Papers by Borislav Dimitrov
Introduction: Components other than the active
ingredients of treatment can have substantial effe... more Introduction: Components other than the active
ingredients of treatment can have substantial effects on
pain and disability. Such ‘non-specific’ components
include: the therapeutic relationship, the healthcare
environment, incidental treatment characteristics,
patients’ beliefs and practitioners’ beliefs. This study
aims to: identify the most powerful non-specific
treatment components for low back pain (LBP),
compare their effects on patient outcomes across
orthodox (physiotherapy) and complementary
(osteopathy, acupuncture) therapies, test which
theoretically derived mechanistic pathways explain the
effects of non-specific components and identify
similarities and differences between the therapies on
patient–practitioner interactions.
Methods and analysis: This research comprises a
prospective questionnaire-based cohort study with a
nested mixed-methods study. A minimum of 144
practitioners will be recruited from public and private
sector settings (48 physiotherapists, 48 osteopaths
and 48 acupuncturists). Practitioners are asked to
recruit 10–30 patients each, by handing out invitation
packs to adult patients presenting with a new episode
of LBP. The planned multilevel analysis requires a
final sample size of 690 patients to detect correlations
between predictors, hypothesised mediators and the
primary outcome (self-reported back-related disability
on the Roland-Morris Disability Questionnaire).
Practitioners and patients complete questionnaires
measuring non-specific treatment components,
mediators and outcomes at: baseline (time 1: after
the first consultation for a new episode of LBP),
during treatment (time 2: 2 weeks post-baseline)
and short-term outcome (time 3: 3 months postbaseline).
A randomly selected subsample of
participants in the questionnaire study will be invited
to take part in a nested mixed-methods study of
patient–practitioner interactions. In the nested
study, 63 consultations (21/therapy) will be audiorecorded
and analysed quantitatively and qualitatively.
Background: The subclinical cerebrovascular disease (SCVD) is an important public health problem ... more Background: The subclinical cerebrovascular disease (SCVD) is an important public health problem with demonstrated prognostic significance for stroke, future cognitive decline, and progression to dementia. The earliest possible detection of the silent presence of SCVD in adults at age at risk with normal functioning is very important for both clinical doctors and scientists.
European journal of dermatology : EJD, Jan 22, 2015
Emergency Medicine Journal, 2015
The objective of this study was to externally validate a clinical prediction rule (CPR)-the &... more The objective of this study was to externally validate a clinical prediction rule (CPR)-the 'Shapiro criteria'-to predict bacteraemia in an acute medical unit (AMU). Prospectively collected data, retrospectively evaluated over 11 months in an AMU in the UK. From 4810 admissions, 635 patients (13%) had blood cultures (BCs) performed. The 100 cases of true bacteraemia were compared with a randomly selected sample of 100 control cases where BCs were sterile. To predict bacteraemia (at a cut-off score of two points), the Shapiro criteria had a sensitivity of 97% (95% CIs 91% to 99%), specificity 37% (28% to 47%), positive likelihood ratio 1.54 (1.3 to 1.8) and a negative likelihood ratio of 0.08 (0.03 to 0.25). The area under the receiver operating curve was 0.80 (0.74 to 0.86), and the Hosmer-Lemeshow p value was 0.45. A cut-off score of two points on the Shapiro criteria had high sensitivity to predict bacteraemia in a study of acute general medical admissions. Application of the rule in patients being considered for a BC could identify those at low risk of bacteraemia. Though the model demonstrated good discrimination, the lengthy number of variables (13) and difficulty automating the CPR may limit its use.
International Journal of Low Radiation, 2009
... Radostina Georgieva* Department of Radiobiology National Centre of Radiobiology and Radiation... more ... Radostina Georgieva* Department of Radiobiology National Centre of Radiobiology and Radiation Protection Ministry of Health 132 Kliment Ohridski Blvd., Sofia 1756, Bulgaria E-mail: [email protected] *Corresponding author Ilona Guleva ...
