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Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits

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Hereditary angioedema (HAE) is often debilitating with a serious effect on quality of life (QOL). Treatment of acute HAE attacks is usually with C1 esterase inhibitor (C1-INH) concentrates; however, treatment can be delayed by patients' travel time for attending emergency units. We assessed the impact of self-administered home therapy with intravenous C1-INH concentrate on QOL in patients with HAE. Nine patients experiencing frequent or severe debilitating HAE attacks were offered self-administration of C1-INH concentrate. QOL was assessed prior to and following home therapy using the Dermatology Life Quality Index (DLQI) and 36-Item Short Form Survey (SF-36) questionnaires. Seven patients were recruited into the study. QOL was assessed at baseline and after 3 to 48 months of home therapy. The mean DLQI score fell from 12.6 +/- 4.65 to 2.7 +/- 1.38 (P < 0.001). Mean SF-36 scores for the individual and combined components also improved significantly. No serious complications were documented during a follow-up period of 27 to 72 months. Self-administration of C1-INH improved QOL on both physical and psychological parameters. Patients were able to resume a normal life without restrictions caused by the condition.
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... The SF-36 is one of the most commonly used generic HRQoL questionnaires worldwide, in studies that measure the impact of a disease on HRQoL in different groups of patients [22][23][24][25][26][27][28][29][30][31], as well as studies that assess the effect of certain therapeutic interventions on HRQoL [32][33][34][35][36][37][38]. It has also been used as a reference in the validation of new instruments [39][40][41][42][43][44]. ...
... It has also been used as a reference in the validation of new instruments [39][40][41][42][43][44]. The SF-36 was used to measure HRQoL in patients with C1-INH-HAE [25][26][27][28][29][30][31] and to assess the effect of some therapeutic interventions [35,36,38,[45][46][47]. However, we have found no evidence of any studies on its psychometric properties in patients with C1-INH-HAE and, to the best of our knowledge, it has yet to be for use in C1-INH-HAE. ...
Article
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Background The generic 36-item Short-Form Health Survey (SF-36v2) has been used to assess health related quality of life in adult patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) even though it has not yet been validated for use in this specific disease. Objective This study aims to validate the SF-36v2 for use in adult patients with C1-INH-HAE. Results There was a very low item non-response rate (1–3.4%), with a high ceiling effect in 25/35 items and a low floor effect in 3/35 items. A moderate ceiling effect was observed in 5/8 dimensions of the SF-36v2, whereas no floor effect was noticed in any of the dimensions. Internal consistency was good to excellent with Cronbach's alpha coefficient ranging between 0.82 and 0.93 for the different dimensions. Construct validity was good: seven out of the 8 hypotheses defined on clinical criteria were confirmed, discriminant validity assessment showed significant differences among patients with different C1-INH-HAE severity, convergent validity showed a good correlation among the physical and mental component summaries of the SF-36v2 and the HAE-QoL total score (0.45 and 0.64 respectively, P < 0.001). Test–retest reliability was high with intraclass correlation coefficient varying from 0.758 to 0.962. The minimal clinically important difference was calculated by distribution methods and small differences in the domain scores and in the component summaries scores were shown to be meaningful. Conclusions The psychometric properties of the SF-36v2 show it can be a useful tool to assess HRQoL in adult patients with C1-INH-HAE, although with some content validity limitation. Methods The psychometric properties of the SF-36v2 were evaluated in an international setting based on responses from 290 adult C1-INH-HAE patients in 11 countries.
... 33 Compared with conventional HCP administration, selfadministration enables patients to manage their disease in their own environment, reducing time off work, hospital visits, travel and the risk of contracting SARS-CoV-2 and/ or other airborne viruses. 34 This alternative treatment practice has been shown to be well tolerated, can improve QoL [34][35][36] and enables patients to become experts in their own disease management. 14,31,35 Real-World Evidence: Patient and Physician Experience with Self-Administration in AATD To demonstrate the applicability of self-administration of IV AAT therapy to the real world, we report a clinical case study of a 52-year-old female patient diagnosed with bronchiectasis and severe AATD (PI*ZZ genotype) who has successfully selfadministered AAT therapy for 3 years (see Table 1 for information). ...
