Category Archives: Artikel

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:
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 ( 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
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.
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].
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.
1. Latry P, Pinet M, Labat A, Magand JP, Peter C, Robinson P, Martin-Latry K, Molimard M. Adherence to anti-inflammatory treatment for asthma in clinical practice in France. Clin Ther. 2008;30:1058–1068. [PubMed]
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]
5. Bender BG, Pedan A, Varasteh LT. Adherence and persistence with fluticasone propionate/salmeterol combination therapy. J Allergy Clin Immunol. 2006;118:899–904. [PubMed]
6. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) [Accessed: 2011-11-18]. [updated December 2010] Available from:
7. Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database Syst Rev. 2008:CD000011. [PubMed]

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

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.


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.


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.


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.).


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.


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

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.

Kabar Gembira!!!!! Ada vaksin antimalaria

NEJM telah melaporkan hasil uji klinik vaksin antimalaria. Berita selengkapnya sebagai berikut:
Original Article
A Field Trial to Assess a Blood-Stage Malaria Vaccine

Mahamadou A. Thera, M.D., M.P.H., Ogobara K. Doumbo, M.D., Ph.D., Drissa Coulibaly, M.D., Matthew B. Laurens, M.D., M.P.H., Amed Ouattara, Pharm.D., Abdoulaye K. Kone, M.D., Ando B. Guindo, M.D., Karim Traore, M.D., Idrissa Traore, M.D., Bourema Kouriba, Pharm.D., Ph.D., Dapa A. Diallo, M.D., Issa Diarra, Pharm.D., Modibo Daou, Pharm.D., Amagana Dolo, Pharm.D., Ph.D., Youssouf Tolo, Pharm.D., Mahamadou S. Sissoko, M.D., M.S.P.H., Amadou Niangaly, Pharm.D., Mady Sissoko, Pharm.D., Shannon Takala-Harrison, Ph.D., Kirsten E. Lyke, M.D., Yukun Wu, Ph.D., William C. Blackwelder, Ph.D., Olivier Godeaux, M.D., Johan Vekemans, M.D., Ph.D., Marie-Claude Dubois, M.Sc., W. Ripley Ballou, M.D., Joe Cohen, Ph.D., Darby Thompson, M.S., Tina Dube, Ph.D., Lorraine Soisson, Ph.D., Carter L. Diggs, M.D., Ph.D., Brent House, Ph.D., David E. Lanar, Ph.D., Sheetij Dutta, Ph.D., D. Gray Heppner, Jr., M.D., and Christopher V. Plowe, M.D., M.P.H.

N Engl J Med 2011; 365:1004-1013September 15, 2011


Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children.

Full Text of Background…

In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain.

Full Text of Methods…

The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P=0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P=0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine.

Full Text of Results…

On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; number, NCT00460525.)

Mana yang lebih menguntungkan Rivaroxaban atau Warfarin pada Nonvalvular Atrial Fibrillation

Non valvular atrial fibrilasis merupakan salah satu faktor risiko stroke iskemia dan embolisme pada pembuluh darah. Selama ini warfarin merupakan salah satu obat pilihan untuk pencegahan strok iskemia maupun pembentukan emboli pada pasien dengan fibrilasis termasuk pasien dengan nonvalvular atrial fibrilasis. Hasil Uji klinis untuk membandingkan kemanjuran rivaroxaban dengan warfarin pada nonvalvular atrial fibrilasis telah dilaporkan oleh NEJM.



faktor risiko cvd

faktior risiko cvd

Original Article

Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation

Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D., Daniel E. Singer, M.D., Werner Hacke, M.D., Ph.D., Günter Breithardt, M.D., Jonathan L. Halperin, M.D., Graeme J. Hankey, M.D., Jonathan P. Piccini, M.D., Richard C. Becker, M.D., Christopher C. Nessel, M.D., John F. Paolini, M.D., Ph.D., Scott D. Berkowitz, M.D., Keith A.A. Fox, M.B., Ch.B., Robert M. Califf, M.D., and the ROCKET AF Steering Committee for the ROCKET AF Investigators

N Engl J Med 2011; 365:883-891September 8, 2011

Comments open through September 14, 2011

Citing Articles (1)
Comments (3)


The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin.

Full Text of Background…


In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism.

Full Text of Methods…


In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.

Full Text of Results…


In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF number, NCT00403767.)

