The therapeutic relationship and adherence to antipsychotic medication in schizophrenia

Objective

Previous research has shown that a better therapeutic relationship (TR) predicts more positive attitudes towards antipsychotic medication, but did not address whether it is also linked with actual adherence. This study investigated whether the TR is associated with adherence to antipsychotics in patients with schizophrenia.

Methods

134 clinicians and 507 of their patients with schizophrenia or a related psychotic disorder participated in a European multi-centre study. A logistic regression model examined how the TR as rated by patients and by clinicians is associated with medication adherence, adjusting for clinician clustering and symptom severity.

Results

Patient and clinician ratings of the TR were weakly inter-correlated (r_s = 0.13, p = 0.004), but each was independently linked with better adherence. After adjusting for patient rated TR and symptom severity, each unit increase in clinician rated TR was associated with an increase of the odds ratio of good compliance by 65.9% (95% CI: 34.6% to 104.5%). After adjusting for clinician rated TR and symptom severity, for each unit increase in patient rated TR the odds ratio of good compliance was increased by 20.8% (95% CI: 4.4% to 39.8%).

Conclusions

A better TR is associated with better adherence to medication among patients with schizophrenia. Patients'' and clinicians'' perspectives of the TR are both important, but may reflect distinct aspects.     

Excellent adherence to antiretrovirals in HIV+ Zambian children is compromised by disrupted routine, HIV nondisclosure, and paradoxical income effects

Introduction

A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence.

Methodology/Principal Findings

Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income.

Conclusions/Significance

Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty.     

The prevalence of natural health product use in patients with acute cardiovascular disease

Background

Natural health products (NHP) use may have implications with respect to adverse effects, drug interactions and adherence yet the prevalence of NHP use by patients with acute cardiovascular disease and the best method to ascertain this information is unknown.

Objective

To identify the best method to ascertain information on NHP, and the prevalence of use in a population with acute cardiovascular disease.

Methods

Structured interviews were conducted with a convenience sample of consecutive patients admitted with acute cardiovascular disease to the University of Alberta Hospital during January 2009. NHP use was explored using structured and open-ended questions based on Health Canada''s definition of NHP. The medical record was reviewed, and documentation of NHP use by physicians, nurses, and pharmacists, compared against the gold-standard structured interview.

Results

88 patients were interviewed (mean age 62 years, standard deviation [SD 14]; 80% male; 41% admitted for acute coronary syndromes). Common co-morbidities included hypertension (59%), diabetes (26%) and renal impairment (19%). NHP use was common (78% of patients) and 75% of NHP users reported daily use. The category of NHP most commonly used was vitamins and minerals (73%) followed by herbal products (20%), traditional medicines including Chinese medicines (9%), homeopathic preparations (1%) and other products including amino acids, essential fatty acids and probiotics (35%). In a multivariable model, only older age was associated with increased NHP use (OR 1.5 per age decile [95%CI 1.03 to 2.2]). When compared to the interview, the highest rate of NHP documentation was the pharmacist history (41%). NHP were documented in 22% of patients by the physician and 19% by the nurse.

Conclusions

NHP use is common in patients admitted with acute cardiovascular disease. However, health professionals do not commonly identify NHP as part of the medication profile despite its potential importance. Structured interview appears to be the best method to accurately identify patient use of NHP.     

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya

Background

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools.

Methods

We conducted a cross-sectional survey amongst a series of new TB patients receiving 6 months of standard TB chemotherapy with FDC under SAT. Adherence was assessed at home with urine testing for Isoniazid (INH), pill count, interviewer-administered questionnaire and visual analogue scale (VAS).