... 34 This alternative treatment practice has been shown to be well tolerated, can improve QoL [34][35][36] and enables patients to become experts in their own disease management. 14,31,35 Real-World Evidence: Patient and Physician Experience with Self-Administration in AATD To demonstrate the applicability of self-administration of IV AAT therapy to the real world, we report a clinical case study of a 52-year-old female patient diagnosed with bronchiectasis and severe AATD (PI*ZZ genotype) who has successfully selfadministered AAT therapy for 3 years (see Table 1 for information). This patient case demonstrates the clinical benefits of self-administration on reducing exacerbation frequency and improving QoL compared with receiving no AAT therapy ( Table 1). ...
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Alpha 1 Antitrypsin deficiency (AATD) is a hereditary condition characterized by low serum Alpha 1 Antitrypsin (AAT) levels and a predisposition towards early-onset emphysema. Infusion of AAT is the only disease-modifying therapy that can sufficiently raise plasma AAT levels above the putative protective threshold and reduce the decline in lung density loss. Several randomized controlled trials (RCTs) and registry studies support the clinical efficacy of AAT therapy in slowing the progression of AATD-related emphysema and improving survival outcomes. The COVID-19 pandemic has prompted physicians to develop additional strategies for delivering AAT therapy, which are not only more convenient for the patient, but are "COVID-19 friendly", thereby reducing the risk of exposing these vulnerable patients. Intravenous (IV) self-administration of AAT therapy is likely to be beneficial in certain subgroups of patients with AATD and can remove the need for weekly hospital visits, thereby improving independence and well-being. Increasing the awareness of self-administration in AATD through the development of formal guidelines and training programs is required among both physicians and patients and will play an essential role, especially post-COVID-19, in encouraging physicians to consider self-administration for AATD in suitable patients. This review summarizes the benefits of AAT therapy on the clinical endpoints of mortality and quality of life (QoL) and discusses the benefits of self-administration therapy compared with conventional therapy administered by a healthcare professional. In addition, this review highlights the challenges of providing AAT therapy during the COVID-19 pandemic and the potential considerations for its implementation thereafter.
... The SF-36 is one of the most commonly used generic HRQoL questionnaires worldwide, in studies that measure the impact of a disease on HRQoL in different groups of patients [22][23][24][25][26][27][28][29][30][31], as well as studies that assess the effect of certain therapeutic interventions on HRQoL [32][33][34][35][36][37][38]. It has also been used as a reference in the validation of new instruments [39][40][41][42][43][44]. ...
... It has also been used as a reference in the validation of new instruments [39][40][41][42][43][44]. The SF-36 was used to measure HRQoL in patients with C1-INH-HAE [25][26][27][28][29][30][31] and to assess the effect of some therapeutic interventions [35,36,38,[45][46][47]. However, we have found no evidence of any studies on its psychometric properties in patients with C1-INH-HAE and, to the best of our knowledge, it has yet to be for use in C1-INH-HAE. ...
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Background The generic 36-item Short-Form Health Survey (SF-36v2) has been used to assess health related quality of life in adult patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) even though it has not yet been validated for use in this specific disease. Objective This study aims to validate the SF-36v2 for use in adult patients with C1-INH-HAE. Results There was a very low item non-response rate (1-3.4%), with a high ceiling effect in 25/35 items and a low floor effect in 3/35 items. A moderate ceiling effect was observed in 5/8 dimensions of the SF-36v2, whereas no floor effect was noticed in any of the dimensions. Internal consistency was good to excellent with Cronbach's alpha coefficient ranging between 0.82 and 0.93 for the different dimensions. Construct validity was good: seven out of the 8 hypotheses defined on clinical criteria were confirmed, discriminant validity assessment showed significant differences among patients with different C1-INH-HAE severity, convergent validity showed a good correlation among the physical and mental component summaries of the SF-36v2 and the HAE-QoL total score (0.45 and 0.64 respectively, P < 0.001). Test- retest reliability was high with intraclass correlation coefficient varying from 0.758 to 0.962. The minimal clinically important difference was calculated by distribution methods and small differences in the domain scores and in the component summaries scores were shown to be meaningful. Conclusions The psychometric properties of the SF-36v2 show it can be a useful tool to assess HRQoL in adult patients with C1-INH-HAE, although with some content validity limitation. Methods The psychometric properties of the SF-36v2 were evaluated in an international setting based on responses from 290 adult C1-INH-HAE patients in 11 countries.
