Le GINA 2006 et l’asthme : quoi de neuf en thérapeutique par rapport aux éditions antérieures ?

The 2006 revision of Global Initiative for Asthma (GINA) included several modifications which concern both adults and children. GINA was established in 1995 and its principal objectives were described then in the NHBLI/WHO Report, Global Strategy for Asthma Management and Prevention. This widely distributed report was revised in 2002 and then again in 2006. GINA 2006 is a document written in a simple fashion, mainly adapted for primary care physicians. It insists on the control of asthma in both children and adults, because that asthma symptoms and their consequences (trouble sleeping, limitation of daily living activities, reduction of respiratory function, use of rescue medications) can be controlled by appropriate treatment. In 2006, GINA proposed to abandon the notion of severity in favour of the concept of control, a concept already adopted in France in 2004 by the Haute Autorité de santé (HAS) in its recommendations on the management of asthmatic patients, both adults and adolescents. Control is defined by the presence or absence of asthma, defined essentially by clinical criteria that take into account the patient's activities over the several weeks (from one week to three months) before the consultation. Control includes three stages: for GINA, the three stages are “controlled”, “partially controlled” and “uncontrolled”, whereas for the Agence nationale d’accréditation et d’évaluation en santé (Anaes) they are “optimal”, acceptable” and “unacceptable”, which mean more-or-less the same thing. This concept is easier for primary care physicians to use. The therapeutic consequences of the GINA revisions will be considered in the present review.     

A hundred years of controversy about the taxonomic status of Echinococcus species

The parasitic diseases which we know today as cystic and alveolar echinococcosis are zoonoses known since antique times, and 1855, respectively. Whether the two clinically and morphologically distinct diseases were caused, according to a “unicistic” and a “dualistic” theory, by only one or two different cestode species was the subject of a fierce, 100 years long debate involving scientists from many countries. The natural life cycle of Echinococcus granulosus was fully clarified in 1855 after successful animal experiments. In contrast, the natural final and intermediate hosts of Echinococcus multilocularis remained unknown, and the advocates of either theory had to draw on a number of surrogate arguments to defend their positions. The seesaw of reasoning and mutual defeats of the two theories, and the final recognition of E. multilocularis as an independent species in the 1950s are described in this article.     

Improved exercise performance and quality of life after percutaneous pulmonary valve implantation

Objective

Percutaneous pulmonary valve implantation (PPVI) has emerged as a new approach to treat patients with dysfunctional pulmonary valve conduits. Short- and midterm results have outlined hemodynamic improvements and increase in exercise performance. However, there is a lack of knowledge about quality of life at short term follow-up.

Patients and methods

From July 2007 to March 2013, we investigated 59 patients (17 female; median age 22.8 years) undergoing PPVI in our institution. 46 had predominant pulmonary stenosis (PS) and 13 had predominant pulmonary regurgitation (PR). They answered the quality of life questionnaire (SF-36) and underwent a cardiopulmonary exercise test and Cardiovascular Magnetic Resonance before and 6 months after PPVI.

Results

Peak oxygen uptake improved significantly from 27.2 (18.9; 34.0) ml/min/kg to 29.2 (22.4; 35.3) ml/min/kg (p < .0001), and from 69.6 (55.9; 83.6) %predicted to 76.3 (67.9; 92.7) %predicted, respectively. Improvements were seen in both, the PS (71.9 to 78.3 %predicted; p < .0001) and PR (62.7 to 73.0 %predicted; p < .0001) group.Self-estimated quality of life was good already before PPVI but increased in almost all domains 6 months after PPVI in PS and PR group. Significant improvements developed in “physical function”, “general health perception” and “health transition” in both groups, and “physical role functioning”, “vitality” and “mental health” only in the PS group.

Conclusions

In patients with dysfunctional pulmonary valve conduits exercise performance and quality of life improve substantially 6 months after successful percutaneous pulmonary valve implantation.     