Results

In November 2008 and in June 2009, 212 of 279 eligible patients were assessed for adherence. Overall, 95.2% [95%CI: 91.3–97.7] of the patients reported not having missed a tablet in the last 4 days. On the VAS, complete adherence was estimated at 92.5% [95%CI: 88.0–95.6]. INH urine test was positive for 97.6% [95%CI: 94.6–99.2] of the patients. Pill count could be assessed among only 70% of the interviewed patients. Among them, it was complete for 82.3% [95%CI: 75.1–88.1]. Among the 212 surveyed patients, 193 (91.0%) were successfully treated (cured or treatment completed). The data suggest a fair agreement between the questionnaire and the INH urine test (k = 0.43) and between the questionnaire and the VAS (k = 0.40). Agreement was poor between the other adherence tools.

Conclusion

These results suggest that SAT, together with the FDC, allows achieving appropriate adherence to antituberculosis treatment in a high TB and HIV burden area. The use of a combination of a VAS and a questionnaire can be an adequate approach to monitor adherence to TB treatment in routine program conditions.     

Early mortality and AIDS progression despite high initial antiretroviral therapy adherence and virologic suppression in Botswana

Background

Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.

Methods

This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%).

Results

Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively.

Conclusions

Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.     

Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Background

Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels.

Methods

Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA <400 copies/ml throughout the study period.

Results

From January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01–0.99; LPV/r: OR 0.29, 95% CI: 0.09–0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62–18.75; LPV/r: OR 5.65, 95% CI: 1.82–17.56).

Conclusions

The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.     

Prescribing trends in bipolar disorder: cohort study in the United Kingdom THIN primary care database 1995-2009

Objectives

To determine changes in prescribing patterns in primary care of antipsychotic and mood stabiliser medication in a representative sample of patients with bipolar disorder in the United Kingdom over a fifteen year period and association with socio-demographic factors.

Methods

We identified 4700 patients in the Health Improvement Network (THIN) primary care database, who had received treatment for bipolar disorder between 1995 and 2009. The proportion of time for which each individual was prescribed a particular medication was studied, along with variation by sex, age and social depravation status (quintiles of Townsend scores). The number of drugs an individual was taking within a particular year was also examined.

Results

In 1995, 40.6% of patients with bipolar disorder were prescribed a psychotropic medication at least twice. By 2009 this had increased to 78.5% of patients. Valproate registered with the greatest increase in use (22.7%) followed by olanzapine (15.7%) and quetiapine (9.9%). There were differences by age and sex; with young (18–30 year old) women having the biggest increase in proportion of time on medication. There were no differences by social deprivation status. By 2009, 34.2% of women of childbearing age were treated with valproate.

Conclusions

Lithium use overall remained relatively constant, whilst second generation antipsychotic and valproate use increased dramatically. Changes in prescribing practice preceded published trial evidence, especially with the use of second generation antipsychotics, perhaps with inferences being made from treatment of schizophrenia and use of first generation antipsychotics. Women of childbearing age were prescribed valproate frequently, against best advice.     

The influence of cognition, anxiety and psychiatric disorders over treatment adherence in uncontrolled hypertensive patients

Background

Poor adherence is estimated to cause 125 thousand deaths per year and is linked to 10% of all hospital stays in the U.S. Up to one third of elderly hypertensive patients don''t have adherence, which is responsible for high proportion of hospitalizations. Hypertension is also related to poor performance in tests that assess cognitive functions. On the other hand, poor cognitive performance is associated with low adherence to treatment.

Objective

To assess the association between cognitive function, anxiety and psychiatric disorders with adherence to drug treatment in patients with hypertension.

Methodology and Principal Findings

This a cohort studies with 56 adult patients with uncontrolled hypertension who participated of all meetings of a pharmaceutical intervention in a randomized clinical trial of pharmaceutical care. Cognitive function was measured by the Mini Mental State Examination (Mini-mental). The memory was measured by digit and word spans, tower and church shadow test, short story test and metamemory. Anxiety and psychiatric disorders were evaluated by the State Trace Anxiety Inventory and the Self-Report Questionnaire, respectively. The participants were classified as adherent or non-adherent to the drug treatment, according to the identification of plasma levels of hydrochlorothiazide. All non-adherent patients (n = 12) and 35 out 44 (79.5%) patients with adherence to treatment had at least one memory test with an altered score (P = 0.180). Participants with an unsatisfactory score in the Mini-mental had six-fold higher risk of non-adherence to treatment when compared to those with a normal score (RR = 5.8; CI 95%: 1.6–20.8; P = 0.007). The scores of anxiety and psychiatric disorders were not associated with adherence to the pharmacological treatment.

