Population-based Clinical Practice Research Datalink study using algorithm modelling to identify the true burden of hidradenitis suppurativa.

BACKGROUND: Epidemiology data regarding hidradenitis suppurativa (HS) are conflicting and prevalence estimates vary 80-fold, from 0·05% in a population-based study to 4%. OBJECTIVES: To assess the hypothesis that previous population-based studies underestimated true HS prevalence by missing undiagnosed cases. METHODS: We performed a population-based observational and case-control study using the U.K. Clinical Practice Research Datalink (CPRD) linked to hospital episode statistics data. Physician-diagnosed cases in the CPRD were identified from specific Read codes. Algorithms identified unrecognized 'proxy' cases, with at least five Read code records for boils in flexural skin sites. Validation of proxy cases was undertaken with general practitioner (GP) questionnaires to confirm criteria-diagnosed cases. A case-control study assessed disease associations. RESULTS: On 30 June 2013, 23 353 physician-diagnosed HS cases were documented in 4 364 308 research-standard records. In total, 68 890 proxy cases were identified, reduced to 10 146 criteria-diagnosed cases after validation, extrapolated from 107 completed questionnaires (61% return rate). Overall point prevalence was 0·77% [95% confidence interval (CI) 0·76-0·78%]. An additional 18 417 cases had a history of one to four flexural skin boils. In physician-diagnosed cases, odds ratios (ORs) for current smoker and obesity (body mass index > 30 kg m-2 ) were 3·61 (95% CI 3·44-3·79) and 3·29 (95% CI 3·14-3·45). HS was associated with type 2 diabetes, Crohn disease, hyperlipidaemia, acne and depression, and not associated with ulcerative colitis or polycystic ovary syndrome. CONCLUSIONS: Contrary to results of previous population-based studies, HS is relatively common, with a U.K. prevalence of 0·77%, one-third being unrecognized, criteria-diagnosed cases using the most stringent disease definition. If individuals with probable cases are included, HS prevalence rises to 1·19%.

The incidence of type 2 diabetes in the United Kingdom from 1991 to 2010.

AIMS: To characterize the incidence of type 2 diabetes in the UK over the previous 20 years; and determine if there has been an increase in people aged 40 years or less at diagnosis. METHODS: For this retrospective cohort study, patients newly diagnosed with type 2 diabetes between 1991 and 2010 were identified from the UK Clinical Practice Research Datalink (CPRD). Patient data were grouped into 5-year intervals by year of diagnosis and age at diagnosis. A standardized incidence ratio (SIR) was determined (1991-1995 = 100). The percentage of newly diagnosed patients for each age group and aged ≤40 years was calculated for each 5-year calendar period. The incidence rate by age and 5-year calendar period was also determined. RESULTS: In 2010, the crude incidence rate of type 2 diabetes was 515 per 100,000 population. The overall SIR increased to 158 (95% CI 157-160, p < 0.001), 237 (235-238, p < 0.001) and 275 (273-276, p < 0.001) for 1996-2000, 2001-2005 and 2006-2010, respectively. For those ≤40, the respective values were 217 (209-226, p < 0.001), 327 (320-335, p < 0.001) and 598 (589-608, p < 0.001). An increase in incidence occurred with increasing 5-year calendar period. The incidence of type 2 diabetes was higher for males after the age of 40 and higher for females aged ≤40. The percentage of patients aged ≤40 years at diagnosis increased with each increasing 5-year calendar period (5.9, 8.4, 8.5 and 12.4%, respectively). CONCLUSIONS: There was a significant increase in the incidence of diagnosed type 2 diabetes between 1991 and 2010 and the proportion of people diagnosed at a relatively early age has increased markedly.

The changing prevalence of diagnosed diabetes and its associated vascular complications in a large region of the UK.

