Detection of potential interactions by the electronic medical record: A new approach to improve patient safety

The European Journal of General Practice has published the article: Prevalence and typology of potential drug interactions occurring in primary care patients. Authors: López-Picazo JJ, Ruiz JC, Sanchez JF, Ariza A, Aguilera B, Lazarus D, Sanz GR.

The objective of this article is to determine the prevalence and type of potential drug interactions in primary care patients.

It is very interesting because its content is directly related to medical errors and their consequences, adverse effects and drug interactions in primary care. This field has a huge impact on the global patient safety due to the high number of visits, the level of prescription and other factors such as pluripathology.

The authors start from the difficulty of identifying and confirming the actual prevalence of drug interactions, to propose a preventive approach. It is acting on potential drug interactions identified by the electronic medical records (and confirmed by prescription -recipes used-), according to the evidence available, and using software that identifies patients likely to suffer these potential interactions. All this would be completed by a warning system, related to the medical record, that, in real time, allows the family physician identify the potential interaction, and with the automatic proposal of safe therapeutic alternatives. Every active ingredient that each patient can be taking simultaneously is analyzed.

The study confirms the existence of a serious safety problem for patients, because 1 in 20 Spanish citizens is subject to the risk of drug interaction. And, more important, with a high rate of serious or high risk interactions.

At the time of analysis 29.4% of the population took medication. Of these patients, 73.9% took more than one drug and, therefore, was at risk of interactions; more than a half of the potential interactions could be clinically important. However, the percentage of interactions observed is usual in the literature.

There are more interactions among people with chronic conditions, the elderly, females and polymedicated patients. The active ingredients most frequently involved were hydrochlorothiazide, ibuprofen and acenocumarol. Respect to interactions that should be avoided, the most common are combinations with omeprazole, acenocumarol and diazepam.

This approach and the results of this study provide us valuable information and, most of all, a new simple and practical approach, which should not be wasted by the professionals or the institutions involved, for the benefit of our patients.


Edited by José Saura Llamas
English version by Erika Céspedes

Europe removes drugs containing rosiglitazone (Avandia®, Avandamet® and Avaglim®)

Finally, rosiglitazone (Avandia®) is no longer available in Europe.

In a previous post we discussed an article of The New York Times, which might help to explain why the FDA refuses its full withdrawal, although rosiglitazone is not better than pioglitazone, but causes more cardiovascular problems.

Yesterday, El País reported extensively on the ban, until Glaxo can "identify the group of patients in which the drug benefit exceeds the risks".

Avandia® sold 920 million Euros last year, and had arrived in 2006 to more than 2000 million. The question is: If the alert was given, and there are equally effective alternative medications, and safer, why was it still prescribed?

+ Info: - Spanish Agency for Drugs and Health Care Products (AEMPS):

Patient information note on the suspension of marketing of drugs containing rosiglitazone (Avandia ®, Avandamet ®, Avaglim ®)

Communication for professionals

- European Medicines Agency (EMA):

Press release: European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim

Questions and answers on the suspension of rosiglitazone-containing medicines (Avandia, Avandamet and Avaglim)


- In this blog:

GSK hid the rosiglitazone (Avandia) is associated with cardiovascular risk

GSK recibe una reprimenda de la FDA por ocultar datos sobre su antidiabético rosiglitazona (Avandia) (GSK receives a rebuke from the FDA for hiding data on its antidiabetic rosiglitazone Avandia)


Posted by Fernando Palacio
English version by Erika Céspedes

Improving quality of antibiotics’ prescription in primary care: a qualitative evaluation of combined training intervention

BMC Family Practice publishes this paper focused on an intervention designed to change primary healthcare professionals’ antibiotic prescription habits.

The educational STAR program (Stemming the Tide of Antibiotic Resistance) has the aims of improving antibiotics’ prescription and to increase the awareness of the problem of antibiotic resistance among primary care physicians.

STAR program is composed of five main parts, complemented by a forum in the web about the course (part 6), and a reinforcement session (part 7) given approximately six months after completing the main program of the course.

Parts 1 and 2 include an online-introduction to antibiotic resistance and prescription. Participants present their own points of view on the subject. Clinical cases are also presented to discuss as well as some of most recent scientific evidence (graphics and abstracts). The objective of these two first parts is to raise clinicians’ awareness on how they treat common infections in everyday practice.

