A multicenter,randomized, open-label pilot trial assessing the efficacy and safety of etanercept 50 mg twice weekly followed by etanercept 25 mg twice weekly,the combination of etanercept 25 mg twice weekly and acitretin,and acitretin alone in patients with moderate to severe psoriasis

Background

Etanercept, a soluble tumor necrosis factor receptor, and acitretin have been shown to be effective in treating psoriasis. Acitretin is widely used in Korea. However, the combination of etanercept plus acitretin has not been evaluated among Korean patients with psoriasis. The objective of this study was to investigate the efficacy and safety of combination therapy with etanercept and acitretin in patients with moderate to severe plaque psoriasis.

Methods

Sixty patients with psoriasis were randomized to receive etanercept 50 mg twice weekly (BIW) for 12 weeks followed by etanercept 25 mg BIW for 12 weeks (ETN-ETN); etanercept 25 mg BIW plus acitretin 10 mg twice daily (BID) for 24 weeks (ETN-ACT); or acitretin 10 mg BID for 24 weeks (ACT). The primary efficacy measurement was the proportion of patients achieving 75 % improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Secondary end points included 50 % improvement in PASI (PASI 50) at week 24 and clear/almost-clear by Physician Global Assessment (PGA) at each visit through week 24.

Results

The proportions of patients achieving PASI 75, PASI 50, and PGA clear/almost-clear at week 24 in the ETN-ETN (52.4, 71.4, and 52.4 %, respectively) and ETN-ACT groups (57.9, 84.2, and 52.6 %, respectively) were higher than in the ACT group (22.2, 44.4, and 16.7 %, respectively). The incidence of adverse events was similar across all arms. This was an open-label study with a small number of patients.

Conclusion

In Korean patients with moderate to severe plaque psoriasis, etanercept alone or in combination with acitretin was more effective than acitretin. All treatments were well tolerated throughout the study.

Trial registration

This study was registered on July 7, 2009 at ClinicalTrials.gov, NCT00936065.

     

Efficacy, safety and medication cost implications of adalimumab 40 mg weekly dosing in patients with psoriasis with suboptimal response to 40 mg every other week dosing: results from an open-label study

Background The clinical utility of increasing to weekly adalimumab therapy in patients with psoriasis with inadequate response to every other week (eow) dosing is unknown. Objectives (i) To determine the effectiveness of escalating adalimumab dosage from 40 mg eow to 40 mg weekly in patients with < PASI 50 response following ≥ 24 weeks treatment. (ii) To identify retrospectively characteristics of patients likely to benefit from dose escalation using classification and regression tree analysis. (iii) To assess cost implications for allowing dose escalation from the private payers’ perspective. Methods Patients with moderate‐to‐severe psoriasis who had received blinded adalimumab 40 mg eow or placebo in antecedent phase II/III studies could enrol in an open‐label extension (OLE) and initially receive open‐label adalimumab 40 mg eow (EOW population). On/after week 24 (OLE), patients with < PASI 50 response relative to baseline of antecedent study could increase to 40 mg weekly. The dosage escalation population continued on weekly dosing until achieving PASI 75 response, then resumed eow dosing. Study visits were 6/12 weeks after dosage escalation, and every 12 weeks thereafter. The percentage of patients who achieved PASI 75 response following dosage escalation was determined (missing PASI scores imputed as nonresponse). Safety was assessed for the dosage escalation population and for all adalimumab exposure that did not follow dosage escalation in the EOW set. Results In total, 349/1256 (27·8%) patients underwent dosage escalation (OLE). At 12/24 weeks after dosage escalation, 93/349 (26·6%)/133/349 (38·1%) were PASI 75 responders or resumed eow dosing. Secondary nonresponders, patients weighing ≤ 102 kg, and those with disease duration < 8·3 years were most likely to benefit from dose escalation. Rates of serious/serious infectious/malignant (excluding nonmelanoma skin cancers or lymphoma) adverse events were 6·8/0·9/1·4 events per 100 patient‐years (dosage escalation population); comparable rates in the EOW set were 6·5/1·2/0·5 events per 100 patient‐years. Conclusions Most patients did not require dose escalation. By 12 weeks after dose escalation, one‐quarter achieved substantial clinical improvement. Safety results were similar between patients who dosage‐escalated and those who did not.     