Benefits of an “angina clinic” for patients with coronary artery disease: A demonstration of health status measures as markers of health care quality

Objective Our purpose was to determine the efficacy of health status measurement in quantifying improvements in quality of care provided by an “angina clinic.” Study Design In a pretest-posttest, nonequivalent control group design in the outpatient clinics of a Veterans Affairs Medical Center, 535 patients with coronary disease were followed up, without intervention, for 3 months and were defined as the “usual-care” group. Concurrently, a clinical trial that optimized the antianginal medications of 100 patients with chronic, stable coronary disease was conducted and defined as the “angina clinic” group. The 3-month change in scores for the Seattle Angina Questionnaire, a valid, reliable, and responsive disease-specific health status measure for patients with coronary disease, was used as the main outcome measure. Results After baseline differences between groups were controlled, the “angina clinic” conferred substantial improvement on patient symptom control (3-month benefit in angina frequency +9.4, P < .001; in angina stability +14.7, P < .001), treatment satisfaction (+8.6, P < .001), quality of life (+6.8, P < .001), and physical limitations resulting from coronary disease (+3.6, P = .047). Only the changes in physical limitation were not clinically significant. Conclusion Disease-specific health status measures can provide valuable insights into the quality of care associated with innovations in health care delivery. These results suggest that patients in a clinical trial optimizing antianginal medications had greater improvements in symptom control, treatment satisfaction, and quality of life compared with similar patients receiving “usual care” in a general medicine clinic. (Am Heart J 2002;143:145-50.)     

Self-reported problems before and after prosthodontic treatments according to newly created Turkish version of oral health impact profile

The aim of the study was to assess patients’ socio-demographic factors with their removable prosthesis in general, as well as to assess their problems with the functional limitation, physical pain, psychological discomfort, physical disability, social disability, and handicap investigate impaired oral health-related quality of life (OHRQoL) in patient treated with removable dentures before treatment and at 1 and 12 months after treatment. The first part of the questionnaire was comprised of 20 questions. It was designed in four different sections as: (i) general socio-demographic factors, (ii) general health, (iii) experience and use of dental and denture care, and (iv) anamnestic sign and symptoms of temporomandibular disorders (TMD). A statistical analysis system (SAS) was used for data management and analysis. Patient-reported problems were studied using the item list contained in the Turkish version of the oral health impact profile (OHIP) in a convenience sample of 136 prosthodontic patients before (m₀), 1 month after (m₁), and 12 months (m₂) after treatment were then examined by using two-way ANOVA with repeated measurement. Differences in OHRQoL were present when item-specific prevalence was stratified by time of total scores; gender, residential area, working status, self-reported general health, smoking status, denture type, importance of the convenient dental care, trauma story, self-reported TMD/pain, and self-reported TMD/difficulty opening mouth wide. At baseline, the most prevalent frequently reported problems “difficulties chewing” (49.3%), “digestion worse” (40.4%), “take longer to complete a meal” (36%), “food catching” (30.9%), and “dentures not fitting” (29.4%), and m₂ the most prevalent frequently reported problems were “avoid going out” (25%), “difficulties chewing” (17.6), “sore jaw” (15.5%), and “take longer to complete a meal” (14%). The study confirmed that denture status is by far the strongest predictor of impaired OHRQoL compared to socio-demographic factors. Subjects with strong or moderate values had significantly fewer oral health-related problems (OHIP-extent) of time of total scores. The number of problems decreased substantially after prosthodontic treatment. The profile of pretreatment and post-treatment problems differed substantially, but in general, only a few problems remained after adaptation to new dentures.     

Personality and reasons for not using asthma medication in young adults

Objectives

To identify young adults' stated reasons for not taking asthma medication and to determine the significance of personality, asthma control and health-related quality of life in relation to these stated reasons.

Background

Reasons for non-adherence to asthma medication treatment have previously been studied, but research on the significance of personality in relation to stated reasons for not taking asthma medication is limited.

Methods

Young adults with asthma (age 22 years; n = 216) stated their most common reasons for not taking asthma medication and completed postal questionnaires on personality, asthma control and health-related quality of life (HRQL).

Results

The most common reason for non-adherence was “No perceived need” (n = 141). Participants giving this reason for not taking asthma medication scored lower on the personality trait Negative Affectivity and reported both higher asthma control and higher mental HRQL. “Insufficient routines” was the second most common reason (n = 66), and participants stating it scored higher on Negative Affectivity and reported lower asthma control. An increase in asthma control increased the odds of stating “No perceived need” as the reason for not taking asthma medication. An increase in Negative Affectivity was associated with an increase in the odds of giving “Insufficient routines” as a reason.