AIMS: To characterize the prevalence of diabetes in a large health district in 2004 and compare it with a previous estimate made in 1996. METHODS: The study population comprised the resident population of Cardiff and the Vale of Glamorgan. Routine record linkage was used to identify patients from various sources of hospital and mortality data. Patients with diabetes were identified according to biochemistry test results, coding on routine data or attendance at a diabetes-related clinic. Diabetes-related complications were ascribed according to coding on routine data. RESULTS: It was possible to identify 17 088 people with diabetes alive on 1 January 2005. Of these patients, 9064 (53.0%) were male and 8024 (47.0%) were female. Mean age (+/- sd) was 59.6 +/- 18.9 years for males and 61.2 +/- 20.4 years for females. The crude prevalence of diabetes in 2005 was 3.9% (3.4% adjusted) compared with 2.5% in 1996 (2.3% adjusted). With the exception of females aged > or = 75 years, the prevalence of diabetes increased in all age- and sex-specific subgroups. Within the 2005 cohort, over two-thirds has no recorded complications compared with approximately one half of the 1996 cohort. The prevalence of individual complications decreased, with the exception of renal complications. CONCLUSIONS: The prevalence of identified diabetes appears to have increased substantially over a relatively short period of 9 years to 2004. The increase in prevalence was 46%, with an increase in numbers of patients with diabetes of 53%. A number of factors are likely to have contributed to this, including an increase in case ascertainment.

A novel inactivated vaccine against Lawsonia intracellularis induces rapid induction of humoral immunity, reduction of bacterial shedding and provides robust gut barrier function.

Porcine proliferative ileitis is a major economic burden for the swine industry, affecting growing pigs and young adult pigs. In this study, the protective efficacy of an inactivated, injectable whole-cell bacteria vaccine against L. intracellularis - Porcilis® Ileitis was evaluated under field conditions. Eighty-five, three-week-old pigs on a commercial farrow-to-finish farm were vaccinated by the intramuscular route, either with a dose of injectable vaccine, or with saline. A subset of vaccinates and control pigs were necropsied at 21 days post-challenge. Incidence and severity of ileitis were evaluated by gross and microscopic observation of ileal tissues. Colonization of the gut after challenge was examined by L. intracellularis-specific immunohistochemistry, and qPCR of ileal scrapings. Integrity of the intestinal barrier was evaluated to quantify a range of intestinal markers including secreted mucin and intestinal alkaline phosphatase, and innate immune markers including Caspase-3 and Calprotectin. A second subset of pigs was monitored for fecal shedding of L. intracellularis, until resolution of shedding. Our investigation indicated that Porcilis Ileitis provided robust protection against ileitis, reduced bacterial shedding 15-fold (p < .05) and preserved normal gut barrier function in the face of an experimental challenge with virulent L. intracellularis.

Conscious sedation services provided in secondary care for restorative dentistry in the UK: a survey.

OBJECTIVES: To assess the views of consultants in restorative dentistry on sedation services in secondary care for restorative dentistry and their involvement in the provision of this. DESIGN: Postal questionnaire survey in the UK. SETTING: Consultants in restorative dentistry. RESULTS: There was an 80% response rate from 179 consultants. Among consultants in restorative dentistry there was a perceived need for sedation services in restorative dentistry within NHS hospitals other than for teaching purposes. Anxiety and level of trauma of dental treatment affected whether consultants felt it appropriate for patients to have such treatment under sedation. One third (48) of consultants treated patients under conscious sedation, a significant number of these held NHS posts and had graduated more recently. Of those (41) who provided treatment under conscious sedation in an NHS setting, most (38, 93%) provided treatment under intravenous sedation of whom only eight (21%) acted as operator/sedationist. Nearly all consultants (135, 94%) felt that specialist registrars in restorative dentistry should undergo some form of training in sedation. CONCLUSIONS: Although consultants in restorative dentistry recognise the need for training in and the provision of sedation in secondary care for restorative dentistry, only one third of respondents currently provide this service.

Relationship between diabetes and mortality: a population study using record linkage.