The authors present a novel approach to develop scalable systems and services for preserving digi... more The authors present a novel approach to develop scalable systems and services for preserving digital content generated from various application domains. The aim is to deliver an integrative scalable approach for digital content preservation across domain verticals. This would involve consolidating approaches for modeling document workflow, preserving the integrity of heterogeneous data, and developing robust and scalable tools for digital
The journal of family planning and reproductive health care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists, Jan 10, 2015
To assess the feasibility and acceptability of screening attendees at a sexual health clinic (SHC... more To assess the feasibility and acceptability of screening attendees at a sexual health clinic (SHC) for alcohol misuse, and delivering a brief intervention (BI). To explore the effect of this BI on drinking and sexual behaviour. A consecutive sample of consenting SHC attendees aged ≥16 years were screened using Alcohol Use Disorders Identification Test Consumption (AUDIT-C). Men scoring ≥5 and women scoring ≥4 were invited to complete the full AUDIT, alcohol diary and baseline questionnaire. Participants were randomised to receive BI by a trained sexual health professional or a standard alcohol leaflet (usual care, UC). All were followed up for changes in alcohol and sexual behaviour at 6 weeks and 6 months. A fidelity check and staff focus group were undertaken. Of 664 participants screened, 215 (32%) were eligible for randomisation and 207 were included in the final analysis: 103 (BI) and 104 (UC). Follow-up rates were 54% and 47% at 6 weeks and 6 months, respectively. Both groups ...
The Lancet, 2015
Incomplete understanding of mechanisms and clinicopathobiological heterogeneity in asthma hinders... more Incomplete understanding of mechanisms and clinicopathobiological heterogeneity in asthma hinders research progress. Pathogenic roles for T-helper-type 17 (Th17) cells and invariant T cells implied by murine data have yet to be assessed in man. We aimed to investigate the role of Th17 and mucosal associated invariant T (MAIT) cells in airway inflammation; to characterise associations between diverse clinical and immunological features of asthma; and to identify novel multidimensional asthma endotypes. In this single-centre, cross-sectional observational study in the UK, we assessed volunteers with mild-to-severe asthma and healthy non-atopic controls using clinical and physiological assessment and immunological sampling of blood, induced sputum, endobronchial biopsy, and bronchoalveolar lavage for flow cytometry and multiplex-electrochemiluminescence assays. Primary outcomes were changes in frequencies of Th17 and MAIT cells between health and asthma using Mann-Whitney U tests and the Jonckheere-Terpstra test (linear trend across ranked groups). The study had 80% power to detect 60% differences in T-cell frequencies at p<0·05. Bayesian Network Analysis (BNA) was used to explore associations between parameters. Topological Data Analysis (TDA) was used to identify multidimensional endotypes. The study had local research ethics approval. All participants provided informed consent. Participants were 84 male and female volunteers (60 with mild-to-severe asthma and 24 healthy, non-atopic controls) aged 18-70 years recruited from clinics and research cohorts. Th17 cells and γδ17 cells were not associated with asthma, even in severe neutrophilic forms. MAIT-cell frequencies were strikingly reduced in asthma compared with health (median frequency in blood 0·9% of CD3+ cells [IQR 0·3-1·8] in asthma vs 1·6 [1·2-2·6] in health, p=0·005; in sputum 1·1 [0·7-2·0] vs 1·8 [1·6-2·3], p=0·002; and in biopsy samples 1·3 [0·7-2·3] vs 3·9% [1·3-5·3%], p=0·02), especially in severe asthma where BAL regulatory T cells were also reduced compared with those in health (4·4, 3·1-6·1, vs 8·1, 5·6-10; p=0·02). BNA and TDA identified six novel clinicopathobiological clusters of underlying disease mechanisms, with elevated mast cell mediators tryptase (p<0·0001), chymase (p=0·02), and carboxypeptidase A3 (p=0·02) in severe asthma. This study suggests that Th17 cells do not have a major pathogenic role in human asthma. We describe a novel deficiency of MAIT cells in severe asthma. We also provide proof of concept for application of TDA to identification of multidimensional clinicopathobiological endotypes. Endotypes will require validation in further cohorts. Wellcome Trust.
Annals of family medicine, 2014
We describe the methodology used to create a register of clinical prediction rules relevant to pr... more We describe the methodology used to create a register of clinical prediction rules relevant to primary care. We also summarize the rules included in the register according to various characteristics. To identify relevant articles, we searched the MEDLINE database (PubMed) for the years 1980 to 2009 and supplemented the results with searches of secondary sources (books on clinical prediction rules) and personal resources (eg, experts in the field). The rules described in relevant articles were classified according to their clinical domain, the stage of development, and the clinical setting in which they were studied. Our search identified clinical prediction rules reported between 1965 and 2009. The largest share of rules (37.2%) were retrieved from PubMed. The number of published rules increased substantially over the study decades. We included 745 articles in the register; many contained more than 1 clinical prediction rule study (eg, both a derivation study and a validation study)...
