Decreasing exposure to thyroid radiation in an orthopaedic theatre setting: an educational intervention.

The use of personal protective equipment (PPE) can significantly reduce staff exposure to harmful radiation and infection. Fluoroscopic procedures in orthopaedic theatre can generate high levels of radiation and good adherence to PPE use is essential to reduce long term cancer risk, including thyroid cancer. To assess baseline compliance with PPE, availability of PPE in theatre and carry out an intervention to promote greater use of PPE. This was a closed-loop interventional study set in a level 1 trauma centre and an elective/rehabilitation unit. Data were collected in 40 cases pre and post-intervention from 26th May-7th July 2017. All health care practitioners present at fluoroscopic screening were observed. PPE availability was audited daily. A questionnaire was used to assess surgical and nursing knowledge/practices regarding radiation/infection safety. An educational presentation was delivered to the groups at highest risk of exposure. 39/41 questionnaires were completed (29 surgeons, 10 nurses). 41% of respondents had taken a radiation training course or felt they had adequate training. There was a significant increase in the use of thyroid guards by surgeons 13/115 (11.3%) pre-intervention to 54/117 (46.2%) post-intervention (p<0.001) and radiographers (p=0.019) post-intervention. Logistic regression showed an 89.7% increased likelihood of thyroid guard use post-intervention and a 12.7% increased chance of thyroid guard use for each extra guard available. A short educational, easily replicated session, significantly improved compliance with thyroid guards by orthopaedic surgeons.

What are the best endpoints for Eczema Area and Severity Index and Scoring Atopic Dermatitis in clinical practice? A prospective observational study.

BACKGROUND: Multiple strategies have been used to evaluate the minimal important change (MIC) of the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD). The meaningfulness of these MICs is not well established across all severities of atopic dermatitis (AD). OBJECTIVES: To determine the MIC of percentage and absolute improvement of EASI and SCORAD scores in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 826). An anchor-based approach was used to determine thresholds for the percentage and absolute MICs of EASI, SCORAD and objective SCORAD (O-SCORAD) at follow-up from baseline. RESULTS: One-grade improvements of Physician's Global Assessment (PGA) and validated Investigator Global Assessment scale for AD (vIGA-AD) were associated with 50%, 35% and 35% decreases of EASI, SCORAD and O-SCORAD, respectively. The thresholds for percentage MIC of EASI (Kruskal-Wallis test, P = 0·61), SCORAD (P = 0·07) and O-SCORAD (P = 0·09) were similar across baseline AD severities. One-grade improvements of PGA and vIGA-AD were associated with 14·0- and 14·9-point decreases of EASI, 19·9- and 14·9-point decreases of SCORAD, and 15·5- and 17·4-point decreases of O-SCORAD. The thresholds for the absolute MIC of EASI (P < 0·001), SCORAD (P < 0·001) and O-SCORAD (P < 0·001) significantly differed by baseline AD severity. Percentage and absolute MICs for EASI and SCORAD were associated with improvements of AD symptoms and quality of life. CONCLUSIONS: EASI 50, SCORAD 35 and O-SCORAD 35 were meaningful percentage MICs regardless of baseline AD severity. The absolute MICs for EASI, SCORAD and O-SCORAD varied by baseline AD severity.

Measurement properties of the Rajka-Langeland severity score in children and adults with atopic dermatitis.

BACKGROUND: Multiple atopic dermatitis (AD) severity scales exist, with no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the Rajka-Langeland score and compare it with other clinician-reported outcomes in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 427). RESULTS: Rajka-Langeland had good concurrent validity with the Eczema Area and Severity Index (Spearman rho = 0·63), SCORing AD (SCORAD) (rho = 0·61), objective-SCORAD (rho = 0·52) and body surface area (rho = 0·51); good convergent validity with the numeric rating scale average-itch (rho = 0·60) and worst-itch (rho = 0·59), Patient-Oriented Eczema Measure (rho = 0·57), Dermatology Life Quality Index (rho = 0·53), Patient-Reported Outcomes Measurement Information System Itch Questionnaire (rho = 0·35-0·55) in adults and/or children; fair discriminant validity for patient- and physician-reported global AD severity; good responsiveness to change of severity of AD and itch; good reliability; internal consistency; with no floor or ceiling effects. Interpretability bands (3, clear/almost clear; 4-5, mild; 6-7, moderate; 8-9, severe) and minimal clinically important difference (1 point) were established. CONCLUSIONS: The Rajka-Langeland score showed good construct validity, reliability, internal consistency and responsiveness in adults and children with AD.