OBJECTIVE: To determine patterns and causes of mortality for patients with diabetes in a district health authority RESEARCH DESIGN AND METHODS: The study used cross-sectional record linkage, combining an electronic death register with a diabetic patient register constructed from a variety of routine health data sources collected from 1991 to 1997. The study was conducted in Cardiff and the Vale of Glamorgan, Wales, U.K., and included all diabetic deaths between 1993 and 1996. RESULTS: Of 1,694 deaths in patients with known diabetes, only 674 (39.8%) had diabetes recorded as an immediate or antecedent cause of death. Mortality rates were 41.8 per 1,000 for the diabetic population and 10.1 per 1,000 for the nondiabetic population. The standard mean ratio for the diabetic population was 1.24 (95% CI 1.12-1.35), with the risk of mortality relative to the nondiabetic population decreasing with age. Males with diabetes lost an average of 7.0 years from the year of diagnosis, and females with diabetes lost an average of 7.5 years. The most common cause of death was cardiovascular disease, which accounted for 49.1% of deaths in the diabetic population. CONCLUSIONS: Diabetes is recorded as a cause of death on a minority of death certificates for patients with diabetes. Using death certificates in isolation, therefore, is a poor method of estimating diabetic mortality, but results can be improved with the use of record linkage techniques. Patients with diabetes have an excess risk of mortality compared with the nondiabetic population. Life-years lost for patients with diabetes is strongly related to age at diagnosis and is a means of expressing mortality without relying on accurate prevalence data.

The epidemiology and cost of inpatient care for peripheral vascular disease, infection, neuropathy, and ulceration in diabetes.

OBJECTIVE: To describe the epidemiology and costs of the acute care of peripheral vascular disease, infection, neuropathy, and ulceration in a U.K. population with special consideration of those patients with diabetes. RESEARCH DESIGN AND METHODS: Routine data describing inpatient care for a 4-year period were analyzed (financial years 1991/1992 to 1994/1995). These data had undergone record-linkage to draw together records from the same patients, and records of patients with diabetes were flagged. Cost estimates were determined by attributing a diagnosis-related group cost-weight to each record. RESULTS: A total of 4,245 admissions (1.2% of all admissions) had a primary diagnosis of peripheral vascular disease, infection, neuropathy, or ulceration, and 7,379 (2.1%) admissions had these categories recorded in any one of six diagnostic fields. These figures were generated by 3,159 and 4,751 patients, respectively. This represented a range of crude annual incidence of admission of between 1.9 and 2.9 per 1,000 people. Patients with diabetes accounted for 625 (15.4%) of primary admissions, a crude annual incidence of admission of 18.8 per 1,000. The age-standardized relative risk of admission for patients with diabetes to the nondiabetic population was 7.61 for men and 6.85 for women. The length of stay for patients with diabetes was almost twice that of the nondiabetic population (15.5 vs. 8.7 days). The relative risk of hospital mortality (diabetes vs. non-diabetes) was 2.83. Surgical procedures were carried out on 857 patients, 272 (31.2%) with diabetes. This represented an age-standardized relative risk of 31.19. The estimated cost of admissions for primary diagnoses in these categories over 4 years was 6,128,211 pounds ($9,743,855). Patients with diabetes accounted for 1,236,623 pounds ($1,966,230), an excess of 87% attributable to the diabetic state. CONCLUSIONS: Diabetes is confirmed as a significant risk factor for peripheral vascular disease, infection, neuropathy, and ulceration. The severity of these disorders in terms of increased risk of hospital mortality, length of stay, and risk of surgical procedure is also demonstrated for those patients with diabetes.

The matrix effects on kinetic rate constants of antibody-antigen interactions reflect solvent viscosity.

This study describes the influence of different matrices on two model antibody-antigen interactions; that between beta2microglobulin and anti beta2microglobulin, and that of rabbit anti mouse Fc fragment (RAMFc) with mouse IgG. The matrices investigated were; phosphate-buffered saline pH 7.4 containing 0.05% Tween 20 detergent, horse serum, a 50:50 mixture of phosphate-buffered saline/Tween 20 and horse serum, and four glycerol solutions of differing concentrations. A recently developed optical biosensor, the IAsys, was used to monitor the interactions in real-time and provide precise determinations of k(ass), k(diss) and KA values. The results show that the rates of association and dissociation for the two different antibody:antigen models are significantly affected by the surrounding matrix. Glycerol of known viscosity was used as a matrix in both models to show that this effect is attributable to the viscosity as opposed to proteins present in the matrix. The viscosity of the matrix has also been shown to have an apparent influence upon the overall equilibrium/affinity constant for the interaction, with measurements of KA tending to increase with viscosity. The significant effects of matrix on kinetic rate constants for antibody-antigen interactions shown here have important implications in the use of immunoassays where non-equilibrium measurements are made in serum matrices.