Dipasang stenting atau terapi obat pada stenosis arteri intracranial?

Telah dilakukan penelitian untuk menilai kemanjuran antara operasi angioplasti dan pemasangan stanting dengan terapi obat pada pasien dengan stenosis arteri intracranial. NEJM edisi Minggu I septem ber 2011 telah melaporkan bahwa terapi obat pada pasien dengan stenosis arteri intracranial lebih menguntungkan jika dibandingkan dengan operasi angioplasti dan pemasangan stenting. Tidak dapat dipungkiri bahwa stenosis arteri intracranial merupakan faktor risiko utama kejadian stroke dan sering berakibat fatal. Makalah selengkapnya silakan baca di:

Original Article

stenosis arteri intracranial

stenosis arteri intracranial

Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis

Marc I. Chimowitz, M.B., Ch.B., Michael J. Lynn, M.S., Colin P. Derdeyn, M.D., Tanya N. Turan, M.D., David Fiorella, M.D., Ph.D., Bethany F. Lane, R.N., L. Scott Janis, Ph.D., Helmi L. Lutsep, M.D., Stanley L. Barnwell, M.D., Ph.D., Michael F. Waters, M.D., Ph.D., Brian L. Hoh, M.D., J. Maurice Hourihane, M.D., Elad I. Levy, M.D., Andrei V. Alexandrov, M.D., Mark R. Harrigan, M.D., David Chiu, M.D., Richard P. Klucznik, M.D., Joni M. Clark, M.D., Cameron G. McDougall, M.D., Mark D. Johnson, M.D., G. Lee Pride, Jr., M.D., Michel T. Torbey, M.D., M.P.H., Osama O. Zaidat, M.D., Zoran Rumboldt, M.D., and Harry J. Cloft, M.D., Ph.D. for the SAMMPRIS Trial Investigators

September 7, 2011 (10.1056/NEJMoa1105335)

Comments open through September 21, 2011



Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial.

Full Text of Background…


We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days.

Full Text of Methods…


Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non–stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group.

Apakah yang kita ketahui tentang BNP?

gagal jantung

gagal jantung

BNP singkatan dari B type natriuretic peptide sering di sebut juga sebagai brain type natriuretic peptide. BNP merupakan peptida yang dihasilkan oleh tubuh kita, yaitu sel otot ventrikel jantung. Saat ini BNP menjadi penting oleh karena dapat menjadi indikator atau marker, dalam bahasa kito=petanda, yang akan mengarah pada adanya kelainan antara lain untuk kondisi yang mengarah kepada gagal jantung. Marker BNP ini lebih peka, artinya sebelum munculnya kelainan klinik, yaitu meskipun belum memunculkan keluhan ke arah gagal jantung, tetapi keberadaan BNP yang berlebihan telah menunjukkan kondisi jantung yang sedang kepayahan. Dengan memantau kadar BNP dapat memantau kebugaran jantung dan mengantisipasi akan terjadinya gagal jantung yang lebih berat. Cerita selengkapnya tentang BNP silakan baca artikel berikut:


BNP (B-type natriuretic peptide) is a cardiac neurohormone secreted from cardiac ventricular myocyte in response to increased ventricular wall stretch or wall tension, increased ventricular volume or pressure. It is a potent vasodilator and it promotes diuresis. The half-live is short, about 18-22 minutes.

  • Circulating BNP level increases in proportion to the severity of heart failure.
  • Conditions that raise BNP level beside heart failure
    • Age, sex (female), left ventricular hypertrophy, acute coronary syndrome, acute myocardial infarction, cardiac inflammation, arrhythmogenic RV with decrease ejection, primary pulmonary hypertension, worsening of corpulmonale with increased RV pressure and volume, acute pulmonary emboli, Kawasaki disease, advanced renal failure, cirrhosis, hyperaldosteronism, Cushing syndrome, and decreased clearance.
  • Heart failure conditions that may have low BNP
    • Flash pulmonary edema within 1 hour, acute chordal rupture, pulmonary congestion-edema from mitral stenosis, severe end stage heart failure, and heart failure in obese patients (BMI>30 kg/m2).

