The recently recognised protein-coding genes MCM7 and TSR1 have shown significant promise for phylogenetic resolution within the Ascomycota and Basidiomycota, but have remained unexamined within other fungal groups (except for Mucorales). We designed and tested primers to amplify these genes across early-diverging fungal clades, with emphasis on the Kickxellomycotina, zygomycetous fungi with characteristic flared septal walls forming pores with lenticular plugs. Phylogenetic tree resolution and congruence with MCM7 and TSR1 were compared against those inferred with nuclear small (SSU) and large subunit (LSU) rRNA genes. We also combined MCM7 and TSR1 data with the rDNA data to create 3- and 4-gene trees of the Kickxellomycotina that help to resolve evolutionary relationships among and within the core clades of this subphylum. Phylogenetic inference suggests that Barbatospora, Orphella, Ramicandelaber and Spiromyces may represent unique lineages. It is suggested that these markers may be more broadly useful for phylogenetic studies among other groups of early-diverging fungi.
DNA replication licensing factor; Harpellales; Kickxellomycotina; MCM7; MS277; MS456; ribosomal biogenesis protein; Trichomycetes; TSR1; Zygomycota
Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 μg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 μg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 μg/ml (VGII); itraconazole, 0.25 μg/ml (VNI), 0.5 μg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 μg/ml (VGIV); posaconazole, 0.25 μg/ml (C. neoformans nontyped and VNI) and 0.5 μg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 μg/ml (VNIV), 0.25 μg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 μg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.
Using a metasynthesis approach, our aim was to articulate new insights relating to the most efficient and effective means of helping homeless women with substance abuse problems to enhance their well-being and become more stably housed. Distorted perceptions of competency, which are shaped by dysfunctional relationships and mental health problems, make it challenging for women with substance abuse problems to resolve homelessness. Women with particularly low or high levels of perceived competency tend to grapple with challenges related to structure and control, trust, and hopelessness. Therapeutic strategies for approaching these women include careful assessment, caring, personalized structure and control, development of interpersonal trust, instillation of hope, and the targeted use of psychotherapeutic agents and counseling. Framing care for homeless women within the context of perceived competency offers a new way of understanding their plight and shaping interventions to more expeditiously move them toward healthy and stable lives.
addiction/substance use; homelessness; metasynthesis; poverty; women’s health
Clinical breakpoints (CBPs) are not available for the Cryptococcus neoformans-Cryptococcus gattii species complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) for C. neoformans and C. gattii versus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs for C. neoformans (including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs for C. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest amphotericin B MICs for C. neoformans were evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for amphotericin B, 0.5 μg/ml for C. neoformans VNI (97.2%) and C. gattii VGI and VGIIa (99.2 and 97.5%, respectively) and 1 μg/ml for C. neoformans (98.5%) and C. gattii nontyped (100%) and VGII (99.2%) isolates; for flucytosine, 4 μg/ml for C. gattii nontyped (96.4%) and VGI (95.7%) isolates, 8 μg/ml for VNI (96.6%) isolates, and 16 μg/ml for C. neoformans nontyped (98.6%) and C. gattii VGII (97.1%) isolates. Other molecular types had apparent variations in MIC distributions, but the number of laboratories contributing data was too low to allow us to ascertain that the differences were due to factors other than assay variation. ECVs may aid in the detection of isolates with acquired resistance mechanisms.
Endometriosis is the most common gynecological diagnosis among women with chronic pelvic pain, but the underlying mechanisms of endometriosis-associated chronic pelvic pain remain unclear. Therefore, the objective of this study was to determine the biopsychosocial predictors of pain improvement among women with endometriosis.
One hundred and fifteen women who presented for treatment of endometriosis-associated chronic pelvic pain at a tertiary referral center at a university-based hospital participated in this prospective observational study of clinical practice. Participants completed questionnaires assessing pain, mental health and catastrophizing at entry and 1 year follow-up. The main outcome measure assessed was the interval change in pain report using the McGill pain 1uestionnaire.