Measurement properties of the product of investigator's global assessment and body surface area in children and adults with atopic dermatitis.

BACKGROUND: Multiple clinician-reported outcome measures exist for atopic dermatitis (AD) severity. However, there is no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the product of validated Investigator's Global Assessment for AD (vIGA) and body surface area (BSA) overall or divided into six categories (cBSA: 0%/0.1, <10%/10, <30%/30, <50%/50, <70%/70 and <90%/90-100%) and compare with other clinician-reported and patient-reported outcomes in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 653). RESULTS: vIGA*BSA and vIGA*cBSA had good convergent validity with BSA (Spearman's ρ = 0.97 and 0.93), eczema area and severity index (ρ = 0.94 and 0.92), and objective SCORAD (ρ = 0.88 and 0.89); and weak-to-good convergent validity with Numeric Rating Scale average itch (ρ = 0.22 and 0.22) and worst itch (ρ = 0.27 and 0.28), Patient-Oriented Eczema Measure (ρ = 0.44 and 0.43), Dermatology Life Quality Index (ρ = 0.48 and 0.49), ItchyQOL (ρ = 0.45 and 0.46), PROMIS Sleep Disturbance (ρ = 0.46 and 0.37) and sleep-related impairment (ρ = 0.31 and 0.31) in adults and/or children; very good discriminant validity for physician-reported global AD severity; good responsiveness to change of severity of AD and itch; and good reliability (intraclass correlation coefficient [95% confidence interval]: 0.72 [0.60-0.81] and 0.74 [0.62-0.82]) with no floor or ceiling effects. Thresholds for interpretability bands and clinically important difference were established. CONCLUSIONS: vIGA*BSA and vIGA*cBSA scores showed good convergent and discriminant validity, reliability, responsiveness and interpretability in adults and children with AD, and were feasible for use in clinical practice. vIGA*BSA and vIGA*cBSA had slightly lower convergent validity than EASI or objective SCORAD, but might be more efficient to collect and score.

Measurement properties of the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire: itch severity assessments in adults with atopic dermatitis.

BACKGROUND: Little is known about the validity of numeric rating scales (NRS) and verbal rating scales (VRS) for itch and itch frequency for assessing itch severity in atopic dermatitis (AD). We evaluated the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessment, including multiple NRS, VRS and frequency of itch assessments, in adults with AD and compared their performance. METHODS: Self-administered questionnaires and skin examinations were performed in 410 patients with AD (aged 18-90 years) in a dermatology practice setting. RESULTS: PIQ NRS, VRS and frequency of itch had good content validity, strong correlations with one another (Spearman correlations P < 0·001) and weak-to-moderate correlations with patient-oriented eczema measure (POEM), Eczema Area and Severity Index (EASI), objective SCORing AD (SCORAD) and Dermatology Life Quality Index (DLQI) (P < 0·001) and very good discriminant validity. Changes from baseline in NRS, VRS and frequency of itch were moderately to strongly correlated with one another, and weakly to moderately correlated with other patient-reported (POEM, SCORAD itch, DLQI) and clinician-reported outcomes (EASI, objective SCORAD). NRS and VRS worst itch and average itch showed moderate-to-good test-retest reliability. There were no floor or ceiling effects for NRS or VRS itch, but there were ceiling effects for itch frequency. Each assessment was completed in < 1 min by all patients. CONCLUSIONS: NRS, VRS and frequency of itch items from PIQ - itch severity showed good content and construct validity, reliability, and/or responsiveness in adults with AD, and were feasible for use in clinical trials and practice. What is already known about this topic? Numeric rating scales (NRS), verbal rating scales (VRS) and frequency of itch have been used to assess the burden of itch. However, there have been limited results demonstrating their validity, responsiveness, interpretability and feasibility, particularly in atopic dermatitis (AD). What does this study add? This study demonstrated that NRS, VRS and frequency of itch items from the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessments had good construct validity, responsiveness, reliability and feasibility in the assessment of adult AD. PIQ NRS, VRS and frequency of itch all appear to have sufficient validity, reliability and feasibility for use as assessments of itch in adults with AD in clinical practice and trials. What are the clinical implications of this work? PIQ NRS and VRS are all simple, valid, reliable and feasible for use in clinical practice and trials to assess itch in adults with AD. Linked Comment: Oosterhaven. Br J Dermatol 2020; 183:802-803.