Cord blood serum does not increase lymphocyte responses in comparison to adult serum.

To date, over 1000 cord blood (CB) transplants have been reported from different centers worldwide and it is generally agreed that CB represents an encouraging alternative to bone marrow (BM) transplantation. There are a variety of reasons for this, however, possibly the two most controversial aspects are (a) whether there is less graft versus host disease (GVHD) with CB compared to BM transplantation, and (b) whether we can use more HLA mismatches with CB transplantation. The major theory regarding the reduced immunological response of CB lymphocytes is that CB T and NK cells are naive and, therefore, not primed for activation. However, the naive phenomena that has been noted in vitro may be bypassed in vivo by unforeseen factors. We show evidence that there are differences in the soluble factors present in CB and adult serum and that these differences play a role in T cell function. Thus, adult serum will enhance both mitogen and IL-2 specific T cell growth whereas CB serum has no effect, suggesting that there is an activation/growth factor present in adult sera, which is absent in CB sera. This work could enable us to identify the molecular mechanisms which are associated with a lower GVHD in CB compared to BM transplanted individuals.

Soluble CD8 stabilizes the HLA class I molecule by promoting beta2M exchange: analysis in real-time.

Human soluble CD8 (sCD8) is secreted by activated CD8+/- cytotoxic T lymphocytes (CTLs). The immunological role of sCD8 is poorly defined, however. We have studied the influence of sCD8 on HLA class I interactions by real-time analysis. Using an optical biosensor we demonstrated that the binding of sCD8 to HLA-A2 promotes exchange of beta2-microglobulin (beta2m) in order to stabilize the complex. Kinetic analysis showed that sCD8 significantly increased the affinity (K(A)) of HLA-A2 for immobilized human beta2m; from 1.14 +/- 0.04 x 10(9) M(-1) in its absence, to 2.18 +/- 0.21 x 10(9) M(-1) following preincubation with sCD8. This suggests that the sCD8:HLA class I complex is unlikely to be degraded at the cell surface. Even in the presence of exogenous peptide (HLA-A2 specific or nonspecific), sCD8 has a stabilizing influence on the HLA class I molecule. These findings point to an immunosuppressive role for sCD8, because the binding of sCD8 to HLA class I would block the binding site for CTL-bound CD8 and, therefore, interfere with T cell activation and proliferation. This may have particular significance in pathological situations where elevated levels of sCD8 are found in extracellular fluids, and sCD8 may provide an alternative approach for immunosuppressive therapy.

Real-time analysis of cell surface HLA class I interactions.

Characterisation of the kinetics of assembly and dissociation of the HLA class I heterotrimeric complex provides valuable insights into the relative contributions of each element to complex stability. However, to date there has been no real-time binding analysis on whole cells. Here we have developed an optical biosensor model to investigate the binding of class I HLA complexes on whole cells to human beta 2-microglobulin (beta 2m) and the effects of different HLA-specific peptides on this binding. We immobilised beta 2m on an IAsys biosensor surface and established conditions to analyse the binding of this to HLA-A2 expressing cells (T2 cells). Using 721.221 cells as an HLA negative control we showed that HLA-A2 binding was optimal using a) a carboxymethylated dextran surface and b) no growth factors or supplements in the culture medium at the binding event. Using these conditions we verified specificity of binding by inhibition of the reaction with free beta 2m and determined the dissociation rate constant for T2 cell binding to beta 2m (0.03 s-1). In addition, we demonstrated the ability of different HLA specific peptides to modulate cellular HLA-A2 binding to beta 2m. This is the first time that interactions of cell surface HLA class I molecules has been investigated using real-time analysis. Furthermore, our peptide analysis has shown that this model can be used to characterise peptide specific HLA-binding responses on the whole cell surface in real-time.