Conclusions

The personality trait Negative Affectivity and perceived asthma control played a role in the young adults' stated reasons for not taking asthma medication, which indicates that these parameters are of importance to young adults' medication management.     

The Anopheles stephensi odorant binding protein 1 (AsteObp1) gene: A new molecular marker for biological forms diagnosis

Anopheles (Cellia) stephensi Liston 1901 is known as an Asian malaria vector. Three biological forms, namely “mysorensis”, “intermediate”, and “type” have been earlier reported in this species. Nevertheless, the present morphological and molecular information is insufficient to diagnose these forms. During this investigation, An. stephensi biological forms were morphologically identified and sequenced for odorant-binding protein 1 (Obp1) gene. Also, intron I sequences were used to construct phylogenetic trees. Despite nucleotide sequence variation in exon of AsteObp1, nearly 100% identity was observed at the amino acid level among the three biological forms. In order to overcome difficulties in using egg morphology characters, intron I sequences of An. stephensi Obp1 opens new molecular way to the identification of the main Asian malaria vector biological forms. However, multidisciplinary studies are needed to establish the taxonomic status of An. stephensi.     

Treatment with arginine vasotocin alters mating calls and decreases call attractiveness in male túngara frogs

The peptide hormone arginine vasotocin (AVT) and its mammalian homolog arginine vasopressin modulate a variety of social behaviors in vertebrates. In anurans, AVT influences the production of advertisement calls, the acoustic signals that males use to attract females and repel rival males. In this study, we investigate the effects of AVT on call characteristics in the túngara frog (Physalaemus pustulosus). Túngara frogs produce a “whine” that is important for species recognition; they may also produce a second, attractive call component, the “chuck”. We used a field playback experiment to determine changes in male calling behavior following treatment with AVT. A previous study showed that AVT alters call rate and the production of chucks; in the current analysis, we focus on changes in the whine. Males produce shorter whines with higher initial frequencies following treatment with AVT. Call changes do not vary with a social stimulus. We also used female phonotaxis experiments to investigate the effects of call changes on female mate choice. Females disfavor the calls produced by males treated with exogenous AVT. We suggest that AVT influences motivation to call and the motor control of call production, but that over-stimulation of the vocal system limited the production of attractive calls in this experimental context.     

Assessing medial collateral ligament knee lesions in general practice

Purpose

To assess the diagnostic value of history-taking and physical examination of medial collateral ligament lesions after a knee injury presenting in general practice.

Methods

Patients aged 18 to 65 years with a traumatic knee injury who consulted their general practitioner within 5 weeks after trauma filled out a questionnaire, underwent a standardized physical examination, and underwent a magnetic resonance imaging scan. Logistic regression analysis was used to test possible associations between determinants from history-taking/physical examination and medial collateral ligament lesions. The diagnostic value of history-taking and physical examination was determined for those variables indicating an association (P <.15) with medial collateral ligament lesions and was assessed by sensitivity, specificity, predictive value, and likelihood ratios.

Results

Of the 134 patients included in this study, 35 had a medial collateral ligament lesion seen on magnetic resonance imaging scan. From history-taking, the determinants “trauma by external force to leg” and “rotational trauma” showed an association with medial collateral ligament lesion after multivariate analysis (P <.15). From physical examination, “pain valgus stress 30°” and “laxity valgus stress 30°” showed an association (P <.15). Isolated determinants from history-taking and physical examination showed some diagnostic value; the likelihood ratio positive was 2.0 for “trauma by external force to leg” and 2.3 for “pain valgus stress 30°.” Adding “pain valgus stress 30°” and “laxity valgus stress 30°” from physical examination to history-taking improved the diagnostic value to a likelihood ratio positive of 6.4.

Conclusion

Medial collateral ligament lesions are frequently seen in patients with traumatic knee injury. History-taking has a diagnostic value, while adding physical examination increases the diagnostic value.     

