Author Archives: akrom

About akrom

Lahir di salah satu desa di kota terkecil "Pati" (menurut kepala sekolah waktu SD) pada tahun 1967, maklum karena waktu itu ditemapat saya belum musimnya menggunakan akte kelahiran untuk bukti pencantuman tanggal lahir siswa diijazah, sehingga tanggal lahir sesuai belas kasihan kepala sekolah yang mengeluarkan ijazah SD saya. Sekolah di SMPN1 Winong, sekolah unggulan di kota kecamatan Winong waktu itu. Setelah lulus SMP melanjutkan di SMA1 N Pati, juga salah satu sekolah SMA terfaforit di kota Pati. Akhirnya kuliahnya tersangkut UMPTN di Farmasi UGM, kesasar di KIMIA Mipa UGM dua tahun dan berakhir di Fakultas Kedokteran UGM. Sudah berkeluarga, dengan enam keturunan, hanya saja salah satunya sudah diminta kembali oleh Sang Maha Kuasa, bair jadi tabungan kami kelak, semoga. Istri juga seorang dokter, yang sangat rajin ngoyak-ngoyak anak-anak untuk belajar sambil praktek di rumah. Baik saya maupun istri, pernah kerja di di beberapa RS tetapi kemudian kami berdua meneguhkan diri di lembaga pendidikan untuk mengabdikan ilmu di pendidikan. Semoga bermanfaat.

BAGAIMANA DM DI INDONESIA? APA YANG SUDAH KITA LAKUKAN? Suatu renungan memperingati hari DM

Penyakit gula darah (DM) telah menjadi wabah di hampir semua negara, tidak peduli, apakah negara maju, telah, sdang atau akan berkembang. Bertambahnya kejadian obesitas pada balita semakin meneguhkan akan semakin tingginya kejadian DM di dunia, termasuk di Indonesia.  Memang obesitas bukan merupakan satu-satunya sinyal awal kejadian DM, tetapi obesitas merupakan isyarat yang muadah untuk dibaca dan dimengerti hubungannya dengan kejadian DM. Dalam waktu tidak lama lagi Indonesia akan menjadi negara keempat terbesar jumlah kejadian DM.

kardiovaskuler stroke gagal ginjal DM merupakan faktor risiko utama terhadap kejadian hipertensi, serangan jantung, gagal jantung, stroke, gagal ginjal dan berbagai penyakit degeneratif lainnya. Apabila kejadian baru DM di masyarakat tidak diantisipasi dan penderita DM tidak dikelola dengan benar maka berbagai penyakit degeneratif dan penyakit berbahaya yang bahayanya level”1″ akan merebak di masyarakat. Maka oleh karenanya melakukan antisipasi untuk menghambat laju insidensi DM dengan berbagai upaya promotif dan edukatif serta upaya pengelolaan yang benar dan efektif pada penderita DM agar tidak muncul komplikasi adalah tuntutan yang seharusnya segera dilakukan oleh berbagai elemen masyarakat dan bangsa ini.

Persoalannya sekarang adalah “apakah yang sudah kita lakukan untuk menghambat laju kejadian DM di Indonesia?”. ” apakah kontribusi positif yang sudah kita sumbangkan untuk peningkatan status kesehatan masyarakat melalui penghambatan laju kejadian DM atau menghambat dampak DM di masyarakat?”

Melakukan kebaikan untuk sesama tidak perlu menunggu orang lain untuk melakukannya. Kita semua dapat melakukannya melalui inisiatif pribadi baik dalam sekala perseorangan maupun sekala berkelompok.

Sungguh setitik kebajikan yang ditebarkan ditengah masyarakat yang berisiko mengalami DM akan mampu memberikan banyak efek posit dan kemanfaatan besar di masyarakat. Mari kita semua mencoba dan berbuat untuk kebaikan kita semua.

Salam

HAKMAA

Bagaimana membangunkan ketaatan masyarakat atau pasien dalam menjalani terapi obat?

Berikut dikopikan hasil penelitian tentang intervensi pendidikan kesehatan untuk menumbuhkan kesadaran pasien asma dalam menjalani terapi obat agar tujuan terapi tercapai. Artikel diambil dari jurnal imunologi alergi asia pasifik.