Part 3 consists of a practical seminar, where attendants meet in presence of a STAR instructor who contributes to the discussion about their prescription habits and data on resistances, collected from samples offered by professionals during the five to ten years previous to the study.

Part 4 presents online videos reflecting clinical settings or patient simulations to show key communication skills to employ in practice, useful for better understanding patients’ attitudes, expectations and worries.

In part 5 physicians are asked to describe three examples of their own clinical experience and to think them over, in order to consolidate the achieved knowledge.

The program’s effectiveness was evaluated in a randomized controlled study in which 244 primary care physicians and nurses took part. This text shows part of the study’s evaluation.

Evaluation was performed by a partly structuralized telephone interview, with digital data registration, to a 31 participants sample, by means of analysis of contents.

The majority of subjects reported higher awareness of antibiotic resistance, greater self confidence to reduce antibiotics’ prescription and at least some change in practice and attitude towards antibiotics’ prescription. Reported changes in practice included adoption of some policy to decrease prescription of antibiotics. Many physicians also reported their increased interest in patients’ expectances that contributes to improve the relationship between patient and physician.

The parts of the intervention that showed greatest influence to change professional’s behaviour were the update of available evidence, the simple and effective communication skills presented on online videos, and self reporting of antibiotic prescription data, combined with showing local resistance data.

Participants considered this educational intervention acceptable, necessary and feasible, obtaining a great impact and positive changes in attitudes and in clinical practice as a result of participation in STAR educational program.


Bekkers MJ, Simpson SA, Dunstan F, Hood K, Hare M, Evans J, et al. Enhancing the quality of antibiotic prescribing in primary care: qualitative evaluation of a blended learning intervention. BMC Fam Pract. 2010;11:34.





Posted by Lola Martín
English version by Erika Céspedes

GSK hid the Rosiglitazone (Avandia) is associated with cardiovascular risk

The New York Times has published an article which alleged that GlaxoSmithKline (GSK) has withheld the results of a study, organized by the very multinational pharmaceutical company, which showed an increased cardiovascular risk in patients treated with rosiglitazone (Avandia).

Rosiglitazone, a drug used in the treatment of diabetes, is also marketed in the European Union, in combination with Metformin (Avandamet) and Glimepiride (Avaglim).

This study, conducted prior to the approval of the product, comparing rosiglitazone with pioglitazone, concluded not only that it was not superior for treatment, but also produced an increased cardiovascular risk. Although the results were clearly unfavorable to the drug of GSK, the laboratory not only did not published them but, according to company files, deliberately concealed them, stealing relevant information for the approval of the regulatory agencies.

Currently, the agencies responsible for authorization of medicines in USA (FDA) and the European Union (EMEA), are assessing the safety of Rosiglitazone, after the publication last year of two studies concluding that it increases the likelihood of suffering serious cardiovascular problems and even death.

That is, new trials agree in indicating cardiovascular risks identified previously by the manufacturer in 1999 and hidden from the authorities, patients and professionals. Meanwhile thousands of patients, only about 80,000 in Spain, are taking a drug that some studies indicate may increase the risk of suffering a cardiovascular event like heart attack, stroke and even death.

There is a fierce debate in the FDA over the decision to take on Avandia, in which the director of new drugs, John Jenkins has defended the retention of the drug on the market, and has even informed GSK managers about the internal deliberations of the agency.

Rosemary Johann-Liang, an former member of that department of the FDA, who was sanctioned for recommending to emphasis Avandia's cardiovascular warnings in its package information leaflets, has now joined the voices calling for a change in the leadership of the FDA.

+ Info on NYT Diabetes Drug Maker Hid Test Data, Files Indicate

See also in this blog: GSK recibe una reprimenda de la FDA por ocultar datos sobre su antidiabético Rosiglitazona (Avandia)


Posted by Jesús Palacio
English version by Jesús Moreno and Erika Céspedes

AEMPS: Information about the use of drugs in case of heat wave

As usual at this time, the Spanish Agency for Drugs and Health Care Products (AEMPS) has issued a safety communication giving information about the use of drugs in case of heat wave.

The Spanish Society of Family and Community Medicine (semFYC) also published in June 2009, in the section of its website aimed at population, its recommendations for preventing the effects of excessive heat.

SemFYC advise to exercise extreme caution with the most vulnerable people including the elderly, the chronically ill and bedridden, obese, young children, psychiatric patients and those who take certain medications.