In-hospital observation after antibiotic switch in pneumonia: a national evaluation

Purpose

To evaluate the clinical benefit of in-hospital observation after the switch from intravenous (IV) to oral antibiotics in a large Medicare population. Retrospective studies of relatively small size indicate that the practice of in-hospital observation after the switch from IV to oral antibiotics for patients hospitalized with community-acquired pneumonia (CAP) is unnecessary.

Methods

We performed a retrospective examination of the US Medicare National Pneumonia Project database. Eligible patients were discharged with an ICD-9-CM diagnosis consistent with community-acquired pneumonia and divided into 2 groups: 1) a “not observed” cohort, in which patients were discharged on the same day as the switch from IV to oral antibiotics and 2) an “observed for 1 day” cohort, in which patients remained hospitalized for 1 day after the switch from IV to oral antibiotics. We compared clinical outcomes between these 2 cohorts.

Results

A total of 39,242 cases were sampled, representing 4341 hospitals in all 50 states and the District of Columbia. There were 5248 elderly patients who fulfilled eligibility criteria involving a length of stay of no more than 7 hospital days (2536 “not observed” and 2712 “observed for 1 day” patients). Mean length of stay was 3.8 days for the “not observed” cohort and 4.5 days for the “observed for 1 day” cohort (P <.0001). There was no significant difference in 14-day hospital readmission rate (7.8% in the “not observed” cohort vs 7.2% “observed for 1 day” cohort, odds ratio 0.91; 95% confidence interval [CI] 0.74-1.12; P =.367) and 30-day mortality rate (5.1% “not observed” cohort vs 4.4% in the “observed for 1 day” cohort, odds ratio 0.86; 95% CI, 0.67-1.11; P =.258) between the “not observed” and “observed for 1 day” cohorts.

Conclusions

Our analysis of the US Medicare Pneumonia Project database provides further evidence that the routine practice of in-hospital observation after the switch from IV to oral antibiotics for patients with CAP may be avoided in patients who are clinically stable although these findings should be verified in a large randomized controlled trial.     

Evidence-based recommendations for PISA measurements in mitral regurgitation: systematic review,clinical and in-vitro study

Background

Guidelines for quantifying mitral regurgitation (MR) using “proximal isovelocity surface area” (PISA) instruct operators to measure the PISA radius from valve orifice to Doppler flow convergence “hemisphere”. Using clinical data and a physically-constructed MR model we (A) analyse the actually-observed colour Doppler PISA shape and (B) test whether instructions to measure a “hemisphere” are helpful.

Methods and results

In part A, the true shape of PISA shells was investigated using three separate approaches. First, a systematic review of published examples consistently showed non-hemispherical, “urchinoid” shapes. Second, our clinical data confirmed that the Doppler-visualized surface is non-hemispherical. Third, in-vitro experiments showed that round orifices never produce a colour Doppler hemisphere.In part B, six observers were instructed to measure hemisphere radius r_h and (on a second viewing) urchinoid distance (d_u) in 11 clinical PISA datasets; 6 established experts also measured PISA distance as the gold standard. r_h measurements, generated using the hemisphere instruction significantly underestimated expert values (− 28%, p < 0.0005), meaning r_h² was underestimated by approximately 2-fold. d_u measurements, generated using the non-hemisphere instruction were less biased (+ 7%, p = 0.03).Finally, frame-to-frame variability in PISA distance was found to have a coefficient of variation (CV) of 25% in patients and 9% in in-vitro data. Beat-to-beat variability had a CV of 15% in patients.

Conclusions

Doppler-visualized PISA shells are not hemispherical: we should avoid advising observers to measure a hemispherical radius because it encourages underestimation of orifice area by approximately two-fold. If precision is needed (e.g. to detect changes reliably) multi-frame averaging is essential.     

Artificially sweetened versus regular mixers increase gastric emptying and alcohol absorption

Background

Mixed alcoholic drinks are increasingly being consumed in “diet” varieties, which could potentially empty more rapidly from the stomach and thereby increase the rate of alcohol absorption when compared with “regular” versions containing sugar.

Methods

We studied 8 healthy males twice in randomized order. On each day, they consumed an orange-flavored vodka beverage (30 g ethanol in 600 mL), made with either “regular” mixer containing sucrose (total 478 kcal), or “diet” mixer (225 kcal).