Validation of Patient-Reported Outcomes Information System Sleep Disturbance and Sleep-Related Impairment in adults with atopic dermatitis.

BACKGROUND: Sleep disturbances are common in adults with atopic dermatitis (AD). Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) are validated questionnaires to assess sleep in adults. Little is known about their measurement properties in adults with AD. OBJECTIVES: To assess the measurement properties of the PROMIS SD and SRI eight-item short forms in AD. METHODS: We performed a prospective dermatology-practice-based study using questionnaires and evaluation by a dermatologist (n = 420). RESULTS: PROMIS SD and SRI showed moderate correlations to each other (ρ = 0·67), and weak correlations with Patient-Oriented Eczema Measure (ρ = 0·43 and 0·39, respectively); average (ρ = 0·31/0·30) and worst numerical rating scale for itch (ρ = 0·32/0·30); Eczema Area and Severity Index (ρ = 0·41/0·31); and Scoring Atopic Dermatitis (SCORAD) (ρ = 0·44/0·30) (Spearman correlations, P < 0·001). PROMIS SD and SRI increased significantly and stepwise with more frequent sleep disturbance, severe itch and self-reported global AD severity (ancova, P < 0·001). PROMIS SD and SRI showed good internal consistency (Cronbach alpha 0·84 and 0·91). Changes from baseline in PROMIS SD and SRI were weakly to moderately correlated with each other and with changes of multiple patient-reported and clinician-reported AD outcomes. There were no floor or ceiling effects for PROMIS SD or SRI. The median completion time for PROMIS SD and SRI was 2 min. CONCLUSIONS: PROMIS SD and SRI showed good construct validity, internal consistency, responsiveness and feasibility to assess sleep in adult patients with AD. What is already known about this topic? The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) scales were found to be valid in adults with chronic disease. However, the validity and feasibility of PROMIS SD and SRI in atopic dermatitis remain unknown. What does this study add? This study demonstrated that PROMIS SD and SRI had good content, concurrent, convergent and discriminant validity; feasibility; and responsiveness, with no floor or ceiling effects observed. What are the clinical implications of this work? The PROMIS SD and SRI eight-item bank short forms appear to have sufficient validity and feasibility to be used as assessments for burden of sleep in adults with atopic dermatitis in clinical practice.

The clinicians´ dilemma with mosaicism-an insight from inner cell mass biopsies.

