laboratories did not include patient-derived materials in calibrator lot verifications and 23% included five to six patient materials. Different combinations of test-specific rules were used for acceptance criteria. For a failed lot, 98% of laboratories would investigate further and take corrective actions. Forty-three percent of laboratories would accept the new reagent lot in the case study. Conclusion: Responses to the survey and case study demonstrated variability in lot verification practices among laboratories.

Post-exercise Cold Water Immersion Does Not Improve Subsequent 4-km Cycling Time-Trial Compared With Passive and Active Recovery in Normothermia.

Background: We investigated whether a brief cold water immersion between two cycling time trials (TT) improves the performance of the latter compared with passive and active recovery in normothermic conditions (~20°C). Methods: In Experiment 1 10 active participants (4 women) completed two 4-km TT (Ex1 and Ex2, each preceded by a 12 min moderate-intensity warm-up) separated by a 15 min recovery period consisting of: (a) passive rest (PAS) or (b) 5 min cold water immersion at 8°C (CWI-5). In Experiment 2, 13 different active males completed the same Ex1 and Ex2 bouts separated by a 15 min recovery consisting of: (a) PAS, (b) 10 min cold water immersion at 8°C (CWI-10) or (c) 15 min of moderate-intensity active recovery (ACT). Results: In both experiments, the time to complete the 4-km TT-s was not different (P > 0.05, ES = 0.1) among the trials neither in Ex1 (Experiment 1: PAS: 414 ± 39 s; CWI-5: 410 ± 39 s; Experiment 2: PAS: 402 ± 41 s; CWI-10: 404 ± 43 s; ACT: 407 ± 41 s) nor Ex2 (Experiment 1: PAS: 432 ± 43 s; CWI-5: 428 ± 47 s; Experiment 2: PAS: 418 ± 52 s; CWI-10: 416 ± 57 s; ACT: 421 ± 50 s). In addition, in all conditions, the time to complete the time trials was longer (P < 0.05, ES = 0.4) in Ex2 than Ex1. Core temperature was lower (P < 0.05) during the majority of Ex2 after CW-5 compared with passive rest (Experiment 1) and after CWI-10 compared with PAS and ACT (Experiment 2). Perceived exertion was also lower (P < 0.05) at mid-point of Ex2 after CWI-5 compared with PAS (Experiment 1) as well as overall lower during the CWI-10 compared with PAS and ACT conditions (Experiment 2). Conclusion: A post-exercise 5-10 min cold water immersion does not influence subsequent 4-km TT performance in normothermia, despite evoking reductions in thermal strain.

iDXA, Prodigy, and DPXL dual-energy X-ray absorptiometry whole-body scans: a cross-calibration study.

PURPOSE: Total body fat, lean, and bone mineral content (BMC) in addition to regional fat and lean mass values for arms, legs, and trunk were compared across a pencil-beam (Lunar DPXL) and 2 fan-beam (GE Lunar Prodigy and GE Lunar iDXA) dual-energy X-ray absorptiometry (DXA) systems. METHODS: Subjects were a multiethnic sample of 99 healthy adult males (47%) and females (mean+/-SD: age, 46.3+/-16.9 yr; weight, 73.4+/-16.6 kg; height, 167.6+/-9.7 cm; body mass index, 26.0+/-5.2 kg/m2) who had whole-body scans performed within a 3-h period on the 3 systems. Repeated measures ANOVA was used to test the null hypothesis that the mean values for the 3 systems were equal. Translation equations between the methods were derived using regression techniques. RESULTS: Bone mineral content (BMC): For both genders, total BMC by iDXA was lower (p

Independent association of insulin resistance with larger amounts of intermuscular adipose tissue and a greater acute insulin response to glucose in African American than in white nondiabetic women.

BACKGROUND: African Americans (AAs) have a higher prevalence of obesity and type 2 diabetes than do whites. Higher insulin resistance and hyperinsulinemia have been reported in adult AAs than in whites. Differences in adipose tissue and its distribution may account for these findings. OBJECTIVE: The objective was to ascertain whether differences between AA and white women in adipose tissue (AT) and skeletal muscle (SM) volumes account for ethnic differences in insulin resistance. DESIGN: We used whole-body magnetic resonance imaging to measure AT and SM volumes and used the intravenous-glucose-tolerance test to measure insulin resistance. RESULTS: AAs (n = 32) were 29-42% more insulin resistant than were whites (n = 28) after adjustment for weight and height or any AT volumes (P < 0.05). After adjustment for SM volume, the difference decreased to 19% and became nonsignificant. AAs had a 163% greater acute insulin response to glucose than did whites; this difference was significant even after adjustment for insulin sensivitity index, weight, height, and any magnetic resonance imaging measures. With respect to regional AT volumes, an association independent of race, weight, height, and SM volume was found only between increased intermuscular AT and lower insulin sensitivity index. CONCLUSIONS: Premenopausal AA women had significantly higher insulin resistance and acute insulin response to glucose than did their white counterparts. Whereas the difference in insulin resistance was partially accounted for by a greater SM volume in the AAs than in the whites, the difference in the acute insulin response to glucose was independent of any AT and SM measures and was disproportionately larger than expected according to the difference in insulin resistance. In addition, whole-body intermuscular AT was an important independent correlate of insulin resistance.