On average, participants experienced a 37.4% reduction in interval pain (P < 0.001). Adjusted for baseline pain, nulliparity (P = 0.002) and catastrophizing (P = 0.04) were associated with decreased probability of interval improvement in pain. Those referred for physical therapy had less interval pain improvement (P = 0.04). However, undergoing hysterectomy was a strong predictor of improvement in pain (P = 0.008).
Our study suggests that chronic pain in endometriosis may be more akin to other idiopathic pain disorders. Specifically, biopsychosocial variables, such as catastrophizing, play an important role in reported severity. Further research on biopsychosocial correlates of chronic pelvic pain in endometriosis is warranted.
chronic pelvic pain; endometriosis; catastrophizing; pain-related outcomes; psychological factors
The purpose of this qualitative systematic review was to explicate attributes of optimal therapeutic strategies for treating incarcerated women who have a history of substance abuse. An expansive search of electronic databases for qualitative research reports relating to substance abuse treatment for incarcerated women was conducted. Nine qualitative research reports comprised the sample for this review. Findings from these reports were extracted, placed into a data analysis matrix, coded, and categorized. Memos were written, and strategies for treating incarcerated women with alcohol problems were identified. Therapeutic effects of treatment programs for incarcerated women with substance-abuse problems appear to be enhanced when trust-based relationships are established, individualized and just care is provided, and treatment facilities are separate from the general prison environment.
Incarceration; substance abuse treatment; systematic review; therapeutic communities; women
The dog leukocyte antigen (DLA) system contains many of the functional genes of the immune system, thereby making it a candidate region for involvement in immune-mediated disorders. A number of studies have identified associations between specific DLA class II haplotypes and canine immune hemolytic anemia, thyroiditis, immune polyarthritis, type I diabetes mellitus, hypoadrenocorticism, systemic lupus erythematosus-related disease complex, necrotizing meningoencephalitis (NME) and anal furunculosis. These studies have relied on sequencing approximately 300 bases of exon 2 of each of the DLA class II genes: DLA-DRB1, DLA-DQA1 and DLA-DQB1. An association (odds ratio = 4.29) was identified by this method between Weimaraner dogs with hypertrophic osteodystrophy (HOD) and DLA-DRB1*01501.
In the present study, a genotyping assay of 126 coding single nucleotide polymorphisms (SNPs) from across the entire DLA, spanning a region of 2.5 Mb (3,320,000–5,830,000) on CFA12, was developed and tested on Weimaraners with HOD, as well as two additional breeds with diseases associated with DLA class II: Nova Scotia duck tolling retrievers with hypoadrenocorticism and Pug dogs with NME. No significant associations were found between Weimaraners with HOD or Nova Scotia duck tolling retrievers with hypoadrenocorticism and SNPs spanning the DLA region. In contrast, significant associations were found with NME in Pug dogs, although the associated region extended beyond the class II genes. By including a larger number of genes from a larger genomic region a SNP genotyping assay was generated that provides coverage of the extended DLA region and may be useful in identifying and fine mapping DLA associations in dogs.
Canine; Inherited disorders; Major histocompatibility complex (MHC); Dog leukocyte antigen (DLA); Disease associations
Viruses hijack host cell functions and optimize them for viral replication causing a severe threat to human health. However, viruses are also tools to understand cell biology and they may be effective reagents in nano-medicine. Studies from the molecular to cellular levels are aimed at understanding the details of viral life cycles and the underlying virus-host interactions. Recent developments in electron microscopy tomography allow viral and cellular events to be observed in fine structural detail in three-dimension. By combining high-resolution structures of individual proteins and macro-complexes obtained by crystallography and electron cryo-microscopy and image reconstruction with reconstructions performed on sub-tomographic volumes, electron tomography has advanced the structural and mechanistic understanding of virus infections both in vitro and in host cells.