STUDY QUESTION: How reliable are cleavage stage and trophectoderm (TE) biopsies compared to inner cell mass (ICM) biopsies? SUMMARY ANSWER: The reliability of TE biopsy compared to ICM biopsy is almost perfect, but only substantial between cleavage stage biopsy and ICM biopsy. WHAT IS KNOWN ALREADY: One of the prevailing reasons for implantation failure is presumed to be chromosomal aneuploidy in human preimplantation embryos. Preimplantation genetic testing for aneuploidies (PGT-A) has been introduced into assisted reproduction in an effort to increase pregnancy rates. Increasing evidence indicates that genetic results obtained following blastomere or TEbiopsy may not accurately reflect the true genetic status of the embryo due to the presence of embryonic mosaicism, and therefore the reliability of PGT is highly controversial. STUDY DESIGN, SIZE, DURATION: This was an observational descriptive study, performed in a private infertility centre from August 2016 to January 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean female age was 33.9 years, ranging from 24 to 46 years, and the mean number of biopsied embryos per couple was 2.2 (range 1-7 embryos). Blastomere biopsies had been performed at cleavage stage on Day 3 (D3) due to the turnover time of genetic testing and the inability to cryopreserve embryos in accordance with the local law governing ART. To confirm the genetic results in embryos not chosen for transfer, additional biopsies of the TE at blastocyst stage (BLASTO-TE) as well as of the ICM (BLASTO-ICM) were performed on D5. Only surplus blastocysts, which had not been selected for transfer and were not cryopreserved in accordance with the law governing ART, had been included. MAIN RESULTS AND THE ROLE OF CHANCE: Comparison of all biopsies (D3/BLASTO-ICM/BLASTO-TE) per embryo demonstrated that 50 (59.5%) out of 84 embryos showed concordance in all three results (= full concordance). Thirty-four (40.4%) embryos had at least two discordant results between the three biopsies, regardless of whether the embryo diagnosis (aneuploid/euploid) was discordant or not, or in aneuploid embryos, whether the chromosomal patterns were inconsistent. Nine (= 10.7%) embryos had complete discordance between all three biopsies. False positive results between D3/BLASTO-TE, D3/BLASTO-ICM and BLASTO-TE/BLASTO-ICM were 26.4%/30.2% and 7.5%, respectively, while the Kappa agreement between the different approaches was 0.647, 0.553 and 0.857, respectively. Therefore the reliability of D3/BLASTO-TE, D3/BLASTO-ICM and BLASTO-TE/BLASTO-ICM can be interpreted as substantial, as moderate and as almost perfect. LIMITATIONS, REASONS FOR CAUTION: The limitation of this study is the possible bias in the concordance/discordance rate because embryos that had been selected for transfer did not undergo biopsy on D5. WIDER IMPLICATIONS OF THE FINDINGS: The obvious discordance between the three different approaches for PGT-A underlines the limitations of genetic testing and highlights the importance of ongoing research in order to improve the accuracy of PGT-A results. Until then reproductive specialists will continue to make challenging decisions on whether to transfer or discard an embryo in light of current evidence questioning the reliability of genetic results. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Igenomix. The funder provided support in the form of salary for R.C. The co-author R.C. is an employee of Igenomix. She participated in the blinded analysis of the samples; however the final data collection and statistical analysis of the results, as well as the decision to publish, was taken by B.L, I.E. and H.F. The authors B.L., I.E., A.L., A.B., A.A., N.D. and H.F. have no competing interests. The funder did not have any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The commercial affiliation of R.C. did not play any role in the study. TRIAL REGISTRATION NUMBER: This study was approved by the Ethics Committee of IVIRMA Middle East Fertility Clinic, Abu Dhabi, UAE (Research Ethics Committee IVI-MEREFA009a/2017).

Measurement properties of three assessments of burden used in atopic dermatitis in adults.

BACKGROUND: Standardized quality-of-life (QoL) assessments can provide important and clinically relevant information. There is currently a lack of standardization in QoL assessments used in atopic dermatitis (AD). OBJECTIVES: To determine the content validity, construct validity, internal consistency, differential reporting, responsiveness, floor or ceiling effects and feasibility of the Dermatology Life Quality Index (DLQI), Itchy Quality of Life (ItchyQoL) and 5-dimensions (5-D) itch scales for assessing burden of AD in adults and to compare their performance. METHODS: Self-administered questionnaires and skin examination were performed in 340 adults with AD in a dermatology practice setting. RESULTS: DLQI, ItchyQoL and 5-D all had good content validity. DLQI, mean ItchyQoL and 5-D itch all had strong correlations with frequency of AD symptoms (Patient-Oriented Eczema Measure) and intensity of itch (numerical rating scale for itch), and moderate correlations with AD severity (Eczema Area and Severity Index and Scoring Atopic Dermatitis) (Spearman correlations, P < 0·001 for all). DLQI and 5-D itch showed good internal consistency (Cronbach's alpha = 0·89 and 0·84), although ItchyQoL appeared to have several redundant items (alpha = 0·96). Uniform and nonuniform differential item functioning by age, sex and/or race/ethnicity was found for multiple items in DLQI, ItchyQoL and 5-D itch. DLQI, ItchyQoL and 5-D itch scores all demonstrated responsiveness, although ItchyQoL demonstrated the greatest responsiveness. There were no floor or ceiling effects for total scores. The median times for completion of DLQI, ItchyQoL and 5-D itch were 2 min. CONCLUSIONS: The DLQI, ItchyQoL and 5-D itch scales all showed good content and construct validity, and responsiveness in the assessment of AD in adults, and were feasible for use in clinical trials and practice.