Recent educational interventions for improvement of asthma medication adherence
Malin Axelssoncorresponding author1,2 and Jan Lötvall1
1Krefting Research Center, Institute of Medicine, Internal Medicine, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
2Department of Nursing, Health and Culture, University West, SE-461 86 Trollhättan, Sweden.
corresponding authorCorresponding author.
Correspondence: Malin Axelsson. Krefting Research Center, Institute of Medicine, Internal Medicine, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden. Tel: +46-31-786-67-16, Fax: +46-31-786-67-30, Email: malin.axelsson@gu.se
Received November 24, 2011; Accepted November 30, 2011.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Poor adherence to asthma medication treatment is a dilemma as it decreases the chance of achieving and maintaining a proper asthma control. Another dilemma is that there seems to be a small range of functional interventions that enhance adherence to long-term medication treatments. The aim was to review the last five years of published educational interventions for improving adherence to asthma medication. Through systematic database searches 20 articles were identified, which matched the inclusion criteria and described educational interventions to improve asthma self-management including adherence. The current review showed that addressing unintentional non-adherence in terms of incorrect inhaler technique by recurrent education improved the technique among many patients, but not among all. Phoning patients, as a means to remove medication beliefs as adherence barriers, seemed to be an effective educational strategy, shown as increased adherence. Involving patients in treatment decisions and individualising or tailoring educational support also seemed to have favourable effect on adherence. To conclude, addressing specific adherence barriers such as poor inhaler technique or medication beliefs could favour adherence. To change adherence behavior, the current review proposes that educational adherence support should be a collaborative effort between the patient and the health-care professional based on each individual patient’s needs and patient factors, including elements such as personality traits.
Keywords: Adherence barriers, Asthma, Medication behavior, Patient education, Personality
INTRODUCTION
A plethora of studies have reported about poor adherence to asthma medication treatment [14]. As an example, an overall adherence to asthma medication of 22% in a sample of 5,500 persons with asthma was reported in one study [5]. People with asthma, who display poor medication adherence, most likely run increased risk of experiencing poor asthma outcomes [4]. The chance of achieving and maintaining the goal of modern asthma treatment: a well-controlled asthma, may also diminish [6]. There are arguments stating that the discovery of effective methods to improve adherence almost certainly would have a more advantageous influence on health than any treatment. However, there seems to be a lack of fruitful interventions, which successfully improve both adherence and treatment outcome [7]. Therefore, the aim was to review the last five years of published educational interventions for improving adherence to asthma medication.
Method
Systematic searches were carried out in the databases PubMed, Cinahl and Scopus with the following limitations: English language, publication between 2007 and 2011, adults (≥18 years) and articles accessible in full-text versions. Inclusion criteria were that the articles should be based on an empirical intervention including efforts to improve adherence in adult persons with asthma. Reviews, guidelines and study protocols were excluded. The following search terms were used: asthma, adherence, compliance, medication and intervention. In PubMed the Mesh terms: behavioral medicine, patient education and health psychology were used and in Cinahl the heading: medication compliance was used. The search terms were used in combinations and together with the Boolean operators OR and AND. Twenty articles matched the stipulated criteria and were included in the current review.
Starting point
Thanks to the large body of adherence research conducted in recent decades, a rather good picture of factors that influence adherence behaviour is obtainable. The World Health Organization (WHO) has organized these factors into five dimensions: social/economic, therapy-related, patient-related, condition-related factors and those related to the health-care team and system [8]. As efforts to improve adherence are recommended to address these dimensions [9], the current review adheres to that recommendation and will present the articles accordingly.
Social and economic factors
In general, the influence of social/economic factors could pose challenges to treatment adherence [8, 10], but their effect on adherence shows an inconsistent pattern [8] and seems to vary by sample [11]. None of the articles included in this review specifically addressed this dimension.
Therapy-related factors
Because asthma medication usually is administered by inhalation, the patients need to have an adequate technique to allow the medication to deposit in the lungs. Although manufacturing companies are striving to develop inhalers that are user friendly, incorrect inhaler use seems common [12, 13]. Another problem is that many patients seem to be unaware of their incorrect inhaler technique [12]. Considering adherence, this could be referred to as unintentional non-adherence, which means that the patient has an intention to adhere to recommended treatment, but fails due to defective inhaler technique [14, 15]. Five of the articles included in this review specifically addressed the issue with incorrect inhaler technique in their educational interventions.
Interventions to improve inhaler technique
In all five studies improvements in patients’ inhaler technique were reported but Hardwell et al. [16] concluded that despite improvements the majority still used a faulty technique. The interventions were carried out by asthma nurses in two studies [16, 17], by pharmacists in two studies [18, 19] and by physicians in one study [20].
Repeated inhaler instructions were used as method to improve inhaler technique in three of the studies [16, 19, 20] and in the other two studies tailored and individualised educational strategies were used [17, 18]. Takemura et al. [20], invited 146 patients of which 25 received repeated instructions of inhaler use and their inhaler technique was checked regularly. The instructions comprised verbal information and demonstration provided by their physician. In the study conducted by Daiane de Oliveira and colleagues [19], patients assigned to the intervention (n=28) received instructions on correct use of medication on four occasions, while the control group (n=27) only received this information once. Hardwell et al. [16] enrolled patients (n=1,092) with uncontrolled asthma prescribed pressurised metered-dose inhaler (pMDI) to check their inhaler technique using an Aerosol Inhalation Monitor (AIM). Patients received specific education on pMDI use, if they failed any of the three set AIM parameters. Takemura et al. [20] reported that their intervention apart from improving inhaler skills also resulted in improvements in self-reported adherence. These findings were partly opposed to those reported by Daiane de Oliveira et al. [19], who reported that there was no difference between the groups as regards reported adherence, but the inhaler technique had improved in the intervention group by the end of the project. The intervention carried out by Hardwell et al. [16] resulted in a statistically significant increase in number of patients with appropriate pDMI use after two and three educational occasions, but a majority of the patients still used faulty inhaler technique.
In a randomised controlled trial, a tailor-made intervention, depending on the patient’s current asthma control, was used to optimise use of asthma medication [18]. The intervention group (n=94) received education on three occasions at the pharmacy and the control group (n=107) received usual care. The effect of this intervention was estimated after six months and was described as higher frequency of filled prescriptions and better inhaler technique in the intervention group compared to the control group. The use of rescue medication was decreased and fewer nighttime awakenings were reported in the intervention group. However, self-reported adherence was similar in both groups [18]. This inconsistency in adherence estimations (frequencies of prescription fills and self-reports) sheds light on the difficulties with adherence monitoring.
An individualised education program was used in patients defined as “poor adherers to asthma medication” [17]. The intervention comprised three individual sessions each lasting 30 min. In the first session a nurse checked the patient’s knowledge and skills about his/her prescribed inhaler. A trained nurse informed and demonstrated the skills for self-management of asthma including inhaler technique. In the second session, a pharmacist informed about dosage, effects and side-effects of the medication but also about the method of controlling dosage based on asthma symptoms and lung function measured with peak expiratory flow (PEF). During the third session, patients were provided a self-asthma action plan describing how to recognise and to handle an asthma attack. The plan also gave clear instructions about how to use the asthma medication, how to interpret PEF rates and to avoid triggers. This intervention specifically improved both inhaler skills and increased PEF values, suggesting that asthma control became better. These effects sustained eight weeks after the intervention and this was the last follow-up [17].
Patient-related factors
Patients’ perceptions of their asthma and their beliefs about asthma medication may influence adherence behaviour [9]. These perceptions and beliefs could result in so called intentional non-adherence, which is a result of a person’s conscious decision to deviate from the recommended treatment, for instance by under or overusing the medication or by prematurely terminating the treatment [14, 15]. Patients, who deny an asthma diagnosis, or patients, who do not perceive their asthma to be a chronic condition, seem more inclined to refrain from the medication treatment [21]. Medication beliefs are also known to influence adherence behavior. For instance, patients who regard the asthma medication as a necessity for their health, seem more motivated to follow the treatment recommendations [2123], whereas those who are concerned with side-effects or becoming dependent, tend to intentionally deviate from the recommendations [21, 23]. Patients who have concerns about regular medication intake, side-effects or poor effect, also tend to display a non-adherent behaviour [24]. In this review, one article specifically addressing illness perceptions and four studies addressing medication beliefs as a means to improve adherence, were included.
Illness perceptions
Illness perceptions as factors influencing adherence were addressed by Smith et al. [25] who intervened by using a self-management model of illness comprising a structured step-wise and patient-centered approach. The intervention lasted nine months and patients were randomised to intervention (n=35) or control group (n=56), which received usual care. The health-care providers used the model to help the patients to identify areas of everyday life when asthma control was difficult to achieve, to set goals and to find strategies how to deal with these problematic situations. Hereby, the patients were working with personal defined goals and strategies. This intervention did not result in improved adherence to asthma medication. Instead asthma control, asthma self-efficacy and asthma quality of life improved in both groups but more in the intervention group.
Medication beliefs
All four studies addressing medication beliefs reported that their approaches had a positive impact on medication barriers and adherence behaviour. In three studies, telephone calls were used as method to carry out the interventions whereas Clerisme-Beaty and colleagues [26] used quite a different method to address adherence and medication beliefs by using a specific drug presentation style. The presentation about the drug was aimed at increasing patients’ expectancy that the asthma medication could control the asthma symptoms adequately. Patients (n=25) who received the medication presented in this manner reported better adherence and they also expressed higher expectancy with the specific asthma medication.
In a randomised controlled trial [27], the effect of phone calls made by pharmacists to patients, who received their first prescription for a long-term disease (ten had asthma), was evaluated. Two weeks after the patients had filled their prescription, a pharmacist phoned the patient to ask if there were any problems with the medication, about adherence and whether any additional information was needed. The pharmacist gave information and advice depending on the patient’s expressed needs. Four weeks later a researcher phoned the patients asking about the medication and adherence. The intervention of the pharmacist calling the patients resulted in better self-reported adherence in comparison to the control group. According to the result section in the abstract, fewer problems with the medication were reported in the intervention group [27].
Telephone calls were combined with educational material sent by mail on three occasions, in an intervention conducted by Park et al. [28]. The study group (n=87) received two telephone calls from a trained care manager with a health-care background. The phone-calls were concentrated on barriers to asthma medication adherence and the development of asthma management strategies. The educational mailings comprised general medication adherence topics and asthma specific information. Each telephone call and mailing did also encourage the participant to carry out proper asthma management. The intervention lasted six months and resulted in a reduction in both adherence barriers and in days when housework and schoolwork were limited due to asthma. Additionally, a reduction in the number of days when the patients was unable to attend to social, recreational and family activities was seen.
The effect of an “interactive voice recognition call” on adherence to asthma medication treatment was evaluated by Bender et al. [29]. The intervention group (n=25) received a maximum of three robot-phone calls during the intervention period of ten weeks and the control group (n=25) received none. By the end of this project, the intervention group reported both increased adherence and a favourable change in medication beliefs.
Condition-related factors
The symptom variability characteristic for asthma is claimed to be an important barrier to remain in regular medication treatment. This typical asthma feature could thus lead to doubts about the diagnosis and the need for regular medication treatment [9], which may explain why initiated medication treatment sometimes is interrupted when the asthma symptoms vanish [22] or when the patients start to feel better [30]. On the other hand, an adherent behaviour seems more likely to occur among those who perceive their asthma as severe [22] but it has also been reported that poor adherence frequently occurs among asthmatics with uncontrolled disease [31, 32]. Two articles were included in this section of the review, of which one succeeded in improving adherence.