Electron tomography; Virus
Although clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available for Aspergillus spp. versus the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for six Aspergillus spp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those for A. fumigatus (3,988/833), A. flavus (793/194), A. nidulans (184/69), A. niger (673/140), A. terreus (545/266), and A. versicolor (135/22). Three sets of data were analyzed: (i) CLSI data gathered in eight independent laboratories in Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory; and (iii) the combined CLSI and EUCAST data. ECVs, expressed in μg/ml, that captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and combined data) were as follows: for A. fumigatus, 2, 2, and 4; for A. flavus, 2, 4, and 4; for A. nidulans, 4, 4, and 4; for A. niger, 2, 2, and 2; for A. terreus, 4, 4, and 8; and for A. versicolor, 2, 2, and 2. Similar to the case for the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of strains with acquired mechanisms of resistance to this agent.
To define a clinical syndrome associated with active drug abuse in HIV-infected individuals.
We performed a retrospective review to identify individuals treated at the Johns Hopkins Hospital from 1993 to 2008 who were HIV-infected and were actively abusing drugs and had bilateral basal ganglia lesions on MRI. They were identified using a key word search in the radiology database, autopsy database, and the Moore HIV clinic database. Clinical, laboratory, and radiographic findings were correlated to define the syndrome.
Ten individuals were identified who presented with a change in mental status or seizures, used cocaine or cocaine with heroin, had uncontrolled HIV infection (>190,000 copies/mL of plasma), elevated CSF protein (63–313 mg/dL), and diffuse hyperintense bilateral basal ganglia lesions on imaging. The majority of patients (8/10) had renal failure and despite supportive therapy most (7/9) ultimately died (median survival 21 days). Postmortem examination in one individual showed the presence of overwhelming microglial activation in the basal ganglia. The 2 surviving individuals were started on combined antiretroviral therapy (CART) during hospitalization.
We describe a unique clinical syndrome of a fulminant encephalopathy associated with primarily basal ganglia involvement in HIV-infected drug abusers. This syndrome is a rare but serious condition that is associated with a high mortality rate. Early CART institution may be useful and neuroprotective in this disorder, although this requires further investigation.
Botulism, a disease of humans characterized by prolonged paralysis, is caused by botulinum neurotoxins (BoNTs), the most poisonous substances known. There are seven serotypes of BoNT (A–G) which differ from each other by 34–64% at the amino acid level. Each serotype is uniquely recognized by polyclonal antibodies, which originally were used to classify serotypes. To determine if there existed monoclonal antibodies (mAbs) capable of binding two or more serotypes, we evaluated the ability of 35 yeast-displayed single-chain variable fragment antibodies generated from vaccinated humans or mice for their ability to bind multiple BoNT serotypes. Two such clonally related human mAbs (1B18 and 4E17) were identified that bound BoNT serotype A (BoNT/A) and B or BoNT/A, B, E and F, respectively, with high affinity. Using molecular evolution techniques, it proved possible to both increase affinity and maintain cross-serotype reactivity for the 4E17 mAb. Both 1B18 and 4E17 bound to a relatively conserved epitope at the tip of the BoNT translocation domain. Immunoglobulin G constructed from affinity matured variants of 1B18 and 4E17 were evaluated for their ability to neutralize BoNT/B and E, respectively, in vivo. Both antibodies potently neutralized BoNT in vivo demonstrating that this epitope is functionally important in the intoxication pathway. Such cross-serotype binding and neutralizing mAbs should simplify the development of antibody-based BoNT diagnostics and therapeutics.
