Quality of life and patient-perceived symptoms in patients with psoriasis undergoing proactive or reactive management with the fixed-dose combination Cal/BD foam: A post-hoc analysis of PSO-LONG.

BACKGROUND: Psoriasis has important physical and psychosocial effects that extend beyond the skin. Understanding the impact of treatment on health-related quality of life (HRQoL) and patient-perceived symptom severity in psoriasis is key to clinical decision-making. OBJECTIVES: This post hoc analysis of the PSO-LONG trial data assessed the impact of long-term proactive or reactive management with fixed-dose combination calcipotriene 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) foam on patient-reported outcomes (PROs) in patients with psoriasis vulgaris. METHODS: Five hundred and twenty-one patients from the Phase 3, randomized, double-blind PSO-LONG trial were included. An initial 4-week, open-label phase of fixed-dose combination Cal/BD foam once daily (QD) was followed by a 52-week maintenance phase, at the start of which patients were randomized to a proactive management arm (Cal/BD foam twice weekly) or reactive management arm (vehicle foam twice weekly). Patient-perceived symptom severity and HRQoL were assessed using the Psoriasis Symptom Inventory (PSI), the Dermatology Life Quality Index (DLQI) and the EuroQol-5D for psoriasis (EQ-5D-5L-PSO). RESULTS: Statistically and clinically significant improvements were observed across all PRO measures. The mean difference (standard deviation) from baseline to Week 4 was -8.97 (6.18) for PSI, -6.02 (5.46) for DLQI and 0.11 (0.15) for EQ-5D-5L-PSO scores. During maintenance, patients receiving reactive management had significantly higher DLQI (15% [p = 0.007]) and PSI (15% [p = 0.0128]) and a numerically lower EQ-5D-5L-PSO mean area under the curve score than patients receiving proactive management (1% [p = 0.0842]). CONCLUSIONS: Cal/BD foam significantly improved DLQI, EQ-5D-5L-PSO and PSI scores during the open-label and maintenance phases. Patients assigned to proactive management had significantly better DLQI and PSI scores and numerically better EQ-5D-5L-PSO versus reactive management. Additionally, baseline flare was associated with worse PROs than the start of a relapse, and patients starting a relapse also had worse PROs than patients in remission.

Obstructive sleep apnoea as a late complication after tracheostomy.

BACKGROUND: Obstructive sleep apnoea occurs consequent to partial or complete upper airway obstruction, caused mostly by the collapse of upper airway musculature. Drug-induced sleep endoscopy represents the 'gold standard' in identifying the obstruction site, from the palatal level to laryngeal entry. Breathing impairment in sleep caused by the collapse of cervical trachea after previous tracheostomy has not yet been described in the literature. METHODS: This report presents two patients with severe obstructive sleep apnoea, in whom pre-operative drug-induced sleep endoscopy revealed upper airway and cervical trachea collapse at the level of previous tracheostomy. RESULTS: The female patient was successfully treated with resection of hypertrophic tissue of the tongue base via lateral pharyngectomy, and resection of the collapsed segment of the trachea with primary reconstruction of the trachea by end-to-end anastomosis. The male patient was recommended continuous positive airway pressure therapy because of serious co-morbidities and high operative risk. CONCLUSION: Drug-induced sleep endoscopy should always be used for visualisation of anatomical structures below the vocal folds in patients with a history of cervical trachea surgery. These two cases demonstrate the importance of drug-induced sleep endoscopy in planning conservative and surgical treatments, contributing significantly to operative success.

Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis.