Conclusion

Cognitive deficit impairs adherence to drug therapy and should be screened as part of a program of pharmaceutical care to improve adherence to treatment.     

Intentional weight loss and dose reductions of anti-diabetic medications--a retrospective cohort study

Background and Aim

Intentional weight loss, primarily by improving insulin resistance, is known to decrease the need for anti-diabetic medications. In this study, we assess the magnitude of weight loss that resulted in dose reductions or discontinuation of anti-diabetic medications in overweight or obese patients with type 2 diabetes (DM) undergoing weight loss treatment.

Methods

Case records of 50 overweight or obese patients with DM who successfully decreased dosage or discontinued diabetes medications after losing weight via attendance at two University-based, outpatient weight management centers were analyzed. Follow-up visits, weight reduction interventions, and decisions for dose reductions or discontinuation of medications were individualized to patient needs by the treating physician.

Results

Mean starting BMI was 35 kg/m², mean age 53.4 years, and 58% were male. All 50 used at least one anti-diabetic medication (30 metformin, 39 sulfonylureas, 31 insulin, 21 sitagliptin) to manage blood sugar. Mean duration of follow-up was 30.2 months. Mean weight loss was 10.8±4.1 kgs (11.1% of initial body weight ±4.7%). 22/50 patients (44%) discontinued anti-diabetes medications (14 sulfonylureas [36%], 7 insulin [23%], 4 sitagliptin [19%]). The mean percentage weight loss achieved at the point of successful discontinuation of medication was 11.2%±3.5% (14% for sulphonylureas, 11% for insulin, and 7.1% for sitagliptin). Mean percentage weight loss of 5.6%±2.8% (5.1% for sulphonylureas, 4.3% for insulin, and 7.1% for sitagliptin) was required for initial dose reduction. For every 5% weight loss, predicted dose reductions were sulphonylureas, 39%; insulin, 42%; and any anti-diabetic medications, 49%.

Conclusion

Among overweight or obese patients with type 2 diabetes, intentional weight loss of 7–14% was typically required for full discontinuation of at least one anti-diabetic medication. Discontinuation of insulin was achieved at a mean weight reduction of 11% of initial body weight.     

Treatment interruption and variation in tablet taking behaviour result in viral failure: a case-control study from Cape Town, South Africa

Background

Understanding of the impact of non-structured treatment interruption (TI) and variation in tablet-taking on failure of first-line antiretroviral therapy (ART) is limited in a resource-poor setting.

Methods

A retrospective matched case-control analysis. Individuals failing ART were matched by time on ART with 4 controls. Viral load (VL) and CD4 count were completed 4-monthly. Adherence percentages, from tablet returns, were calculated 4-monthly (interval) and from ART start (cumulative). Variation between intervals and TI (>27 days off ART) were recorded. Conditional multivariate logistic regression analysis was performed to estimate the effect of cumulative adherence <90%, at least one episode of adherence variation >10% and TI on virological failure. Age, gender, baseline log VL and CD4 were included as possible confounders in the multivariate model.

Results

244 patients (44 cases, 200 controls) were included. Median age was 32 years (IQR28–37), baseline CD4 108 cells/mm3 (IQR56–151), VL 4.82 log (IQR4.48–5.23). 94% (96% controls, 86% failures) had cumulative adherence >90%. The odds of failure increased 3 times (aOR 3.01, 95%CI 0.81–11.21) in individuals with cumulative adherence <90%, 2.2 times (aOR 2.20, 95%CI 1.04–4.64) in individuals with at least one episode of fluctuating adherence of >10% and 4.01 times (aOR 4.01, 95%CI 1.45–11.10) in individuals with TIs. For individuals with TI and cumulative adherence >95%, the odds of failing were 5.65 (CI 1.40–22.85).

