實證醫學報告 藥劑科 黃佳真 藥師

實證醫學的五大進行步驟 Five Steps to Practice EBM Formulate an answerable question. (PICO) 由個案的臨床資料形成可回答的臨床問題 Track down the best evidence. (Search database) 尋找最佳的實證﹝各種文獻及資料庫，包括發表及未發表資料﹞ Critically appraise the evidence for validity, impact, and applicability. (VIP) 評估各種醫學報告的可信度、臨床重要性，以及可應用性 Integrate with our clinical expertise and patient values. 整合並應用於實際患者的治療決策﹝臨床應用﹞ Evaluate our effectiveness and efficacy. 效果評估

Clinical scenario 感控室發現最近有一個問題，即同一病房中爆發 3例疥瘡(Scabies)感染，因醫療人員需長期接觸病人 ，為預防感染擴大，故感控室考慮是否讓護理站工 作人員使用治療疥瘡之藥物 , 該如何處理才最適當?

Background knowledge Common causes infestation of human mite Sarcoptes scabiei. close or direct skin-to-skin contact Symptoms/signs Intense nocturnal pruritus within 1-4 weeks after infection. Severely itchy lesions typically present as small papules with noticeable curvy or straight burrows commonly located in skin folds. Secondary signs may include general rash, urticaria, eczema, excoriation, and impetigo. Incubation appears to be 1-4 weeks, most patients are asymptomatic during that time Scabies mites can survive for 48-72h off the human body

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Problem , PICO Patient and/or problem: No symptomatic staff who contact scabies patient Intervention : Mediation for treat scabies Comparison intervention : No intervention Outcomes : Prevent scabies outbreak ,感染率?

Search strategy

Search strategy-1 result: 19 papers found 1 2

Search strategy-2 result: 13 medical topic found

Search strategy-3 Search terms: scabies and asymptomatic limits: Title/Abstract, published in the last 10 years, only items with links to full text result: 8 papers found Discard irrelevant papers Finally, 1 paper is cited terms: scabies and outbreak → 221 papers limits: Title/Abstract, published in the last 5 years, only items with links to full text, English result: 14 papers found Finally, 2 paper are cited

英國Oxford Center證據應用等級 Level Therapy/Prevention, Aetilogy/Harm 1 a 將隨機對照臨床研究(Randomized Clinical Trial, RCT)以系統性評論(systemic review, SR)後的結果。 b 具有嚴格的信賴區間的個別RCT研究。 c 無論使用何種研究方法，但其研究結果為完全正面、完全負面或完全無效果(all or none)的研究結果。 2 a 將同質性的世代研究(cohort studies)以系統性評論的結果。 個別世代研究或是質量較不足的RCT研究。 以多數結果為基礎的研究，及生態學的研究("Outcomes" research; ecological studies)。 3 a 將同質的個案對照研究(case control studies)以系統性評論後的結果。 個別的個案對照研究(individual case control study)。 4 病例統計報告，以及質量較不足的個案對照研究。 5 未經嚴謹評估的意見，或者基礎生理學、一般實驗室研究及必要原則。

Citations-1 張淑美、梁宇峰:南部某區域教學醫院加護病房疥瘡感染群突發之調查。院內感染控制雜誌 2002;12卷第6期 林金絲、葉玉蓉:疥瘡的防治。台灣醫學 2000;4卷第6期 Randolph LP, Steven MO. Scabies. http://www.mdconsult.com. First Consult medical topics 2007 sep.