botulism; botulinum neurotoxin; molecular evolution; single-chain Fv; yeast display
Although Clinical and Laboratory Standards Institute (CLSI) disk diffusion assay standard conditions are available for susceptibility testing of filamentous fungi (molds) to antifungal agents, quality control (QC) disk diffusion zone diameter ranges have not been established. This multicenter study documented the reproducibility of tests for one isolate each of five molds (Paecilomyces variotii ATCC MYA-3630, Aspergillus fumigatus ATCC MYA-3626, A. flavus ATCC MYA-3631, A. terreus ATCC MYA-3633, and Fusarium verticillioides [moniliforme] ATCC MYA-3629) and Candida krusei ATCC 6258 by the CLSI disk diffusion method (M51-A document). The zone diameter ranges for selected QC isolates were as follows: P. variotii ATCC MYA-3630, amphotericin B (15 to 24 mm), itraconazole (20 to 31 mm), and posaconazole (33 to 43 mm); A. fumigatus ATCC MYA-3626, amphotericin B (18 to 25 mm), itraconazole (11 to 21 mm), posaconazole (28 to 35 mm), and voriconazole (25 to 33 mm); and C. krusei, amphotericin B (18 to 27 mm), itraconazole (18 to 26 mm), posaconazole (28 to 38 mm), and voriconazole (29 to 39 mm). Due to low testing reproducibility, zone diameter ranges were not proposed for the other three molds.
This systematic review was conducted to more fully analyze qualitative research findings relating to community-based court-supervised substance abuse treatment for women and to make recommendations regarding treatment enhancement. Five reports of qualitative research met the inclusion criteria. Findings from these reports were extracted and analyzed using constant comparative methods. Women who are referred to court-sanctioned substance abuse treatment programs may initially be reluctant to participate. Once engaged, however, they advocate for a full complement of well-financed comprehensive services. To optimize treatment effectiveness, women recommend gender-specific programs in which ambivalence is diminished, hope is instilled, and care is individualized.
Court-mandated; criminal justice; substance abuse treatment; rehabilitation; women
Clinical breakpoints have not been established for mold testing. Epidemiologic cutoff values (ECVs) are available for six Aspergillus spp. and the triazoles, but not for caspofungin. Wild-type (WT) minimal effective concentration (MEC) distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for six Aspergillus spp. and caspofungin. The number of available isolates was as follows: 1,691 A. fumigatus, 432 A. flavus, 192 A. nidulans, 440 A. niger, 385 A. terreus, and 75 A. versicolor isolates. CLSI broth microdilution MEC data gathered in five independent laboratories in Canada, Europe, and the United States were aggregated for the analyses. ECVs expressed in μg/ml that captured 95% and 99% of the modeled wild-type population were for A. fumigatus 0.5 and 1, A. flavus 0.25 and 0.5, A. nidulans 0.5 and 0.5, A. niger 0.25 and 0.25, A. terreus 0.25 and 0.5, and A. versicolor 0.25 and 0.5. Although caspofungin ECVs are not designed to predict the outcome of therapy, they may aid in the detection of strains with reduced antifungal susceptibility to this agent and acquired resistance mechanisms.
The relationships between lifestyle behaviors of diet, smoking and physical activity and the subsequent prevalence of age-related macular degeneration (AMD) were investigated.
The population included 1,313 participants (55 to 74 years) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study (WHIOS). Scores on a modified 2005 Healthy Eating Index (mHEI) were assigned using responses to a food frequency questionnaire administered at WHIOS baseline (1994-1998). Physical activity and lifetime smoking history were queried. An average of six years later, stereoscopic fundus photographs were taken to assess presence and severity of AMD; present in 202 women, 94% of whom had early AMD, the primary outcome.
In multivariate models, women whose diets scored in the highest compared with the lowest quintile on the mHEI had a 46% lower odds for early AMD. Women in the highest vs. lowest quintile for physical activity (MET- Hrs/Wk) had 54% lower odds for early AMD. Although smoking, alone was not independently associated with AMD, having a combination of three healthy lifestyles (healthy diet, physical activity and not smoking) was associated with a 71% lower odds for AMD compared with having high risk scores (P=0.0004).