Conclusion

It is well known that poor cumulative adherence increases risk of virological failure, but less well understood that TI and variations in tablet-taking also play a key role, despite otherwise excellent adherence.     

Heart failure and preserved left ventricular function: long term clinical outcome

Background

Patients with heart failure (HF) have a poor prognosis. The proportion of patients with HF and preserved left ventricular function (LVF) is increasing. Long term prognosis of HF with preserved LVF may not be so benign.

Objectives

To evaluate the long term clinical outcome of patients with HF and preserved LVF and predictors of outcome.

Methods

We prospectively evaluated 309 patients hospitalized with a definite clinical diagnosis of HF. Patients were followed for a mean of 6.5 years for clinical outcome.

Results

More than a third (36%) of the patients had preserved systolic LVF based on echocardiography. The long term survival rate in this group was poor and not significantly different from patients with reduced LVF (28% vs 23% respectively, P = 0.2). The adjusted survival rate by Cox regression analysis was also not significantly different (hazard ratio 1.16, 95% confidence interval 0.87–1.55, P = 0.31). The event free survival from death or heart failure re-hospitalization was also low in both groups and not significantly different between patients with preserved vs. reduced LVF (12% vs. 10% respectively, P = 0.2). Predictors of mortality in patients with preserved LVF were age, functional capacity and serum urea levels.

Conclusions

The long term clinical outcome of patients with heart failure and preserved LVF is poor and not significantly different from patients with reduced LVF.     

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru

Background

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use.

Methodology and Results

A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions.

Conclusions

Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.     

Healthcare reform and the next generation: United States medical student attitudes toward the Patient Protection and Affordable Care Act

Context

Over one year after passage of the Patient Protection and Affordable Care Act (PPACA), legislators, healthcare experts, physicians, and the general public continue to debate the implications of the law and its repeal. The PPACA will have a significant impact on future physicians, yet medical student perspectives on the legislation have not been well documented.

Objective

To evaluate medical students'' understanding of and attitudes toward healthcare reform and the PPACA including issues of quality, access and cost.

Design, Setting, and Participants

An anonymous electronic survey was sent to medical students at 10 medical schools (total of 6982 students) between October–December 2010, with 1232 students responding and a response rate of 18%.

Main Outcome Measures

Medical students'' views and attitudes regarding the PPACA and related topics, measured with Likert scale and open response items.

Results

Of medical students surveyed, 94.8% agreed that the existing United States healthcare system needs to be reformed, 31.4% believed the PPACA will improve healthcare quality, while 20.9% disagreed and almost half (47.7%) were unsure if quality will be improved. Two thirds (67.6%) believed that the PPACA will increase access, 6.5% disagreed and the remaining 25.9% were unsure. With regard to containing healthcare costs, 45.4% of participants indicated that they are unsure if the provisions of the PPACA will do so. Overall, 80.1% of respondents indicated that they support the PPACA, and 78.3% also indicated that they did not feel that reform efforts had gone far enough. A majority of respondents (58.8%) opposed repeal of the PPACA, while 15.0% supported repeal, and 26.1% were undecided.

Conclusion

The overwhelming majority of medical students recognized healthcare reform is needed and expressed support for the PPACA but echoed concerns about whether it will address issues of quality or cost containment.     

Determinants of Medication Adherence to Antihypertensive Medications among a Chinese Population Using Morisky Medication Adherence Scale

Background and Objectives

Poor adherence to medications is one of the major public health challenges. Only one-third of the population reported successful control of blood pressure, mostly caused by poor drug adherence. However, there are relatively few reports studying the adherence levels and their associated factors among Chinese patients. This study aimed to study the adherence profiles and the factors associated with antihypertensive drug adherence among Chinese patients.