BACKGROUND: Three biotherapies - etanercept, adalimumab and ustekinumab - are licensed in childhood psoriasis. The few data available on their efficacy and tolerance are mainly derived from industry trials. However, biological drug survival impacts long-term performance in real-life settings. OBJECTIVE: The objective of this study was to evaluate the survival rates of biological therapies in children with psoriasis in real-life conditions. Secondary objectives were to evaluate the factors associated with the choice of the biological therapy and to report severe adverse events. MATERIALS AND METHODS: This study was an observational retrospective study. Data were extracted from the clinical records of 134 children. Kaplan-Meier estimates were used to analyse drug survival overall and in subgroups of plaque psoriasis, bio-naïve and non-naïve patients. RESULTS: We analysed 184 treatment courses: 70 with etanercept, 68 with adalimumab and 46 with ustekinumab. Factors associated with the choice of first-line biological agent were age at initiation (younger for adalimumab, P < 0.0001), age at onset of psoriasis (younger for adalimumab and etanercept, P = 0.03) and baseline Psoriasis Assessment Severity Index and Physician global assessment (both higher for adalimumab, P < 0.001). Drug survival rates were higher for ustekinumab than for adalimumab and etanercept (P < 0.0001) for all treatment and all psoriasis types, plaque-type psoriasis (P = 0.0003), patients naïve for biological agents (P = 0.0007) and non-naïve patients (P = 0.007). We reported eight serious adverse events (SAEs): severe infections (n = 3), significant weight gain (n = 2), psoriasis flare (n = 1) and malaise (n = 1). Biological therapy was discontinued in three children (one with psoriasis flare and two with weight gain). Only the two cases of weight gain resulted in an unfavourable outcome. CONCLUSIONS: Our real-life comparative study found that ustekinumab had the best drug survival outcome. The profile of SAEs in children was comparable to that in adults. These results will assist dermatologists in the decision-making process when choosing treatment options for children with psoriasis in daily practice.

Psoriatic arthritis screening by the dermatologist: development and first validation of the 'PURE-4 scale'.

BACKGROUND: Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identify patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice. OBJECTIVE: To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis. METHODS: After the literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012 and 2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques. RESULTS: One hundred and sixty-eight patients were recruited, of whom nine were excluded for known PsA and 21 did not attend the rheumatologist consultation. Of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained four independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged <50. A total score (the PURE-4) was computed (0-4 points) that demonstrated excellent discriminative power (AUC = 87.6%; Sensitivity = 85.7% and Specificity = 83.6% at the threshold of ≥1/4 points), with no evidence for over-optimism in bootstrapped internal validation. CONCLUSION: These findings demonstrate the good diagnostic properties of a new screening scale using only four easy-to-collect items. If confirmed in other populations, it may prove useful in outpatient dermatology clinics for triage of psoriasis patients requiring further assessment by the rheumatologist.

Absence of Helicobacter pylori in healthy laryngeal mucosa.

OBJECTIVES: To evaluate the presence of Helicobacter pylori in healthy laryngeal mucosa. DESIGN: Prospective analysis of Helicobacter pylori colonisation in healthy laryngeal mucosa, using the 13C urea breath test and polymerase chain reaction analysis. SUBJECTS: Twenty randomly chosen men (28-78 years) without laryngeal pathology or gastrointestinal disease were investigated. All subjects were scheduled for elective operative procedures, under general, endotracheal anaesthesia. Cytobrush samples were taken for Helicobacter pylori DNA detection. Nested polymerase chain reaction testing was performed on DNA solutions using two primer pairs from the urease A gene of the Helicobacter pylori genome. The 13C urea breath test was performed on two exhalation samples. RESULTS: Eight (40 per cent) of the subjects were positive for urease on urea breath testing; none were positive for Helicobacter pylori DNA on polymerase chain reaction testing. CONCLUSION: Based on these results, we do not consider Helicobacter pylori to be a normal constituent of healthy laryngeal microflora.

Immunohistochemical analysis and prognostic value of cathepsin D determination in laryngeal squamous cell carcinoma.