Potential usefulness are:

1. Diagnosis for HF
      • Utilization of BNP level to help differentiate heart failure from other causes of dyspnea in ER or urgent care setting, using Point of Care measurement technique. BNP level over 100 pg/ml favors the diagnosis of heart failure. The range of BNP level in most heart failure patients is from a few hundreds to >1000 pg/ml. BNP should not be a stand alone test. Clinical judgment is always important, Elevated BNP are seen in other conditions (Table 1). Low BNP may be found in few acute heart failure conditions and in obese patients with heart failure.

Table 1. Common causes of BNP elevation in routine clinical practice

Age. Female
Renal failure (Cr >2) or on dialysis
Myocardial infarction
Acute coronary syndrome
Pulmonary disease with right-side failure
Acute pulmonary embolism
Baseline left ventricular dysfunction

Utilization of BNP level as a diagnostic tool for heart failure with preserved systolic function. A heart failure patient with normal echocardiographic LV systolic function, abnormal diastolic filling abnormalities and elevated BNP should favor this diagnosis.

2. Follow up and Prognosis of heart failure

    • During inpatient treatment of heart failure. Rising of the discharged BNP level from the admission level is a good predictor of poor prognosis and near future unfavorable outcome i.e… early readmission.
    • During outpatient treatment followup, BNP guiding intensity of treatment may be useful.
    • During acute MI, rising of BNP level few days after admission level indicates poorer prognosis
    • Baseline BNP is necessary for comparison.
3. Treatment for acute decompensation
    • Nesiritide (Natrecor) is a human recombinant BNP.
    • Dosage: Intravenous 2 microgram/kg bolus, followed by infusion of 0.01 microgram/kg/min
    • Duration: Up to 7 days (or more?).
    • Action: Hemodynamic effect is observed in an hour or less. There is no tolerance for several days of infusion. Hemodynamic effect resolves by 2-4 hours after cessation of the infusion.
    • Nesiritide promotes diuresis.
    • Use appropriate dose of diuretic. Over diuresing may potentiate hypotension side effect.
    • Side effects: Hypotension (more in cases taking ACEI), nausea, headache.
    • Caution: Volume depletion, aortic stenosis, hypertrophic cardiomyopathy, cardiogenic shock.
    • Usually does not require hemodynamic monitoring.
    • Beware of drug incompatibility in the infusion process.
    • May obtain proBNP but not BNP level during nesiritide infusion.
    • In the responder cases, if the BNP level is checked 2 hours (BNP five halve life time) after stopping the infusion it should be lower than the preinfusion level.

4. Potential outpatient intermittent treatment in severe heart failure

(Waiting for FUSION 2 trial)

5. NT-proBNP (NT = N Terminal)

When cardiac myocyte Pro-BNP enter the circulation it split into BNP which is an active neurohormone and NT-proBNP which is inactive part but with longer half life. Level of NT-proBNP can be used for diagnosis, follow up and prognosis of heart failure the same way as BNP level. The physicians need to know whether the report are BNP or NT-proBNP since the level are significantly different and some laboratory may not label it correctly.


Bagaimana berita baru tentang medication error?

FDA memberikan layanan kusus tentang perkembangan terkini kejadian medication error. Kejadian medication error yang masih tinggi di masyarakat telah menjadi isue utama pada sistem layanan kesehatan dan menjadi keprihatinan para pengambil kebijakan bidang kesehatan di dunia.  Gambaran global tentang layanan informasi medication error dari FDA adalah sebagai berikut:

Medication Errors


FDA receives medication error reports on marketed human drugs (including prescription drugs, generic drugs, and over-the-counter drugs) and nonvaccine biological products and devices.  The National Coordinating Council for Medication Error Reporting and Prevention defines a medication error as “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer. Such events may be related to professional practice, health care products, procedures, and systems, including prescribing; order communication; product labeling, packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use.”

The American Hospital Association lists the following as some common types of medication errors:

  • incomplete patient information (not knowing about patients’ allergies, other medicines they are taking, previous diagnoses, and lab results, for example);
  • unavailable drug information (such as lack of up-to-date warnings);
  • miscommunication of drug orders, which can involve poor handwriting, confusion between drugs with similar names, misuse of zeroes and decimal points, confusion of metric and other dosing units, and inappropriate abbreviations;
  • lack of appropriate labeling as a drug is prepared and repackaged into smaller units; and
  • environmental factors, such as lighting, heat, noise, and interruptions, that can distract health professionals from their medical tasks.