Citations-2 Chambliss NL.Treating asymptomatic bodily contacts of patients with scabies. Arch Fam Med. 2000 May;9:473-4. (level 2A) Scheinfeld N. Controlling scabies in institutional settings: a review of medications, treatment models, and implementation. Am J Clin Dermatol. 2004;5:31-7 Vorou R, Remoudaki HD, Maltezou HC. Nosocomial scabies. J Hosp Infect. 2007 Jan;65:9-14. Level: 2c

南部某區域教學醫院加護病房疥瘡感染群突發之調查 院內感控雜誌 2002 此疥瘡群突發發生在南部某區域教學醫院的加護病房，於七月份下旬，至民國90年7月31日為止，有十位護理人員及一位住院病患受到感染及疑似感染，分別於四肢、軀幹、背部及腹部等不同部位有癢及紅疹情形，其中有5位護理人員及1位住院病患共6位經皮膚科診斷確定為感染疥瘡，護理人員感染率為13.2 %，該ICU住院病人感染率為4％。 該單位已感染疥瘡之病患及護理人員予以Scalphen oint治療，疑似感染及接觸者予以Eurax（Crotamiton）治療，照護感染病患時採接觸隔離，並加強洗手、穿隔離衣、戴手套以及隔離防護之再教育等。 追究極可能由於醫護人員認為感染來源之病患已擦藥二星期傳染力減低而未適時採取適當隔離措施所致，後經皮膚科醫師診斷及藥物治療以及嚴格的防護措施，該單位未再發現任何新的疥瘡個案。

疥瘡的防治 台灣醫學 2000 照顧疥瘡患者之工作人員有40-70%的侵襲率(attack rate) 。國內群突發調查工作人員遭受疥瘡感染之侵襲率也近四成。 根據Degelar處理長期照護機構疥瘡群發之經驗，依其傳染途徑將治療方式分為三類;第一類是高傳染途徑性，例如挪威疥或身上疹子大於50個。第二是一般疹，或疑似疥蟲感染，且身上蟲子小於50個。第三類包括所有無症狀但曾經接觸第一、二類患者，或覺得皮膚搔癢，但無任何疹子者。使用5% Permethrin全身塗抹8~14hrs即有治療效果， 第二、三類ㄧ次治療即可。

台灣醫學 2000

疥瘡的防治 台灣醫學 2000 在評估接觸者方面，許多文獻調查發現，只有治療感染者會造成控制失敗，因此，對象應包括病患、員工及兩者家屬。 疥瘡的防治 台灣醫學 2000 在評估接觸者方面，許多文獻調查發現，只有治療感染者會造成控制失敗，因此，對象應包括病患、員工及兩者家屬。 至於是否使用預防性用藥，可根據該醫院過去之疥瘡盛行率來決定。

Controlling scabies in institutional settings: a review of medications, treatment models, and implementation Am J Clin Dermatol. 2004 Control of an epidemic can only be achieved by treatment of the entire population at risk. In an outbreak of scabies in a nursing home, residents, staff, and frequent visitors should all be treated even if they are not symptomatic. The standard treatment for scabies is 5% permethrin cream. Ivermectin is useful in treating patients with Norwegian or crusted scabies, or who are debilitated. Only oral treatment, is not approved for scabies in the US.

Treatment Models to Stop Epidemics Controlling scabies in institutional settings: a review of medications, treatment models, and implementation Am J Clin Dermatol. 2004 Treatment Models to Stop Epidemics Model treatment plans to control scabies epidemics have been developed that involve treatment of staff, patients, and contacts. The plans include disinfection of the premises, clothing, and furniture.

Treating asymptomatic bodily contacts of patients with scabies Arch Fam Med. 2000 Patients who are first exposed to scabies often do not develop symptoms for several weeks. A well documented case report detailed the spread of scabies in a day care center, in which 21% of the staff and children were eventually infected. Prevention Due to long asymptomatic incubation period and high level of infectivity The standard treatment for scabies is 5% permethrin cream applied from the neck down. Alternatives include 1% lindane, which should be avoided in children and pregnant women.