Four commonly used dual-energy X-ray absorptiometry scanners do not identically classify subjects for osteopenia or osteoporosis by T-score in four bone regions BIz11.5.

We investigated whether four commonly used dual-energy X-ray absorptiometry (DXA) scanners (DPX, DPX-L,and Prodigy by GE Lunar, and Delphi-A by Hologic) could classify identical subjects as osteopenic or osteoporotic using the T-score for bone mineral density in four regions of interest: PA spine (L1-L4), femur (total), forearm (total),and 33% radius in 77 adults (38 females) free of treatment for bone metabolic disease (age range 20-81 yr). There were no significant differences between T-score means for posterior-anterior spine by DPX, DPX-L, and Prodigy, but they were higher than the mean T-score by Delphi-A (p < 0.05). Prodigy gave the lowest and DPX and Delphi-A gave the highest T-score for 33% radius (p < 0.05). No subject was classified as osteoporotic in the femur region by the four scanners, although other classifications varied by region and scanner. No two scanners classified subjects identically for osteopenia in any of the four regions. These results indicate that classification of bone density in individual subjects using T-scores varies by different DXA scanners, even the scanners were made by the same manufacturer.

False negative antigen tests in dogs infected with heartworm and placed on macrocyclic lactone preventives.

BACKGROUND: Dogs with chronic inflammation, including those with heartworm being managed with macrocyclic lactones and doxycycline (slow kill, SK), may develop immune complexes that block detection of Dirofilaria immitis antigen on commercial tests. METHODS: To determine if SK could result in development of false-negative antigen tests, we collected serum samples from dogs that had been diagnosed with heartworm by antigen detection, with or without confirmation by detection of D. immitis microfilariae, placed on monthly macrocyclic lactones and doxycycline, and that later tested negative on an antigen test, and then tested them for antigen of D. immitis before and after treatment to disrupt immune complexes. RESULTS: Serum samples from a total of 15 dogs managed with SK were negative for antigen prior to heating on commercial assay (DiroCHEK, Zoetis) by colorimetric detection and spectrophotometry, but after heat treatment, 8/15 (53.3%) samples converted to positive. Review of the medical records of each dog indicated that, after the heartworm diagnosis, only 7/15 (46.7%) dogs appeared to receive preventive monthly as prescribed, including 3 dogs that had detectable antigen after heating the sample and 4 dogs that did not have detectable antigen after heating. Whole blood was available from 9 dogs; microfilariae of D. immitis were detected in 1 sample. CONCLUSIONS: These data suggest that immune complex formation in dogs infected with heartworm and managed with SK can induce false negative antigen test results, misleading veterinarians and owners about the efficacy of this approach. Moreover, compliance with preventive administration appears poor, even after a heartworm diagnosis. The presence of persistent microfilaremia in at least one dog has implications for resistance selection.

Analytical evaluation of hemoglobin A(1c) dual kit assay on Bio-Rad Variant II: an automated HPLC hemoglobin analyzer for the management of diabetic patients.

OBJECTIVES: To evaluate the analytical performance of the Bio-Rad Variant II HbA(1c) dual kit assay. DESIGN AND METHODS: Precision, carryover, linearity and analytical range were investigated. 139 patients' HbA(1c) results analyzed by the Variant II were compared to the Variant I method. 49 blood samples analyzed by the Variant II at Toronto Medical Laboratories (TML) were compared to the Variant II at Hospital for Sick Children (HSC). RESULTS: Total imprecision was less than 2% for the Variant II assay. The method had a wide analytical range with no carryover. HbA(1c) results were not changed after switching back and forth from the beta thalassemia to HbA(1c) assay. The Variant II showed an average of 0.0027 negative bias compared to the Variant I method. There was an average of 0.0020 negative bias for HbA(1c) results on the Variant II at TML compared to the Variant II at HSC. CONCLUSIONS: HbA(1c) analysis on the Variant II HbA(1c) dual kit is a relatively fast and reproducible method.

Role of a quality management system in improving patient safety - laboratory aspects.