Patients with “difficult asthma” were invited to a two phase intervention [33]. The first phase comprised a “concordance discussion”, which addressed whether the patient was adherent or not. Briefly, poor adherence was determined using prescription refill frequency, and a plan to address adherence obstacles was actively discussed with the appropriate patients. At six months follow-up, an improvement in adherence among the patients (n=83) was seen, which was associated with improved lung function and a reduction of hospital admissions. The second phase comprised an individual psycho-educational intervention, which was planned in light of the patient’s stated reasons for not adhering to the prescribed asthma medication treatment. Nine patients were randomised to the intervention and 11 to the control group. The effect of the intervention was determined at 12 months and was seen in an increase in prescriptions filled, as well as a reduction in total oral corticosteroid doses taken [33].
Patients with moderate and severe asthma (n=333) participated in a randomised controlled trial testing whether an individualised problem-solving intervention improved adherence to inhaled corticosteroids and asthma outcomes [34]. The intervention group (n=165) took part in four 30 min sessions aimed at improving or maintaining adherence by addressing individual barriers to adherence and finding solutions to remove the barriers. The control group (n=168) received standard asthma education during four 30 min sessions covering asthma topics exclusive of adherence. Adherence, which was measured electronically, decreased in both groups. In contrast, both asthma control and asthma quality of life improved, but emergency department visits and hospitalisation were unaffected [34].
Provider-related factors
Patients’ dissatisfaction with the patient-provider interaction may have a negative impact on adherence behaviour. Another factor related to the health-care system could be that the appointments with the physicians are too short to include patient education and to provide written information about asthma [9]. Patients and physicians seem to have different perceptions about the content during appointments. For instance, patients think that inhaler technique and side-effects with the asthma medication is discussed more rarely than do the physicians [35]. Two of the articles included in this review addressed the interaction between the patient and the health-care provider and six studies focused on patient education.
Patient-provider interaction
Both studies included in this section of the review focused on stimulating to a collaborative effort between the patient and the health-care provider to improve adherence to asthma medication. The effect of “shared decision making” between the patient and clinician as regards asthma medication was investigated in a randomised controlled trial. The intervention group (n=182) shared in making decisions about the medication, in the other group the clinician made the decisions (n=180) and the third group received usual care (n=189). At follow-up after one year, the patients, who shared in making decisions about their asthma medication treatment, improved their adherence based on pharmacy data, but at follow-up after two years the intervention effect did not occur. Nevertheless, adherence was better at year two compared to baseline scores [36].
A “cueing therapeutic communication” between patients and their clinicians was used to improve adherence to inhaled corticosteroids and asthma control in another study. The cue intervention comprised of visually standardised interpreted peak flow graphs, which were aimed to enhance the communication about the patient’s treatment plan. Sixty-eight patients assigned to 22 clinicians were randomised to the intervention group and 71 patients assigned to 21 clinicians to the control group. At the first visit the patients received a brief education session and a booklet. Adherence was measured electronically but in some cases the inhalers’ own dose counters were used. This intervention did not improve adherence but it seemed that it had a positive influence on asthma control, as patients who participated in the intervention used fewer courses of oral steroids during winter and spring, reported fewer asthma worsenings and made fewer urgent care visits during winter in comparison to the control group. However, there was no difference in the patients’ perceptions of the communication between the clinicians between the two groups [37].
Asthma education
This section of the review comprises articles describing rather extensive educational interventions covering important aspects of asthma management required for an adequate self-management.
The two studies in which interventions had a clear effect on adherence, were conducted by Morisky et al. [38] and by Armour et al. [39]. The first study was a two year prospective evaluation of a cohort comprising of 15,275 patients, of which 35% had asthma. The aim was to determine the effect of a disease management program addressing physiological and behavioural health indicators by tailored education. The results in the asthma subgroup showed significant increase in adherence in relation to asthma medication and improved asthma symptoms in regard to severity, frequency, nocturnal awakenings and activity limitations. Additionally, the patient’s use of PEF monitoring to assess asthma was increased [38]. The second study tested the effect of a pharmacy asthma care program comprising targeted education on the asthma, medication, lifestyle, inhaler technique, adherence, medication problems and goal-setting. Fifty pharmacies were randomised to the intervention and control pharmacies and 165 patients completed the intervention and 186 control patients finalised the study. The intervention resulted in improved adherence to preventer medication and a simultaneous reduction in reliever medication use in the intervention group. Moreover, the risk of non-adherence decreased and asthma quality of life, asthma knowledge and asthma control improved [39].
Three additional studies using educational programs reported important progress in self-management but the effect was not clearly reflected in adherence behaviour.
The effect of asthma education in two intervention groups, which received specific asthma education comprising elements of asthma management, inhaler use techniques as well as written information, was investigated by Kritikos et al. [40]. In one intervention group, the education was provided by specially trained pharmacists and the other group by pharmacist researchers trained as asthma educators. The control group did only receive written information – the same as in the intervention groups. Adherence measured through self-reports improved in both intervention groups but not more than in the control group.
In the next study, Wang et al. [41] explored whether there were any differences in outcomes if the patients were provided with asthma education by a nurse, or asthma counseling by a pharmacist. The patients were randomly assigned to two intervention groups and one control group. The first intervention group (n=35) received education from a nurse including asthma knowledge, monitoring disease severity, PEF use, information about asthma medication and self-management such as triggers and handling asthma attacks. The second group (n=34) received the same education in combination with information about the function and side-effects of the asthma medication by a pharmacist. The control group received usual care. At the last follow-up after six months, the two intervention groups had no significantly higher adherence compared to the control group.
The impact of self-management education on adherence to asthma medication was studied by Janson et al. [42]. Eighty-four participants were randomised to an individualised self-management education (n=45) or to a control group (n=39) receiving usual care. The intervention lasted 30 minutes and was given on three occasions with two weeks interval. The first was held by a nurse and a respiratory therapist both certified as asthma educators. There was also a personalised part addressing results from spirometry, PEF, skin prick tests and specific strategies to remove triggers. Adherence was monitored electronically. Mean adherence did not differ between the intervention and the control groups. When adherence scores were dichotomised as ≥60% or <60%, the odds of maintaining ≥60% adherence was nine-fold for the intervention group. These odds were maintained at 24 weeks, when the intervention was finalised.
These last three studies considered, a positive effect on patient’s asthma knowledge was seen [4042]. In Wang’s study [41] no improvements in asthma quality of life were seen but in Kritikos’ study [40] an improvement in both asthma quality of life and inhaler technique was found in the intervention groups. Kritikos et al. [40] also found a reduction in severe asthma and in Janson’s study [42], the intervention group reported fewer symptoms than the controls but mean symptom scores decreased in both groups. The nocturnal awakenings decreased in the intervention group and the odds of experiencing awakenings decreased in this group. The use of rescue medication decreased in the intervention group versus in the control group but both groups decreased their use during the intervention.
The final study had a different approach in comparison with the other studies in this section as a learner centered intervention was used. The focus was on interactive discussions, problem-solving, social support and procedures to change asthma specific behaviour. Additionally, the participants were encouraged to support each other. Twenty-four patients were randomised to the intervention group and 21 in the control group. The intervention comprised seven weekly meetings lasting two hours. The effect of this self-management program was reflected in improved asthma knowledge and asthma quality of life, self-efficacy and patient activation. As regards use of controller medication the mean was already at intervention start 6.8 of a maximum 7 scores, which did not leave much space for an improvement [43].
DISCUSSION
With reference to the interventions accounted for in the present review, a reasonable conclusion is that stimulating the asthma patients to active participation in treatment planning seems to improve their self-management of asthma including adherence to prescribed asthma medication. As an example, increased adherence was seen among patients who shared in decisions about medication treatment [36] and among patients, whose medication problems and own treatment goals, were considered [39]. However, solving the dilemma with poor adherence is not that as easy as just engaging the patients, which was learnt from the study conducted by Smith et al. [25]. Regardless of ambitious efforts, not all interventions accounted for in the current review led to improved adherence. In some cases, because the control patients also improved their adherence behaviour, which brings to mind the famous Hawthorne effect [44].
Another conclusion is that medication barriers, which prevent adequate adherence to asthma medication, may be demolished by simple phone calls from a health-care professional [2729]. If we could spare a couple of minutes to make a phone call to follow-up on our asthma patients’ potential medication concerns, we may have a cost-effective method to promote adherence, which in continuation prevents poor asthma control. Another effective method may be to address unintentional non-adherence like poor inhaler skills with repeated instructions [16, 19, 20]. It is to be noted, as Hardwell et al. [16] put forward, that many patients have an incorrect technique despite having received education, which recommends that such instructions should be tailored to each patient’s ability and that inhaler technique should be checked at each health-care appointment.
Another important remark is that dif ferent health-care professions have an educational role in promoting adherence to medication as part of proper asthma self-management. Addressing adherence in various health-care relations and contexts may emphasise its importance as the connecting link between the prescribed asthma medication and advantageous asthma outcomes. This work may be facilitated by identification of persons with high probability to display poorer adherence behaviour to asthma medication. The tricky part is to estimate accurate adherence level and to identify which patients are likely to deviate from a prescribed treatment, in daily practice in clinical settings [45]. The influence of patients’ personality on health behaviours such as adherence to medication treatment could be one guiding tool in this aspect.
Personality could be described in terms of five broad and bipolar personality traits Neuroticism, Extraversion, Openness to experience, Agreeableness and Conscientiousness. Each of the five personality traits are hierarchical constructed by more specific personality traits. These five personality traits contribute to enduring and individual differences in disposition to display a certain behaviour in a given situation [46]. We have previously reported that persons with various chronic diseases, who scored higher on Neuroticism, lower on Agreeableness or lower on Conscientiousness, seemed more inclined to display poorer adherence to medication treatment [47]. In yet another study, we found that more impulsive young adults with asthma reported lower adherence to asthma medication than the less impulsive. Young adult men, who were either more antagonistic or alexithymic, also reported lower adherence to asthma medication [48]. Associations between Neuroticism and poorer adherence in men with asthma have also been reported [49]. The advantage of assessing personality in relation to adherence is that it provides an indication of potential personal needs [50], which could be useful targets when planning adherence support. For instance, less conscientiousness or impulsive persons, who tend to be less goal-directed and structured [46], may be less inclined to plan ahead. This behavior may not be conducive to regular medication intake. For that reason, they may benefit from support with reminders or incorporation of routines for their medication intake. In contrast, persons scoring high on Neuroticism, who could be described as worried and with difficulties handling stress [50], most likely need another type of adherence support.
Some of the interventions in the currently reviewed articles were described as individualised for instance in terms of using the patients level of asthma knowledge, inhaler or PEF skills as points of departures [17] or interpretation of spirometry, PEF rate or control over environmental exposures [42], which certainly is of significance. Nevertheless, none of the interventions focused on individual differences in terms of personality among the selected patients, as personality is a major contributor of behavior, including health behavior [47, 48]. Fig. 1 shows a hypothetical personality perspective on adherence interventions. As a suggestion, future interventions aimed at promoting adherence and preventing poor asthma control should focus on persons with high risk of displaying poor adherence to the prescribed asthma medication treatment. In this work, assessment of personality could provide a useful tool to identify patients’ different needs and resources [50], which could function as targets when planning forthcoming adherence support.
Fig. 1
Fig. 1