Arthritis Care & Research, 2015
Objective. To investigate whether a strategy combining clinical and ultrasound (US) assessment ca... more Objective. To investigate whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti-tumor necrosis factor (anti-TNF) therapies. Methods. As part of a real-world approach, patients with RA receiving anti-TNF therapies were reviewed in a dedicated biologic therapy clinic. Patients not taking oral corticosteroids with both Disease Activity Score in 28 joints (DAS28) remission (£2.6) and absent synovitis on power Doppler US (PDUS 0) for >6 months were invited to reduce their anti-TNF therapy dose by one-third. Results. Between January 2012 and February 2014, a total of 70 patients underwent anti-TNF dose reduction. Combined DAS28 and PDUS remission was maintained by 96% of patients at 3 months followup, 63% at 6 months, 37% at 9 months, and 34% at 18 months followup. However, 88% of patients maintained at least low disease activity (LDA) with DAS28 <3.2 and PDUS £1 at 6 months. The addition of PDUS identified 8 patients (25% of those that flared) in DAS28 remission, with subclinically active disease. Those who maintained dose reduction were more likely to be rheumatoid factor (RF) negative (46% versus 17%; P 5 0.03) and have lower DAS28 scores at biologic therapy initiation (5.58 versus 5.96; P 5 0.038). Conclusion. Combined clinical and US assessment identifies individuals in remission who may be suitable for anti-TNF dose reduction and enhances safe monitoring for subclinical disease flares. Despite longstanding severe RA, a subset of our cohort sustained prolonged DAS28 and PDUS remission. LDA at biologic therapy initiation and RF status appeared predictive of sustained remission.
PLOS ONE, 2015
Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathog... more Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers.
Ophthalmology, 2015
ABSTRACT This study aimed to compare VA measured by Tumbling-E and Landolt-C charts with the gold... more ABSTRACT This study aimed to compare VA measured by Tumbling-E and Landolt-C charts with the gold standard ETDRS charts, thus helping to standardize clinical data across populations not using the Roman alphabet, such as many of those native to eastern Europe, the Middle East, Indian subcontinent, and Asia, as well as people using Latin languages who may be illiterate, particularly in the developing world. Patients presenting at a community ophthalmology practice were invited to participate; 112 patients with an average age of 63 years (range 18-87) were recruited. The analysis included 221 eyes, almost one-half (48.9%) were healthy and various pathologic conditions affected remaining eyes (Table 1, available at www.aaojournal.org). Three low-vision eyes were excluded because no ETDRS optotypes could be determined at 1 meter. Patients were refracted according to the Age-related Eye Disease Study (AREDS) Manual of Procedures.4 Vision was tested using ETDRS, Landolt-C, and Tumbling-E charts, with separate versions of each for right and left eyes (Precision Vision, La Salle, IL; CAT Nos: 2122, 2123, 2210, 2210A, 2305, and 2305A). Charts were mounted in a retro-illuminated cabinet with luminance of 85 cd/m2 (Precision Vision; CAT No: 2425). The order of chart presentation was randomized and instructions to patients and VA scoring were in accordance with the AREDS manual, with minor modifications allowing for the Landolt-C and Tumbling-E charts. Institutional ethics committee approval was granted by Trinity College Dublin Research Ethics Committee.
Archives of Medical Science, 2015
Central European Journal of Biology, 2010
Best available descriptions of malaria incidence and mortality dynamics are important to improve ... more Best available descriptions of malaria incidence and mortality dynamics are important to improve and evaluate the implementation of programs to monitor (e.g., remote sensing) and control disease, especially in endemic zones. High-frequency (e.g., semi-annual and seasonal) cycles in malaria incidence have been observed in various countries and they coincide with cycles in the natural environment (e.g., temperature, heliogeophysical activity, etc.). However, neither trend nor cyclical oscillations beyond a 6-month (0.5-year) period for this vector-borne disease were reported in a recent analysis on monthly notifications in Burundi for the years 1997-2003. Since the examination of graphical plots indicated an eventual existence of trans-year (multiannual) variations, we further analyzed the same data in more detail. Here we explore whether low-frequency cycles (beyond seasonality) might exist (e.g., trans-year cycles with periods of 13-24 months or longer). Monthly incidence rate per 100 inhabitants from the Province of Karuzi, Burundi, over the years 1997-2003 was analysed. The exploration of underlying chronomes (time structures) was done by linear and non-linear parametric regression models, autocorrelation, spectral analysis (e.g., fast Fourier transforms) , periodogram regression analysis (PRA) and wavelet transform (WT). By using a periodogram regression analysis, we describe a multicomponent cyclic chronome with periods T>12 months (19 and 86 months, all at P<0.05). Notably, the strongest cyclic pattern in the periodogram of the detrended malaria rates (whereas the peak was suppressed and beyond the semi-annual cycle of 6 months) was ≈1.5-1.6 years (T=19.0 months, R=0.32). A dynamic pattern of "shortening" of the length (period) of the cycles was observed during the pre-epidemic interval (from 8-9 to 5-6 months and from 20-22 to 16-18 months in years 1997-2000) that can be used to anticipate a forthcoming incidence increase and epidemic levels of malaria at a regional level. Indeed, these cycles in malaria incidence correspond to cyclic components of heliogeophysical activity (HGA) such as the sunspot cycle impulses of 0.5-2.0 years as well as the quasi-biennial solar magnetic cycle of 1.5-2.5 years and further, detailed analyses are warranted to investigate such relationships. A multicomponent dynamic cyclical pattern of malaria incidence variations in Burundi (1997Burundi ( -2003 exists thus allowing further, more specific analyses and modelling as well as correlations with similar environmental cycles to be explored. These results might also contribute to better estimates for forecasting, prevention and understanding of malaria dynamics and aetiology.