Cathepsin D, a protease with the capability of degrading matrix proteins, is implicated in the process of breast and colorectal cancer invasion and metastasis. Biochemical studies in laryngeal cancer have shown a potential prognostic significance of cathepsin D content determination. We studied immunohistochemical positivity of cathepsin D in tumor epithelium and stroma of 61 surgical specimens of squamous cell laryngeal cancer. Immunohistochemical reaction was quantitatively assessed using a PC-based image analysis system SFORM-VAMS. The results were correlated to clinical and morphological parameters and survival. Immunohistochemical positivity was noted in neoplastic cells and tumor stroma. Significant prognostic value for cathepsin D was established separately for epithelial tumor component and tumor stroma using log-rank test, the Cox proportional hazards regression model, and C4.5 machine learning system. In all groups, patients above the median cathepsin D staining showed significantly shorter survival time. C4.5 machine learning system extracted cutoff values for the decision tree that defines the probabilities of patients survival and death with high sensitivity (92.8% alive, 73.6% dead), 100% specificity, and 86.9% accuracy. This makes immunohistochemical cathepsin D estimation an independent prognostic parameter in laryngeal carcinomas within a 5-year period from the time of tumor surgery.

Prognostic factors in squamous cell carcinoma of the larynx.

Sixty-three patients with squamous cell carcinoma of the larynx were included in a retrospective study examining the influence of the following prognostic indicators: localization, size of primary tumor, presence or absence of neck metastases, disease stage and histologic grade of differentiation. Flow cytometric analysis of the cell cycle, DNA ploidy and proliferative activity as direct prognostic indicators of tumor aggression was performed on paraffin-embedded blocks of specimens taken from 36 patients. Supraglottic tumor localization (p = 0.008), greater tumor size (p = 0.0064), local neck metastases (p = 0.00009), higher clinical disease stage (p = 0.0030), DNA aneuploidy (p = 0.0091), higher overall activity (p = 0.0001), and higher overall proliferative activity of diploid tumors (p = 0.0017) were found to be significant single unfavorable prognostic indicators of overall survival, whereas the histological grade of differentiation was not found to be a reliable prognostic indicator (p = 0.988). Only a higher overall proliferative activity of tumor cells was confirmed by the multivariate analysis as a reliable unfavorable prognostic indicator (p = 0.013). Cellular DNA content (ploidy, overall proliferative activity and overall proliferative activity of diploid tumors) correlated significantly with primary localization and size of the tumor, the presence of local metastases in the neck and the disease stage.

Prognostic factors in carcinoma of the larynx: relevance of DNA ploidy, S-fractions and localization of the tumour.

The influence of the cell cycle profile and the site of the primary tumour on the overall survival were examined in 36 patients with squamous cell carcinoma of the larynx. DNA ploidy (p = 0.0091), the overall proliferative activity (p = 0.0001), the overall proliferative activity of diploid tumour cells (p = 0.0017) and primary tumour site (p = 0.0008) were found to be significant single prognostic factors of the overall survival. Multivariate analysis showed that only the overall proliferative activity was prognostically significant (p = 0.013). The results of the study show that the supraglottic site of the tumours correlates significantly with DNA ploidy (p = 0.0334) and the overall proliferative activity of tumour cells (p = 0.0159), whereas the correlation with proliferative activity of diploid tumour cells (p = 0.1416) has not been confirmed by this study. Glottic tumours showed a prognostically significant correlation with the overall proliferative activity (p = 0.0037) and proliferative activity of diploid tumour (p = 0.0054). Such a prognostic correlation was not found for DNA ploidy (p = 0.6542).

Mortality caused by war wounds to the head and neck encountered at the Slavonski Brod Hospital during the 1991-1992 war in Croatia.