Hypothetical model suggesting the potential effect of personality on adherence interventions, symbolised by dashed arrows.
References
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2. Gamble J, Stevenson M, McClean E, Heaney LG. The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009;180:817–822. [PubMed]
3. Jones C, Santanello NC, Boccuzzi SJ, Wogen J, Strub P, Nelsen LM. Adherence to prescribed treatment for asthma: evidence from pharmacy benefits data. J Asthma. 2003;40:93–101. [PubMed]
4. Williams LK, Pladevall M, Xi H, Peterson EL, Joseph C, Lafata JE, Ownby DR, Johnson CC. Relationship between adherence to inhaled corticosteroids and poor outcomes among adults with asthma. J Allergy Clin Immunol. 2004;114:1288–1293. [PubMed]
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Bagaimana perkembangan penatalaksanaan penderita asma terkini?

NEJM baru saja menerbitkan artikel review tentang perkembangan penatalaksanaan pasien asma. artikel lengkapnya sbb”

A Patient with Asthma Seeks Medical Advice in 1828, 1928, and 2012″

People have suffered from asthma for millennia.1 Although the clinical presentation of asthma has probably changed little, there are many more people who now bear its consequences than there were 200 years ago. As a result of an intense interest in the condition, our understanding of its pathobiology, how to diagnose it, and — most important — how to treat it has evolved dramatically over the past two centuries. To illustrate this change, we provide three fictional reports of consultations performed for essentially the same patient, who has what we in 2012 would refer to as asthma. (A timeline of the major advances in the treatment of asthma from 1812 through 2012 is available with the full text of this article at NEJM.org.)

The first report is from 1828, the year that the New England Journal of Medicine and Surgery and Collateral Branches of Science joined with the Medical Intelligencer to form the Boston Medical and Surgical Journal. The second is from 1928 when the title of the publication was changed to the New England Journal of Medicine, and the third report is from the present.

The three accounts reflect the way in which care was delivered at the time. The first account is in the voice of a general practitioner who was contacted for consultation about a woman with intermittent episodes of dyspnea. The second is in the voice of a generalist who works in a private practice and has an interest in asthma; the patient has been referred to this physician by her own general physician. The third account is in the voice of a sub-subspecialty physician whose practice is limited to the care of patients with asthma. The contemporary patient identified this physician as a specialist in asthma through an Internet search and is consulting him for a second opinion about the appropriateness of her asthma care. She brings to the consultation a detailed history that she wrote, as well as notes from her primary care physician and an allergist.

Our three views of this medical consultation for a patient with asthma are not meant to provide a history of asthma but rather to offer a set of snapshots of the care that the same patient might have received had she sought medical advice in these distinct epochs. There are many diagnostic and therapeutic techniques that we do not mention; this does not mean that they are not important; it simply means that their use does not fit the time frame of our fictitious consultations. Finally, since this article is meant to contribute to the celebration of the Journal‘s 200th anniversary, we have largely, but not exclusively, used literature from the Journal; our apologies to others who claim primacy.

1828

Office Note on Mrs. A. Smith

I attended at the home of a woman aged 35 years who had just moved with her family to Boston. Her household includes herself and her husband of 17 years, four children, a cook, two maids, a stable boy, and a footman. She sent for me with a complaint of repeated shortness of breath.

The History of Her Illness

When a fit of dyspnea occurs, the patient hears a musical noise in her chest, and she must labor to draw and expel a full breath. When she is stricken, it is her custom to stop all her activities and to inhale the steam coming from the spout of a kettle that her cook keeps always at the ready. With such treatment, she usually recovers within one or two days. Once or twice a year she has a severe fit, which may last for a week, and she is confined to her sick bed.

She has suffered such fits of laborious breathing since her childhood. They occur at any time of the year but are more common in the spring, when the trees bloom, and in the late summer than at other times. In the winter she reports that it is common for her to be so stricken when she walks from the harbor to her home, a distance of nearly a mile along a path that ascends steeply. This difficulty of respiration has become such a frequent occurrence that she now routinely calls for her coach even for very short journeys outside her home. During each of her periods of confinement for childbearing, the fits were far less numerous and severe in character, but within a few months after she had given birth, they returned.

Often, even when she is not suffering from laborious breathing, she will arise in the dark of the night and stand at the open window, gasping for air. By the time that dawn arrives she has usually regained control of her breathing and returns to sleep.

Her difficulty of respiration is accompanied by itchy eyes and a runny nose. She has a cough with these fits, but she does not produce phlegm. She does not have hemoptysis. No one among her family or close acquaintances has died from consumption. Her weight has been stable, and when she is not suffering from laborious breathing, her strength is good. She has not had rheumatic fever.

Her mother, now deceased, also suffered from difficulty of respiration; her father did not. Of her four children, ages 14, 12, 9, and 7, her two eldest, both boys, have suffered from the same symptoms, although her oldest son has not had a fit of laborious breathing for more than a year.

My Examination

Observation of her breathing on the occasion of my consultation revealed nothing far out of the ordinary. Her speech was full and normal. The movements of her chest were full. I could palpate nothing abnormal in her heart motion. There was no swelling of her liver or her legs. I used a newly acquired stethoscope to examine her chest. Although the patient could not hear the musical sounds that have been termed “wheezes,” I was able to hear them.

My Opinion

The patient clearly suffers from an asthma; she may also have what has been described as “hay fever” in the spring and fall.2 I believe her fits of laborious breathing are similar to the asthmatic fits that Sir John Floyer suffered from and described in his “Treatise of the Asthma.”3 He describes this type of asthma as follows: “[T]he expiration is very slow and leisurely and wheezing, and the asthmatic can neither cough, sneeze, spit nor speak freely; and in the asthmatic fit, the muscular fibres of the bronchia and vesiculae of the lungs are contracted, and that produces the wheezing noise which is most often observable in expiration.” I have no concern that she suffers from consumption or from conditions of the heart that may lead to dropsy.

I think that she may benefit from smoking the leaf of Datura stramonium, also known as the thorn-apple plant. Many asthma sufferers have tried this remedy, and it seems to provide relief from a fit, even though it will not prevent a recurrence. Several years ago, Dr. Bree reported in the New England Journal of Medicine and Surgery that such smoking had a deleterious effect on a number of patients suffering from difficulty of respiration.4 However, in my experience, patients such as this woman will derive benefit from such treatment in that it shortens the duration of their indisposition from an asthmatic fit. I recommended this treatment to my patient, and she tells me that she has benefited from it.

Comment: In the early 1800s, there were many “asthmas,” since this was the term for any episodic shortness of breath. The physician needed to be sure that the primary cause was not tuberculosis or cardiac disease (e.g., mitral stenosis); both were very common at the time. Once a diagnosis of asthma (as we know it now) was established, the number of effective treatments was quite limited; inhalation of smoke from burning Datura stramonium was probably the best. This agent had anticholinergic properties and was the forerunner of the currently used antimuscarinic agents, such as ipratropium and tiotropium.5 There were numerous other treatments, such as inhalation of the fumes of hydrocyanic acid6 or inflation of the lungs with a bellows.7 Fortunately, such treatments and many others that produced no benefit and probably caused harm are no longer used.

1928

Letter Regarding Mrs. A. Smith

Dear Dr. Jones,

Thank you for referring your patient, Mrs. A. Smith, for evaluation concerning a possible diagnosis of asthma. I found the patient’s history, as recounted in your office notes, to be complete and accurate.

History

The critical feature of her case is that Mrs. Smith, age 35, has been having “asthma attacks” since her early childhood. Her attacks are characterized by the relatively sudden onset of dyspnea; they are more frequent in the spring and fall, when they are often preceded by symptoms of rhino-conjunctivitis. If untreated, an attack will last for a few days, but if she is treated with a subcutaneous injection of adrenaline, as you have administered at your office, she often has relief from acute symptoms, and the attack may or may not recur. Recently, her attacks have been more frequent, and she does not feel that her breathing is improved to the point where she can carry out her responsibilities as a wife and mother.

Her mother carried a diagnosis of asthma, as do two of her children. She is currently not using any medications.