Scabies treatments treatment agent Am J Clin Dermatol 2004;5(1) treatment agent US FDA approved for scabies treatment comments Permethrin Yes First-line therapy Lindane Neurotoxic; second-line therapy Crotamiton Not very effective; weak antipruritic Malathion Approved for head lice treatment Not uesd in the US Allethrin spray No Used in Europe 6-10% precipitated sulfur Well tolerated in children under 2 months of age and pregnant women Benzyl benzoate lvermectin Approved for strongyloidiasis and onchocerciasis treatment Oral, effective dose 200μg/kg

First Consult medical topics 2007 Scabies First Consult medical topics 2007 Management in special circumstances For outbreaks in nursing homes or other communal living areas, a comprehensive approach becomes necessary. This includes mass screening of patients, staff, and support personnel; infection control measures (e.g. cleaning of linen, bed clothes), and treatment for infected individuals. In cases of hospitalized or institutionalized patients with Norwegian scabies, use contact isolation methods to prevent infection of other patients. Prognosis Scabies is generally treated successfully with one application of medication. Prevention Treat all close contacts Wash clothing and bedding of infectied people with hot water

Conclusion 當爆發疥瘡(Scabies)感染時，許多文獻調查發現,只有治療感染者會造成控制失敗，因照護的醫療人員與這些病人為接觸最頻繁者，為預防再度傳染給它人及防止疫情的再度擴大，故建議可讓相關人員使用治療疥瘡之藥物。

本院治療疥瘡之藥物品項 γ-benzene hexachloride Benzyl Benzoate (B.B lotion) Delice (Lindane) 1%, 10ml/pk   Benzyl Benzoate (B.B lotion) 25%,100ml/bot crotamiton 10%+ hydrocortisone 0.25% (Ulex) 10g/tube

Topical therapy-1 Benzyl benzoate 10–25% widely used in adults and also in diluted form for children, babies, and breastfeeding mothers. most common adverse event : initial severe burning sensation from local irritation. Lancet Infect Dis 2006

Topical therapy-2 Lindane (γ-benzene hexachloride ) widely prescribed topical scabicide because of its efficacy and cost-effectiveness. Appears to be most toxic scabicidal agent, but adverse effects more common in children and patient with extensive skin disease. remove by bathing after 8-12 hours Lancet Infect Dis 2006

Topical therapy-3 Crotamiton therapy of common scabies is recommended for newborn babies and infants . Apply thinly from neck down and massage nightly for 2 consecutive nights, and wash off 24 hours after second application Less effective than permethrin, similar efficacy to lindane Lancet Infect Dis 2006

Cost per course (adult) Cost comparison Drug Application schedule 單價 Cost per course (adult) Benzyl benzoate 25% (B.B lotion) one application 自費價205 (100ml/bot) 205元 (100ml) Crotamiton (Ulex) 2 applications 24 hours apart 健保價15.4元 (10gm/tub) 92.4元 γ-BHC (Lindane) 1% 自費價35元 (10ml/pk) 350元 (100ml) Ref.中央健保局 and 義大醫院藥品基本檔

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Cost effectiveness Walker GJA, Johnstone PW. Interventions for treating scabies. Cochrane Database of Systematic Reviews 2004, Issue 1

Nosocomial scabies J Hosp Infect. 2007 Infection control Prompt recognition of scabies followed by immediate implementation of preventive measures is the mainstay for the containment of a nosocomial outbreak. Treatment In a systemic review of 11 randomized trials comparing the effectiveness of various agents, no differences in clinical cure rates or adverse events were demonstrated. Permethrin may be preferable to lindane or crotamiton based on traditional reviews, professional opinions or on published experience with nosocomial outbreaks. Conclusions The onset of a nosocomial outbreak of scabies is associated with considerable morbidity and economic burden. Prompt recognition of cases, immediate implementation of infection control measures, simultaneous treatment of all contacts, and prolonged monitoring after the outbreak are of principal importance for its control.

Evidence Evidence regarding the effectivess of permethrin vs lindane is conflicting. This systematic review found four RCTs comparing these agents. Two small trials found clinical cure at 28 days was greater with permethrin, but the other two RCTs, including the largest of the four trials, failed to show any significant difference in clinical outcome. Permethrin, however, to be more effective in controlling persistent itch (Level A) Interventions for treating scabies. Cochrane Database of Systematic Reviews 2004, Issue 1