Prescribing patterns, adherence and LDL-cholesterol response of type 2 diabetes patients initiating statin on low-dose versus standard-dose treatment: a descriptive study.

AIMS: The aim of this study was to describe and compare treatment modifications and discontinuation, adherence levels and response to treatment in patients with type 2 diabetes initiating on low-dose vs. standard-dose statin treatment. METHODS: A 2-year follow-up cohort study was performed using data from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database in patients with type 2 diabetes initiating statin treatment between January 2007 and December 2012. First, we determined whether there were differences in treatment modifications and discontinuation after statin initiation between patients starting on a low-dose vs. standard-dose. Second, we looked at differences in adherence and LDL-cholesterol response after 2 years follow-up between these groups. RESULTS: Around 22% of patients initiated statin treatment on a dose lower than recommended. More than half of them remained on a low dose during a 2-year follow-up period, whereas less than 15% received a dose increase. Of the patients initiating on standard-dose, also more than half remained on the same treatment during this period, whereas 8% received a dose decrease without subsequent increase. Over 25% of patients starting on low-dose or standard-dose treatment discontinued treatment, often within the first 180 days after initiation or after a first treatment change. Patients on low-dose treatment had lower adherence levels and were less likely to have adequate LDL-cholesterol response compared with patients on standard-dose after 2 years follow-up. CONCLUSIONS: Current patterns of statin treatment in patients with type 2 diabetes are suboptimal, with discontinuation, inadequate adherence levels and lack of treatment intensification seen in those who had inadequate LDL-cholesterol response after 2 years of follow-up. Patients starting on low-dose had more treatment modifications, discontinuation and adherence problems as compared with those starting on standard-dose treatment, which calls for a closer look at the rationale of starting patients on low-dose statin treatment.

Emergence of pan-resistance in KPC-2 carbapenemase-producing Klebsiella pneumoniae in Crete, Greece: a close call.

OBJECTIVES: KPC-2-producing Klebsiella pneumoniae (KPC-KP) ST258 has been rapidly expanding and is often associated with serious nosocomial infections. Last-line antibiotics such as colistin and tigecycline often remain the only treatment option. We describe here the evolving genetic background of KPC-KP isolates in Crete, Greece. METHODS: We tested the antibiotic susceptibility of 34 clinical isolates from patients hospitalized in 2010 and 2013-14. Whole-genome sequences of these isolates were analysed for acquired resistance genes and gene mutations. RESULTS: All KPC-KP isolates belonged to ST258 with the exception of one ST147 isolate. From 2014, 26% of isolates were non-susceptible to all antibiotics, compared with 0 of 11 isolates from 2010. Colistin resistance was associated with mutations in mgrB, which was present in 61% of isolates from 2014. Core-genome MLST analysis showed that pan-resistant isolates were closely related and appeared in two separate clusters. CONCLUSIONS: KPC-KP is rapidly evolving to pan-resistance in Crete. We identified molecular resistance markers for pan-resistant isolates and showed that core-genome MLST is a promising tool for molecular fingerprinting of KPC-KP ST258.

Adherence to standard-dose or low-dose statin treatment and low-density lipoprotein cholesterol response in type 2 diabetes patients.