Physical Examination

Her physical examination, at a time when she was not having acute asthmatic symptoms, showed normal body temperature, blood pressure, and pulse. She had no rashes. Her nasal passages were closely examined and showed inflammation and edema but no polyps. Her respirations were 24 and slightly labored. She had diminished tactile fremitus. Expiratory wheezing of modest profusion was audible in all lung fields. Her cardiac examination was normal. There was no clubbing, cyanosis, or edema.

Laboratory Studies

I examined the radiograph of the chest that she brought with her, which was taken within the last month. It showed hyperinflation of the lungs, but there were no abnormal shadows; there were no findings that would suggest tuberculosis. Her cardiac silhouette did not show any abnormalities.

A blood smear was made, showing 14 per cent eosinophils; in a normal person this is most often less than 5 per cent. A sputum sample was also examined, and all the polymorphonuclear leukocytes observed were eosinophils. Specialized skin testing was performed. She had positive reactions to extracts of ragweed and horse dander.

My Opinion

Your diagnosis of asthma is correct. The episodes are characteristic, and there is no other likely cause suggested by her medical history or the physical examination and laboratory findings. In fact, the presence of eosinophils in the blood and sputum makes the diagnosis virtually certain. The positive skin tests make this case one of extrinsic asthma. Hypersensitivity to proteins is the likely physiological basis of asthma, although the exact mechanisms leading to sensitization are not clear.

Treatment is difficult. Your use of adrenaline injections for acute attacks is appropriate8; there is reason to believe that treatment with oral ephedrine may also help with her asthmatic episodes.9 The relief is of longer duration than with injected adrenaline and the patient can administer it herself. Ephedrine is not a substitute for injections of adrenaline when the patient is in extremis.

The critical factor in treatment is removing the patient from exposure to the proteins to which she is sensitive. Her positive skin test to ragweed pollen extract is in agreement with the clinical history of worsening disease in the autumn. However, there may be proteins to which she is allergic that were not included in our skin test panel. In my experience, removing a protein from a patient’s exposure is very hard to accomplish. One strategy, which I am loath to suggest unless there is no other hope, is a move to a climate where there are fewer proteins in the air to which the patient would be exposed.10

Comment: By 1928, the differential diagnosis of asthma was well established, and diagnostic techniques were available that made it possible to be reasonably certain that patients did not have heart disease or pneumonia when they were labeled as asthmatic.11 Physicians of the time often used the term “asthma” to refer to episodic dyspnea, but qualifiers such as “cardiac” were used. By 1928, eosinophils in the blood and sputum were known to be characteristic of asthma.12 Skin tests for allergies had been developed and were used clinically to help clinicians identify specific offending environmental proteins. The issues that plague us today — allergies to multiple allergens and difficulty in interpreting skin tests — were of concern to physicians in 1928.

There was not much available in the way of treatment. Ephedrine, an orally active sympathomimetic agent, had been discovered in China9 and used in asthma treatment, but other than allergen removal and adrenaline injections, there was little to offer patients with asthma beyond advising them to smoke “asthma cigarettes” (made from the leaves of D. stramonium [Figure 1Figure 1Asthma Cigarettes.]). Theophylline was available but was used as a diuretic; its value in the treatment of asthma had not yet been discovered. Aerosol inhalation therapy had not been widely adopted by 1928, but by the 1940s an inhaled formulation of epinephrine was marketed for asthma treatment (Figure 2Figure 2Personal Inhaler.).

2012

E-Mail Message to Ms. Smith

Dear Ms. Smith,

Thank you for asking me to provide you with a direct personal consultation concerning your asthma and your asthma care. I will summarize the salient facts from the detailed written history and physician’s note you kindly provided.

As pointed out in your written history, you have had asthma since childhood. Among your earliest recollections is receiving injection treatments and later inhalation treatments for asthma in an emergency room. In your early teenage years you started treatment with inhaled Vanceril (beclomethasone), two puffs twice a day; 10 years ago, you switched to inhaled Qvar (beclomethasone driven by a hydrofluoroalkane [an ozone-layer–friendly] propellant), and Singulair (montelukast) was added to your regimen. Over the past 10 years, you have tried two different “combination inhalers,” containing both inhaled glucocorticoids and long-acting β2-agonists — namely, Advair (fluticasone propionate and salmeterol) and Symbicort (budesonide and formoterol fumarate dehydrate). These medications did not improve your symptoms or lung function as compared with inhaled beclomethasone alone, and you switched backed to Qvar.

Even with this regimen, however, your asthma symptoms are still present and bothersome. For example, two to three times a month you are awakened from your sleep between 3 a.m. and 4 a.m. by shortness of breath and cough; you can hear yourself wheeze. If you use your rescue albuterol inhaler, you are usually able to get back to sleep by 5 a.m.

Two years ago, skin tests were performed, and your total IgE level was measured. Your only positive skin tests were for house-dust mites and ragweed. Your total IgE level was 75 IU per milliliter. The allergist who did the testing suggested that you add a nonsedating antihistamine, such as loratadine, to your treatment during the times of year when you are most susceptible to symptoms; the loratadine was of some small help in controlling your runny nose, but there was no change in your asthma symptoms. Your allergist also referred you to a gastroenterologist, who performed 24-hour esophageal pH monitoring and found no abnormalities.

In the past decade, you have required treatment with oral prednisone on three occasions; the last instance was in 2009. Each of these exacerbations occurred during your allergy season. You have a peak-flow meter, which you use occasionally. Your best reading is 500 liters per minute; on most days, your peak-flow values are between 350 and 400 liters per minute.

You work in an office. You live with your husband and two children in a single-family home heated and air-conditioned with forced air. You have taken extensive measures to remove allergens from your home, including having the air ducts cleaned and tested for allergens. You have no pets. You have never smoked, and the same is true for your husband and your children. Smoking has not been allowed in your workplace for more than a decade. Your mother had asthma.

Your current medications are Qvar, 80 μg per puff, two puffs twice a day; Singulair, 10 mg per day, taken at night; and one multivitamin per day.

You would like a single consultation and confidential second opinion as to how your asthma has been managed and how to improve your asthma control.

On physical examination today, you looked well. Your weight was 135 lb [61.2 kg]. Your blood pressure was 110/75 mm Hg, and your pulse was 77 beats per minute according to the pulse oximeter, which also indicated that your hemoglobin saturation while you were breathing ambient air was 95%. Your physical examination was largely normal. No abnormalities were noted in your eyes, nose, or ears. Your chest examination was normal except for the presence of scattered expiratory wheezes, which were heard best during rapid, shallow breathing. There were no abnormalities in your extremities. Your neurologic examination was normal as well. Lung-function testing was performed in our laboratory; the results are attached to this letter (Figure 3Figure 3Spirometric Results for Ms. Smith.).

I think that the diagnosis of asthma is well established. You have a long history of asthma and have had salutary symptomatic responses to asthma treatments, your lung-function tests still show reversibility of airway obstruction of more than 15% with albuterol, and no other competing diagnosis has emerged over many years. The major issue now is to determine whether there are additional treatments that could help suppress your asthmatic symptoms without increasing the treatment burden.

You and your physicians have done an excellent job of managing your asthma. The treatments you are using now are well established and known to be effective. There are three treatments that could be added to your regimen, but it is difficult to be certain that they would be effective. First, oral theophylline could be added to your regimen. Although you cannot recall having received treatment with theophylline, given your age and asthma history, it is likely that you were treated with this agent as a child. This therapy could be of value, but it is necessary to monitor blood levels of the drug to obtain an optimum response, and some patients find testing to be burdensome. There is a small chance that theophylline could make your asthma worse by relaxing the muscle that separates your stomach from your esophagus; if this occurred, the treatment would be stopped.

Second, Singulair could be replaced with Zyflo CR (zileuton, controlled release). The active ingredient in Singulair is montelukast, which blocks the action of the cysteinyl leukotrienes at the CysLT1 receptor, whereas zileuton prevents the synthesis of both cysteinyl leukotrienes and dihydroxy leukotrienes. There are theoretical reasons to believe that controlled-release zileuton would yield a clinical benefit, but there are no compelling data to support this approach. Monitoring of liver function is required during initiation of treatment with zileuton.

Third, Xolair (omalizumab) could be added to your regimen. This anti-IgE monoclonal antibody is given once a month by injection. There is clearly an allergic component of your disease; your total IgE level is elevated, but it is not so high as to preclude the use of omalizumab.

As we discussed, I think your primary care physician has done an excellent job in designing your asthma treatment. You should discuss our consultation with her and decide what is in your best interest.