Thrombosis and Haemostasis, 2011
The Surgeon, 2014
The association of leg length discrepancy (LLD) with a number of clinical disorders has made its ... more The association of leg length discrepancy (LLD) with a number of clinical disorders has made its determination a significant part of the physical examination. We believe that submalleolar causes of LLD may be under-acknowledged. The most common clinical method used to measure LLD is by tape from the anterior superior iliac spine (ASIS) to medial malleolus which disregards the potential for LLD arising from asymmetry in the foot distal to the tibiotalar joint. The present pilot study involves a group of 5 volunteers (experimental group) and a group of 3 patients with flexible flat feet (clinical study). The differences in tibial tubercle height from the ground between full pronation and full supination were measured using the CODA MPX 30(®) system (Charnwood Dynamics Limited, Leicestershire, England). Correlations of the patterns within each group were produced. A significant relationship with leg lengths was found in the experimental group when they induced maximum pronation (R-squared = 0.62, p = 0.007) while an inverse relationship occurred with supination, although marginally significant (R-squared = 0.37, p = 0.064). We have demonstrated that significant leg length discrepancy can occur in patients who do not have obvious deformity when non weight bearing. We recommend using the blocks method routinely. Appropriately measuring LLD is of vital importance to properly diagnosing and treating patients with unequal leg lengths or related symptoms.
New England Journal of Medicine, 2012
Women with cystic fibrosis are at increased risk for mucoid conversion of Pseudomonas aeruginosa,... more Women with cystic fibrosis are at increased risk for mucoid conversion of Pseudomonas aeruginosa, which contributes to a sexual dichotomy in disease severity.
Journal of the American Society of Nephrology, 2007
The Mycophenolate Steroids Sparing (MYSS) study found that in renal transplant recipients who wer... more The Mycophenolate Steroids Sparing (MYSS) study found that in renal transplant recipients who were on immunosuppressive therapy with the cyclosporine microemulsion Neoral, mycophenolate mofetil (MMF) was not better than azathioprine in preventing acute rejection at 21 mo after transplantation and was 15 times more expensive. The MYSS Follow-up Study, an extension of MYSS, was aimed at comparing long-term outcome of 248 MYSS patients according to their original randomization to MMF (1 g twice daily) or azathioprine (75 to 100 mg/d). Primary outcome was estimated GFR at 5 yr after transplantation. Mean 5-yr GFR difference between azathioprine and mycophenolate was 4.67 ml/min per 1.73 m 2 (95% confidence interval [CI] ؊0.43 to 9.77 ml/min per 1.73 m 2 ; P ؍ 0.07). GFR from month 6 (mean ؎ SEM: 54.3 ؎ 1.6 versus 53.9 ؎ 1.5 ml/min per 1.73 m 2 ; P ؍ 0.83) to month 72 after transplantation (49.5 ؎ 2.2 versus 47.3 ؎ 2.4 ml/min per 1.73 m 2 ; P ؍ 0.50); GFR slopes (mean ؎ SEM: ؊1.10 ؎ 0.56 versus ؊1.23 ؎ 0.31 ml/min per 1.73 m 2 per year; P ؍ 0.83); and 72-mo patient mortality (4.0 versus 4.0% [P ؍ 0.95]; HR 0.96; 95% CI 0.28 to 3.31; P ؍ 0.95), graft loss (6.8 versus 6.1% [P ؍ 0.82]; HR 0.89; 95% CI 0.32 to 2.46; P ؍ 0.83), incidence of persistent proteinuria (25.0 versus 27.4%; P ؍ 0.72), late (>6 mo after transplantation) rejections (25.3 versus 21.2%; P ؍ 0.53), and adverse events were similar on azathioprine (n ؍ 124) and MMF (n , respectively. Outcomes in the two groups were comparable also among patients with or without steroid therapy, considered separately. In kidney transplantation, the long-term risk/benefit profile of MMF and azathioprine therapy in combination with cyclosporine Neoral is similar. In view of the cost, standard immunosuppression regimens for kidney transplantation should perhaps include azathioprine rather than MMF.