Results

Gastric half-emptying time measured by ultrasound (mean ± standard deviation) was less for the “diet” than the “regular” drink (21.1 ± 9.5 vs 36.3 ± 15.3 minutes, P <.01). Both the peak blood ethanol concentration (0.053 ± 0.006 vs 0.034 ± 0.008 g%, P <.001) and the area under the blood ethanol concentration curve between 0 and 180 minutes (5.2 ± 0.7 vs 3.2 ± 0.7 units, P <.001) were greater with the “diet” drink.

Conclusions

Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages may have a marked effect on the rate of gastric emptying and the blood alcohol response.     

Risk of coronary artery disease in patients with idiopathic inflammatory myopathies: A systematic review and meta-analysis of observational studies

Objectives

To investigate the risk of coronary artery disease in patients with idiopathic inflammatory myopathies (IIM).

Methods

We conducted a systematic review and meta-analysis of observational studies that reported odds ratios, relative risks, hazard ratios, or standardized incidence ratios comparing the risk of coronary artery disease in patients with IIM versus non-IIM participants. We searched published studies indexed in MEDLINE, EMBASE, and the Cochrane database from inception to December 2013 using the terms “coronary artery disease” OR “coronary heart disease” OR “myocardial infarction” OR “atherosclerosis” combined with the terms “dermatomyositis” OR “polymyositis” OR “Idiopathic inflammatory myopathy.” Pooled risk ratio and 95% confidence interval were calculated using a random-effect, generic inverse variance method.

Result

Overall, four studies were identified and included for data analysis. The pooled risk ratio of CAD in patients with IIM was 2.24 (95% CI: 1.02–4.92). The statistical heterogeneity of this meta-analysis was high with an I² of 97%.

Conclusion

Our study demonstrated a statistically significant increased risk of CAD among patients with IIM.     

Hot temperatures can force delayed mosquito outbreaks via sequential changes in Aedes aegypti demographic parameters in autocorrelated environments

Aedes aegypti L. (Diptera: Culicidae) is a common pantropical urban mosquito, vector of dengue, Yellow Fever and chikungunya viruses. Studies have shown Ae. aegypti abundance to be associated with environmental fluctuations, revealing patterns such as the occurrence of delayed mosquito outbreaks, i.e., sudden extraordinary increases in mosquito abundance following transient extreme high temperatures. Here, we use a two-stage (larvae and adults) matrix model to propose a mechanism for environmental signal canalization into demographic parameters of Ae. aegypti that could explain delayed high temperature induced mosquito outbreaks. We performed model simulations using parameters estimated from a weekly time series from Thailand, assuming either independent or autocorrelated environments. For autocorrelated environments, we found that long delays in the association between the onset of “hot” environments and mosquito outbreaks (10 weeks, as observed in Thailand) can be generated when “hot” environments sequentially trigger a larval survival decrease and over-compensatory fecundity increase, which lasts for the whole “hot” period, in conjunction with a larval survival increase followed by a fecundity decrease when the environment returns to “normal”. This result was not observed for independent environments. Finally, we discuss our results implications for prospective entomological research and vector management under changing environments.     

International noninterventional study of acarbose treatment in patients with type 2 diabetes mellitus

Aim

To obtain data on efficacy, safety and tolerability of acarbose monotherapy or combination therapy during daily-life treatment.

Methods

This prospective, non-controlled, observational study enrolled patients with type 2 diabetes, whose physician decided that acarbose treatment was appropriate, from China, Middle East, Indonesia, Morocco, Pakistan, Philippines, Poland and Taiwan. The observation period included an initial visit and up to three follow-up visits; an extension of 2 years was realized in Pakistan and Poland.

Results

Of 14,574 patients enrolled, 14,418 comprised the intent-to-treat population. At the initial visit, 74.1% of patients had been treated with a glucose-lowering agent. Fasting blood glucose was reduced from 175.2 mg/dL at the initial visit to 133.7 mg/dL at the last visit (mean of 11.3 weeks after initial visit; P < 0.0001). Mean 2-h postprandial blood glucose decreased from 244.7 mg/dL to 172.4 mg/dL (P < 0.0001). HbA1c reduced from 8.4% to 7.4% (P < 0.0001). Glycemic efficacy was maintained over the 2-year extension period. There were 432 adverse events in 293 patients (2.03%), mainly gastrointestinal. Physicians assessed efficacy as “very good”/“good” in 85.1% of patients, and were “very satisfied”/“satisfied” with acarbose therapy in 94.3% of cases.