In 1992, the FDA began monitoring medication error reports that are forwarded to FDA from the United States Pharmacopeia (USP) and the Institute for Safe Medication Practices (ISMP). The Agency also reviews MedWatch reports for possible medication errors. Currently, medication errors are reported to the FDA as manufacturer reports (adverse events resulting in serious injury and for which a medication error may be a component), direct contact reports (MedWatch), or reports from USP or ISMP.

The Division of Medication Errors and Technical Support includes a medication error prevention program staffed with pharmacists and support personnel. Among their many duties, program staff review medication error reports sent to the USP Medication Errors Reporting Program and MedWatch, evaluate causality, and analyze the data to provide feedback to others at FDA.

 Campaign to Eliminate Use of Error-Prone Abbreviations

FDA and the Institute for Safe Medication Practices (ISMP) have launched a national education campaign to eliminate the use of ambiguous medical abbreviations that are frequently misinterpreted and lead to mistakes that result in patient harm. The campaign seeks to promote safe practices among those who communicate medical information.

As part of the campaign, FDA recommends that healthcare professionals consider ISMP’s List of Error-Prone Abbreviations, Symbols, and Dose Designations [external link] whenever medical information is communicated. In addition, FDA and ISMP have provided a toolkit of resource materials available at ISMP and FDA Campaign to Eliminate Use of Error-Prone Abbreviations. [external link]

FDA News: FDA and ISMP Launch Campaign to Reduce Medication Mistakes Caused by Unclear Medical Abbreviations.

Federal Regulations and Guidances

Other Resources

Drug Products Associated with Medication Errors

Medication Errors Information from FDA

Contact Us

Division of Drug Information (CDER)

Office of Communications

Feedback Form

10001 New Hampshire Avenue

Hillandale Building, 4th Floor

Silver Spring, MD 20993

Page Last Updated: 06/17/2011
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.

Bagaimana layanan kesehatan yang tepat, dilema layanan kesehatan ke depan

Keberadaan dan peran dokter dalam layanan kesehatan di masyarakat sudah menjadi keniscayaan. Sejak jaman Yunan sampai jaman modern saat ini, peran dokter dalam sistem layanan kesehatan di masyarakat tidak sedikit.  Dalam islam keberadaan dokter maupun profesi kesehatan lainnya agar terselenggara sistem layanan kesehatan yang efektif dan efisien serta mampu meningkatkan derajat kesehatan masyarakat termasuk dalam hukum fardu kifayah. Bagaimana seharusnya menjadi dokter yang sesuai tuntutan jaman tetapi juga sesuai tuntunan etika ternyata tidaklah mudah. Artikel berikut memberikan gambaran bagaimana seharusnya seorang dokter di jaman modern.


The Doctor’s Dilemma — What Is “Appropriate” Care?

NEJM | August 17, 2011 | Topics: Comparative Effectiveness, Cost of Health Care

Victor R. Fuchs, Ph.D.

Most physicians want to deliver “appropriate” care. Most want to practice “ethically.” But the transformation of a small-scale professional service into a technologically complex sector that consumes more than 17% of the nation’s gross domestic product makes it increasingly difficult to know what is “appropriate” and what is “ethical.” When escalating health care expenditures threaten the solvency of the federal government and the viability of the U.S. economy, physicians are forced to reexamine the choices they make in caring for patients.

In an effort to address this issue, physicians’ organizations representing more than half of all U.S. physicians have endorsed a “Physician Charter” that commits doctors to “medical professionalism in the new millennium.” The charter states three fundamental principles, the first of which is the “primacy of patient welfare.” It also sets out 10 “commitments,” one of which states that “while meeting the needs of individual patients, physicians are required to provide health care that is based on the wise and cost-effective management of limited clinical resources.” How can a commitment to cost-effective care be reconciled with a fundamental principle of primacy of patient welfare?

The dilemma arises for two main reasons. First, recent decades have witnessed a flood of new, expensive medical technologies (drugs, imaging devices, surgical procedures) that are of varying degrees of value to patients. A few are true breakthroughs, with strong favorable effects on mortality and morbidity. Others make a meager contribution, at best, to health outcomes. Moreover, technologies that may provide high value for carefully selected patients are often used indiscriminately for a much larger cohort of patients. Second, health insurance, private or public, has become so widespread that 90% of the country’s health care bill is paid by third parties, not by the patient receiving the service.