OBJECTIVE: To determine the association between adherence, dose and low-density lipoprotein (LDL) cholesterol response in patients with type 2 diabetes initiating statin treatment. RESEARCH DESIGN AND METHODS: This cohort study was performed using data for 2007-2012 from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database. The association between adherence to a standard-dose statin and LDL cholesterol response was assessed using linear regression, adjusting for covariates. The effect of low-dose versus standard-dose was assessed in a propensity-score matched cohort. Adherence rates, defined as the proportion of days covered (PDC), were estimated between statin initiation and LDL outcome measurement. MAIN OUTCOME MEASURE: LDL cholesterol level at follow-up. RESULTS: The effect of adherence on LDL cholesterol response, measured in 2160 patients, was dependent on the baseline LDL cholesterol level. For patients with a baseline LDL cholesterol of 3.7 mmol/l and an adherence rate of 80%, a 40% reduction in LDL cholesterol was predicted. In the matched sample of 1144 patients, the treatment dose showed a difference in impact on the outcome for adherence rates higher than 50%. It was estimated that a patient with a baseline LDL cholesterol of 3.7 mmol/l will need an adherence rate of at least 76% on low-dose and 63% on standard-dose treatment to reach the LDL cholesterol target of 2.5 mmol/l. LIMITATIONS: Adherence was measured as the PDC, which is known to overestimate actual adherence. Also, we were not able to adjust for lifestyle factors. CONCLUSIONS: We determined the concurrent effect of treatment adherence and dose on LDL cholesterol outcomes. Given the adherence levels seen in clinical practice, diabetes patients initiating statin treatment are at high risk of not reaching the recommended cholesterol target, especially when they start on a low-dose statin.

Cardiometabolic treatment decisions in patients with type 2 diabetes: the role of repeated measurements and medication burden.

PURPOSE: Clinical guidelines for cardiometabolic risk management indicate a simple threshold-based strategy for treatment, but physicians and their patients may be reluctant to modify drug treatment after a single elevated measurement. We determined how repeated measurements of blood pressure, cholesterol and haemoglobin A1c affect general practitioners' decisions to start or intensify medication in patients with type 2 diabetes. We also evaluated whether medication burden altered these decisions. METHODS: We conducted a cohort study in 3029 patients managed by 62 general practitioners (GPs). We assessed the predictive value of the last risk factor measurement, the number of successive measurements above target level and the percentage change between the last two measurements. Medication burden was assessed as the number of drugs concurrently used. Effects on treatment decisions were estimated by multilevel logistic regression analysis, correcting for clustering at GP level. RESULTS: Repeated high levels of diastolic blood pressure increased the likelihood to start antihypertensive medication (OR=2.08, CI 1.37 to 3.17). Repeated high haemoglobin A1c levels affected intensification of oral glucose-lowering medication (OR=1.71, CI 1.44 to 2.03). Modification of lipid-lowering medication was limited, and only affected by the last total cholesterol level. Starting treatment for all three risk factors, as well as intensifying antihypertensive treatment, was more likely in patients already using more drugs for other chronic diseases. CONCLUSIONS: Waiting for the next measurement before deciding to change medication can explain in part the apparent undertreatment for hypertension and hyperglycaemia, but not for hypercholesterolaemia. Medication burden was not a barrier for treatment modification.

Uso de mosquiteros y otros materiales impregnados con insecticida para el control de la malaria en las Américas / Use of insecticide impregnated mosquito nets and other impregnated materials for malaria control in the Americas

En el presente artículo se analiza el uso actual de mosquiteros y de otros materiales impregnados con insecticida en las Américas. Se examinan diversos estudios efectuados en Brasil, Colombia, Ecuador, Guatemala, Perú, Suriname y Venezuela y se llega a la conclusión de que, en su mayor parte, estos estudios adolecen de graves deficiencias de diseño experimental, problemas de excesiva brevedad, y medición inadecuada de indicadores de salud. En el análisis se resalta la gran dificultad de llevar a cabo estudios científicos que buscan determinar el efecto de los materiales tratados con insecticida en la incidencia de malaria. En particular, la baja incidencia de malaria en las Américas, la elevada prevalencia de Plasmodium vivax y de casos recurrentes, y la relación existente entre los patrones de actividad del ser humano y los hábitos de picadura crepusculares de ciertos vectores de la malaria impiden hacer experimentos de fácil diseño y ejecución. Por ahora sería prematuro usar mosquiteros u otros materiales impregandos con insecticida como componentes principales de un programa integral para el control de la malaria. No obstante, se recomienda que se considere la posibilidad de realizar ensayos e intervenciones bien diseñados a gran escala, siempre que se basen en un conocimiento profundo de la dinámica de la transmisión de la malaria en la zona en estudio