"The drugs that physician should take into account include diuretics (to increase the amount of urine), antihistamines (allergy), anticholinergics (depression, Parkinson's, etc), beta blockers (hypertension), phenothiazines (mental disorders)."

"In any case, you should never remove or reduce the pharmacological treatment without the risk-benefit assessment."


Posted by Jesús Palacio
Englilsh version by Erika Céspedes

Pharmacotherapeutic follow-up DaderWeb

The journal Atención Primaria have published the overall results during the first year of initiation and piloting a new Primary Care database accessible from DaderWeb.

This web application arises from the need to optimize all data related to the program Dáder. The program was designed by the Research Group on Pharmaceutical Care, University of Granada, in 1999, and is currently being used in different countries by hundreds of pharmaceutical professionals in thousands of patients. It is based on obtaining the patient's pharmaceutical record in the community pharmacy and the personal pharmaceutical monitoring (SFT) by detecting, preventing and resolving drug-related problems on a continuous, systematic and documented way. It cooperates with the patient and all professionals of the Health System, in order to achieve concrete results that improve the quality of life of patients.

This first year of initiation and piloting is aimed to improve the organization of the information provided, to avoid loss of it, to optimize the processing of data and, ultimately, to enhance the quality of the information stored in it by:

a) Preparation of records and collection of information about its activity,

b) Location and access to updated information and quality,

c) Communication between professionals.

Among the registration documents available in DaderWeb we distinguish the pharmaceutical intervention sheet (HIF), which refer to a possible pharmaceutical care across countries and fields on the detection and intervention on negative results associated with the use of drugs (RNM).

Among their findings, only in the field of primary care in Spain, 234 HIF sent (a RNM for HIF) by 27 community pharmacies, 147 patients involved, with a mean age of 66 years (SD 11.8) and 59.4% of women. The 88.5% of the RNM was clinically manifested when detected.

The most frequent RNM were related to the ineffectiveness of drug therapy, supporting the need for closer monitoring of clinical outcomes of medications.

As most prevalent causes of failure were identified the neglect (17.9%) and the not appropriate dose, regime or duration of treatment (13.7%). In the 16% of cases they did not identify any cause and in a 36.9%, although there was a problem in the application process, it was not specify in the default list provided by the HIF3.

In the 35.9% of cases the pharmacist intervened independently through direct patient education to resolve the RNM. After measuring the appropriate clinical variables indicating, in each case, the development of RNM, these were resolved in the 81.2% of the times.

To systematize the SFT has made great strides thanks to the Dáder program. The evaluation of the quality of the prescription allows to detect any differences, points of improvement and to develop and design appropriate interventions to optimize outcomes in the health field. The Dáder, certainly, is a huge step that should appeal to all community pharmacists in improving the SFT and to build on its steps.

Sabater-Hernández D, Faus D, Fikri-Benbrahim N, García-Cárdenas V. Resultados globales de la base de datos del Programa Dáder de Seguimiento Farmacoterapéutico: 2008. Aten Primaria. 2010;42:297-8.


Contribution by M ª José Montero Fernández. Primary Care Pharmaceutical, Area 4, Madrid.
English version by Jesús Moreno

From Evidence-based Medicine to Marketing-based Medicine

A study published in the Journal of Bioethical Inquiry shows how pharmaceutical companies use business marketing strategies that serve to provide very flattering data, with respect to its products, in terms of efficacy and safety. In this way they get to influence the opinion of prescribers and clearly enhance their marketing interests.

The study uses several internal documents from the pharmaceutical industry and analyzes which strategies are used. Some of the most significant are the Suppression and spinning of negative data and the publication of their studies in journals of high reputation, using the name of well-known professionals who lend their names to change counterparts, whereas the real authors of the article corresponds to a 'ghost' hired by the company. The objective of this technique is to get scientific credibility among readers.

The authors present examples of strategies used in the field of mental health by different companies, transforming studies whose results show a lack of efficacy or questionable efficacy in an effective study.

Other strategies used serve to increase the indications for its products, especially in subclinical or borderline situations. It highlights how the industry segments the market according to the personal profile of the physicians, directing their efforts mainly towards those profiles that are more easily influenced.