Modifying lifestyles might reduce risk for early AMD as much as 3-fold, lowering the risk for advanced AMD in a person's lifetime and the social and economic costs of AMD to society.
Clinical breakpoints have not been established for mold testing. Wild-type (WT) MIC distributions (organisms in a species/drug combination with no detectable acquired resistance mechanisms) were defined in order to establish epidemiologic cutoff values (ECVs) for five Aspergillus spp. and itraconazole, posaconazole, and voriconazole. Also, we have expanded prior ECV data for Aspergillus fumigatus. The number of available isolates varied according to the species/triazole combination as follows: 1,684 to 2,815 for A. fumigatus, 323 to 592 for A. flavus, 131 to 143 for A. nidulans, 366 to 520 for A. niger, 330 to 462 for A. terreus, and 45 to 84 for A. versicolor. CLSI broth microdilution MIC data gathered in five independent laboratories in Europe and the United States were aggregated for the analyses. ECVs expressed in μg/ml were as follows (percentages of isolates for which MICs were equal to or less than the ECV are in parentheses): A. fumigatus, itraconazole, 1 (98.8%); posaconazole, 0.5 (99.2%); voriconazole, 1 (97.7%); A. flavus, itraconazole, 1 (99.6%); posaconazole, 0.25 (95%); voriconazole, 1 (98.1%); A. nidulans, itraconazole, 1 (95%); posaconazole, 1 (97.7%); voriconazole, 2 (99.3%); A. niger, itraconazole, 2 (100%); posaconazole, 0.5 (96.9%); voriconazole, 2 (99.4%); A. terreus, itraconazole, 1 (100%); posaconazole, 0.5 (99.7%); voriconazole, 1 (99.1%); A. versicolor, itraconazole, 2 (100%); posaconazole, 1 (not applicable); voriconazole, 2 (97.5%). Although ECVs do not predict therapy outcome as clinical breakpoints do, they may aid in detection of azole resistance (non-WT MIC) due to cyp51A mutations, a resistance mechanism in some Aspergillus spp. These ECVs should be considered for inclusion in the future CLSI M38-A2 document revision.
We report the repeated isolation of the fungus Geosmithia argillacea from sputum samples of people with cystic fibrosis. Identification was based on morphology and DNA sequence analysis. Isolation of G. argillacea did not appear to be associated with clinical deterioration. The pathogenic potential of G. argillacea is discussed.
Current research efforts have mainly concentrated on evaluating the role of substances present in animal food in the aetiology of chronic diseases in humans, with relatively little attention given to evaluating the role of transmissible agents that are also present. Meat workers are exposed to a variety of transmissible agents present in food animals and their products. This study investigates mortality from non-malignant diseases in workers with these exposures.
A cohort mortality study was conducted between 1949 and 1989, of 8520 meat workers in a union in Baltimore, Maryland, who worked in manufacturing plants where animals were killed or processed, and who had high exposures to transmissible agents. Mortality in meat workers was compared with that in a control group of 6081 workers in the same union, and also with the US general population. Risk was estimated by proportional mortality and standardised mortality ratios (SMRs) and relative SMR.
A clear excess of mortality from septicaemia, subarachnoid haemorrhage, chronic nephritis, acute and subacute endocarditis, functional diseases of the heart, and decreased risk of mortality from pre-cerebral, cerebral artery stenosis were observed in meat workers when compared to the control group or to the US general population.
The authors hypothesise that zoonotic transmissible agents present in food animals and their products may be responsible for the occurrence of some cases of circulatory, neurological and other diseases in meat workers, and possibly in the general population exposed to these agents.