Ultrasonic angiographic and pathologic correlation of noncystic-appearing renal masses.

The ultrasonic echo pattern of renal masses is retrospectively correlated with the angiographic vascular pattern in 36 cases where a noncystic-appearing mass was identified by either study. Pathologic or cytologic correlation was available in 31 of these masses. In carcinomas the echogenicity was usually found to correlate well with the degree of neovascularity.

Patterns and costs of hospital care for coronary heart disease related and not related to diabetes.

OBJECTIVE: To describe the epidemiology and costs of coronary heart disease (CHD) requiring hospital admission, with particular reference to diabetes. SETTING: The former South Glamorgan Health Authority, South Wales. METHODS: Routine hospital activity data were record linked and all diabetic and non-diabetic individuals over a four year period (1991-95) were identified. A cost weight was included for each admission based on diagnosis related groups. RESULTS: There were 10,214 patients admitted with a primary diagnostic code for CHD, representing an incidence of 6.3 per 1000 per annum. Including all CHD and non-CHD admissions, these individuals were responsible for 17% of acute inpatient activity. Men had a consistently higher age specific prevalence of CHD than women. The age adjusted relative risk of CHD for patients with diabetes compared with those without was 4.1 for men and 5.5 for women. Patients with diabetes accounted for 16.9% of CHD related admissions and had a fourfold increased probability of undergoing a cardiac procedure. The total cost of CHD was estimated to be 6% of NHS revenue at 1994-95 pay and prices. Patients with diabetes were responsible for 16% of this expenditure. This translated to an estimated NHS acute hospital expenditure for CHD of 1.1 billion pounds per year at 1994-95 pay and prices. CONCLUSIONS: CHD was responsible for a larger proportion of NHS expenditure than had previously been reported. Nearly one in five acute hospital admissions were for patients whose condition included cardiac problems. The relation between diabetes and CHD was particularly evident, and may offer opportunities for disease prevention.

Assessing with CARE: an innovative method of testing the approach and casualty assessment components of basic life support, using video recording.

The resuscitation community is now moving towards a set of basic life support guidelines but different countries and training centres have their own individual methods of instruction. It would be advantageous if a universal testing method were available to facilitate intercentre comparison. This could lead to an international course which had been rigorously assessed and evaluated. Taking this as a starting point, the Cardiff Assessment of Response and Evaluation (CARE) was developed. CARE is an innovative assessment technique using video recording for testing the preliminary steps of life support as outlined by the European Resuscitation Council. The assessment was validated by testing 67 members of the public who had been trained in cardiopulmonary resuscitation, 27 shortly after instruction and 40 between 6 and 18 months after instruction. All subjects were tested without prior warning and video recorded for independent scoring by two researchers and a paramedic training officer. Scores were compared using the k correlation which showed a high level of agreement between observers. Video recording and marking using the CARE schedule and guidelines is a reliable method for assessing the preliminary steps in life support.

Evaluating CPR performance in basic life support: the VIDRAP protocol.

This paper presents the second part of the validated Cardiff test for one rescuer basic life support skills, based on observation of video recording combined with the Recording Resusci Anne printout (VIDRAP). The authors believe that this is a robust evaluation tool which is capable of assessing the potential value to a casualty of a simulated resuscitation. The adoption of a widely accepted test methodology would facilitate comparison of research in different centres, which is not possible at present.

Kindler syndrome: a rare cause of desquamative lesions of the gingiva.

Kindler syndrome is a rare syndrome with cutaneous and intraoral manifestations. It has been suggested that there is an overlap between this syndrome and another called Weary syndrome. Only 68 cases of Weary and Kindler syndromes have been reported, with fewer solely attributed to Kindler syndrome. The salient cutaneous features are neonatal bullae, poikiloderma, photosensitivity, and acral atrophy. This article presents the clinical intraoral findings of two siblings of consanguineous descent diagnosed as having Kindler syndrome. Both had an erythematous and erosive appearance of the gingiva; one sibling had poor oral hygiene and a rapidly progressive form of periodontal disease; the other, whose oral hygiene was acceptable, had no detectable bone loss.

