The impact of the COVID-19 pandemic on cardiovascular disease prevention and corresponding geographical inequalities in England: interrupted time series analysis.

BACKGROUND: There has been disruption to the detection and management of those with hypertension and atrial fibrillation (AF) during the COVID-19 pandemic. This is likely to vary geographically and could have implications for future mortality and morbidity. We aimed to estimate the change in diagnosed prevalence, treatment and prescription indicators for AF and hypertension and assess corresponding geographical inequalities. METHODS: Using the Quality and Outcomes Framework (2016/17 to 2021/22) and the English Prescribing Datasets (2018 to 2022), we described age standardised prevalence, treatment and prescription item rates for hypertension and AF by geography and over time. Using an interrupted time-series (ITS) analysis, we estimated the impact of the pandemic (from April 2020) on missed diagnoses and on the percentage change in medicines prescribed for these conditions. Finally, we described changes in treatment indicators against Public Health England 2029 cardiovascular risk targets. RESULTS: We observed 143,822 fewer (-143,822, 95%CI:-226,144, -61,500, p = 0.001) diagnoses of hypertension, 60,330 fewer (-60,330, 95%CI: -83,216, -37,444, p = 0.001) diagnoses of AF and 1.79% fewer (-1.79%, 95%CI: -2.37%, -1.22%), p < 0.0001) prescriptions for these conditions over the COVID-19 impact period. There was substantial variation across geography in England in terms of the indirect impact of the COVID-19 pandemic on the diagnosis, prescription, and treatment rates of hypertension and AF. 20% of Sub Integrated Care Boards account for approximately 62% of all missed diagnoses of hypertension. The percentage of individuals who had their hypertension controlled fell from 75.8% in 2019/20 to 64.1% in 2021/22 and the percentage of individuals with AF who were risk assessed fell from 97.2% to 90.7%. CONCLUSIONS: Hypertension and AF detection and management were disrupted during the COVID-19 pandemic. The disruption varied considerably across diseases and geography. This highlights the utility of administrative and geographically granular datasets to inform targeted efforts to mitigate the indirect impacts of the pandemic through applied secondary prevention measures.

Sociodemographic and health-related differences in undiagnosed hypertension in the health survey for England 2015-2019: a cross-sectional cohort study.

Background: Hypertension is a leading cause of morbidity and mortality worldwide, yet a substantial proportion of cases are undiagnosed. Understanding the scale of undiagnosed hypertension and identifying groups most at risk is important to inform approaches to detection. Methods: In this cross-sectional cohort study, we used data from the 2015 to 2019 Health Survey for England, an annual, cross-sectional, nationally representative survey. The survey follows a multi-stage stratified probability sampling design, involving a random sample of primary sampling units based on postcode sectors, followed by a random sample of postal addresses within these units. Within each selected household, all adults (aged ≥16 years) and up to four children, were eligible for participation. For the current study, individuals aged 16 years and over who were not pregnant and had valid blood pressure data were included in the analysis. The primary outcome was undiagnosed hypertension, defined by a measured blood pressure of 140/90 mmHg or above but no history of diagnosis. Age-adjusted prevalence of undiagnosed hypertension was estimated across sociodemographic and health-related characteristics, including ethnicity, region, rural-urban classification, relationship status, highest educational qualification, National Statistics Socio-Economic Classification (NS-SEC), Body Mass Index (BMI), self-reported general health, and smoking status. To assess the independent association between undiagnosed hypertension and each characteristic, we fitted a logistic regression model adjusted for sociodemographic factors. Findings: The sample included 21,476 individuals, of whom 55.8% were female and 89.3% reported a White ethnic background. An estimated 30.7% (95% confidence interval 29.0-32.4) of men with hypertension and 27.6% (26.1-29.1) of women with hypertension were undiagnosed. Younger age, lower BMI, and better self-reported general health were associated with an increased likelihood of hypertension being undiagnosed for men and women. Living in rural areas and in regions outside of London and the East of England were also associated with an increased likelihood of hypertension being undiagnosed for men, as were being married or in a civil partnership and having higher educational qualifications for women. Interpretation: Hypertension is commonly undiagnosed, and some of the groups that are at the lowest risk of hypertension are the most likely to be undiagnosed. Given the high lifetime risk of hypertension and its strong links with morbidity and mortality, our findings suggest a need for greater awareness of the potential for undiagnosed hypertension, including among those typically considered 'low risk'. Further research is needed to assess the impact of extending hypertension screening to lower-risk groups. Funding: None.