What is a conscientious physician to do? Some new cancer drugs cost thousands of dollars per month for a single patient. The bills for many surgical procedures run to five or even six figures. Noninvasive imaging devices can offer information to assist in diagnosis, at a cumulative cost in the billions of dollars. U.S. patients, on average, get almost three times as many magnetic resonance imaging scans as Canadian patients; there is no evidence that this large differential can be explained by national differences in the medical condition of patients or that it results in significant national differences in health outcomes. So what level of utilization deserves to be called “appropriate”?

If insurance were not widespread, many physicians would be reluctant to order an expensive intervention unless it offered a good chance of substantial benefit — that is, unless it was cost-effective. Indeed, without U.S.-style cost-insensitive insurance, many expensive diagnostic and therapeutic innovations would not be developed and brought to market.1 The insured patient, on the other hand, will usually want any and all care that might possibly be of net benefit, regardless of cost. The physician may recognize that the intervention under consideration is not cost-effective but may recommend it anyway, for a variety of reasons: to keep the goodwill of the patient, to protect against a malpractice suit, or in the belief that the “primacy of patient welfare” makes the denial of such care “inappropriate” and “unethical.”

The doctor’s dilemma is the nation’s problem. Some policy experts think that if patients had “more skin in the game” — that is, had less insurance — the problem would be solved. It would not. Even the most ardent advocates of deductibles and copayments acknowledge the need for an annual cap on patients’ payments, beyond which insurance takes over completely. There is no consensus on the right level for the cap, but it is generally recognized that the average U.S. household, with large debts and minimal financial assets, could not handle much more than $5,000. But the extreme skew in annual health care expenditures, with 5% of individuals accounting for 50% of spending in any given year, means that many health care decisions, and especially those involving big-ticket interventions, will be made by and for patients whose costs have exceeded the cap.

Another popular “solution” is to eliminate care that does more harm than good — that is, “unnecessary” care. Such elimination would be desirable, but the potential savings from this source are smaller than is usually claimed. It is true that after the fact, many interventions turn out to be useless or even harmful for some patients. But the heterogeneity of patient populations and uncertainty about the response of individual patients to an intervention means that it is often difficult or impossible to determine in advance which ones will prove to help particular patients and which will turn out to have been unnecessary.

There is no escaping the fact that many interventions are valuable for some patients even if, for the population as a whole, their cost is greater than their benefit. Under what circumstances are they likely to be ordered, and when are they likely to be withheld? The context within which the physician practices, his or her assumption about the behavior of other physicians, and the economic and health consequences of ordering all the care that might do some good versus practicing cost-effective medicine will affect the physician’s choice. If the physician is paid on a fee-for-service basis and the patient has open-ended insurance, the scales are tipped in favor of doing as much as possible and against limiting interventions to those that are cost-effective. In that setting, who would benefit from the resources that are saved by practicing cost-effective medicine is not obvious to the physician.

In contrast, if the physician is practicing in a setting that has accepted responsibility for the health of a defined population and the organization receives an annual fee per enrollee, the chances of the physician’s practicing cost-effective medicine are substantially increased, even though all patients are insured. The physician’s colleagues are practicing the same way, and the resources saved can be used for the benefit of the defined population, which includes the physician’s patient. In Canada, which has universal insurance, per capita spending on health care is only 55% of the U.S. level because there is a limited overall budget, and all physicians in the system recognize the need for prudence in making decisions about care.

In short, when physicians are collectively caring for a defined population within a fixed annual budget, it is easier for the individual physician to resolve the dilemma in favor of cost-effective medicine. That becomes “appropriate” care. And it is an ethical choice, as defined by philosopher Immanuel Kant, because if all physicians act the same way, all patients benefit.2

Disclosure forms provided by the author are available with the full text of this article at

Source Information

From Stanford University, Stanford, CA.


    1. Weisbrod B. The health care quadrilemma: an essay on technological change, insurance, quality of care, and cost containment. J Econ Lit 1991;29:523-552Web of Science

  1. Kant I. Critique of practical reason and other writings in moral philosophy. Beck LW, trans. Chicago: University of Chicago Press, 1949.