... 31 Selfadministration has also been utilized and demonstrated QoL benefits in other therapy areas such as Fabry disease, 32 primary immune deficiency, 33 hemophilia, 34 and HAE. 35 The benefits of self-administration are exemplified by its implementation in HAE, a disease that has several parallels with AATD: both are genetic disorders associated with genes in the SERPIN superfamily of serine proteases and are treated with IV plasma products to replace deficient proteins. HAE is a rare autosomal dominant disorder characterized by severe attacks of swelling in the limbs, face, intestinal tract and airways, which can be fatal. ...
... 36 Patients with severe HAE attacks have reported improvements in QoL after IV selfadministration at home in comparison to administration at the clinic. 35 In addition, self-administration has been shown to reduce hospital administration for acute HAE attacks and related healthcare costs. 37 Together, these benefits from self-administration in HAE are transferable to AATD for the perspective of patient convenience and likely to be transferable in terms of healthcare system cost. ...
Article
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Alpha-1 Antitrypsin Deficiency (AATD) is a rare genetic condition that predisposes patients to lung and liver disease and is often underdiagnosed due to incomplete diagnosis of chronic obstructive pulmonary disease (COPD) and asthma. Improvements in physician awareness have been made, but better strategies for both diagnosis and management are still required. The only current disease-modifying therapy for AATD is the infusion of the missing Alpha-1 Antitrypsin (AAT) protein, which can slow progression of emphysema. However, AAT treatment can impact patient freedom and quality of life due to the need for weekly intravenous infusions. A symposium was held to discuss patient-centric aspects of care that have impact on the lives of patients with AATD, including exacerbations of their lung disease, self-administration of intravenous AAT therapy and pulmonary rehabilitation. Intravenous self-infusion of drugs is an established treatment strategy for patients with a variety of conditions and can improve patient quality of life, freedom and mental well-being. Experience from these areas show that patients typically manage their treatment well and without complications. When applied to AATD, training patients to self-infuse therapy can be successful, but formal guidelines would be beneficial. In addition to pharmacological intervention, individualized pulmonary rehabilitation, exercise and educational programs can encourage health-enhancing patient behavior and further improve patient quality of life. However, differences in skeletal muscle adaptations to pulmonary rehabilitation exercise regimens have been observed between patients with AATD and non-AATD COPD, highlighting the need to develop training programs specifically designed for patients with AATD.
... Implementation of this treatment usually requires weekly home visits from nursing staff or visits to outpatient infusion clinics-a process that places significant burdens on patients and their families. To alleviate these burdens, users of other IV therapies, such as hereditary angioedema and hemophilia, have successfully transitioned to self-infusion regimens [27,28]. In a recent review, Herth and colleagues outline the practical considerations of self-infusion for AATD patients, in light of the COVID-19 pandemic [29]. ...
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Introduction: Alpha-1 antitrypsin (AAT) deficiency is an autosomal co-dominant genetic condition that predisposes individuals to pulmonary and hepatic disease, and in severe cases is treated with augmentation by intravenous infusion. Our aim was to assess patient reluctance to transition to self-administered augmentation of alpha-1-antitrypsin, during the pandemic of SARS-CoV-2. Methods: A phone questionnaire was administered to 22 patients with severe alpha-1-antitrypsin deficiency who were currently receiving AAT augmentation therapy. Inclusion criteria included patients [Formula: see text] 18 years old, diagnosed with AATD, and receiving intravenous AAT protein augmentation therapy. Information was gathered regarding demographics, perspectives on transitioning to self-administered treatment, and anxiety and depression prevalence. Results were collected anonymously using REDCap. Joint and marginal statistical analysis was done to quantify links between participants' willingness to transition to self-infusion and correlations with sex, age, years of therapy, anxiety, and depression. Results: Of 22 patients, 14 were male and eight were female. Ages ranged from 36 to 79 years, with an average of 62.5. Genotypes were ZZ (14), MZ (3), and SZ (2) among others. Average length of intravenous augmentation was 9.5 years. The majority, 16 participants, were aware self-infusion was an option. Eight participants were willing to consider transitioning to self-infusion if trained and educated. Eight patients reported that fear of COVID-19 transmission influenced their decision-making. Above-normal anxiety, and depression scores, were found in four, and six patients, respectively. Neither sex, age, years of treatment, anxiety, or depression were found to be associated with willingness to consider self-infusion therapy. Conclusions: Although there are many reasons AATD patients may benefit from AAT self-infusion, including decreased exposure to SARS-CoV-2, the majority preferred home nurse-infused therapy.