Methods

A cross-sectional study was conducted in an outpatient clinic located in the New Territories Region of Hong Kong. Adult patients who were currently taking at least one antihypertensive drug were invited to complete a self-administered questionnaire, consisting of basic socio-demographic profile, self-perceived health status, and self-reported medication adherence. The outcome measure was the Morisky Medication Adherence Scale (MMAS-8). Good adherence was defined as MMAS scores greater than 6 points (out of a total score of 8 points).

Results

From 1114 patients, 725 (65.1%) had good adherence to antihypertensive agents. Binary logistic regression analysis was conducted. Younger age, shorter duration of antihypertensive agents used, job status being employed, and poor or very poor self-perceived health status were negatively associated with drug adherence.

Conclusion

This study reported a high proportion of poor medication adherence among hypertensive subjects. Patients with factors associated with poor adherence should be more closely monitored to optimize their drug taking behavior.     

Socioeconomic status and incident type 2 diabetes mellitus: data from the Women's Health Study

Objectives

We prospectively examined whether socioeconomic status (SES) predicts incident type II diabetes (diabetes), a cardiovascular risk equivalent and burgeoning public health epidemic among women.

Methods

Participants include 23,992 women with Hb_A1c levels <6% and no CVD or diabetes at baseline followed from February 1993 to March 2007. SES was measured by education and income while diabetes was self-reported.

Results

Over 12.3 years of follow-up, 1,262 women developed diabetes. In age and race adjusted models, the relative risk of diabetes decreased with increasing education (<2 years of nursing, 2 to <4 years of nursing, bachelor''s degree, master''s degree, and doctorate: 1.0, 0.7 [95% Confidence Interval (CI), 0.6–0.8], 0.6 (95% CI, 0.5–0.7), 0.5 (95% CI, 0.4–0.6), 0.4 (95% CI, 0.3–0.5); p_trend<0.001). Adjustment for traditional and non-traditional cardiovascular risk factors attenuated this relationship (education: p_trend = 0.96). Similar associations were observed between income categories and diabetes.

Conclusion

Advanced education and increasing income were both inversely associated with incident diabetes even in this relatively well-educated cohort. This relationship was largely explained by behavioral factors, particularly body mass index.     

Hypertension in women of reproductive age in the United States: NHANES 1999-2008

Objective

To examine the epidemiology of hypertension in women of reproductive age.

Methods

Using NHANES from 1999–2008, we identified 5,521 women age 20–44 years old. Hypertension status was determined using blood pressure measurements and/or self-reported medication use.

Results

The estimated prevalence of hypertension in women of reproductive age was 7.7% (95% confidence interval (CI): 6.9%–8.5%). The prevalence of anti-hypertensive pharmacologic therapy was 4.2% (95% CI 3.5%–4.9%). The prevalence of hypertension was relatively stable across the study period; the age and race adjusted odds of hypertension in 2007–2008 did not differ significantly from 1999–2000 (odds ratio 1.2, CI 0.8 to 1.7, p = 0.45). Significant independent risk factors associated with hypertension included older age, non-Hispanic black race (compared to non-Hispanic whites), diabetes mellitus, chronic kidney disease, and higher body mass index. The most commonly used antihypertensive medications included diuretics, angiotensin-converting enzyme inhibitors (ACE), and beta blockers.

Conclusion

Hypertension occurs in about 8% of women of reproductive age. There are remarkable differences in the prevalence of hypertension between racial/ethnic groups. Obesity is a risk factor of particular importance in this population because it affects over 30% of young women in the U.S., is associated with more than 4 fold increased risk of hypertension, and is potentially modifiable.     

Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in the Gambia

Background

Chlorproguanil-dapsone (Lapdap), developed as a low-cost antimalarial, was withdrawn in 2008 after concerns about safety in G6PD deficient patients. This trial was conducted in 2004 to evaluate the safety and effectiveness of CD and comparison with artemether-lumefantrine (AL) under conditions of routine use in G6PD normal and G6PD deficient patients with uncomplicated malaria in The Gambia. We also examined the effects of a common genetic variant that affects chlorproguanil metabolism on risk of treatment failure.

Methods

1238 children aged 6 months to 10 years with uncomplicated malaria were randomized to receive CD or artemether-lumefantrine (AL) and followed for 28 days. The first dose was supervised, subsequent doses given unsupervised at home. G6PD genotype was determined to assess the interaction between treatment and G6PD status in their effects on anaemia. The main endpoints were clinical treatment failure by day 28, incidence of severe anaemia (Hb<5 g/dL), and haemoglobin concentration on day 3.

Findings

One third of patients treated with AL, and 6% of patients treated with CD, did not complete their course of medication. 18% (109/595) of children treated with CD and 6.1% (36/587) with AL required rescue medication within 4 weeks, risk difference 12% (95%CI 8.9%–16%). 23 children developed severe anaemia (17 (2.9%) treated with CD and 6 (1.0%) with AL, risk difference 1.8%, 95%CI 0.3%–3.4%, P = 0.02). Haemoglobin concentration on day 3 was lower among children treated with CD than AL (difference 0.43 g/dL, 95% CI 0.24 to 0.62), and within the CD group was lower among those children who had higher parasite density at enrolment. Only 17 out of 1069 children who were typed were G6PD A- deficient, of these 2/9 treated with CD and 1/8 treated with AL developed severe anaemia. 5/9 treated with CD had a fall of 2 g/dL or more in haemoglobin concentration by day 3.

Interpretation

AL was well tolerated and highly effective and when given under operational conditions despite poor adherence to the six-dose regimen. There were more cases of severe malaria and anaemia after CD treatment although G6PD deficiency was uncommon.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00118794","term_id":"NCT00118794"}}NCT00118794     

Pharmacological undertreatment of coronary risk factors in patients with psoriasis: observational study of the Danish nationwide registries

Background

Patients with psoriasis have increased prevalence of coronary risk factors and limited recent results have suggested that these risk factors are undertreated in patients with psoriasis. This may contribute to the increased risk of cardiovascular diseases observed in patients with psoriasis.

Objective

To examine the pharmacological treatment of coronary risk factors in patients with severe psoriasis treated with biologic agents in a real-world setting.

Methods and Findings

Medical history of patients with severe psoriasis treated with biologic agents in the time period 2007–09 was retrieved from a Danish nationwide registry (DERMBIO). Individual-level linkage of nationwide administrative registries of hospitalizations, concomitant medications, and socioeconomic status was performed to gain insights into the use of pharmacological treatment. A total of 693 patients (mean age 46.1±12.7 years, 65.7% male) with severe psoriasis treated with biologic agents were identified. Hypertension, hypercholesterolemia, and diabetes mellitus were identified in 16.6%, 9.2%, and 6.7% of cases, respectively. Patients with severe psoriasis were significantly less likely to receive cardiovascular pharmacotherapy compared to age, sex, and coronary risk factor matched controls. In psoriatic patients with hypertension 27.7% received no antihypertensive pharmacotherapy. Patients with dyslipidemia received cholesterol-lowering medications in 55.8% of cases and patients with diabetes mellitus received angiotensin converting enzyme inhibitors/angiotensin II receptor blockers and cholesterol-lowering medications in 42.1% and 23.7% of cases, respectively. Similar results were found for the subset of patients with >1 coronary risk factor and for high risk patients with established atherosclerotic disease.

Conclusion

This nationwide study of patients with severe psoriasis demonstrated substantial undertreatment of coronary risk factors. Increased focus on identifying cardiovascular risk factors and initiation of preventive cardiovascular pharmacotherapy in patients with psoriasis is warranted.