Era baru administrasi layanan kesehatan, Rekam medik elektronik

rekam medik elektronik

sistem rekam medik elektronik

Era baru sistem administrasi kesehatan. Perkembangan IT/TI telah merasuki seluruh sendi kehidupan dan  secara masife merubah cara hidup manusia termasuk pada cara bagaimana meningkatkan derajat kesehatan masyarakat. Salah satu bagian dari proses perubahan dalam layanan administrasi oleh adanya TI adalah layanan administrasi kesehatan. Laporan berikut menunjukkan adanya arus besar menuju perubahan yang mendasar pada sistem administrasi layanan kesehatan.

Special Article

Electronic Health Records and Quality of Diabetes Care

NEJM | August 31, 2011 | Topics: Health IT, Quality of Care

Randall D. Cebul, M.D., Thomas E. Love, Ph.D., Anil K. Jain, M.D., and Christopher J. Hebert, M.D.

Incentives to increase adoption and meaningful use of electronic health records (EHRs) anticipate a quality-related financial return.1,2 However, empirical data showing either quality improvement or cost savings from EHR adoption are scarce. Available studies have shown few quality-related advantages of current EHR systems over traditional paper-based medical-record systems.1-5 Projected cost savings are mostly based on models with largely unsupported assumptions about adherence to and the effect of fully functional EHR systems.6,7 Data are particularly scarce on EHR adoption by “priority primary care providers” — health care professionals practicing in small groups and those serving vulnerable populations, as such providers are defined in the Health Information Technology for Economic and Clinical Health (HITECH) Act.8 EHR adoption by such providers is supported by the national network of Health Information Technology Regional Extension Centers.

Innovations in care delivery as specified in the Affordable Care Act, such as accountable care organizations and patient-centered medical homes (PCMHs), also provide incentives for using information most easily obtained through EHR systems.9,10 Data regarding the benefits of PCMHs have come largely from reports by EHR-based organizations,11-13 and these data support the posited links among EHR use, quality improvement, and cost savings. However, these reports did not compare EHR and paper-based systems.

Regional quality-improvement initiatives, such as those supported by the Robert Wood Johnson Foundation’s Aligning Forces for Quality (AF4Q) program,14 by Medicare and state Medicaid initiatives,15,16 and by multistakeholder collaboratives,17 provide an opportunity to evaluate the effectiveness of EHRs and refinements in national payment policy.15,18 In greater Cleveland, one of 16 AF4Q sites nationwide, diverse EHR-based and paper-based ambulatory practices publicly report on the quality and outcomes of care for patients with chronic medical conditions. Regional achievement of diabetes-related standards has been reported six times to date. The reported data come from practices with high concentrations of priority primary care providers and allow a comparison of quality standards for EHRs and paper records, after adjustment for important patient-level attributes. We examined the independent association of EHR use with achievement of quality standards for the care of patients with diabetes.


Study Design

We analyzed data from a retrospective cohort of primary care practices of seven diverse health care organizations that publicly reported achievement of quality standards for adults with diabetes between July 2007 and June 2010. Data reported here include the most recent yearlong cross section (July 2009 through June 2010) as well as practice-level trends across three years of reports.

Setting and Subjects

The primary care practice partners of Better Health Greater Cleveland (hereafter referred to as Better Health) are responsible for the majority of medical care for people with chronic disease in Cuyahoga County, an urban area in northeastern Ohio with 1.3 million residents; the county includes Cleveland, one of the nation’s poorest large cities, and its affluent suburbs. Participating practices include 21 sites of large not-for-profit health care organizations, 1 of which serves many vulnerable (“safety net”) patients; 12 sites of a large safety-net public hospital system; 1 safety-net practice of a university hospital; and the safety-net practices of all 3 of the county’s federally qualified health centers. Since the program’s inception in 2007, reporting primary care providers have included physicians in general internal medicine, family practice, and medicine–pediatrics. In July 2009, nurse practitioners and other health care professionals with prescription-writing privileges were added to the list of reporting providers. Patients include all adults (18 to 75 years of age) with diabetes who made at least two visits to the same primary care practice during each yearlong measurement interval.