From July 1, 1991, until January 1, 1993, a total of 7,720 patients (soldiers and civilians) with war wounds were treated at Dr. Josip Bencevic General Hospital in Slavonski Brod, Croatia. Treatment was provided for 7,043 patients, whereas 677 individuals (8.8%) killed in action (KIA) were examined at the Forensic Department. There were 1,456 patients (18.9%) with head and neck wounds: 1,176 soldiers and 280 civilians. The mortality rate was significantly greater in patients with head and neck wounds (N = 271, 40.0%) than in those with injuries to the thorax (N = 163, 24.1%) and abdomen (N = 62, 9.2%; p < 0.01 for both). During treatment, 188 patients (2.4%) died of wounds (DOW). The DOW mortality was 5.2% (61 of 1,185), 4.0% (41 of 1,026), and 2.9% (25 of 867) for wounds of the head and neck, thorax, and abdomen, respectively. There was no significant difference in the mortality rate between head and neck and thorax wounds: however, the former exceeded the mortality rate recorded for abdominal wounds (p < 0.05). No significant differences were observed between soldiers and civilians with head and neck injuries either in the KIA (205 of 1,176, 17.4% vs. 66 of 280, 23.5%, respectively) or the DOW group (51 of 971, 5.3% vs. 10 of 214, 4.7%, respectively. According to the mechanism of head and neck wounding, there were 1,046 explosive (71.9%), 226 gunshot (15.5%), and 184 other (12.6%) wounds. Lethal outcome was significantly more common in gushot than in explosive wounds (79 of 226, 35% vs. 243 of 1,046, 23.2%; p < 0.01). The proportion of head and neck injuries did not differ significantly from literature reports on recent conventional wars. The site of wounding, i.e., at the battlefield or elsewhere, had no effect on the prognosis of wounds to the head and neck. Gunshot head and neck injuries showed a significantly higher mortality rate.

War injuries to the head and neck.

During the 1991-1992 war in Croatia, 7,043 wounded persons were treated at Dr Josip Bencevic General Hospital in Slavonski Brod. Among them, 728 (580 soldiers and 148 civilians) had war injuries to the head and neck and were admitted to the Department of Otorhinolaryngology and Cervicofacial Surgery. There were 541 (74.3%) patients with head injuries, 117 (16.0%) with neck injuries, and 70 (9.6%) with a combination of head and neck injuries. The wounds were mostly inflicted by shell and bomb fragments (542 wounds, or 74.5%). War injuries of the facial bones were preliminarily or definitively treated. Preliminary treatment was used for the wounds with multifragmentary fractures and extensive soft-tissue defects. Definitive treatment was used in lesions of cervical structures. Immediate exploration of the neck was performed on 84 patients with penetrating neck wounds. Exploration was positive in 49 patients. Concerning long-term complications, two cases of partial paralysis of the cranial plexus and one case each of quadriplegia, hemiplegia, and glottic paralysis were recorded. To our knowledge, primary closure of war wounds to the head and neck (supported by antibiotic therapy) and reconstruction of extensive laryngotracheal injuries with the medial layer of the cervical deep fascia were used for the first time as war surgery procedures.

Organization and work of medical service during 1992 military operations in north Bosnia (Bosanska Posavina).

During military operations in Bosanska Posavina in 1992, 6,105 soldiers of the army of the Croatian Defence Council (Bosnian Croats and Muslims) were treated at various health care levels: 920 soldiers were killed, 3,258 were heavily wounded, and 1,927 lightly wounded. The treatment was provided in medical units organized on the front line, in the combat area, and in the communication area. On the front line, medical service was organized as battalion units, whereas the area in general was medically covered by the Slavonski Brod Medical Center in Croatia. Slavonski Brod played a key role with surgical treatment of 5,418 wounded, and definitive care was offered to most subjects seeking medical aid. Scarcity of medical personnel on the front lines and long lines of transportation resulted in a 6.5% death rate (354 patients) during transportation from Bosnian battlefields to Slavonski Brod. In contrast, the mortality rate in the Slavonski Brod Hospital was 3.0% (161 patients). Convalescence homes were established in the Slavonski Brod surroundings, whereas specialized health institutions and rehabilitation centers throughout Croatia accommodated those needing advanced treatment.

Acute laryngeal trauma: a comparison between peace time and war injuries.

Thirty-six patients with acute laryngeal trauma are presented. Sixteen patients had peace-time and 20 had war injuries. Peace-time injuries were mostly due to car accidents, violence and suicide using a knife, whereas the war injuries were caused by shell and mine fragments. Nine patients were treated conservatively (eight peace-time and one war-time) and 27 by surgery (eight peace-time and 19 war-time). Surgical experience showed that acute laryngeal trauma must be treated within the first 24 hours after injury. Primary treatment must be a definite one. In that way complications and uncontrolled healing can be successfully avoided.