Validation of patient-reported global severity of atopic dermatitis in adults.

BACKGROUND: Atopic dermatitis (AD) is associated with a heterogeneous presentation and clinical course. There is a lack of simple and validated severity assessments that are feasible for clinical practice and epidemiological research. OBJECTIVES: We sought to validate patient-reported global AD severity in adults. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 265). RESULTS: At baseline and follow-up, patient-reported global AD severity significantly correlated with oSCORAD (Spearman ρ = 0.56 and 0.49), SCORAD (0.64 and 0.56), EASI (0.56 and 0.50), BSA (0.52 and 0.45), NRS-itch (0.60 and 0.53), POEM (0.50 and 0.48), and DLQI (0.50 and 0.49) (P < .0001 for all). Patient-reported moderate and severe AD vs mild AD were associated with significantly higher oSCORAD, SCORAD, EASI, BSA, NRS-itch, POEM, and DLQI (P < .0001 for all). There was moderate concordance between patient-reported AD severity (mild, moderate, and severe) and previously developed severity strata for oSCORAD (κ = 0.39), SCORAD (κ = 0.47), EASI (κ = 0.37), NRS-itch (κ = 0.49), POEM (κ = 0.37), and DLQI (κ = 0.40). Among patients with severe disease at baseline, those who reported mild or moderate disease on follow-up had significantly greater absolute reductions of oSCORAD (-23.4/-9.7/-1.8), SCORAD (-33.0/-13.2/-2.3), EASI (-17.1/-9.8/-3.2), BSA (-46%/-15%/-4%), NRS-itch (-5/-2/0), POEM (-5/-2/0), and DLQI (-8/-6/-1) than those who continued to report severe disease (Kruskal-Wallis, P ≤ .0003 for all). CONCLUSIONS: Patient-reported AD severity appears to be sufficiently valid for assessing AD severity in the clinical and epidemiological setting.

Severity strata for five patient-reported outcomes in adults with atopic dermatitis.

BACKGROUND: Several patient-reported outcomes have been used to assess the burden of atopic dermatitis (AD). Some are disease specific, such as the Patient-Oriented Eczema Measure (POEM), while others pertain to itch, for example the numerical rating scale (NRS)-itch, ItchyQoL and 5-D itch, or dermatological disease in general, for example the Dermatology Life Quality Index (DLQI). Development of severity strata is essential for proper interpretability of these assessments. OBJECTIVES: To confirm previously developed strata for POEM, DLQI and raw ItchyQoL, and develop strata for the NRS-itch, mean ItchyQoL and 5-D itch scale for use in adults with AD. METHODS: Self-administered questionnaires were completed by 210 adults with AD in a dermatology practice setting. Strata were selected using an anchoring approach based on patient-reported disease severity. RESULTS: We confirmed the existing strata for POEM (mild 0-7, moderate 8-16, severe 17-28; κ = 0·440), DLQI (mild 0-5, moderate 6-10, severe 11-30; κ = 0·398) and NRS-itch (mild 0-3, moderate 4-6, severe 7-10; κ = 0·499). However, the preferred band for raw ItchyQoL was mild 22-58, moderate 59-74 and severe 75-110 (κ = 0·379) and for mean ItchyQoL, mild 1-2·9, moderate 3·0-3·9, severe 4·0-5·0 (κ = 0·374). The preferred band for 5-D itch scale was mild 0-11, moderate 12-17 and severe 18-25 (κ = 0·331). CONCLUSIONS: Existing strata for POEM and DLQI performed well in adult AD. Previously reported strata for visual analogue scale-itch performed best for NRS-itch. We identified banding for the raw ItchyQoL for our AD population that varies slightly from the banding published for a more heterogeneous population. Finally, we proposed strata for mean ItchyQoL and 5-D itch scale in adult AD.

Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis.