... 8 Significant developments have been made in the understanding of disease pathophysiology during the last decade. 9,10 Additionally, advances from treatments exclusively administered in a clinical setting to self-treatment at home became possible through the introduction of innovative therapies and patient education programmes, 11,12 considerably improving the health-related quality of life of patients with HAE-1/2. 13,14 HAE-1/2 is widely held to show considerable variation in disease activity not only between patients but also within patients over time. ...
Article
Background Hereditary angioedema due to C1 inhibitor deficiency (HAE-1/2) is a chronic and debilitating disease. The unpredictable clinical course represents a significant patient burden. Objective To analyze longitudinal registry data from the Icatibant Outcome Survey (IOS) to characterize temporal changes in disease activity in patients with HAE-1/2. Methods IOS (NCT01034969) is an international observational registry monitoring the clinical outcomes of patients eligible for icatibant treatment. The current analyses are based on data collected between July 2009 and July 2019. Retrospective data for attacks recorded in the 12 months prior to IOS enrollment and for each 12-month period up to 7 years were analyzed. Results Included patients reported angioedema attacks without long-term prophylaxis (LTP; n = 315) and with LTP (n = 292) use at the time of attack onset. Androgens were the most frequently used LTP option (80.8%). At the population level, regardless of LTP use, most patients (52‒80%) reporting <5 attacks in Year 1 continued experiencing this rate; similarly, many patients (25‒76%) who reported high attack frequency continued reporting ≥10 attacks/year. However, year on year, 31‒51% of patients experienced notable changes (increase/decrease of ≥5 attacks) in annual attack frequency. Of patients who reported an absolute change of ≥10 attacks from Year 1 to 2, 17‒50% continued to experience a change of this magnitude in subsequent years. Conclusion At the population level, attack frequency was generally consistent over 7 years. At the small group level, 28.8-34.5% of patients reported a change in attack frequency of ≥5 attacks from Year 1 to 2; up to half of these patients continued to experience this magnitude of variation in disease activity in later years, reflecting high intra-patient variability.
... It is recommended that patients be evaluated for long-term prophylaxis at least once a year [1]. An increasing trend toward home-based treatment has been associated with increased quality of life and may facilitate timely treatment, increase patients' self-confidence in managing their HAE, and provide patients with greater flexibility and convenience, thus enabling them to lead more normal lives [1,[77][78][79][80][81]. Home-based treatment may enhance adherence to routine HAE prophylaxis, possibly because of the added convenience and reduced requirement to travel to physician's offices or infusion centers [82]. ...
Article
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The majority of angioedema cases encountered in clinical practice are histamine-mediated (allergic); however, some cases are bradykinin-related (non-allergic) and do not respond to standard anti-allergy medications. Among bradykinin-related angioedema, hereditary angioedema (hae) is a rare, but chronic and debilitating condition. The majority of hae is caused by deficiency (type 1) or abnormal function (type 2) of the naturally occurring protein, c1-inhibitor (c1-inh)—a major inhibitor of proteases in the contact (kallikrein-bradykinin cascade), fibrinolytic pathway, and complement systems. Failure to recognize hae and initiate appropriate intervention can lead to years of pain, disability, impaired quality of life (qol) and, in cases of laryngeal involvement, it can be life-threatening. Hae must be considered in the differential diagnosis of non-urticarial angioedema, particularly for patients with a history of recurrent angioedema attacks, family history of hae, symptom onset in childhood/adolescence, prodromal signs/symptoms before swellings, recurrent/painful abdominal symptoms, and upper airway edema. Management strategies for hae include on-demand treatment for acute attacks, short-term prophylaxis prior to attack-triggering events/procedures, and long-term or routine prophylaxis for attack prevention. Patients should be evaluated at least annually to assess need for routine prophylaxis. Hae specific medications like plasma-derived and recombinant c1-inh products, kallikrein inhibitors, and bradykinin b2 receptor antagonists, have improved management of hae. While the introduction of intravenous c1-inh represented a major breakthrough in routine hae prophylaxis, some patients fail to achieve adequate control and others have psychological barriers or experience complications related to intravenous administration. Subcutaneous (sc) c1-inh, sc monoclonal antibody (mab)-based therapies, and an oral kallikrein inhibitor offer effective alternatives for hae attack prevention and may facilitate self-administration. Hae management should be individualized, with qol improvement being a key goal. This can be achieved with broader availability of existing options for routine prophylaxis, including greater global availability of c1-inh(sc), mab-based therapy, oral treatments, and multiple on-demand therapies.