Journal of Substance Abuse Treatment, 2011
This study aims to identify periods of elevated risk of drug related mortality during methadone m... more This study aims to identify periods of elevated risk of drug related mortality during methadone maintenance treatment (MMT) in primary care using a cohort of 3,162
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Papers by Borislav Dimitrov
ingredients of treatment can have substantial effects on
pain and disability. Such ‘non-specific’ components
include: the therapeutic relationship, the healthcare
environment, incidental treatment characteristics,
patients’ beliefs and practitioners’ beliefs. This study
aims to: identify the most powerful non-specific
treatment components for low back pain (LBP),
compare their effects on patient outcomes across
orthodox (physiotherapy) and complementary
(osteopathy, acupuncture) therapies, test which
theoretically derived mechanistic pathways explain the
effects of non-specific components and identify
similarities and differences between the therapies on
patient–practitioner interactions.
Methods and analysis: This research comprises a
prospective questionnaire-based cohort study with a
nested mixed-methods study. A minimum of 144
practitioners will be recruited from public and private
sector settings (48 physiotherapists, 48 osteopaths
and 48 acupuncturists). Practitioners are asked to
recruit 10–30 patients each, by handing out invitation
packs to adult patients presenting with a new episode
of LBP. The planned multilevel analysis requires a
final sample size of 690 patients to detect correlations
between predictors, hypothesised mediators and the
primary outcome (self-reported back-related disability
on the Roland-Morris Disability Questionnaire).
Practitioners and patients complete questionnaires
measuring non-specific treatment components,
mediators and outcomes at: baseline (time 1: after
the first consultation for a new episode of LBP),
during treatment (time 2: 2 weeks post-baseline)
and short-term outcome (time 3: 3 months postbaseline).
A randomly selected subsample of
participants in the questionnaire study will be invited
to take part in a nested mixed-methods study of
patient–practitioner interactions. In the nested
study, 63 consultations (21/therapy) will be audiorecorded
and analysed quantitatively and qualitatively.
ingredients of treatment can have substantial effects on
pain and disability. Such ‘non-specific’ components
include: the therapeutic relationship, the healthcare
environment, incidental treatment characteristics,
patients’ beliefs and practitioners’ beliefs. This study
aims to: identify the most powerful non-specific
treatment components for low back pain (LBP),
compare their effects on patient outcomes across
orthodox (physiotherapy) and complementary
(osteopathy, acupuncture) therapies, test which
theoretically derived mechanistic pathways explain the
effects of non-specific components and identify
similarities and differences between the therapies on
patient–practitioner interactions.
Methods and analysis: This research comprises a
prospective questionnaire-based cohort study with a
nested mixed-methods study. A minimum of 144
practitioners will be recruited from public and private
sector settings (48 physiotherapists, 48 osteopaths
and 48 acupuncturists). Practitioners are asked to
recruit 10–30 patients each, by handing out invitation
packs to adult patients presenting with a new episode
of LBP. The planned multilevel analysis requires a
final sample size of 690 patients to detect correlations
between predictors, hypothesised mediators and the
primary outcome (self-reported back-related disability
on the Roland-Morris Disability Questionnaire).
Practitioners and patients complete questionnaires
measuring non-specific treatment components,
mediators and outcomes at: baseline (time 1: after
the first consultation for a new episode of LBP),
during treatment (time 2: 2 weeks post-baseline)
and short-term outcome (time 3: 3 months postbaseline).
A randomly selected subsample of
participants in the questionnaire study will be invited
to take part in a nested mixed-methods study of
patient–practitioner interactions. In the nested
study, 63 consultations (21/therapy) will be audiorecorded
and analysed quantitatively and qualitatively.