Delay in the diagnosis of leprosy in the Metropolitan Region of Vitória, Brazil

This paper reports on the time between the onset of the first lesion and diagnosis, defined as delay, and is based on results obtained by interviewers from a survey carried out amongst 450 leprosy patients in a leprosy endemic area in the Metropolitan Region of Vitória (MRV), state of Espirito Santo, Brazil. The mean age at diagnosis in all cases was 41.47 years and the median was 42.5 years. The mean age at diagnosis in MB (42.9 years) was greater than in PB (38.5 years). The mean of the delay in all cases was 25.25 months, median 12 months and range 0-360 months. The mean of the delay in MB (27.2 months) was greater than in PB (21.3 months). The results of this study suggest that although the delay in leprosy diagnosis in this region of Brazil was not too long when it was compared with other studies in endemic countries, it is still a problem: 65.4% of patients were diagnosed after a delay of 6 months. The Leprosy Control Programme in this state needs more effective health education in order to reduce the current period of delay before diagnosis.     

Prevalence and incidence of pressure injuries in pediatric hospitals in the city of São Paulo,SP, Brazil

Objective

To identify the incidence and prevalence of pressure injuries (PIs) in children admitted to hospitals in the city of São Paulo, and assess the association between sociodemographic and clinical characteristics with hospital-acquired pressure injuries (HAPIs).

Prevalence of Behçet's disease in Istanbul, Turkey

Background The prevalence of Behçet's disease (BD) is much higher in countries along the ancient Silk Route, extending from Japan to Mediterranean countries including Turkey, than in northern Europe and the USA. Three previous epidemiologic surveys have been carried out in different regions of Turkey. Patients and methods This study investigated the cross‐sectional prevalence of BD in individuals aged > 12 years in Istanbul, Turkey, in two stages. The first stage aimed to identify individuals with recurrent oral ulcers (ROUs) by visiting them in their homes, and the second stage aimed to further examine those with ROUs for the presence of other BD‐related manifestations under hospital conditions. The sample size was determined to be 24,000 with an expected BD prevalence rate of 1/1000 and a sampling error of 4/10,000, with a 95% confidence interval (CI) of 6–14/10,000. The number of individuals to be screened in each district was determined in proportion to the population of all districts in Istanbul. Results The standard questionnaire was applied to a total of 23,986 individuals at their homes. A history of ROU was recorded in 2289 individuals (9.5%), and a previous diagnosis of BD was recorded in 47. The diagnosis of ROU was confirmed in 700, and the diagnosis of BD was established in 101 according to the International Study Group criteria. The prevalence rate of BD was estimated as 42/10,000 (95% CI, 34–51/10,000) in Istanbul, Turkey. Conclusions This survey conducted in Istanbul, the largest cosmopolitan city in Turkey with immigrants from all over the country, has a larger sample size than other previous studies, and therefore the reported prevalence rate of BD has a more acceptable confidence interval. This study aids in the estimation of the prevalence of BD in Turkey, and supports previous findings that Turkey has the highest prevalence rate of the disease in the world.     

Acne in Lomé, Togo: clinical aspects and quality of life of patients

Background

Acne is a chronic inflammatory condition affecting the pilosebaceous follicle that mainly affects adolescents and young adults. The aim of this study was to assess the quality of life (QOL) of patients with acne, and to determine the correlation between the QOL and the severity of acne, in Lomé (Togo).

Method

From July 2017 to February 2018, we conducted a study in three dermatology departments of Lomé. The clinical evaluation of acne and assessment of the QOL were done using the ECLA (Echelle de Cotation des Lésions d’acné) and CADI (Cardiff Acne Disability Index) scores respectively.

Results

We enrolled 300 patients aged 12 to 52 years; 71.3% of whom were female. The face was affected by acne in 100% of cases and papulopustular acne was the most common clinical form (66.7%). Acne was mild to moderate in 162 patients (54%) and severe in 138 (46%). Impairment was observed in all patients’ QOL (scores ranged from 1 to 14 points). There was a positive correlation between severity of acne and QOL impairment in the patients (r?=?0.21; p?=?0.0002). We also found a positive correlation between overall CADI score and factors F1 and F3 of the ECLA scale: the severity of facial acne (r?=?0.15; p?=?0.0073) and the presence of scars (r?=?0.21; p?=?0.0002). In contrast, the global ECLA score was significantly correlated with items 2, 3, and 5 of the CADI questionnaire: the patient’s relationship (r?=?0.13; p?=?0.0241), avoidance behaviors (r?=?0.21; p?=?0.0002) and perception of acne (r?=?0.16; p?=?0.0067).

Conclusion

Acne negatively impacts the QOL of patients. The severity of acne has an impact on the patient’s relationships, avoidance behaviors and perception of the acne.

     

Serum concentration of IL-6, IL-2, TNF-α, and IFNγ in Vitiligo patients

Background:

Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research has greatly supported the ‘Autoimmune theory’ and this is supported by the frequent association of vitiligo with disorders that have an autoimmune origin, including Hashimoto''s thyroiditis, Graves disease, type 1 insulin-dependent diabetes mellitus, and Addison''s disease. As cytokines are important mediators of immunity, there is evidence to suggest that they play a major role in the pathogenesis of autoimmune diseases.