Potential Financial Effects on Hospitals of the Removal of Common Orthopaedic and Spinal Procedures From Medicare's "Inpatient-Only" List: A Comparison of the Medicare Fee-for-service Payment Model Versus Maryland's Global Budget Revenue Model.

BACKGROUND: When treating Medicare beneficiaries, orthopaedic surgeons must follow Centers for Medicare & Medicaid Services (CMS) policies regarding whether to perform surgical treatments under inpatient or outpatient status. Recently, most orthopaedic and spinal procedures were removed from the CMS's "inpatient-only" list (IPOL). We investigated differences in hospital payments under the Diagnosis Related Group (DRG)/Ambulatory Payment Classification (APC) system when common orthopaedic/spinal procedures are done under outpatient rather than inpatient status. We compared these differences under the DRG/APC model with differences in payments to Maryland hospitals, which are paid under the alternative Global Budget Revenue model. METHODS: We used the CMS Inpatient Pricer and CMS Addendum B to retrieve the mean duration-of-stay data, estimated DRG (inpatient) payment, and APC (outpatient) payment for eight common orthopaedic/spinal procedures for four non-Maryland hospitals (2 urban academic hospitals and 2 neighboring community hospitals). We retrieved Maryland's Health Services Cost Review Commission hospital rates for the same eight procedures done under inpatient or outpatient status to estimate hospital charges for a Maryland urban academic hospital and a neighboring community hospital. RESULTS: Among the four non-Maryland hospitals, estimated differences in payment for hospitalizations under inpatient versus outpatient status for common orthopaedic/spinal procedures with a mean duration of stay of <2 days, whose status would be most subject to change from inpatient to outpatient by its removal from the IPOL, ranged from $19 to $13,042. For the two Maryland hospitals, differences in outpatient versus inpatient payment for these same procedures ranged from $182 to $1,273. DISCUSSION: Non-Maryland hospitals receive widely different CMS payments for common orthopaedic/spinal procedures based on a change in hospitalization status (inpatient to outpatient) prompted by the procedure being removed from the IPOL. The Maryland global budget revenue mitigates most of the effect of hospitalization status on hospital payment and may serve as a guide toward DRG/APC payment reassessment. LEVEL OF EVIDENCE: N/A.

Lymphoedema management by independent hospices: a cohort study.

OBJECTIVES: To consider the type and cost of clinical services delivered for patients with lymphoedema. DESIGN: Clinical cohort. SETTING: Independent hospices in the North East of England. PARTICIPANTS: All those attending lymphoedema services delivered by the independent hospice sector 2017/2018. RESULTS: 13 914 lymphoedema appointments were recorded across four independent hospices. Twelve thousand nine hundred and sixty-five were attended, which equates to an approximate cost of £1.56 million. Those with lymphoedema were predominately aged over 65 (54.5%) years with females across all age groups being more predominant (3.3:1). Where the cause was recorded, 66% of activity related to lymphoedema was not secondary to cancer. CONCLUSION: Independent hospices are providing a specialist lymphoedema service, which is high in volume and largely invisible. This service is delivered at not insignificant cost. In contrast to previous work, in the North East of England, lymphoedema sufferers are more likely to be female and not have the condition in association with cancer. The availability of rigorous data collection will allow the independent hospices to understand better the delivery and associated costs of lymphoedema services.

Prognostic Value of Vasodilator Stress Cardiac Magnetic Resonance Imaging: A Multicenter Study With 48 000 Patient-Years of Follow-up.

Importance: Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown. Objective: To determine whether stress CMR is associated with patient mortality. Design, Setting, and Participants: Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index. Main Outcomes and Measures: All-cause patient mortality. Results: Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P < .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P < .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P < .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (HR, 1.883; 95% CI, 1.680-2.112; P < .001), patients with (HR, 1.955; 95% CI, 1.712-2.233; P < .001) and without (HR, 1.578; 95% CI, 1.235-2.2018; P < .001) a history of CAD, and patients with normal (HR, 1.385; 95% CI, 1.194-1.606; P < .001) and abnormal left ventricular ejection fraction (HR, 1.836; 95% CI, 1.299-2.594; P < .001). Conclusions and Relevance: Clinical vasodilator stress CMR is associated with patient mortality in a large, diverse population of patients with known or suspected CAD as well as in multiple subpopulations defined by history of CAD and left ventricular ejection fraction. These findings provide a foundational motivation to study the comparative effectiveness of stress CMR against other modalities.