The authors conclude that the impact of marketing-based medicine is a poorer health outcomes and increased costs, making it necessary to propose solutions that enable a transparent dissemination of studies conducted by pharmaceutical companies. Those solutions are the prospective registry of clinical trials and their results in public acces registries, public access to regulatory agency reports, as well as a more rigorous role of the editors of medical journals.

These behaviors are obviously hidden, making it difficult to know its extent. That raises the need to reform the system for development and approval of new treatments to enhance transparency and independence in the assessment of both their effectiveness and safety.

Full text: Spielmans GI, Parry PI. From Evidence-based Medicine to Marketing-based Medicine: Evidence from Internal Industry Documents. Journal of Bioethical Inquiry. 2007; 7:1(13-29)

See also Industria farmaceútica y promoción de medicamentos ¿todo vale?


Posted by Guadalupe Olivera
English version by Erika Céspedes

Drugs and driving

The Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) has posted on its website a new section of drugs and driving.

The packages of medicines that can produce effects that impair the ability to operate a car or a dangerous machine shall have the symbol illustrated here before 2011.

You can consult on this page which active ingredients have to use or not the symbol.

Posted by Jesús Palacio
English version by Erika Céspedes

Side effects of statin treatment in England and Wales

British Medical Journal published an analysis of the effects (benefits / risks) or unintentional side of statin therapy, registered in health centers in England and Wales. Includes the calculation of the NNT (number needed to treat to benefit) and the NNH (number needed to risk of adverse effects).

Cardiovascular disease is the leading cause of premature death in developed countries. Numerous published scientific papers recommending the use of statins to reduce cardiovascular risk among high-risk patients. Thus, statins have become one of the most prescribed drugs in primary care, and is likely to go to continue to increase their prescription. Side effects of these treatments, particularly those that appear over time are an underdeveloped area of research so far. However, having this information enables more informed decisions with a risk/ benefit balance shared with our patients.

The results presented in this research are from a prospective cohort study (six years) on a electronic medical records of patients whose information is dumped into a research database as many British health centers. We identified those patients treated with statins, at least one year, aged between 30 and 84 years.

Clinically relevant outcomes sought were: acute renal failure, venous thromboembolism, Parkinson's disease, dementia, rheumatoid arthritis, cataracts, osteoporotic fractures, common cancers (stomach, colon, esophagus, lung, kidney, breast, prostate, melanoma) impaired liver function moderate / severe in patients without prior liver involvement, myopathy moderate / severe or rhabdomyolysis.

The study could not confirm the potential protective effect of statins in reducing the risk of developing Parkinson's disease, pulmonary embolism, rheumatoid arthritis, osteoporotic fractures, and dementia. The authors acknowledge that the study has potential uncontrolled confounding biases. In connection with the development of cancers, it is confirmed that there is no clear link between taking statins and common cancers, except for esophageal cancer in which there is a risk reduction, and in the colon that appears pravastatin ruvastatina protective effect and increases the risk.

Confirm an adverse effect of class in relation to the occurrence of myopathy, liver dysfunction, acute renal failure and cataract.

These risks persist throughout the treatment time and were mostly in the first year of treatment. After stopping treatment, the risk of cataract, esophagus cancer, kidney failure and liver dysfunction at initial returns to age within one to three years.

As main contribution, the study provides the national estimate of the number of expected additional adverse effects associated with statin therapy per 10,000 populations, if all patients with high cardiovascular risk (15% and 20% risk of QRISK2) received statin therapy. We summarize the highlights in the following table.

	QRISK2 score >20%: risk at 5 years without treatment	NNH o NNT [IC 95%] (*)	No cases prevented / at risk per 10,000 patients [95%]
Potential damage in women
Acute renal failure	0.0041	434(284-783)	23(13-35)
Cataracts	0.1089	33(28-38)	307 (260-355)
Liver disfunction	0.0140	136 (109-175)	74 (57-91)
Myopathy	0.0020	259(186-375)	39 (27-54)
Potential damage in men
Acute renal failure	0.0047	346 (245-539)	29 (19-41)
Cataracts	0.0630	52 (44-63)	191 (158-225)
Liver disfunction	0.0133	142 (115-180)	71 (56-87)
Myopathy	0.0021	91 (74-112)	110 (90-134)
Benefits in women
Cardiovascular disease	0.1184	-37 (-64­_-27)	-271 (-374_-157)
Esophageal cancer	0.0025	-1266 (-3460_-850)	-8 (-12_-3)
Benefits in men
Cardiovascular disease	0.1326	-33 (-57_-24)	-301 (-417_-174)
Esophageal cancer	0.0042	-1082 (-2807_-711)	-9 (-14_-4)