Comment: There have been three major changes in our understanding of asthma between 1928 and 2012. First, spirometry, which had been invented in the 1840s,13 was refined by adding time to volume output, and between the late 1940s and early 1950s, measurements made from forced exhalations were used in the diagnosis and treatment of asthma.14 Other lung-function tests were developed and used, and the relationships between clinical physiology and symptoms were delineated.15 Second, glucocorticoids were identified as an effective and useful asthma treatment. They were first used systemically in the early 1950s16 and were subsequently made available in inhaled form17,18,; these agents remain the standard of care today. Third, our understanding of the immunobiology of asthma progressed beyond the view that the essential mechanism was an immediate hypersensitivity reaction.19,20, Unfortunately, these advances in understanding the cell biology of asthma have not yet been translated into new therapies, although new therapies have been derived from our improved understanding of immediate hypersensitivity responses — notably, the use of leukotriene modifiers21 and anti-IgE antibodies.22

Our patient is current in her medical knowledge and is using medical information widely available on the Internet to help in the management of her chronic condition. The consultant used measures of lung function to quantify her physiological deficit. The consultant also measured the patient’s IgE level, which was consistent with allergic asthma, and provided the information needed for anti-IgE treatment, should the patient elect this approach. The patient has used all the standard asthma therapies but has residual symptoms. The consultant outlines other asthma treatments that the patient could try, highlighting the need to try different treatments to see whether one or another will work. Sadly, we still do not have a way to predict a given patient’s response to therapy.

Conclusions

These three case histories illustrate that asthma as a disease has not changed for two centuries. We have made real progress in identifying patients with asthma and in understanding its biologic basis and its treatment. Progress has also been made in diagnostic testing, which has been refined to measure lung function with great accuracy and repeatability. In addition, we can measure the lung’s responsiveness to triggering agents and thereby obtain objective indications of disease activity, in addition to the patient’s history. We have come to realize that allergic responses often substantially contribute to both chronic persistent asthma and acute exacerbations of asthma symptoms, although this association may have been overemphasized. The current focus is on immune responses in affected patients; we believe that airway inflammation plays a critical role in asthma, but the precise nature of that inflammation remains a mystery. The knowledge that asthma runs in families has become the basis for very sophisticated studies of the genetics of asthma, but not much of its heritability can be explained by all the genes identified to date. In spite of all the progress achieved over the past two centuries, we still do not understand the fundamental causes of asthma. Hence, we do not have therapies that address the underlying mechanisms; we have no cure for asthma. The medications at hand provide relief of symptoms and improve lung function and airway responsiveness, but they do not prevent exacerbations or progression of disease, and the most desirable accomplishment, the primary prevention of asthma, is a vision that has not yet become a reality.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Source Information

From the Division of Pneumology–Allergology, University Children’s Hospital, Munich, Germany (E.M.); and the Pulmonary Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston (J.M.D.).

Address reprint requests to Dr. von Mutius at Pneumologie and Allergologie, Dr. von Haunersches Kinderspital, Lindwurmstr. 4, D-80337 Munich, Germany.

Menjamin keamanan dan kualitas alkes dan obat-obatan diperlukan PMS

NEJM telah mempublikasikan naskah yang berjudul “Postmarketing Surveillance of Medical Devices — Filling in the Gaps”, mari kita simak bersama:

Failures of implantable medical devices, although rare, can carry a substantial risk of serious injury. From 2000 through 2011, more than 150 new high-risk medical devices were approved by the Food and Drug Administration (FDA) through the premarket approval (known as PMA) process, and an additional 600 devices were cleared through the less demanding 510(k) process, in four medical specialty areas (cardiovascular care, neurology, obstetrics and gynecology, and orthopedics; see graphNumbers of High-Risk (Class III) Medical Devices Approved or Cleared by the FDA in Cardiovascular Care, Neurology, Obstetrics and Gynecology, and Orthopedics, 2000–2011.). The problem that Hauser describes (10.1056/NEJMp1114695) — the erosion of the insulation in St. Jude Medical’s Riata leads for implantable cardioverter–defibrillators — highlights the fact that medical devices are complex assemblies of multiple components, and the failure of any single component can lead to unexpected and serious safety problems. Because it is impossible to design an implantable medical device with zero risk of failure, effective systems for monitoring safety after a device is on the market are essential for protecting the public health. Moreover, since incremental changes are made in medical devices throughout their life cycles, it is impractical to prospectively study each change comprehensively before marketing. Balancing the need for robust postmarketing safety monitoring with the need to avoid the stifling of innovation is a prime responsibility of the Center for Devices and Radiological Health (CDRH) at the FDA.

The FDA’s safety-surveillance strategy has relied on physicians, health care institutions, manufacturers, and patients to report medical device failures and complications through the Medical Device Reporting system. This system can identify unanticipated medical device failures and complications but requires extensive analytic review and has important limitations.1 Although the CDRH receives more than 100,000 reports annually, the proportion of medical device failures that are registered is estimated to be less than 0.5%; this low reporting rate greatly limits the information available regarding the balance of risk and health improvement associated with a given medical device.2

Several FDA initiatives have been launched to fill the gaps in the passive event-reporting system. In 2002, the CDRH established the Medical Product Safety Network, which represents more than 300 health care institutions that collaborate to identify and investigate trends in device failures and adverse events. In 2007, the FDA was given the regulatory authority to mandate follow-up safety studies after initial market approval (the Section 522 rule) — a change that improves the agency’s flexibility to investigate potential safety concerns. In 2009, the FDA launched the Sentinel initiative, a program to integrate the electronic health records of large, representative U.S. populations for postmarketing safety analysis. However, despite great success in linking nearly 100 million claims-based health records, Sentinel projects have thus far focused only on medications — at least in part because of the very limited information about medical devices currently available in billing claims data.

In contrast to drugs, medical devices suffer from a major impediment to safety monitoring: the lack of unique device identifiers (UDIs). To address this limitation, the FDA Amendments Act of 2007 authorized the agency to develop a comprehensive UDI system, which is currently under review within the Office of Management and Budget. As a UDI system is integrated with administrative and claims databases, it will become possible to identify patients who have been exposed to specific devices. However, the complex interplay among device design, the procedural safety of implantation, the learning curve associated with medical devices, and the risks to individual patients will continue to make it difficult to conduct effective and reliable safety surveillance using only billing data.

There are important opportunities to leverage large, disease-specific clinical registries for monitoring device safety. In many countries, such registries are a mandatory component of the health care system and required for all implantations of high-risk devices. In the United States, there is no national system to ensure that registries exist for high-risk medical devices. Nevertheless, several nonprofit professional medical organizations in the United States have recognized the critical need for medical device registries and have spearheaded their development in an effort to monitor and improve the quality of care. The American College of Cardiology, in conjunction with several partner organizations, has established detailed clinical registries covering many high-risk cardiovascular devices, including coronary stents, implantable defibrillators, and defibrillator leads, which together contain information on approximately 4 million implantation procedures. The recently developed transcatheter heart-valve registry will provide early postmarketing information about the safety of this revolutionary treatment for patients with high-risk aortic-valve stenosis. Clinical registries in cardiac surgery already exist, and newer efforts by professional societies related to orthopedics, ophthalmology, and other fields are under way.

Perhaps the most successful example of a coordinated effort to study newly introduced devices has been the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), established to capture detailed clinical data on all patients receiving implantable ventricular assist pumps in the United States. Its success is related to the requirement by the Centers for Medicare and Medicaid Services (CMS) that patient information be entered into an audited national registry as a condition of reimbursement. INTERMACS now serves as a ready infrastructure to support the postapproval study of every new generation of mechanical cardiac support device, saving manufacturers substantial time and resources that they would otherwise have to invest in establishing new systems of data collection, auditing, and analysis.3

Creating and maintaining these detailed clinical registries is challenging and expensive. Many registries are supported by voluntary submissions from health care providers, so hospitals must bear the costs of collecting and submitting information. Emerging standards for electronic health records, including “meaningful use” regulations, will provide unprecedented opportunities for securely mapping clinical information to distributed clinical registries.

But having reliable and complete clinical data is not enough. The development of sound methods and practical tools for monitoring safety over a product’s life cycle is essential. We have advocated a strategy of automated prospective surveillance of high-risk implantable devices, using database monitoring tools to support continuous surveillance of clinical registries.4 Such tools are capable of monitoring hundreds of high-risk medical devices simultaneously, to maximize efficiency in detecting unrecognized safety problems. Automated surveillance systems constantly watch a growing database of clinical experience and trigger an alert when the rate of a device failure or complication rises above threshold levels. Automated monitoring tools must incorporate the best available statistical methods to account for the complexity of the surveillance of device safety, including risk differences among patients, effects of physicians’ learning curves, and interactions between the device and medications; they must also balance specificity and sensitivity in the detection of safety signals to permit efficient epidemiologic exploration of such alerts.