Changes in health in the countries of the UK and 150 English Local Authority areas 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: Previous studies have reported national and regional Global Burden of Disease (GBD) estimates for the UK. Because of substantial variation in health within the UK, action to improve it requires comparable estimates of disease burden and risks at country and local levels. The slowdown in the rate of improvement in life expectancy requires further investigation. We use GBD 2016 data on mortality, causes of death, and disability to analyse the burden of disease in the countries of the UK and within local authorities in England by deprivation quintile. METHODS: We extracted data from the GBD 2016 to estimate years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and attributable risks from 1990 to 2016 for England, Scotland, Wales, Northern Ireland, the UK, and 150 English Upper-Tier Local Authorities. We estimated the burden of disease by cause of death, condition, year, and sex. We analysed the association between burden of disease and socioeconomic deprivation using the Index of Multiple Deprivation. We present results for all 264 GBD causes of death combined and the leading 20 specific causes, and all 84 GBD risks or risk clusters combined and 17 specific risks or risk clusters. FINDINGS: The leading causes of age-adjusted YLLs in all UK countries in 2016 were ischaemic heart disease, lung cancers, cerebrovascular disease, and chronic obstructive pulmonary disease. Age-standardised rates of YLLs for all causes varied by two times between local areas in England according to levels of socioeconomic deprivation (from 14 274 per 100 000 population [95% uncertainty interval 12 791-15 875] in Blackpool to 6888 [6145-7739] in Wokingham). Some Upper-Tier Local Authorities, particularly those in London, did better than expected for their level of deprivation. Allowing for differences in age structure, more deprived Upper-Tier Local Authorities had higher attributable YLLs for most major risk factors in the GBD. The population attributable fractions for all-cause YLLs for individual major risk factors varied across Upper-Tier Local Authorities. Life expectancy and YLLs have improved more slowly since 2010 in all UK countries compared with 1990-2010. In nine of 150 Upper-Tier Local Authorities, YLLs increased after 2010. For attributable YLLs, the rate of improvement slowed most substantially for cardiovascular disease and breast, colorectal, and lung cancers, and showed little change for Alzheimer's disease and other dementias. Morbidity makes an increasing contribution to overall burden in the UK compared with mortality. The age-standardised UK DALY rate for low back and neck pain (1795 [1258-2356]) was higher than for ischaemic heart disease (1200 [1155-1246]) or lung cancer (660 [642-679]). The leading causes of ill health (measured through YLDs) in the UK in 2016 were low back and neck pain, skin and subcutaneous diseases, migraine, depressive disorders, and sense organ disease. Age-standardised YLD rates varied much less than equivalent YLL rates across the UK, which reflects the relative scarcity of local data on causes of ill health. INTERPRETATION: These estimates at local, regional, and national level will allow policy makers to match resources and priorities to levels of burden and risk factors. Improvement in YLLs and life expectancy slowed notably after 2010, particularly in cardiovascular disease and cancer, and targeted actions are needed if the rate of improvement is to recover. A targeted policy response is also required to address the increasing proportion of burden due to morbidity, such as musculoskeletal problems and depression. Improving the quality and completeness of available data on these causes is an essential component of this response. FUNDING: Bill & Melinda Gates Foundation and Public Health England.

Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England.

A Simple Approach to Assessment of a Total Knee Replacement's Rotationary Profile Using Computed Tomography.

Malrotation is a cause of persistent pain and poor functioning postoperatively in those who undergo a total knee replacement (TKR). The accurate measurement of malrotation is not routinely available in most hospital settings due to an absence of three-dimensional computed tomography (CT) software. An accessible, uncomplicated technique to demonstrate TKR prosthesis malrotation would be of benefit to orthopaedic surgeons worldwide. A patient was reviewed with persistent postoperative pain, having undergone a right TKR 3 years previously for progressive osteoarthritis. Postoperative prosthetic infection, instability, loosening, and fracture were ruled out as causes for the persistent pain. A two-dimensional CT scan was obtained of the patient's affected right knee. Adhesive pieces of paper (Post-it notes) were used to highlight the posterior tibial prosthesis axis, the tibial tuberosity axis, the posterior condylar axis of the femoral prosthesis and the femoral surgical transepicondylar axis, as per the technique described by Berger et al. A protractor was used to assess the degree of malrotation of the tibial and femoral prostheses. Allowing for human error and that of parallax, an immediate assessment was made of the patient's prosthesis using a readily available imaging modality, and malrotation was quickly identified using accessible, affordable everyday stationary equipment.