Uso de mosquiteros y otros materiales impregnados con insecticida para el control de la malaria en las Américas / Use of insecticide impregnated mosquito nets and other impregnated materials for malaria control in the Americas

En el presente artículo se analiza el uso actual de mosquiteros y de otros materiales impregnados con insecticida en las Américas. Se examinan diversos estudios efectuados en Brasil, Colombia, Ecuador, Guatemala, Perú, Suriname y Venezuela y se llega a la conclusión de que, en su mayor parte, estos estudios adolecen de graves deficiencias de diseño experimental, problemas de excesiva brevedad, y medición inadecuada de indicadores de salud. En el análisis se resalta la gran dificultad de llevar a cabo estudios científicos que buscan determinar el efecto de los materiales tratados con insecticida en la incidencia de malaria. En particular, la baja incidencia de malaria en las Américas, la elevada prevalencia de Plasmodium vivax y de casos recurrentes, y la relación existente entre los patrones de actividad del ser humano y los hábitos de picadura crepusculares de ciertos vectores de la malaria impiden hacer experimentos de fácil diseño y ejecución. Por ahora sería prematuro usar mosquiteros u otros materiales impregandos con insecticida como componentes principales de un programa integral para el control de la malaria. No obstante, se recomienda que se considere la posibilidad de realizar ensayos e intervenciones bien diseñados a gran escala, siempre que se basen en un conocimiento profundo de la dinámica de la transmisión de la malaria en la zona en estudio

Use of insecticide-impregnated mosquito nets and other impregnated materials for malaria control in the Americas.

This article reviews the current status of the use of insecticide-impregnated mosquito nets and other impregnated materials in the Americas. Studies from Brazil, Colombia, Ecuador, Guatemala, Peru, Suriname, and Venezuela are examined. It is concluded that most studies have suffered from experimental design errors, short duration problems, and/or inadequate measurement of health indicators. The review brings out the great difficulty of conducting scientific studies that attempt to measure the impact of insecticide-treated materials on malaria incidence. In particular, the low incidence of malaria in the Americas, the high prevalences of P. vivax and relapsing cases, and the relationship between human activity patterns and the crepuscular biting patterns of certain malaria vectors stand in the way of easy experimental design and execution. The utilization of impregnated mosquito nets or other impregnated materials as a major component of an integrated malaria control program would be premature at this time. However, it is recommended that well-conceived large-scale trials and interventions be considered when they are based on a thorough understanding of the dynamics of malaria transmission in the area of study.

Use of insecticide-impregnated mosquito nets and other impregnated materials for malaria control in the Americas

This article reviews the current status of the use of insecticide-impregnated mosquito nets and other impregnated materials in the Americas. Studies from Brazil, Colombia, Ecuador, Guatemala, Peru, Suriname, and Venezuela are examined. It is concluded that most studies have suffered from experimental design errors, short duration problems, and/or inadequate measurement of health indicators. The review brings out the great difficulty of conducting scientific studies that attempt to measure the impact of insecticide-treated materials on malaria incidence. In particular, the low incidence of malaria in the Americas, the high prevalences of P. vivax and relapsing cases, and the relationship between human activity patterns and the crepuscular biting patterns of certain malaria vectors stand in the way of easy experimental design and execution. The utilization of impregnated mosquito nets or other impregnated materials as a major component of an integrated malaria control program would be premature at this time. However, it is recommended that well-conceived large-scale trials and interventions be considered when they are based on a thorough understanding of the dynamics of malaria transmission in the area of study (AU)

Use of insecticide-impregnated mosquito nets and other impregnated materials for malaria control in the Americas / Uso de mosquiteros y otros materiales impregnados para el control de la malaria en las Américas