Effectiveness of the BBC's 999 training roadshows on cardiopulmonary resuscitation: video performance of cohort of unforewarned participants at home six months afterwards.

OBJECTIVE: To examine the competence of a cohort trained in cardiopulmonary resuscitation by the BBC's 999 training roadshows. DESIGN: Descriptive cohort study applying an innovative testing procedure to a nationwide systematic sample. The test sample received an unsolicited home visit and without warning were required to perform cardiopulmonary resuscitation on a manikin while being videoed. The videos were then analysed for effectiveness and safety using the new test. SETTING: Nine cities and surrounding areas in the United Kingdom. SUBJECTS: 280 people aged between 11 and 72. RESULTS: Thirty three (12%) trainees were able to perform effective cardiopulmonary resuscitation, but of these 14 (5%) performed one or more elements in a way that was deemed to be potentially injurious. Thus only 19 (7%) trainees were able at six months to provide safe cardiopulmonary resuscitation. In addition, large numbers of subjects failed to shout for help, effectively assess the status of the patient, or alert an ambulance. Significantly better performances were recorded by those under 45 years old (31 (14%) v 2 (4%) gave effective performances respectively, P < 0.05), those who had attended a subsequent cardiopulmonary resuscitation course (8 (40%) v 25 (10%) gave effective performances respectively, P < 0.0001), and those confident in their initial ability (26 (20%) v 7 (6%) gave effective performances respectively, P < 0.005). Females were significantly less likely than males to perform procedures in a harmful way (117 (62%) v 10 (12%) performed safely respectively, P < 0.005). CONCLUSION: Television is an effective means of generating large training cohorts. Volunteers will cooperate with unsolicited testing in their home, such testing being a realistic simulation of the stress and lack of forewarning that would surround a real event. Under such conditions the performance of cardiopulmonary resuscitation was disappointing. However, retraining greatly improves performance.

Odors as cues for the recall of words unrelated to odor.

The effectiveness of an ambient odor as a retrieval cue for words unrelated to odor was investigated. After incidental learning of 40 adjectives, 40 participants were tested for recall during three unannounced recall phases (15 min., 48 hr., and 5 days). Participants in two control conditions learned with no odor present and either had no odor present during any recall phase or only during recall after 5 days. Participants in two conditions learned with an odor present and either had the odor present during recall only after 5 days or during recall both after 15 min. and after 5 days. Analyses indicated that, while participants in the control conditions recalled significantly less during each succeeding recall phase, recall by participants in the two experimental conditions did not decrease significantly. Recall by participants in the two experimental conditions was significantly higher during recall after 5 days (when the odor was reintroduced) than either control group. The addition of a salient cue during learning and retrieval facilitated recall more than the presence of constant environmental cues.

Effects of subliminal backward-recorded messages on attitudes.

This study was designed to measure the effects of subliminal backward messages on attitudes. It was hypothesized that subliminal backward-recorded messages would influence the attitudes of listeners. Three subliminal backward-recorded messages from a popular song were used. 82 undergraduates were randomly assigned to one of four conditions: a three-message group heard a tape containing the backward messages recorded three times in succession, a six-message group heard a tape with the same backward messages recorded six times in succession, two control groups heard nonbackward recorded music. No statistically significant differences were found between the groups on a posttape attitude questionnaire. The results are discussed in terms of unconscious processing and the tricomponent theory of attitudes and attitude change.

Patient knowledge concerning their referral to a restorative dental unit in a community clinic: a pilot study.

One hundred patients referred to a Community Dental Service completed a questionnaire, the purpose of which was to find out why they perceived they had been referred and to whom they thought they had been referred. The results showed that most patients (64) perceived they would see a Specialist rather than a Consultant and most (63) thought they had been referred because their dentist could not treat their problem. There was no significant relationship between age and to whom the patient thought they had been referred, and further analysis to estimate the effect of age, gender and length of time with the current dentist or the reasons for referral failed to show any significant relationships.