Aim:

Keeping this in view we have assayed sera for cytokine IL-6, IL-2, Tumor necrosis factor (TNF)-α, and IFNγ in 80 cases of vitiligo and compared it with healthy subjects, in order to find out whether they play a role in the pathogenesis of vitiligo or not.

Materials and Methods:

Serum IL-6, IL-2, TNF-α, and IFNγ were done by the indirect enzyme linked immunosorbent assay (ELISA).

Results:

The mean serum IL-6 and IL-2 levels in the patient group were significantly higher when compared with those of the normal controls. The mean serum IFNγ level in patients with vitiligo was significantly lower than that in the control group. There was no significant difference in the serum level of TNF-α between vitiligo and healthy controls.

Conclusion:

An increase in the production of proinflammatory cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role in melanocytic cytotoxicity. Thus, we speculate that the cytokine production of epidermal microenvironment may be involved in vitiligo.     

以利福平每日450mg、或每月一次1200mg、伴服DDS每日50mg、治疗瘤型麻风病人的疗效

对30例瘤型麻风病人在常规服用DDS的同时,加服利福平每日450mg或每月一次1200mg以观察其对临床、细菌及组织病理学方面的效果。利福平每月一次1200mg,共6个月的疗法对于菌多的麻风病(LL.LI及BL)作大规模的、一次的和强力的治疗时,在治疗上和经济上都是比较理想和易于管理监督的。此种试验在极大范围内解决了关于以利福平治疗麻风病的剂量、治疗间歇和治疗期限的问题,因为这些问题在许多年来,一直使麻风病学家们感到为难。这次具有控制性的临床试验,指出了一种有实际性和实用性的疗法,即是对于多菌性各型麻风,可以使用此种利福平每月一次的疗法。有人提议用DDS 50～100mg/日(1.5～2mg/kg体重),LamprenelOOmg及利福平每月一次1200mg,三种药物交替服用6个月,作长期随访,以观察研究。以此三种药物轮流交替治疗LL、LI和BL病人,将会证明是有效的,相当安全的和很经济的。而且此种联合疗法,能够更迅速地控制传染和防止抗药性的产生。     

Sunscreen applied at ≥ 2 mg cm−2 during a sunny holiday prevents erythema,a biomarker of ultraviolet radiation-induced DNA damage and suppression of acquired immunity

Rates of skin cancer are increasing more rapidly in the UK than any other form of cancer. The deadliest form of the disease is melanoma skin cancer, which affects 128% more people now than it did 28 years ago. Sun protection factors (SPFs) are known to protect the skin from sunburn when sunscreen is applied at 2 mg per cm^-2. However, whilst on holiday, people typically apply just 0.8 mg cm^-2 of sunscreen. This study aimed to identify if typical sunscreen application during a holiday with daily sun exposure results in skin cancer risk factors such as sunburn. Participants spent one week in Tenerife, a country with a very high ultraviolet index. 22 participants applied their own sunscreen without instruction and 40 participants were given SPF 15 sunscreen and guidance on effective application (three times daily at 2 mg cm^-2). It was found that participants who followed typical sunscreen application displayed significantly greater levels of sunburn and other risk factors associated with skin cancer compared to those who followed optimal application guidelines to achieve SPF 15. Individuals who followed the effective application guidelines with SPF 15 sunscreen had no sunburn on five exposed body sites. The results of this study highlight how typical sunscreen use is not providing sufficient protection from the sun in the majority of people. As well as this, it is demonstrated that sunburn is associated with an increased risk of developing skin cancer. Therefore, achieving an adequate SPF by teaching the general public how to properly apply sunscreen may be an important step in preventing skin cancer.     

Clinical and histological characteristics,and management of melanoma in French Guiana, 2007–2018

There are few studies available on melanoma in Afro-Caribbean and Amerindian populations of South America. French Guiana deserves a study due to its specific health system and diversity of phototypes. The objectives of this study were to evaluate the incidence, histological and clinical characteristics of melanoma in French Guiana. A retrospective study was conducted from October 2007 to January 2018 on all primary melanomas observed at the Cayenne Hospital Centre. Thirty-nine patients were included. The incidence rate (1.61/10⁶ inhabitants/year) was low compared with mainland France. Median age was 58, and gender ratio 1 : 16. Clear phototype (I/II) patients were the most frequent (38.5%), but a significant amount of melanoma also occurred in darker skin. Median Breslow was higher in dark phototypes than in fair-skinned patients. Superficial spreading melanoma (SSM) was the most common histological type (33.3%), particularly in patients with clear phototype (61.5%). Acral lentiginous melanoma was found only in darker-skinned patients (29.1%). The trunk was involved in 66.6% in the clearest group whereas foot was the most common location in the darkest group (60% in V/VI phototypes). Surgery was the most frequently used treatment (79.5%). At the end of the study period, 53.8% had been lost to follow-up. In conclusion, the incidence of melanoma in French Guiana is lower than in mainland France but remains a public health concern, as dark-skinned populations often present with advanced diseases. Awareness and prevention in these communities must be improved.     