This article reviews the current status of the use of insecticide-impregnated mosquito nets and other impregnated materials in the Americas. Studies from Brazil, Colombia, Ecuador, Guatemala, Peru, Suriname, and Venezuela are examined. It is concluded that most studies have suffered from experimental design errors, short duration problems, and/or inadequate measurement of health indicators. The review brings out the great difficulty of conducting scientific studies that attempt to measure the impact of insecticide-treated materials on malaria incidence. In particular, the low incidence of malaria in the Americas, the high prevalences of P. vivax and relapsing cases, and the relationship between human activity patterns and the crepuscular biting patterns of certain malaria vectors stand in the way of easy experimental design and execution. The utilization of impregnated mosquito nets or other impregnated materials as a major component of an integrated malaria control program would be premature at this time. However, it is recommended that well-conceived large-scale trials and interventions be considered when they are based on a thorough understanding of the dynamics of malaria transmission in the area of study

En este artículo se revisa el uso actual en las Américas de mosquiteros y otros materiales impregnados con insecticida. Se examinan diversos estudios efectuados en el Brasil, Colombia, Ecuador, Guatemala, Perú, Suriname y Venezuela y se llega a la conclusión de que en su mayor parte estos estudios adolecen de graves deficiencias de diseño, problemas de excesiva brevedad, o de una medición inadecuada de los indicadores de salud. La revisión resalta la gran dificultad de llevar a cabo estudios que buscan medir el impacto de los materiales tratados con insecticidas sobre la incidencia de malaria. En particular, la baja incidencia de malaria en las Américas, las altas prevalencias de Plasmodium vivax y de casos recurrentes y la relación entre los patrones de actividad de los seres humanos y los hábitos de picadura crepusculares de los mosquitos impiden hacer experimentos de fácil diseño y ejecución. Por ahora sería prematuro usar mosquiteros u otros materiales impregnados como componentes principales de un programa integral para el control de la malaria. No obstante, se recomienda que se considere llevar a cabo ensayos bien diseñados a gran escala siempre que se basen en un conocimiento profundo de la dinámica de la transmisión de la malaria en la zona del estudio.

The use of wide-mesh gauze impregnated with lambda-cyhalothrin covering wall openings in huts as a vector control method in Suriname.

An alternative vector control method, using lambda-cyhalothrin impregnated wide-mesh gauze covering openings in the walls of the houses was developed in an area in the Eastern part of the interior of Suriname. Experimental hut observations showed that Anopheles darlingi greatly reduced their biting activity (99-100%) during the first 5 months after impregnation. A model assay showed high mortality both of mosquitoes repelled by the gauze as well as of those that succeeded in getting through it. A field application test in 270 huts showed good acceptance by the population and good durability of the applied gauze. After introducing the method in the entire working area, replacing DDT residual housespraying, the malaria prevalence, of 25-37% before application dropped and stabilized at between 5 and 10% within one year. The operational costs were less than those of the previously used DDT housespraying program, due to a 50% reduction in the cost of materials used. The method using wide-mesh gauze impregnated with lambda-cyhalothrin strongly affects the behavior of An. darlingi. It is important to examine the effect of the method on malaria transmission further, since data indirectly obtained suggest substantial positive results.

PIP: Field application testing in Suriname confirmed that use of wide-mesh gauze impregnated with lambda-cyhalothrin to cover openings in the walls of Bush Negro homes represents an effective, acceptable, and low-cost vector control method. In experimental hut observations in the Eastern part of the interior of Suriname, this method reduced the biting activity of Anopheles darlingi by 99-100% in the first 5 months after impregnation. A model assay showed high mortality among mosquitoes repelled by the gauze and 100% mortality in insects that were able to cross through the mesh. A field application test in 270 huts showed good acceptance by the population, with no conflicts with local cultural customs, and excellent durability. After replacement of DDT residual house-spraying (associated with a malaria prevalence of 25-37%) with the impregnated gauze method, malaria prevalence dropped to 5-10% and material costs were halved. When the Suriname Government resumed responsibility for health care in the interior in 1992 when political strife stopped, use of this vector control method was not continued despite its demonstrated benefits.