The complexity of device-safety surveillance requires the use of complementary approaches in an organized, prospective strategy. A comprehensive national safety surveillance system must include several key elements, beginning with the adoption of the proposed UDI system. We recommend expedited review and finalization of the UDI rule to permit implementation as soon as possible. Next, the FDA, together with the CMS, should require that detailed information regarding the use of high-risk devices and clinical outcomes be submitted to selected national registries operated by independent academic or professional medical organizations. We recommend that the FDA retain full rights of access to the data for additional analysis as needed. Third, the FDA should redirect a portion of the resources currently spent by the medical device industry on underpowered condition-of-approval studies to support the national device-safety registries. Fourth, automated safety-surveillance tools should be applied to device registries to prospectively monitor for the most severe and the most common device failures and complications. Finally, methods for linking information across premarketing studies, the new registries, and existing FDA surveillance systems to provide valid safety estimates require further development.

Complementing existing event-reporting systems with enhanced prospective surveillance of high-quality registries will permit the FDA to efficiently monitor the safety of increasingly complex and widely used medical devices.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article (10.1056/NEJMp1114865) was published on February 14, 2012, at NEJM.org.

Source Information

From the Cardiovascular Division, Brigham and Women’s Hospital (F.S.R.); the Department of Health Care Policy, Harvard Medical School (S.-L.T.N.); and the Department of Biostatistics, Harvard School of Public Health (S.-L.T.N.) — all in Boston

4 Februari Hari Kanker sedunia, bagaimana kita mensikapi kanker?

Kanker, sesuai namanya, memang salah satu penyakit yang sangat ditakuti. Disamping bersifat sebagai pembunuh, penyakit ini kadang-kadang sulit diduga datangnya. Sayang saat ini penyakit ini masih banyak disandang masyarakat kita.
Mungkin ada yang bertanya “apa saja faktor yang dapat mencegah atau mengurangi kejadian kanker dan faktor – faktor apa saja yang dapat meningkatkan kejadian kanker?”.
Kanker merupakan penyakit yang pemunculannya melalui proses yang komplek. Mula proses kejadian kanker pada seseorang bisa dari faktor lingkungan, faktor biologis individu (genetik dan kekebalan, maupun faktor gaya hidup atau perilaku. Manakah yang lebih dominan apakah faktor lingkungan (karsinogen misalnya asap dapur, asap kendaraan, asap rokok), faktor biologis (genetik) ataukah faktor perilaku, itu juga bervariasi sesuai dengan jenis kanker. Namun yang jelas kanker biasanya melibatkan berbagai komponen dalam perjalanan dan penjelmaannya.Oleh karena itu untuk menjawab faktor apa yang dapat mengurangi kejadian kanker juga akan bervariasi, tetapi secara umum adalah sbb:
1. perbaiki lingkungan, kurangi cemaran pada lingkungan dimana masyarakat umum banyak dan sering melakukan aktivitas. Asap kendaraan dan asap rokok merupakan salah satu sumber cemaran udara perkotaan yang kaya karsinogen (bahan pemacu proses pembentukan kanker). Senyawa hidrokarbon aromatik yang terkandung pada asap kendaraan dan asap rokok merupakan bahan karsinogen kuat yang menyebabkan kejadian kanker paru, kanker payudara maupun kanker kulit pada sebagian besar masyarakat yang sering kontak atau menghirup udara kotor. tersebut. Kebijakan pemerintah dengan …. bersambung

Apakah obat herbal tanpa efek samping?

Sering diperbandingkan keamanan obat herbal dengan obat sintetik. Obat herbal dianggap oleh sebagian masyarakat lebih aman jika dibandingkan dengan obat sintetik. Alasan yang selalu menjadi dasar pijakan rasionalisasi berfikir mereka adalah bahwa obat herbal adalah obat alamiah, sesuatu yang alamiah adalah asli sesuai dengan pemberian pembuatnya sehingga tetap murni, artinya tidak kotor atau terkotori atau tercampuri.  Sebagian masyarakat bahkan berkeyakinan bahwa obat herbal pasti aman dan pasti tanpa efek samping. Benarkah anggapan seperti itu? Anda berpendapat bagaimana? Tuangkan pendapat Saudara di media ini sebagai bahan diskusi. Ayo siapa mencoba?

Sirgunggu bukan hanya obat gurah tetapi juga sebagai imunomodulator

Tindakan pencegahan dari kemungkinan sakit dapat dilakukan dengan meningkatkan daya tahan tubuh melalui pemberian suatu bahan yang disebut dengan imunomodulator. Imunomodulator adalah suatu senyawa atau bahan yang dapat meningkatkan sistem imun. Meningkatnya sistem imun akan meningkatkan ketahanan tubuh terhadap berbagai pathogen yang masuk kedalam tubuh seperti infeksi berbagai mikroorganisme misalnya oleh bakteri, pirogenik dan virus.

obat gurah

imunomodulator

Bahan alam yang sering digunakan untuk meningkatkan daya tahan tubuh antara lain dengan tanaman sirgunggu (C. serratum (L) Moon). Secara turun-temurun tanaman sirgunggu (C. serratum(L) Moon) sudah banyak dipakai oleh masyarakat Giriloyo (Imogiri) khususnya untuk gurah. Gurah merupakan pengobatan tradisional yang pada umumnya dilakukan dengan meneteskan ramuan kedalam lubang hidung dengan tujuan mengeluarkan kotoran-kotoran yang ada diseluruh tubuh bersamaan dengan keluarnya lendir melalui lubang hidung (Djawadi, 2000).

imunomodulator

gurah

Kandungan sirgunggu (C. serratum (L) Moon) diduga sebagai imunomodulator yaitu kemampuan suatu zat untuk memodulasi (meningkatkan/menurunkan) imunitas (Anonim,2003). Tanaman ini mengandung senyawa flavonoid dan polifenol pada daunnya, dimana kedua senyawa tersebut sebagai imunomodulator yang dapat mengeluarkan lendir yang dibantu oleh makrofag maka akan memacu keluarnya sitokin sebagai akibat inflamasi, mencegah detoksifikasi (keracunan dalam sel) dengan cara mengeluarkan lendir dari dalam tubuh. Sedangkan pada kulit akarnya mengandung glikosida fenol, manitol, dan sitoserol serta polifenol (Anonim, 2003). Flavonoid dan polifenol pada tanaman lain terbukti memiliki efek sebagai imunostimulansia.

Makrofag sebagai efektor pada sistem imun, berperan memusnahkan kuman atau patogen yang akan merusak tubuh (Harijanto, 2000), baik melalui mekanisme fagositosis langsung maupun melalui mekanisme tak langsung dengan melepaskan Reaktive Oxygen Intermediates (ROI) dan sitokin (Wijayanti, 2000). Hal ini ditandai dengan perubahan bentuk, perubahan biokimiawi, serta perubahan fungsi dari makrofag (Baratawidjaya, 2000 ; Harijanto, 2000). Aktivitas fagositosis makrofag dapat ditingkatkan oleh zat-zat imunogen termasuk imunogen dari tanaman. Telah dibuktikan bahwa pemberian ekstrak etanol sirgunggu meningkatkan aktivitas fagositosis makrofag. Ini berarti bahwa ekstrak etanol sirgunggu dapat berlaku sebagai imunomodulator yaitu meningkatkan aktivitas fagositosis atau kemampuan membunuh sel pembunuh. Selamat mencoba

masihkah ada harapan sembuh bagi penderita DM tipe I?

Penyakit gula akibat kerusakan pankreas yang sering dialami sejak usia anak-anak merupakan penyakit autoimun. Upaya pencarian obat untuk penyakit gula ini senantiasa dilakukan, karena penderita penyakit ini bila organ pankresnya tidak membaik maka mereka membutuhkan insulin seumur hidupnya, tentu itu akan berhubungan dengan biaya, risiko ketidaknyamanan dalam cara pemberian insulin, reaksi penolakan atau adanya komplikasi. Baru-baru ini NEJM melaporkan hasil penelitian klinik obat baru bagi penderita baru DM tipe I yang berjudul” GAD65 Antigen Therapy in Recently Diagnosed Type 1 Diabetes Mellitus” namun penelitian ini masih belum memberikan hasil sebagaimana yang diharapkan. Hasil selengkapnya abstrak laporan tersebut silakan baca pada kopian sbb:GAD65 Antigen Therapy in Recently Diagnosed Type 1 Diabetes Mellitus

Johnny Ludvigsson, M.D., Ph.D., David Krisky, M.D., Ph.D., Rosaura Casas, Ph.D., Tadej Battelino, M.D., Ph.D., Luis Castaño, M.D., Ph.D., James Greening, M.D., Olga Kordonouri, M.D., Timo Otonkoski, M.D., Ph.D., Paolo Pozzilli, M.D., Jean-Jacques Robert, M.D., Ph.D., Henk J. Veeze, M.D., Ph.D., and Jerry Palmer, M.D.

N Engl J Med 2012; 366:433-442February 2, 2012

Abstract
Article
References
Background

The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.

