Psychometric validation and responder definition of the sleep disturbance numerical rating scale in moderate-to-severe atopic dermatitis.

BACKGROUND: Sleep disturbance (SD) is an important part of the burden of atopic dermatitis (AD), but patient-reported outcomes that are easy to understand and interpret in the target population have been lacking. A daily, single-item, self-reported SD 11-point numerical rating scale (NRS) was recently developed to assess SD for patients with moderate-to-severe AD, but its psychometric properties have not yet been described. OBJECTIVES: To assess the psychometric properties of the SD NRS in patients with moderate-to-severe AD. METHODS: The psychometric properties of the SD NRS were assessed using data from a phase IIb clinical trial in 218 adults with moderate-to-severe AD. RESULTS: Test-retest reliability of the SD NRS was substantial to almost perfect (interclass correlation 0·66-1·00) in participants who had stable SD or stable pruritus scores over 1 week. Baseline correlations were moderate to large (r > 0·30) between SD NRS and pruritus or sleep loss scores, but were small (r = -0·11 to 0·17) between SD NRS and EQ-5D-3L index and visual analogue scores, Hospital Anxiety and Depression Scale, Scoring Atopic Dermatitis, and Investigator's Global Assessment. The SD NRS could discriminate groups of participants in the expected direction according to different quality-of-life scores but not according to different clinician-reported disease severity scores. SD NRS scores significantly decreased as sleep loss, itch and quality-of-life scores improved. Analysis of meaningful change suggested a 2-5-point improvement as the initial range of responder definition in the SD NRS score. CONCLUSIONS: The SD NRS is a reliable, valid and responsive measure of SD in adults with moderate-to-severe AD.

Longitudinal course and phenotypes of health-related quality of life in adults with atopic dermatitis.

BACKGROUND: The real-world course of health-related quality of life (HRQoL) in atopic dermatitis (AD) is not well established. AIM: To examine predictors, longitudinal course and phenotypes of HRQoL in adult patients with AD. METHODS: This was a prospective dermatology-practice based study of 955 patients with AD (age 18-97 years). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. HRQoL was assessed using the 10-item short-form Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health (PGH). AD severity and impact was assessed by patient-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), Objective SCORing Atopic Dermatitis (O-SCORAD), Investigator's Global Assessment (IGA), Numerical Rating Scale (NRS) average and worst itch, PROMIS sleep-related impairment (SRI), and nine-item Patient Health Questionnaire (PHQ)-9. Repeated-measures regression models were constructed to examine itch over time. RESULTS: In multivariable linear regression models controlling for age, race/ethnicity, history of asthma, hay fever and food allergy, baseline PGH-physical (PGH-P4) T scores were inversely associated with patient-reported global AD severity, POEM, EASI, objective SCORAD, IGA, NRS average and worst itch, PROMIS SRI and PHQ-9, with stepwise decreases of physical health with worsening severity. PGH-mental health (PGH-M4) T scores were associated with all aforementioned severity measures aside from POEM. In multivariable repeated measures linear regression models, decreased PGH-P4 and PGH-M4 T scores and mapped five-dimension EuroQoL over time were associated with self-reported global AD severity, NRS worst and mean itch, POEM, PROMIS sleep disturbance and SRI, EASI, objective SCORAD, IGA and PHQ-9. Latent class analysis identified six classes of HRQoL, which were associated with measures of AD severity, nonwhite race, Hispanic ethnicity and having only public health insurance, but not age or sex. CONCLUSION: Patients with AD have a heterogeneous longitudinal course and distinct patterns of HRQoL. Many patients had fluctuating HRQoL over time. Most patients with moderate to severe disease at baseline had persistent HRQoL impairment over time.

Clinical characteristics and disease burden in prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus, but information on patient experience and impact on quality of life (QoL) remains understudied. AIM: To characterize disease characteristics and QoL in a global sample of patients with PN. METHODS: An anonymous survey was distributed via patient support groups for PN. RESULTS: In total, 231 members responded to the survey. The majority of respondents reported itch localized both to nodules and to intervening skin (67.0%). Associated symptoms included prickling, pain, stinging and burning. The extensor lower legs (69% right, 67.3% left) and flexor forearms (66.1% right, 62% left) were the most common sites of itch. Participants reported frequent healthcare utilization, with 36.3% visiting a doctor ≥ 10 times in the past year. Physician-diagnosed anxiety (45.4%), depression (16.4%) and the atopic triad (18.7%) were commonly reported. Patients with PN had mean scores of 16.4, 11.6 and 16.8 on the Dermatology Life Quality Index, Pittsburgh Sleep Quality Index and 5-Dimensions Itch, respectively. CONCLUSIONS: Severe pruritus with accompanying pain, stinging and burning is characteristic of PN, with the majority of patients experiencing itch in both nodular and interlesional skin. Patients further report decreased QoL scores and impaired sleep. Patient experiences should guide future management of PN.

Association of prurigo nodularis and infectious disease hospitalizations: a national cross-sectional study.