Can the material properties of regenerate bone be predicted with non-invasive methods of assessment? Exploring the correlation between dual X-ray absorptiometry and compression testing to failure in an animal model of distraction osteogenesis.

Evaluation of the material properties of regenerate bone is of fundamental importance to a successful outcome following distraction osteogenesis using an external fixator. Plain radiographs are in widespread use for assessment of alignment and the distraction gap but are unable to detect bone formation in the early stages of distraction osteogenesis and do not quantify accurately the structural properties of the regenerate. Dual X-ray absorptiometry (DXA) is a widely available non-invasive imaging modality that, unlike X-ray, can be used to measure bone mineral content (BMC) and density quantitatively. In order to be useful as a clinical investigation; however, the structural two-dimensional geometry and density distributions assessed by DXA should reflect material properties such as modulus and also predict the structural mechanical properties of the regenerate bone formed. We explored the hypothesis that there is a relationship between DXA assessment of regenerate bone and structural mechanical properties in an animal model of distraction osteogenesis. Distraction osteogenesis was carried out on the tibial diaphysis of 41 male, 12 week old, New Zealand white rabbits as part of a larger study. Distraction started after a latent period of 24 h at a rate of 0.375 mm every 12 h and continued for 10-days, achieving average lengthening of 7.1 mm. Following an 18-day period of consolidation, the regenerate bone was subject to bone density measurements using a total body dual-energy X-ray densitometer. This produced measurement of BMC, bone mineral density (BMD) and volumetric bone mineral density (vBMD). The tibiae were then disarticulated and cleaned of soft tissue before loading in compression to failure using an Instron mechanical testing machine (Instron Corporation, Massachusetts USA). Using Spearman rank correlation and linear regression, there was a significant correlation between vBMD and the Modulus of Elasticity, Yield Stress and Failure Stress of the bone. No correlation was seen between BMC, BMD, vBMR and any mechanical parameter. DXA is a promising tool for the assessment of regenerate bone formed by DO during limb lengthening and requires further investigation.

Interobserver and intraobserver reliability assessment of calcaneal fracture classification systems.

The aim of the present study was to assess the reliability of commonly used intra-articular calcaneal fracture classification systems and to compare them with the newer AO Integral Classification of Injuries (ICI) system. Forty computed tomography and radiographic images of 40 intra-articular calcaneal fractures were reviewed independently by 3 reviewers on 2 separate occasions and classified according to the Essex-Lopresti, Atkins, Zwipp and Tscherne, Sanders, and AO-ICI classification systems. The reviewers were unaware of the patients' identity and all aspects of clinical care. The data were analyzed using kappa (κ) statistics to assess the intra- and interobserver reliability. The κ values were calculated for Essex-Lopresti (κ = 0.85 intraobserver, κ = 0.78 interobserver), Atkins (κ = 0.42 intraobserver, κ = 0.73 interobserver), Zwipp and Tscherne (κ = 0.40 intraobserver, κ = 0.47 interobserver), Sanders (κ = 0.31 intraobserver, κ = 0.35 interobserver), and AO-ICI (κ = 0.41 intraobserver, κ = 0.33 interobserver). The AO-ICI classification system had levels of reproducibility similar to that of the Sanders classification, currently the most widely used system. The Essex-Lopresti classification demonstrated improved reliability compared with that reported in previous studies. This can be attributed to using sagittal computed tomography images, in addition to the originally described plain radiographs, for assessment. This improvement is relevant because of its accepted prognostic predictability.

Ultrasound assessment of the anatomical validity of T3 and L4 as sEMG recording sites.