Conclusion

Acarbose therapy was efficacious and well tolerated in daily life in patients with type 2 diabetes.     

Le ressenti des patients vis-à-vis d’une corticothérapie orale prolongée influence l’adhérence déclarée à ce traitement

Background

In patients treated with systemic glucocorticoids (GCs), it is unknown if beliefs about the treatment are associated with level of reported adherence.

Patients and methods

Cross-sectional study conducted in two departments of internal medicine during a six-month period. All patients receiving long-term GCs therapy were asked to fill in a questionnaire regarding their beliefs about (specific scale of the Beliefs about Medicines Questionnaire) and their adherence to (four-item Morisky-Green scale) GCs. Logistic regression analysis was used to assess association between beliefs about GCs and adherence to treatment.

Results

One hundred and eighty one questionnaires were analysed (women: 79%, median age [IQR]: 47 [33–61] years, median duration of treatment: 18 [7–72] months, median daily dosage of prednisone equivalent: 10 [6–20] mg). Among these 181 patients, 83 (46%) reported a “concern” score equal to or higher than the “necessity” score. Nineteen percent of patients reported a low adherence level. In multivariate analysis, these patients were significantly younger (OR: 0.96 [0.93–0.98] per increasing year of age, P = 0.002) and reported more frequently a “concern” score higher than a “necessity” score (OR: 3.08 [1.27–7.46], P = 0.01) as compared to patients reporting a high adherence level.

Conclusion

Informing patients about the “necessity” of GCs and taking into account their “concerns” about adverse events or their fear of becoming dependent on the medication may improve their adherence to treatment.     

Glucagon-like peptide-1 receptor agonists and pancreatitis: A meta-analysis of randomized clinical trials

Aims

Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis.

Methods

An extensive Medline, Embase, and Cochrane Database search for “exenatide”, “liraglutide”, “albiglutide”, “taspoglutide”, “dulaglutide”, “lixisenatide”, and “semaglutide” was performed up to March 31st, 2013. Inclusion criteria: (i) randomized trials, (ii) duration ≥12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel–Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis.

Results

80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient × years (8353 and 5980 patient × years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p = 0.99).

Conclusions

The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide.     

pfcrt is more than the Plasmodium falciparum chloroquine resistance gene: a functional and evolutionary perspective

Genetic, physiological and pharmacological studies are gradually revealing the molecular basis of chloroquine resistance (CQR) in the malaria parasite, Plasmodium falciparum. Recent highlights include the discovery of a key gene associated with resistance, pfcrt (Plasmodium falciparum chloroquine resistance transporter; PfCRT), encoding a novel transporter, and the characterization of global selective sweeps of haplotypes containing a K76T amino acid change within this protein. Little is known about the cellular mechanism by which resistant parasites escape the effects of chloroquine (CQ), one of the most promising drugs ever deployed, due in part to an unresolved mechanism of action. The worldwide spread of CQR argues that investigations into these mechanisms are of little value. We propose, to the contrary, that the reconstruction of the evolutionary and molecular events underlying CQR is important at many levels, including: (i) its potential to assist in the development of rational approaches to thwart future drug resistances; (ii) the stimulation of the use of CQ-like compounds in drug combinations for new therapeutic approaches; and (iii) the consideration of how the CQ-selected genome will function as the context in which current and future drugs will act, particularly in light of the many reports of multidrug resistance. The purpose of this review is to highlight, discuss and in some cases challenge the interpretations of recent findings on CQR. We consider the natural function of the PfCRT protein, the role of multiple genes and “genetic background” in the CQR mechanism, and the evolution of CQR in parasite populations. Genetic transformation techniques are improving in P. falciparum and continue to provide important insight into CQR. Here, we also discuss more subtle, yet important pharmacological approaches that may have been overlooked in a traditional “gene for drug resistance” way of thinking.