BACKGROUND: Prurigo nodularis (PN) is associated with a variety of systemic comorbidities, including infectious diseases such as HIV and viral hepatitis. There are limited data on other infectious disease comorbidities in patients with PN. AIM: To characterize infectious disease hospitalizations among patients with PN and the associated cost burden. METHODS: We searched the 2016-2017 National Inpatient Sample, a cross-sectional sample of 20% of all US hospitalizations, for infectious disease hospitalizations among patients with PN. Associations of PN with infections and related costs were determined using multivariable logistic and linear regression, adjusting for age, race, sex and insurance type. RESULTS: PN was associated with any infection overall (OR = 2.98, 95% CI 2.49-3.56), and with HIV, cutaneous, hepatobiliary, central nervous system, bacterial, viral and fungal/parasitic infections and for sepsis. Patients with PN had a higher mean cost of care (US$11 667 vs. US$8893, P < 0.001) and length of stay (5.5 vs. 4.2 days, P < 0.001) for any infection overall and for 7 of 13 other infections. Adjusting for age, race, sex and insurance coverage, PN was associated with higher cost (+30%, 95% CI +17 to +44%) and higher length of stay (+30%, 95% CI +18 to +44%) for any infection overall, and for several specific infections. These associations remained with alternate regression models adjusting for severity of illness. CONCLUSION: There is a high infectious disease burden among patients with PN, corresponding to higher healthcare utilization and spending. Clinicians must be aware of these associations when treating these patients with immunomodulatory drugs.

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.

Methyl aminolevulinate daylight photodynamic therapy applied at home for non-hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany.

BACKGROUND: The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies. OBJECTIVE: To evaluate patient-reported outcomes, effectiveness and tolerability of patient self-applied MAL DL-PDT. PATIENTS AND METHODS: An open study was conducted in Germany in patients with thin or non-hyperkeratotic and non-pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL-PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post-treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded. RESULTS: Patients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation). CONCLUSIONS: Patient self-application of MAL DL-PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.

Evaluation of coamoxiclav and other antibiotics against S pneumoniae and H influenae from paediatric cases of acute respiratory infections.

Streptococcus pneumoniae and Haemophilus influenzae are most important respiratory pathogens with increasing antimicrobial resistance among the key pathogens responsible for community-acquired respiratory tract infections and have the potential to limit the effectiveness of antibiotics available to treat these infections. In the present study, a total of 18 isolates of Streptococcus pneumoniae and 9 isolates of Haemophilus influenzae were characterised from specimens obtained from patients of acute respiratory tract infections including otitis media, tonsillitis, bronchitis, pneumonia and sinusitis. In the present study, all the Streptococcus pneumoniae isolates were sensitive to coamoxiclav and to cefixime, while they showed variable resistance to the other antibiotics screened. The degree of resistance to various antibiotics was as follows: Streptococcus pneumoniae showed resistance to cotrimoxazole (66.7%), azithromycin (55.6%), erythromycin (16.7%), chloramphenicol (16.7%), clindamycin (11.1%) and penicillin (11.1%). Haemophilus influenzae showed resistance to cefixime 100%, chloramphenicol 88.9%, penicillin 77.8%, erythromycin 77.8%, cefuroxime 77.8%, azithromycin 77.8%, and clindamycin 11.1%. The present study showed the emergence of variable resistance to penicillin, cotrimoxazole and other antibiotics.

Efficacy and tolerability of aripiprazole in patients with schizophrenia & schizoaffective disorders.

Before the 1990s, treatment of psychoses centred on conventional agents whose tolerability was limited by extrapyramidal symptoms (EPS). The past decade has seen the emergence of newer generation of antipsychotic agents. These agents provide better negative symptom efficacy, less impaired cognition and lower risk of extrapyramidal syndromes. Aripiprazole, a new atypical antipsychotic drug, displayed efficacy similar to risperidone and haloperidol in numerous clinical trials. Aripiprazole does not cause significant prolactin elevation and is associated with a low rate of clinically significant weight gain compared with other atypical antipsychotics. Aripiprazole is a study drug for treating schizophrenia and has a novel pharmacologic profile. Aripiprazole provides a new treatment option with limited adverse effects for patients in need of antipsychotic therapy. The present study is a 4-week, open-labelled, randomized postmarketing clinical study conducted using aripiprazole as the study drug. Fixed doses of 15mg of the drug were administered throughout the study. A total of 249 patients with a primary diagnosis of schizophrenia or schizoaffective disorder were randomized. Efficacy measures included the Positive And Negative Syndrome Scale (PANSS) total, PANSS positive, PANSS negative and general psychopathology. Patients were evaluated for efficacy parameters at the end of 2(nd) week and also at the end of study. Unlike the other antipsychotics, aripiprazole was not associated with significant EPS, increase in body weight or increase in QTc interval. Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder.

The role of glucocorticoid pulse therapy in pulmonary involvement in leptospirosis.

OBJECTIVES: This study discusses incidence and clinical profile of pulmonary involvement in leptospirosis in South Gujarat. It also tries to evaluate the effect of high dose glucocorticoid pulse therapy (GPT) on it. METHOD: A study was carried out on hundred and two patients of suspected leptospirosis, referred to Government Medical College, New Civil Hospital, Surat between June 99 to September 99. The incidence, clinical profile, and specific investigations were studied in patients having pulmonary involvement. Some of the patients were given high dose glucocorticoid pulse therapy. Their outcomes were compared with those who had not been given glucocorticoid pulse therapy. RESULTS: Out of seventy seven seropositive patients 13 (16.8%) developed pulmonary involvement. Mortality was two out of eight patients in the group that received GPT and four out of five patients in the group that did not receive GPT. Two patients who died in the steroid treated group received the drug after 12 hours of onset of dyspnea. CONCLUSIONS: High dose GPT should be given as early as possible after the onset of dyspnea to all the patients with pulmonary involvement in leptospirosis. Further studies are required to establish the GPT as a standard regimen in treatment of pulmonary involvement in leptospirosis.

The fortuitous diagnosis of cholera in a two-year-old girl.

We are reporting the fortuitous diagnosis of a case of cholera and the unusual failure of the commercial bacteriologic media that led to the unexpected isolation of Vibrio cholerae. The case demonstrates the need for communication between the medical staff and laboratory personnel when an uncommon disease, such as cholera, is suspected. This case also alerts the clinician to the possibility of multiple enteric pathogens coinfecting a traveller.