氟康唑每日50mg治疗慢性甲沟炎

慢性指甲甲沟炎多为念珠菌属所致。该文报告了口服广谱抗真菌药氟康唑 5 0ｍｇ/ｄ治疗慢性甲沟炎的疗效和安全性。试验为开放性研究 ,1 5例患者 (女 1 3例 ,男 2例 ,年龄 2 7～ 48岁 )每日口服氟康唑 5 0ｍｇ ,共 3个月。所有患者分别有 2～ 7个手指甲沟炎 ,5例合并有甲癣 ,病史 6月至 4年 ,均曾用过局部抗真菌治疗 ,其中 4例曾口服酮康唑和伊曲康唑治疗无效。患者均体健 ,无银屑病或“特应性”病史。患者治疗前、后作真菌学检查 ,并在疗前及治疗中每 4周进行血常规、全血细胞计数和肝肾功能检查。在治疗的第 4、8和 1 2周及停药后 6周和 6…     

Epidemiology of Kaposi's sarcoma in patients with acquired immunodeficiency syndrome in São Paulo, Brazil

Background Kaposi's sarcoma (KS) is the most frequent neoplasm in patients with acquired immunodeficiency syndrome (AIDS). Although many studies on KS epidemiology have been performed in other countries, few have been carried out in Brazil despite the high incidence of AIDS. Methods One hundred and seven KS patients seen in São Paulo, Brazil, between August 1995 and November 1998 were studied. The patients were followed for 1 year with assessment of the immunologic status, improvement of the lesions, treatment, and causes of death at the end of this period. Results KS occurred mainly in men (94.4%) with a mean age of 37 years, and 25.2% of these patients were found to be human immunodeficiency virus (HIV) seropositive through KS. HIV was acquired mainly through homosexual contact. The patients presented an average of 15.9 KS lesions at the first visit and the mean duration of KS lesions before the first visit was 15.5 months. The clinical presentation was predominantly papules and plaques, and 33.6% presented with mucosal and/or visceral disease. KS affected mainly the lower limbs. The mean time since the diagnosis of HIV infection was 42.4 months. The CD4+ cell count was lower than 200 cell/mm³ in 60.8% of patients, but patients with a complete response showed an improvement in immune status after 1 year. Patients who did not show progression received a protease inhibitor as part of highly active antiretroviral therapy (HAART). Patients treated exclusively with HAART presented a complete response (61.6%), partial response (23%) or progression (15.4%) of KS. Conclusions An improvement in immune status and the use of HAART were the most important prognostic features.     

司库奇尤单抗300 mg和150 mg治疗银屑病性关节炎长期疗效比较meta分析

目的：比较司库奇尤单抗300 mg和150 mg治疗银屑病性关节炎(PsA)长期疗效的差异。方法：在Pubmed、Cochrane Library、 MEDLINE、EMBASE、中国知网、万方数据库和维普数据库中检索司库奇尤单抗300 mg和150 mg治疗PsA的随机对照试验（RCTs），提取相关数据，用RevMan5.3软件进行meta分析。结果：根据纳入标准共纳入5篇文献进行分析，包括3项RCTs。52周时，司库奇尤单抗300 mg治疗后美国风湿病学会疗效标准改善20%、50%及70%（ACR 20/50/70）的应答率、起止点炎缓解率、指趾炎缓解率与150 mg相比无显著差异，而300 mg治疗的PASI提高75%、90%（PASI 75/90）应答率均高于150 mg（P=0.002，0.01）。52周时，接受过肿瘤坏死因子抑制剂治疗(TNFi-exposed)的患者司库奇尤单抗300 mg治疗后ACR 20和PASI 75应答率均高于150 mg（P=0.006，0.04），而在未接受过肿瘤坏死因子抑制剂治疗(TNFi-naive)患者中300 mg和150 mg治疗后ACR 20和PASI 75应答率无显著差异(P=0.85，0.59)。结论：在长期疗效方面，司库奇尤单抗300 mg对PsA患者关节损害及功能的改善与150 mg无显著差异，而对皮损的改善有优势；对TNFi-exposed的PsA患者，司库奇尤单抗300 mg比150 mg有更好的疗效。