(*) No negative indicate number needed to treat or cases prevented. No. positive indicate number needed to harm or cases are extra

Julia Hippisley-Cox and Carol Coupland.Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database
BMJ 2010;340:c2197, doi: 10.1136/bmj.c2197 (Published 20 May 2010)

See also: High doses of simvastatin and risk of muscular and renal impairment


Posted by Pilar Astier
English version by Jesús Moreno

Proton pump inhibitors and risk of fracture

The FDA has issued a note, both for professionals and patients, reporting the revision of the prescription of the proton pump inhibitors to include new safety information about a possible increased risk of fractures of the hip, wrist, and spine.

This information is based on the review of seven epidemiological studies that suggested that the increased risk of such fractures may depend on the dose, duration of the treatment or both.

At present, there is uncertainty about the magnitude of this risk. So, when prescribing PPIs, healthcare professionals should consider a lower dose or shorter duration of treatment, when required.

+ Info: Press release by the FDA

The widespread use of PPIs requires to take into account this risk, especially when deciding the appropriateness of the initiation or maintenance treatment of the treatment with these drugs.

There are several reliable publications on the appropriate of PPIs, for example, this synthetic and clear note of the Dirección General de Farmacia del Servicio Canario de Salud.


Posted by Guadalupe Olivera and Jesús Palacio
English version by Erika Céspedes

A more ambitious pharmacovigilance

A year ago we mentioned in this blog the Palmarès Prescrire 2008.
Again, in the Palmarès 2009, the main categories “Pilule d'Or” and “Tableau d'honneur” were not awarded. These categories are attributed to new drugs that would constitute a breakthrough for the treatment of certain diseases, because of its efficacy or its lower incidence or severity of adverse effects.

The announcement of the results took place in Paris in January 2010 and was preceded by a panel discussion about adverse effects of drugs.Joan-Ramon Laporte, Director of the Catalan Institute of Pharmacology, participated as speaker. Prescrire has published his interesting speech.

Laporte highlights the magnitude and severity of adverse effects of drugs that are one of the leading causes of morbidity and mortality in developed countries and, therefore, the key role of Pharmacovigilance for Public Health.

This pharmacovigilance depends heavily on spontaneous reporting of adverse reactions by health professionals. But this notifications are necessary but not sufficient, because they depend on the motivation of professionals and the training, knowledge and participation in reporting systems.

The professionals would notify fundamentally the rare and new events because these ones call their attention. More proactive pharmacovigilance strategies would carry out observational studies and meta-analysis to let us know the effects of drugs usually used in the treatment of common diseases. This has happened with substances such as NSAIDS, SSRIs, neuroleptics in dementia, ezetimibe, glitazones, bisphosphonates, etc.

In regard to health professionals, Laporte also argues that the prevention of adverse effects requires a more rational prescribing, and so an independent, continuing and qualified education.

Regarding the role of health authorities we want to note the demand for new drugs that demonstrate to bring a therapeutic progress, to be more effective or safer than the reference drugs, to get their marketing.

The authorities should act with full independence and require transparency to pharmaceutical firms.

It is truly interesting to read the data and reflections of Laporte on the European Commission's proposals in pharmacovigilance that seems to be elaborated to ensure the health of the products instead of citizen´s health.


Posted by Marian López Orive
English version by Erika Céspedes

Welcome to the English version of Sano y Salvo

Sano y Salvo is currently the only website focused on patient safety in primary care. We receive visits from all over the world, which has made us consider the publication of our contents in English.

So we have created the blog safeanhealthypatient.org, in which we will publish the translation of sanoysalvo.es posts.

Publication at this site of the spanish originals will not be exhaustive or synchronous. We will publish the translation of new posts and, as we can, some of the older posts.

Sano y Salvo is currently a collection of the most relevant items published about patient safety in primary care, both at the national (Spain) and international level. Our web searcher engine and the links on the right column allow anyone to find relevant contents and interesting experiences to improve patient safety in primary care.

Now we also consider making these material worldwide available, in English.


Posted by Jesus Palacio, editor of sanoysalvo.es and Erika Céspedes, manager of the English version published in safeandhealthypatient.org