BACKGROUND: Scoring systems for assessing the signs of atopic dermatitis (AD) are complex and difficult to interpret. Severity strata are helpful to interpret these assessments properly. OBJECTIVES: To confirm previously reported strata for the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) and the objective component of SCORAD (oSCORAD), and to develop strata for the modified EASI (mEASI), Atopic Dermatitis Severity Index (ADSI) and body surface area (BSA) for use in adults with AD. METHODS: Skin examination was performed in 673 adolescents and adults (age ≥ 13 years) with diagnosed AD, in a dermatology practice setting. Strata were selected using an anchoring approach based on a four-point Investigator's Global Assessment of severity (clear of active skin lesions, mild, moderate or severe disease). RESULTS: We determined potential severity strata for EASI (0 clear, 0·1-5·9 mild, 6·0-22·9 moderate, 23·0-72 severe; κ = 0·69), mEASI (0-0·9 clear, 1-8·9 mild, 9·0-29·9 moderate, 30·0-90 severe; κ = 0·71), oSCORAD (0-7·9 clear, 8·0-23·9 mild, 24·0-37·9 moderate, 38·0-83 severe; κ = 0·70), SCORAD (0-9·9 clear, 10·0-28·9 mild, 29·0-48·9 moderate, 49·0-103 severe; κ = 0·68), ADSI (0-1·9 clear, 2-5·9 mild, 6·0-8·9 moderate, 9·0-15 severe; κ = 0·55) and BSA (0 clear, 0·1-15·9 mild, 16·0-39·9 moderate, 40·0-100 severe; κ = 0·66). oSCORAD values > 0 were found in clear skin due to the presence of xerosis, which is scored in oSCORAD. Similarly, SCORAD values > 0 were found in clear skin due to the scoring of xerosis, pruritus and sleeplessness. Similarly, mEASI and ADSI scores > 0 occurred in patients with clear skin due to scoring of pruritus. CONCLUSIONS: We recommend using these strata for interpretation of their respective measures in clinical trials of AD. There are important differences between the five assessments, which profoundly impact the interpretation of their scores.

Severity assessments used for inclusion criteria and baseline severity evaluation in atopic dermatitis clinical trials: a systematic review.

BACKGROUND: Numerous inclusion criteria and baseline severity assessments are used in clinical trials of atopic dermatitis (AD), which may limit comparison of results. OBJECTIVE: We sought to characterize the inclusion criteria and baseline severity assessments used in randomized controlled trials (RCT) of AD internationally. METHODS: We performed a systematic review of RCT with a pharmacological intervention from 2007 to 2016. Cochrane Library, EMBASE, GREAT, LILACS, MEDLINE and Scopus were searched. Two authors independently performed study selection and data extraction. RESULTS: Overall, 212 RCT met inclusion/exclusion criteria. Target population and inclusion criteria based on AD severity were not documented in 78 (36.8%) and 25 (18.7%) studies, respectively. Thirty and 58 severity assessments were used for inclusion criteria and baseline severity, respectively, with only 60.3% concordance between their uses. Global assessments were most frequently used for both inclusion criteria and baseline severity assessment in North America (39.5% and 32.1%), while SCORing AD (SCORAD) or objective-SCORAD index was most frequently used in Europe (23.5% and 23.0%) and Asia (34.2% and 43.5%). Minimum and maximum thresholds of severity assessments were inconsistently used between studies for inclusion criteria, even within similar target populations. SCORAD, global assessments and body surface area were most frequently used for both inclusion criteria and baseline severity assessment. IGA was particularly used in trials of topical agents. CONCLUSIONS: There were considerable variability and poor documentation of inclusion criteria and baseline severity assessments in RCT for AD. These differences may limit interpretation of a study and comparison of results between studies.

Gene delivery to the spinal cord using MRI-guided focused ultrasound.

Non-invasive gene delivery across the blood-spinal cord barrier (BSCB) remains a challenge for treatment of spinal cord injury and disease. Here, we demonstrate the use of magnetic resonance image-guided focused ultrasound (MRIgFUS) to mediate non-surgical gene delivery to the spinal cord using self-complementary adeno-associated virus serotype 9 (scAAV9). scAAV9 encoding green fluorescent protein (GFP) was injected intravenously in rats at three dosages: 4 × 10(8), 2 × 10(9) and 7 × 10(9) vector genomes per gram (VG g(-1)). MRIgFUS allowed for transient, targeted permeabilization of the BSCB through the interaction of focused ultrasound (FUS) with systemically injected Definity lipid-shelled microbubbles. Viral delivery at 2 × 10(9) and 7 × 10(9) VG g(-1) leads to robust GFP expression in FUS-targeted regions of the spinal cord. At a dose of 2 × 10(9) VG g(-1), GFP expression was found in 36% of oligodendrocytes, and in 87% of neurons in FUS-treated areas. FUS applications to the spinal cord could address a long-term goal of gene therapy: delivering vectors from the circulation to diseased areas in a non-invasive manner.