Antifungal susceptibility testing of Aspergillus species has been standardized by both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recent studies suggest the emergence of strains of Aspergillus fumigatus with acquired resistance to azoles. The mechanisms of resistance involve mutations in the cyp51A (sterol demethylase) gene, and patterns of azole cross-resistance have been linked to specific mutations. Studies using the EUCAST broth microdilution (BMD) method have defined wild-type (WT) MIC distributions, epidemiological cutoff values (ECVs), and cross-resistance among the azoles. We tested a collection of 637 clinical isolates of A. fumigatus for which itraconazole MICs were ≤2 μg/ml against posaconazole and voriconazole using the CLSI BMD method. An ECV of ≤1 μg/ml encompassed the WT population of A. fumigatus for itraconazole and voriconazole, whereas an ECV of ≤0.25 μg/ml was established for posaconazole. Our results demonstrate that the WT distribution and ECVs for A. fumigatus and the mold-active triazoles were the same when determined by the CLSI or the EUCAST BMD method. A collection of 43 isolates for which itraconazole MICs fell outside of the ECV were used to assess cross-resistance. Cross-resistance between itraconazole and posaconazole was seen for 53.5% of the isolates, whereas cross-resistance between itraconazole and voriconazole was apparent in only 7% of the isolates. The establishment of the WT MIC distribution and ECVs for the azoles and A. fumigatus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.
The area burned in the North American boreal forest is controlled by the frequency of mid-tropospheric blocking highs that cause rapid fuel drying. Climate controls the area burned through changing the dynamics of large-scale teleconnection patterns (Pacific Decadal Oscillation/El Niño Southern Oscillation and Arctic Oscillation, PDO/ENSO and AO) that control the frequency of blocking highs over the continent at different time scales. Changes in these teleconnections may be caused by the current global warming. Thus, an increase in temperature alone need not be associated with an increase in area burned in the North American boreal forest. Since the end of the Little Ice Age, the climate has been unusually moist and variable: large fire years have occurred in unusual years, fire frequency has decreased and fire–climate relationships have occurred at interannual to decadal time scales. Prolonged and severe droughts were common in the past and were partly associated with changes in the PDO/ENSO system. Under these conditions, large fire years become common, fire frequency increases and fire–climate relationships occur at decadal to centennial time scales. A suggested return to the drier climate regimes of the past would imply major changes in the temporal dynamics of fire–climate relationships and in area burned, a reduction in the mean age of the forest, and changes in species composition of the North American boreal forest.
Alaska; area burned by wildfire; Canada; climate change; Pacific Decadal Oscillation; Arctic Oscillation
We assessed whether a novel programme to evaluate/communicate predicted coronary heart disease (CHD) risk could lower patients' predicted Framingham CHD risk vs. usual care.
The Risk Evaluation and Communication Health Outcomes and Utilization Trial was a prospective, controlled, cluster-randomised trial in nine European countries, among patients at moderate cardiovascular risk. Following baseline assessments, physicians in the intervention group calculated patients' predicted CHD risk and were instructed to advise patients according to a risk evaluation/communication programme. Usual care physicians did not calculate patients' risk and provided usual care only. The primary end-point was Framingham 10-year CHD risk at 6 months with intervention vs. usual care.
Of 1103 patients across 100 sites, 524 patients receiving intervention, and 461 receiving usual care, were analysed for efficacy. After 6 months, mean predicted risks were 12.5% with intervention, and 13.7% with usual care [odds ratio = 0.896; p = 0.001, adjusted for risk at baseline (17.2% intervention; 16.9% usual care) and other covariates]. The proportion of patients achieving both blood pressure and low-density lipoprotein cholesterol targets was significantly higher with intervention (25.4%) than usual care (14.1%; p < 0.001), and 29.3% of smokers in the intervention group quit smoking vs. 21.4% of those receiving usual care (p = 0.04).
A physician-implemented CHD risk evaluation/communication programme improved patients' modifiable risk factor profile, and lowered predicted CHD risk compared with usual care. By combining this strategy with more intensive treatment to reduce residual modifiable risk, we believe that substantial improvements in cardiovascular disease prevention could be achieved in clinical practice.