Care and Outcome Standards

Better Health’s Clinical Advisory Committee approved nine quality standards for diabetes, including four standards of care and five standards of intermediate outcomes. Care standards are reported by standard and as an all-or-none composite19; outcome standards are reported by standard and as a composite indicating achievement of at least four of the five standards. Care standards include receipt of a glycated hemoglobin value, testing for urinary microalbumin or prescription of an angiotensin-converting–enzyme inhibitor or an angiotensin-receptor blocker, an eye examination to screen for diabetic retinopathy, and administration of a pneumococcal vaccination. Intermediate-outcome standards include a glycated hemoglobin value below 8%, a blood pressure below 140/80 mm Hg, a low-density lipoprotein (LDL) cholesterol value below 100 mg per deciliter or documented prescription for a statin medication, a body-mass index (the weight in kilograms divided by the square of the height in meters) below 30, and nonsmoking status. All care and outcome standards pertain to the most recent result documented in the measurement interval, except pneumococcal vaccination (administration at any time is sufficient for meeting this standard).


Patient information was collected regarding several sociodemographic variables, including insurance type (Medicare, commercial, Medicaid, or uninsured), race or ethnic group (white, black, Hispanic, or other), age, sex, estimated household income, and educational level, all prespecified for our analyses. Insurance type is the primary insurance reported during the most recent doctor’s visit. Data on race or ethnic group were primarily obtained through self-report. Household income and educational level were estimated by linking each patient’s home address to Census 2000 summaries.

Data Collection and Study Oversight

Clinical practices or health care organizations submitted a unique study code for each patient and health care provider to Better Health’s Data Management Center. EHR-based organizations provided data on all eligible patients. Data from paper-based organizations were gathered by centrally trained chart abstractors for a random sample of patients selected by the Data Management Center. More than 95% of patients in the sample had charts available for review. Each site reviewed summary results for accuracy before publicly reporting data. The MetroHealth System’s Human Privacy Board approved data collection and submission protocols.

Quality-Improvement Assistance

The collaborative supports three types of quality-improvement assistance. First, partner sites receive comparisons with other practices in their organization and regionwide for case mix, achievement of Better Health’s standards, and quality improvement. Practice directors can identify data regarding specific providers. Public reports highlight the top 10% of practice sites with respect to achievement of standards or improvement, by insurance category and overall. Second, Better Health sponsors semiannual daylong summits featuring national speakers and sharing of best practices in quality improvement and management of reported chronic conditions. Third, since mid-2009, all practices have had the opportunity to receive program-sponsored practice coaching. Coaching has principally focused on culture change, workflow redesign, and quality-improvement projects related to specific metrics.


Apixaban sebagai inhibitor faktor Xa diduga dapat mencegah serangan ulang jantung iskemia jika ditambahkan pada antiplatelet. Proyek penelitian APPRAISE yang melibatkan lebih dari 7000 relawan, bertujuan untuk mengetahui kemanjuran penambahan apixaban pada terapi standar antiplatelet untuk mencegah serangan ulang pada pasien dengan acute coronary syndroma. Hasil penelitian selengkapnya dapat dibaca di NEJM:

Original Article

Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome

John H. Alexander, M.D., M.H.S., Renato D. Lopes, M.D., Ph.D., Stefan James, M.D., Ph.D., Rakhi Kilaru, M.S., Yaohua He, M.D., Ph.D., Puneet Mohan, M.D., Ph.D., Deepak L. Bhatt, M.D., M.P.H., Shaun Goodman, M.D., Freek W. Verheugt, M.D., Ph.D., Marcus Flather, M.D., Kurt Huber, M.D., Danny Liaw, M.D., Ph.D., Steen E. Husted, M.D., Jose Lopez-Sendon, M.D., Raffaele De Caterina, M.D., Petr Jansky, M.D., Harald Darius, M.D., Dragos Vinereanu, M.D., Jan H. Cornel, M.D., Frank Cools, M.D., Dan Atar, M.D., Jose Luis Leiva-Pons, M.D., Matyas Keltai, M.D., Hisao Ogawa, M.D., Ph.D., Prem Pais, M.D., Alexander Parkhomenko, M.D., Witold Ruzyllo, M.D., Rafael Diaz, M.D., Harvey White, M.D., Mikhail Ruda, M.D., Margarida Geraldes, Ph.D., Jack Lawrence, M.D., Robert A. Harrington, M.D., and Lars Wallentin, M.D., Ph.D. for the APPRAISE-2 Investigators

N Engl J Med 2011; 365:699-708August 25, 2011



Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.

Full Text of Background…


We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.

Full Text of Methods…


The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P=0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P=0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo.

Full Text of Results…


The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 number, NCT00831441.)