Descriptive epidemiology of enteric disease in Chennai, India.

There are very few data on the prevalence of coccidian enteric parasites among low-income adults hospitalized in Chennai, India. Stool samples from 200 patients were screened for selected parasites, enteric bacterial pathogens, and other protozoa over a 3-month period. The study identified 42 (21%) Cryptosporidium, 36 (18%) V. cholerae, 17 (9%) Salmonella, 12 (6%) Isospora, six (3%) helminths, five (3%) Shigella, one (1%) Cyclospora, one (1%) other protozoan, and 0% V. parahaemolyticus cases. Co-infection was present in 21 patients. Cryptosporidium was detected in 17 (81%) of co-infected patients. Our findings highlighted the relatively high proportion of patients in this population with Cryptosporidium and Isospora and suggest that further study be undertaken to determine the utility of broader use of diagnostic testing for coccidian parasites in India. Detection may be beneficial because isosporiasis is treatable and both Isospora and Cryptosporidium are important pathogens in AIDS patients.

The effects of dietary weight loss with or without exercise training on liver enzymes in obese metabolic syndrome subjects.

AIM: Insulin resistance and visceral adiposity are predisposing factors for fatty liver disease. The main objectives of this study were (i) to compare the effects of caloric restriction (CR) alone or together with moderate-intensity aerobic exercise training (CR+EX) on liver enzymes, a surrogate marker of liver injury, in obese metabolic syndrome (MetS) subjects and (ii) to identify anthropometric, metabolic, cardiovascular and dietary predictors of changes in liver enzymes. METHODS: Sedentary men and women (n = 63), aged 55 ± 6 (s.d.) years with body mass index 32.7 ± 4.1 kg/m(2) and confirmed MetS, were randomized to 12-week CR, CR+EX or no treatment (Control). RESULTS: Weight loss averaged 7.6% in the CR and 9.1% in the CR+EX group (time effect, p < 0.001; group effect, p = 0.11); insulin sensitivity improved by 49 and 45%, respectively (both p < 0.001). Fitness (maximal oxygen consumption) increased by 19% in the CR+EX group only (p < 0.001). Alanine aminotransferase (ALT) levels decreased by 20% in the CR and 24% in the CR+EX group (time effect, both p < 0.001; group effect, p = 0.68); corresponding values for γ-glutamyltransferase (GGT) were -28 and -33%, respectively (time effect, both p < 0.001; group effect, p = 0.28). Reduction in abdominal fat mass (measured by DXA from L1 to L4) independently predicted ΔALT (r = 0.42, p = 0.005) and ΔGGT (r = 0.55, p < 0.001), whereas change in dietary saturated fat intake was independently associated with ΔALT (r = 0.35, p = 0.03). CONCLUSIONS: Reductions in central adiposity and saturated fat intake are key drivers of improvement in liver enzymes during lifestyle interventions. Exercise training did not confer significant incremental benefits in this study.

Use of pulse oximetry during nitrous oxide- oxygen inhalation sedation: mandatory or recommended?

AIM: There is skepticism amongst many dentists about the interference of nitrous oxide with the physiological parameters. This commentary attempts to make clear recommendations on the use of pulse oximeter during nitrous oxide inhalation sedation. BACKGROUND: Nitrous oxide is used commonly in dentistry as a tool to reduce fear/ anxiety and build a positive dental attitude. Dentists use pulse oximeter to monitor oxygen saturation during the period of administration of nitrous oxide. There is no consensus amongst various guidelines across the world on the necessity of using pulse oximeter during the period of administration of nitrous oxide CONCLUSION: Pulse oximetry may not be considered mandatory when nitrous oxide gas is being administered for minimal sedation to a healthy patient having no pre- existing diseases/illness.

Development of a patient-reported outcomes and experience measure for Orthognathic surgery: validation of the Northwick Park Orthognathic Questionnaire (NOQ).