Management of war-related neck injuries during the war in Croatia, 1991-1992.

From 1 September 1991 to 31 December 1992, a total of 7,043 wounded patients were treated in the War Hospital in Slavonski Brod. Seven hundred and twenty eight patients with head and neck injuries were treated in the Department of Otorhinolaryngology and Cervicofacial Surgery. Of this number, 187 had neck injuries. Ninety-two (49.2%) of them were treated in outpatient facilities and 95 (50.8%) as inpatients. Immediate exploration was done in 84 patients with penetrating neck injuries. Vital structures were involved in 49 patients: major blood vessels (40 cases), larynx (17 cases), pharynx (8 cases), trachea (5 cases), thyroid gland (3 cases) and esophagus (2 cases). Definitive treatment was given to all of these injuries. Primary wound closure was performed upon exploration in 74 patients who were treated within the first 6 h after trauma. Secondary wound closure was performed in 10 patients with neck exploration performed more than 6 h after injury, and in those with extensive defects of tissue requiring the use of larger local flaps or free flaps. The mortality among patients with neck injuries was 2.1%.

Work of the Slavonski Brod General Hospital during the war in Croatia and Bosnia and Herzegovina in 1991-1992.

Between September 1, 1991, and December 31, 1992, 7,043 wounded persons, 4,566 of them heavily wounded, were treated at the Slavonski Brod General Hospital. There were three characteristic periods in the work of the hospital during the war. Until March 31, 1992, the hospital provided care for the wounded from the east- and west-Slavonian fronts, at the level of the fourth echelon. The second period started with war actions in Bosanska Posavina and Bosnia and Herzegovina, when the Slavonski Brod General Hospital was the only place offering appropriate care to the wounded from the area. During that period, surgical professions and, to a limited extent, conservative professions were working at the hospital. The third period began with the fall of Bosanska Posavina, toward the end of October 1992, and lasted until the end of the year. During that period, the number of the wounded and previously surgically treated at the Tolisa War Hospital, in the unoccupied area of Bosnia and Herzegovina, admitted to the Slavonski Brod General Hospital, decreased. The total mortality rate in the treated subjects was 2.66%, whereas during the war in Bosanska Posavina it was 3.0%. Throughout the war, there was no interruption in the work of hospital conservative professions, although the extent of their work was reduced.

Reconstruction of laryngotracheal war injuries with the median layer of the deep cervical fascia.

Surgical exploration and immediate reconstruction with the median layer of the deep cervical fascia (MLDCF) was performed in 8 of 22 patients with exogenous war injuries of larynx and cervical trachea. A surgical technique of reconstruction with the median layer of the deep cervical fascia is described. The 7 surviving patients had good respiration without signs of stenosis of the larynx and/or the trachea. Four had good and 3 satisfactory, phonation, and none had swallowing difficulties. Owing to the simplicity of the surgical approach, its size and biological properties, the median layer of deep cervical fascia proved itself to be a suitable material in the immediate reconstruction of exogenerous war injuries of the larynx and cervical trachea.

Laryngeal war injuries.

During the war in Croatia in the region of Brodska Posavina at the Medical Center in Slavonski Brod, 7,043 wounded were treated. The Otolaryngology and Oral Surgery Service treated 728 wounded, of whom 20 had laryngeal injuries. Most of the injuries were caused by shrapnel from shells, mines, and hand grenades. Nineteen wounded had associated injuries of the neck, head, and the neck and/or other parts of the body. The authors performed in 8 surgical explorations and immediate reconstruction with the median layer of the deep cervical fascia (MLDCF). Upon termination of the treatment, the nineteen wounded had good respiration without signs of stenosis of the larynx. Twelve had good phonation, five satisfactory phonation, and two bad. None had swallowing difficulties. Among the eight wounded on whom the reconstruction of the larynx was done with cervical fascia, four had very good phonation, three satisfactory, and the eight died on the sixth postoperative day because of associated injuries to the cervical spine. The cervical fascia proved itself to be a suitable material in the immediate reconstruction of exogenous war injuries of the larynx.