OBJECTIVES: The aim of this study is to describe how implementation of a quality management system (QMS) based on ISO 15189 enhances patient safety. DESIGN AND METHODS: A literature review showed that several European hospitals implemented a QMS based on ISO 9001 and assessed the impact on patient safety. An Internet search showed that problems affecting patient safety have occurred in a number of laboratories across Canada. The requirements of a QMS based on ISO 15189 are outlined, and the impact of the implementation of each requirement on patient safety is summarized. The Quality Management Program - Laboratory Services in Ontario is briefly described, and the experience of Ontario laboratories with Ontario Laboratory Accreditation, based on ISO 15189, is outlined. RESULTS: Several hospitals that implemented ISO 9001 reported either a positive impact or no impact on patient safety. Patient safety problems in Canadian laboratories are described. Implementation of each requirement of the QMS can be seen to have a positive effect on patient safety. Average laboratory conformance on Ontario Laboratory Accreditation is very high, and laboratories must address and resolve any nonconformities. Other standards, practices, and quality requirements may also contribute to patient safety. CONCLUSION: Implementation of a QMS based on ISO 15189 provides a solid foundation for quality in the laboratory and enhances patient safety. It helps to prevent patient safety issues; when such issues do occur, effective processes are in place for investigation and resolution. Patient safety problems in Canadian laboratories might have been prevented had effective QMSs been in place. Ontario Laboratory Accreditation has had a positive impact on quality in Ontario laboratories.

A randomised controlled trial of biopsy forceps and cannula aspiration for transcervical chorionic villus sampling.

OBJECTIVE: This trial compared two instruments for transcervical chorionic villus sampling (CVS). DESIGN: Randomised controlled trial. SETTING: Regional university prenatal diagnosis and treatment centre. POPULATION: Two hundred women were randomised at 10(+0)-12(+6) weeks of gestation to transcervical CVS using cannula aspiration (CA) or biopsy forceps (BF). METHODS: Women undergoing indicated CVS signed informed consent. Randomisation after decision to perform transcervical CVS. PRIMARY OUTCOME: the rise in maternal serum alpha-fetoprotein (alpha-FP). SECONDARY OUTCOMES: (i) placental trauma (fetomaternal haemorrhage [FMH]); (ii) laboratory, procedure, and cytogenetic results and pregnancy outcomes; (iii) patient and operator satisfaction; and (iv) economic analyses. Analyses were performed by intention to treat. RESULTS: The -FP rise did not differ between groups; there was no other evidence of placental trauma. BF were better tolerated by women, provided culturable tissue, after fewer instrument passes, with greater ease and in less time. BF were associated with cost savings. CONCLUSIONS: Unlike -FP, other markers of FMH were unaltered, questioning the reliability of alpha-FP as an indicator of FMH. Compared with CA, transcervical BF caused comparable placental trauma, appeared to be similarly effective and safe and were preferred by operators and patients.

IFCC handbook on Master Program in clinical laboratory sciences.

This document summarizes the steps in development of a new IFCC Master Program and outlines some of the ways the IFCC would assist in setting up such a regional Program. This is intended to be of assistance to those who wish to embark on such an endeavour.

Outcome validation of the Beckman Coulter access analyzer in a second-trimester Down syndrome serum screening application.

BACKGROUND: Mid-trimester maternal serum alpha-fetoprotein (AFP) and unconjugated estriol (uE3) are 30% lower and human chorionic gonadotropin (hCG) is twofold higher in Down syndrome pregnancies compared with unaffected pregnancies. In maternal serum screening, patient-specific risks are calculated using published gaussian frequency distribution parameters for these three markers obtained with previously available immunoassays. New immunoassays must generate similar distribution parameters if the accuracy of assigned risks and overall performance of prenatal screening are to be maintained. METHODS: Agreement between the Beckman Coulter Access and the Bayer Immuno 1 assays for AFP and hCG and the Amersham Amerlex-M RIA for uE3 was assessed in 558 fresh sera. Precision was measured over 6 weeks. Median concentrations were calculated by regression of 568 Caucasian singleton pregnancy samples against gestational age in days. Frozen mid-trimester sera from 44 confirmed Down syndrome singleton pregnancies (cases) were selected without conscious bias for reanalysis, and each case was matched with five control specimens from unaffected pregnancies. Serum markers were expressed as the multiple of the median (MoM) concentration derived from the control samples, corrected for maternal weight and converted to their log-equivalent values. Normality was assessed using probability plots and the Shapiro-Wilk W-test. Gaussian distribution parameters were compared with established values, and Down syndrome risk calculations were assessed with a commonly used risk algorithm. RESULTS: The Access AFP and hCG assays had consistent proportional agreement with the established assays, whereas agreement between the uE3 methods was less consistent. Analytical imprecision was 3-6% at mid-trimester concentrations. Normal distributions were obtained for the log MoM values of all three markers in both the Down syndrome and unaffected populations, and their gaussian distribution parameters compared well with established values. The performance of the Access assays in an established trivariate risk algorithm for Down syndrome was equal to the performance exhibited by traditional methods. CONCLUSION: The Beckman Coulter Access analyzer provides valid mid-trimester serum AFP, uE3, and hCG results and risk assessments when applied in a prenatal Down syndrome screening service.