Full Text of Background…
Methods

We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.

Full Text of Methods…
Results

The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.

Full Text of Results…
Conclusions

Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.)

imatinib mesylate tablet, untuk apakah?

FDA telah mengeluarkan ijin untuk penggunaan imatinib mesylate secara oral.
Obat ini cukup lusas penggunaannya di kedokteran. Berita selengkapnya silakan baca pada artikel berikut:
Imatinib Mesylate Tablets

On January 31, 2012, the U.S. Food and Drug Administration (FDA) granted regular approval for imatinib mesylate tablets (Gleevec, Novartis Pharmaceuticals) for the adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive Gastrointestinal Stromal Tumors (GIST). Accelerated approval for this indication was granted in December 2008. Labeling is also revised to include the results of a randomized trial demonstrating that recurrence-free survival (RFS) and overall survival (OS) were improved by continuing adjuvant imatinib therapy to 36 months.

An adjuvant, multicenter, open label, phase 3 trial randomly allocated patients to receive either 12 or 36 months of imatinib treatment. Patients received imatinib, 400 mg orally daily, in both treatment duration arms.

Eligible patients had one of the following criteria: tumor diameter >5 cm and mitotic count >5/50 high power fields (HPF), or tumor diameter >10 cm and any mitotic count, or tumor of any size with mitotic count >10/50 HPF, or tumors that ruptured into the peritoneal cavity. There were 199 patients on the 12-month arm and 198 patients on the 36-month arm. The median age of patients was 61 years (range, 22-84 years).

RFS was defined as the time from date of randomization to the date of recurrence or death from any cause. The median follow-up for patients without a RFS event was 42 months. There were 84 (42%) RFS events in the 12-month treatment arm and 50 (25%) RFS events in the 36-month treatment arm. Thirty-six months of imatinib treatment significantly prolonged RFS compared to 12 months [HR=0.46, (95% CI: 0.32, 0.65), p

The median follow-up for OS in patients still alive was 48 months. There were 25 (13%) deaths in the 12-month treatment arm and 12 (6%) deaths in the 36-month treatment arm. Thirty-six months of imatinib treatment significantly prolonged OS compared to 12 months [HR=0.45, (95% CI: 0.22, 0.89), p=0.0187].

Discontinuation of imatinib therapy due to adverse reactions occurred in 15 patients (8%) and 27 patients (14%) of the 12- and 36-month treatment arms, respectively. The most common adverse reactions, as noted in this and previous imatinib trials, were swelling (edema), nausea, vomiting, muscle cramps, bone or muscle pain, diarrhea, rash, fatigue, and abdominal pain.

imatinib mesylate

imatinib mesylat

Imatinib received accelerated approval for patients with Kit (CD117) positive unresectable and/or metastatic GIST in February 2002. This indication subsequently received regular approval in September 2008.

The recommended dose of imatinib for adjuvant treatment is 400 mg/day administered with meals daily for three years. The optimal duration of treatment is not known.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021588s035lbl.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Bagaimana perkambangan ilmu dan teknologi kesehatan untuk masalah fibrosis uterus?

Fibroid uterin sudah menjadi masalah kesehatan sejak jaman purbakala namun sampai saat ini masih meninggalkan banyak masalah. Pada terbitan edisi minggu ini NEJM bagian editorialnya membahas masalah fibroid uterin. Judul yang dipilih pada editorial nejm tersebut adalah”Uterine Fibroids and Evidence-Based Medicine — Not an Oxymoron”. bagaimana paparan editorial ini? silakan kutipan selengkapnya sebagai berikut:

Elizabeth A. Stewart, M.D.

N Engl J Med 2012; 366:471-473February 2, 2012

Article
References

The 2011 report from the Agency for Healthcare Research and Quality on comparative management of uterine fibroids noted, “Despite the prevalence and possible complications of uterine fibroids, few published studies examining the effectiveness of treatment strategies exist.”1 Few therapies are approved by the Food and Drug Administration (FDA) for fibroids; leuprolide acetate, a gonadotropin-releasing hormone (GnRH) agonist, was approved in 1995 for preoperative treatment of fibroids, with the addition of iron. In the past decade, uterine-artery embolization and magnetic-resonance–guided focused ultrasound surgery have also been therapeutic options. Surgeries for fibroids, especially hysterectomy, still predominate, and fibroids remain the leading cause of hysterectomy.2

Whereas estrogen was long considered to be the key factor in the pathogenesis of fibroids,3 it has been recognized more recently that progesterone also plays a critical role, as do inherited and somatic mutations, growth-factor dysregulation, and an active extracellular matrix.2 Several studies, including relatively small, randomized clinical trials, have supported the safety and efficacy of selective progesterone-receptor modulators in reducing uterine volume and controlling menstrual bleeding.4-6 However, this class of agent has not been approved for the treatment of fibroids, in part because of political issues surrounding the use of mifepristone.7

In this issue of the Journal, Donnez et al. report the results of two randomized clinical trials that support the efficacy of the progesterone-receptor modulator ulipristal acetate for preoperative treatment of symptomatic uterine fibroids.8,9 In one report, two doses of ulipristal acetate were compared with placebo among women with anemia; all the women in this trial also received iron supplementation.8 In the second, the same doses of ulipristal acetate were compared in a noninferiority trial with leuprolide acetate9; women in this trial received iron supplementation at the discretion of the treating physician. GnRH agonists are highly effective for the treatment of fibroids because they induce amenorrhea, resulting in cessation of heavy menstrual periods, and a reduction in fibroid volume, resulting in relief of symptoms related to leiomyoma bulk.3 However, GnRH agonists cause severe hypoestrogenic symptoms and long-term effects on bone density, thus limiting the safety and negatively affecting the side-effect profile of the drugs.

Ulipristal acetate was superior to placebo and noninferior to leuprolide acetate for the control of bleeding; more than 90% of the women treated with either dose of ulipristal acetate had a clinically significant decrease in bleeding, and approximately three fourths became amenorrheic. In addition, there was no initial steroidal flare with ulipristal acetate as there is with leuprolide acetate — an advantage for women with excessive menses and anemia. Ulipristal acetate induced amenorrhea more quickly than did leuprolide acetate and resulted in a greater increase in hemoglobin level than did placebo, although iron supplementation alone has been shown to be quite effective for the preoperative management of anemia.10

For symptoms related to leiomyoma bulk, leuprolide acetate appeared to be more effective than ulipristal acetate, resulting in a greater reduction in fibroid volume. However, data in the Supplementary Appendix (available with the full text of the article at NEJM.org) on the subset of women who did not undergo surgery support the results of prior studies that suggest that progesterone-receptor modulators provide more prolonged volume reduction after treatment is discontinued, as compared with the rapid regrowth seen after discontinuation of GnRH agonist therapy.4

There were no major safety concerns with ulipristal acetate in these short-term studies. Ulipristal acetate had a better side-effect profile than did leuprolide acetate, with less profound suppression of estradiol levels, significantly fewer hot flashes, and few substantial effects on markers of bone turnover.9

The trials also shed some light on the major potential safety issue with progesterone-receptor modulators — their effect on the endometrium. Since progestins protect against estrogen-induced proliferation of endometrium, the question remains whether long-term use of progesterone-receptor modulators might lead to endometrial hyperplasia or carcinoma. Therapy with progesterone-receptor modulators causes a unique nonphysiologic pattern of endometrial changes with glandular dilatation and dyssynchronous changes between the glands and stroma, which have some hallmarks of malignant change but which, on intensive study, appear to be benign.11

In approximately 60% of the women in these trials who were treated with ulipristal acetate, endometrial biopsy samples showed changes typically associated with progesterone-receptor modulators after 3 months of therapy, but these changes resolved after a 6-month drug-free period.8 If longer-term studies confirm a carryover effect of progesterone-receptor modulators on reduction of uterine volume, as well as resolution of endometrial changes, women with symptomatic fibroids may have the option of a unique intermittent therapy that maximizes efficacy while minimizing safety concerns.

Several limitations of the current studies, in addition to the short duration of treatment, should be noted. Few black women were included, yet black women have a greater risk of fibroids, a more severe phenotype, and an earlier age of onset than do white women.2 This lack of diversity is unfortunately common in clinical trials of treatments for fibroids.12 Participants in these trials also tended to be thinner than the general population of women with fibroids, and their uteri were only moderately enlarged as compared with the uteri in women in other trials of innovative fibroid therapies.13,14 Women were not screened for ovulatory function, and thus leiomyomas may not be the sole explanation for bleeding in the women.

Studies of progesterone-receptor modulators as treatment for fibroids date back almost two decades. Since that time, innovations in interventional therapies have provided effective, minimally invasive alternatives to hysterectomy. Unfortunately, the rate of hysterectomy continues to be high,15 and there remains substantial need for effective medical therapy.2 The present studies represent an important step in that direction.