Reappearance of Plasmodium malariae in Suriname?

Plasmodium malariae has not been reported from Suriname since 1979. In 1989 an increasing number of P. vivax infections among Bush-negroes returning from the eastern part of the interior was reported in Paramaribo. A microscopical re-examination of all malaria cases in the eastern part of the country failed to confirm any P. vivax infections, but instead P. malariae infections were diagnosed. A study followed to determine the Duffy blood group antigens of 4 Bush-negroes allegedly with a P. vivax infection in their medical history and of 28 and 32 unselected Bush-negroes and Amerindians respectively. Three of the 4 former Bush-negroes had the FyB antigen, while only 7% of the unselected Bush-negroes had this antigen. This low frequency of the genotype is incompatible with reports of high P. vivax prevalences in Bush-negro populations. The Amerindians tested showed a low proportion of Fy0 genotype, which is compatible with the frequent diagnosis of P. vivax among this ethnic group. Reports of P. vivax infections among Bush-negroes are due to misdiagnosis of P. malariae, emphasizing the need to include all 4 species of human Plasmodium when (re)training microscopists. The question whether P. malariae reappeared in Suriname due to increased contact with the simian reservoir, or was simply missed, is discussed.

Efficacy of mosquito nets treated with permethrin in Suriname.

In the rain-forest of Suriname, where malaria is endemic, 95% of the Maroons (who call themselves bush-negroes) and all Amerindians use mosquito nets made of cotton cloth or, less frequently, nylon or cotton gauze over their hammocks or beds. Bush-negroes usually wash their nets weekly; Amerindians wash nets at 1-4 month intervals. Females of the principal local malaria vector, Anopheles darlingi Root, were seen blood-feeding through cotton cloth netting (at 22.30-23.30 hours) on a person sleeping in a hammock; others fed successfully after the net was opened in the morning. Cotton cloth impregnated with permethrin at a rate of 0.5 g/m2 killed all An. darlingi females exposed for 2 min, but after the material had been washed twice in soapy water the bioassay mortality fell to only 21.4%. Exit traps on a hut with a single sleeper protected by a permethrin-impregnated net yielded 185 An. darlingi females (12% blood-fed) in 74 nights, compared with 276 females (19% blood-fed) from another hut with a sleeper using an untreated net on the same nights (P less than 0.001). No An. darlingi females remained resting alive indoors in these huts during the daytime, and very few were found dead on the floor in the mornings (one treated, seven untreated). The 24 h mortality rate for those collected in exit traps was 58.4% for the test hut and 27.1% for the control hut (P less than 0.001). Bioassays of permethrin-treated cotton cloth using laboratory-reared sugar-fed Culex quinquefasciatus Say females showed that sprayed nets were less effective than nets impregnated by soaking (at equivalent dosages of 0.16-1.34 g/m2 measured by chemical assay) and confirmed that washing causes severe decline in insecticidal activity. The feasibility of local mass treatment of mosquito nets is discussed.

Behavioral responses of Anopheles darlingi in Suriname to DDT residues on house walls.

A study was conducted in Suriname on the effects of DDT residual house spray on the main vector of malaria, Anopheles darlingi. Results obtained with an experimental hut sprayed with DDT wettable powder (2 g/m2 AI) were compared with results obtained with an unsprayed control hut. In the sprayed hut, entry rates were reduced by 32% and feeding success by 43.6%. The 24-h mortality of mosquitoes which entered the sprayed hut was 95% (range 85-100%) over the 10-month study period. After furnishing the sprayed hut according to local custom, no reduction in mortality was observed despite an abundance of unsprayed resting surfaces. Bioassays showed that the DDT deposits remained effective for at least 14 months. With excito-repellency test boxes an irritant effect caused by DDT on recently fed An. darlingi females was shown. With a choice-box experiment no preference for unsprayed over sprayed resting places could be demonstrated.