... Indeed, several HAE-specific HR-QoL questionnaires have been developed to measure the health status of C1-INH-HAE patients. As of today, 3 questionnaires are available that are specific to angioedema [16,17]. ...
Article
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The Angioedema Quality of Life Questionnaire (AE-QoL) is an angioedema (AE)-specific validated questionnaire, which surveys the quality of life of diagnosed patients. The questionnaire has been used in multiple clinical trials. Our aim was to investigate how the questionnaire can assist physicians in the everyday practice of following up and managing C1-inhibitor deficiency patients. In a prospective trial conducted in our center between 2016 and 2018, 125 hereditary angioedema and 10 diagnosed with acquired angioedema completed an AE-QoL during their annual follow-up visit. Laboratory indices (i.e., complement levels) were obtained for each patient. Statistical analysis comparing clinical data with QoL parameters was performed. Results of the analysis show that AE-QoL total score and number of AE attacks per year correlated well (r = 0.47; p < 0.0001). Women reached higher AE-QoL total score values than men, over a 3-year period (p = 0.0014). The highest AE-QoL total scores were reached by the 41–60-year age group; we obtained a similar result, when analyzing the four domains. No correlation was found between the AE-QoL total score and complement parameters. Patients with a negative correlation between AE-QoL total score and number of AE attacks had a positive correlation with psychologic attributes like fatigue/mood and fears/shame domains. Patients that acquired HAE showed a significant correlation between the annual number of AE attacks and the AE-QoL total scores (r = 0.46; p < 0.0001). The study establishes the use of AE-QoL as a clinical tool for follow-up which can help in the complex assessment of both hereditary and acquired HAE patients, and help to develop better therapeutic strategies.
... Not surprisingly, a high burden of depression has also been reported in patients with C1-INH-HAE [9,10]. The negative impact of HAE on health-related quality of life (HRQoL) has been well documented in a number of studies [2,[9][10][11][12][13][14][15][16][17][18][19][20], and improving HRQoL has become an increasing focus of HAE management guidelines [21]. ...
Article
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Background: Long-term prophylaxis with subcutaneous C1-inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) in patients with hereditary angioedema (HAE) due to C1-INH deficiency (C1-INH-HAE) was evaluated in an open-label extension follow-up study to the international, double-blind, placebo-controlled COMPACT study. The current analysis evaluated patient-reported health-related quality of life (HRQoL) data from 126 patients in the open-label extension study randomized to treatment with C1-INH(SC) 40 IU/kg (n = 63) or 60 IU/kg (n = 63) twice weekly for 52 weeks. HRQoL was evaluated at the beginning of the open-label study and at various time points using the European Quality of Life-5 Dimensions Questionnaire (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication. The disease-specific Angioedema Quality of Life Questionnaire (AE-QoL) and HAE quality of life questionnaire (HAE-QoL) instruments were administered in a subset of patients. Statistical significance was determined by change-from-baseline 95% confidence intervals (CIs) excluding zero. No adjustment for multiplicity was done. Results: Mean baseline EQ-5D scores (Health State Value, 0.90; Visual Analog Scale, 81.32) were slightly higher (better) than United States population norms (0.825, 80.0, respectively) and mean HADS anxiety (5.48) and depression (2.88) scores were within "normal" range (0-7). Yet, patients using C1-INH(SC) 60 IU/kg demonstrated significant improvement from baseline to end-of-study on the EQ-5D Health State Value (mean change [95% CI], 0.07 [0.01, 0.12] and Visual Analog Scale (7.45 [3.29, 11.62]). In the C1-INH(SC) 60 IU/kg group, there were significant improvements in the HADS anxiety scale (mean change [95% CI], - 1.23 [- 2.08, - 0.38]), HADS depression scale (- 0.95 [- 1.57, - 0.34]), and WPAI-assessed presenteeism (mean change [95% CI], - 23.33% [- 34.86, - 11.81]), work productivity loss (- 26.68% [- 39.92, - 13.44]), and activity impairment (- 16.14% [- 26.36, - 5.91]). Clinically important improvements were achieved in ≥ 25% of patients for all domains except WPAI-assessed absenteeism (which was very low at baseline). Mean AE-QoL total score by visit ranged from 13.39 to 17.89 (scale 0-100; lower scores = less impairment). Mean HAE-QoL global scores at each visit (115.7-122.3) were close to the maximum (best) possible score of 135. Conclusions: Long-term C1-INH(SC) replacement therapy in patients with C1-INH-HAE leads to significant and sustained improvements in multiple measures of HRQoL. Trial registration A Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema, NCT02316353. Registered December 12, 2014, https://clinicaltrials.gov/ct2/show/NCT02316353 .