Orthognathic surgery aims to correct dentoskeletal and facial discrepancies. The expected benefits are functional, cosmetic, and psychological. In a previous publication, this group assessed the determinants of patient satisfaction to formulate the Northwick Park Orthognathic Questionnaire (NOQ). The aim of the present study was to validate this questionnaire. A total of 118 postoperative patients prospectively completed the NOQ, 30 of whom completed the questionnaire a second time. The mean completion rate was 87.6 ± 10%. Response reproducibility was high: 92% of patients gave identical responses (range 81-100%). The intra-class correlation coefficient (ICC) was 0.96 (0.96 ± 0.072). Average test-retest scores for each domain were as follows (range in parenthesis): reasons for treatment 93% (60-100%), preoperative experience 96% (81-100%), preparation for surgery 95% (81-100%), inpatient experience 89% (55-100%), post-discharge experience 83% (55-100%), benefits of treatment 92% (71-100%), overall patient education 91% (62-100%). Internal validity using Cronbach's alpha was 0.72 (standard deviation 0.23, range 0.5-1). The results confirm the consistency of responses and the reliability of the information collected with the NOQ. The NOQ is a novel questionnaire and a valid metric to quantify a patient's perception of their experience. Its adoption may aid in making targeted improvements to patient care.

A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody/Fc-gamma chain chimeric receptor gene recognizing a human ovarian cancer antigen.

In order to treat common cancers with immunotherapy, chimeric receptors have been developed that combine the tumor specificity of antibodies with T-cell effector functions. Previously, we demonstrated that T cells transduced with a chimeric receptor gene against human ovarian cancer were able to recognize ovarian cancer cells in vitro and in vivo. We now report that recipients of bone marrow cells transduced with these genes exhibited significant antitumor activity in vivo. Moreover, in vivo depletion of T cells in reconstituted mice did not affect antitumor activity, suggesting that other immune cells expressing the chimeric receptor gene may play an important role in tumor rejection.

Traumatic posterior fracture-dislocation of the fifth lumbar vertebra: report of two cases with review of literature.

INTRODUCTION: Posterior fracture-dislocation of fifth lumbar vertebra (L5) is a rare injury pattern. Existing Aihara classification system lacks its mention. CASE PRESENTATION: We report two cases of posterior fracture-dislocation of L5 with comminuted fracture of body that presented with cauda equina syndrome. The smaller anteroinferior vertebral body fragment of L5 had its relationship maintained with sacrum, whereas the larger posterosuperior fragment of the body was retropulsed. Decompression and instrumented fusion through posterior approach yielded good clinical outcome. DISCUSSION: We also present literature review with special emphasis on fracture characteristics and suggest its possible inclusion as a separate sub-type in existing Aihara classification.

Radiation dose tracking in computed tomography: Red alerts and feedback. Implementing a radiation dose alert system in CT.

INTRODUCTION: This study investigates instances of elevated radiation dose on a radiation tracking system to determine their aetiologies. It aimed to investigate the impact of radiographer feedback on these alerts. METHODS: Over two six-month periods 11,298 CT examinations were assessed using DoseWatch. Red alerts (dose length products twice the median) were identified and two independent reviewers established whether alerts were true (unjustifiable) or false (justifiable). During the second time period radiographers used a feedback tool to state the cause of the alert. A Chi-Square test was used to assess whether red alert incidence decreased following the implementation of radiographer feedback. RESULTS: There were 206 and 357 alerts during the first and second time periods, respectively. These occurred commonly with CT pulmonary angiography, brain, and body examinations. Procedural documentation errors and patient size accounted for 57% and 43% of false alerts, respectively. Radiographer feedback was provided for 17% of studies; this was not associated with a significant change in the number of alerts, but the number of true alerts declined (from 7 to 3) (χ2 = 4.14; p = 0.04). CONCLUSION: Procedural documentation errors as well as patient-related factors are associated with false alerts in DoseWatch. Implementation of a radiographer feedback tool reduced true alerts. IMPLICATIONS FOR PRACTICE: The implementation of a radiographer feedback tool reduced the rate of true dose alerts. Low uptake with dose alert systems is an issue; the workflow needs to be considered to address this.