Article
Hereditary angioedema (HAE) is a rare, chronic, genetic disease that presents with nonpruritic angioedema of the face, extremities, airway (can be life-threatening), genitourinary system, and abdomen. These symptoms can significantly impair daily activities. HAE is classified into either HAE due to a deficiency of functional C1-INH (HAE-C1-INH) or HAE with normal C1INH (HAE-nl-C1INH). Both type I and II HAE-C1-INH result from inherited or spontaneous mutations in the SERPING1 gene, which encodes for C1-INH. These mutations result in C1INH dysfunction, leading to uncontrolled plasma kallikrein activity with excessive bradykinin production. Bradykinin receptor activation leads to vasodilation, increased vascular permeability, and smooth muscle contractions, resulting in submucosal angioedema via fluid extravasation. HAE-nl-C1INH is secondary to either a known or unknown (labeled HAE-U) genetic mutation. The underlying mechanism of HAE-nl-C1INH is less well understood but thought to be related to bradykinin signaling. Plasma kallikrein inhibitors have been developed to inhibit the kallikrein-kinin pathway to prevent (prophylactic) and treat on-demand (acute) HAE attacks. Several of these medications are delivered via subcutaneous or intravenous injection, though new and emerging therapies include oral formulations. This manuscript provides a historical review and describes the evolving landscape of available kallikrein inhibitors to treat HAE-C1-INH.
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A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
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Hereditary angioedema is manifested by attacks of swelling of the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously or secondary to trauma. It is inherited as an autosomal dominant trait and is due to deficient activity of the inhibitor of the activated first component of complement. The clinical diagnosis can be confirmed by the findings of low levels of C4 or C1 esterase inhibitor activity, or both. Therapy may be divided into three phases: long-term prophylaxis of attacks, short-term prophylaxis of attacks, and treatment of acute attacks. Long-term prophylaxis may be achieved with antifibrinolytic agents and androgens. Short-term prophylaxis with these agents and plasma transfusions has been successful. Specific therapy for acute attacks is not available, but good supportive care, together with a knowledge of the course of the disease, can prevent asphyxiation from airway obstruction. Before the advent of therapy, mortality was reported as high as 30%.
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A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
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Two hundred and twenty-six patients with inherited C1 inhibitor (C1-INH) deficiency, also known as hereditary angioedema (HAE), have been studied. They belonged to 80 unrelated families, and in 11 of them C1-INH was functionally deficient but antigenically normal (type II HAE). Genetic analysis of type 1 families demonstrated restriction fragment length polymorphisms in 11% and abnormal mRNAs in 25%. In type II families, the site of the mutation appeared to determine the rate of catabolism of the dysfunctional C1-INH and its antigenic plasma levels. Clinical symptoms (subcutaneous and mucous swellings) generally first appeared within the second decade of life. The frequency of symptoms was highly variable from patient to patient, but a few patients remained asymptomatic throughout their lives. Prophylactic treatment with attenuated androgens was administered to 59 patients and was totally effective in 57, without significant side effects. Sixty-seven laryngeal and 15 abdominal attacks were treated with C1-INH plasma concentrate, yielding initial regression of symptoms in 30 to 90 minutes. The acquired deficiency of C1-INH, also known as acquired angioedema, was diagnosed in 9 patients. Eight of them had an autoantibody against C1-INH; the only patient without the autoantibody had associated chronic lymphocytic leukemia. Prophylactic treatment with attenuated androgens was effective in this last patient, while those with the autoantibody against C1-INH benefited from prophylaxis with antifibrinolytic agents. Replacement therapy with C1-INH concentrate was necessary only for patients with autoantibodies and required doses 3 or 4 times higher than those used in HAE.