The accuracy of surface EMG measurement is dependent upon minimizing potential crosstalk from other muscles. Although they are deeply situated, in places the erector spinae are covered with electrically silent aponeuroses rather than active muscle tissue. Theoretically these aponeuroses can serve as windows for sEMG recordings. A recent anatomical study concluded that T3 and L4 are ideal sites for recording the ES because the superficial muscle aponeuroses are wide at these sites. The aim of this prospective study was to investigate these sites in vivo using real time ultrasound. Ultrasound images from 20 subjects (10<30 years and 10>70 years; equal numbers of males and females in each group) were acquired during rest and in prone extension with the arms in three different positions. The most superficial aponeurosis widths were measured. The mean T3 aponeurosis width reduced significantly in extension from 4.4±4.7mm at rest to 1.8±2.6mm in extension (p<0.0001). Males had significantly smaller T3 aponeurosis widths than females (p=0.049). The mean L4 aponeurosis width also significantly decreased in extension from 35.5±7.0mm at rest to 29.9±7.2mm in extension (p<0.0001) due to 'doming' of the aponeurosis. Our results demonstrate that T3 is not a reliable site over which to record the ES because the aponeurosis width is too narrow. L4 is a good site if the electrodes are placed no more than 20mm from the midline.

In vitro assessment of EmboGel and UltraGel radiopaque hydrogels for the endovascular treatment of aneurysms.

PURPOSE: To describe two hydrogel embolic materials, the alginate-based EmboGel and the polyethylene glycol diacrylate-based UltraGel and examine their use as embolic agents in in vitro models of abdominal aortic aneurysm (AAA) endoleak and saccular aneurysms. MATERIALS AND METHODS: EmboGel is a mixture of iohexol and alginate, with a calcium chloride solution used to induce polymerization. UltraGel is a mixture of igracure, iohexol, and polyethylene glycol diacrylate and polymerizes in the presence of ultraviolet (UV) light. Modified microcatheter delivery systems were used in both cases to demonstrate use of the hydrogels in fusiform and saccular aneurysm models. RESULTS: Preliminary in vitro results suggest that EmboGel and UltraGel provide effective embolization in fusiform and saccular aneurysm models, respectively. Due to the rapid polymerization of EmboGel, the agent was delivered in a strand-like form. When used in conjunction with a stent in an AAA endoleak model, this form was able to effectively fill the aneurysmal cavity and occlude it from the central blood flow. UltraGel, conversely, was delivered as a liquid and slowly polymerized in the presence of UV light. This system in a saccular aneurysm model was able to form a solid cast inside the aneurysm wall, again showing complete occlusion from the parent flow. CONCLUSIONS: Preliminary results indicate these two novel hydrogel applications may prove effective for the treatment of saccular and fusiform aneurysms.

Evidence-based assessment: evaluation of the formocresol versus ferric sulfate primary molar pulpotomy.

PURPOSE: Formocresol and ferric sulfate were evaluated as pulpotomy medicaments using evidence-based dentistry principles. Formocresol has been challenged as a potential carcinogen and mutagen, leading to consideration of ferric sulfate. METHODS: The PICOT statement was: (P) In human carious primary molars with reversible coronal pulpitis, (I) does a pulpotomy performed with ferric sulfate, (C) compared with formocresol, (O) result in dinical/radiographic success, (T) in time periods up to exfoliation? Relevant papers (N=894) were identified from databases and inclusion criteria were applied; 94 papers remained (randomized clinical trials [RCTs]=7; clinical trials [CTs]=28; case-control studies=14; opinions, cohort, and cross-sectional studies=4; reviews=22; irretrievable papers=19). Three RCTs and 10 CTs (total teeth: formocresol=753; ferric sulfate=90) were meta-analyzed; 1 RCT and 1 CT were tested for homogeneity (odds ratios; 95% confidence intervals); 3 RCTs and 10 CTs were examined by student's t test. RESULTS: Clinical data indicated ferric sulfate was significantly more successful than formocresol (OR=1.95; CI=1.01-3.80). Radiographic data indicated no difference between medicaments (OR=0.90; CI=0.58-1.39). Medicaments did not differ with t-tests of clinical (P>.10) and radiographic (P>.50) data. CONCLUSIONS: This evidence-based assessment concluded that, in human carious primary molars with reversible coronal pulpitis, pulpotomies performed with either formocresol or ferric sulfate are likely to have similar clinical/radiographic success.

Assessment of the reproducibility of intradermal administration of capsaicin as a model for inducing human pain.

The reproducibility and tolerability of intradermal (i.d.) administration of capsaicin as a method for eliciting human pain was assessed in healthy male volunteers (n = 12). The primary endpoints for assessing pain were spontaneous pain response and areas of allodynia, pinprick hyperalgesia and neurogenic inflammation. These were recorded before, immediately after, and at regular intervals following each of four doses (250 microg) of capsaicin (two per trial day). Within- and between-subject variability to the technique was assessed by measuring the maximum recorded values (max), time to maximum value (t(max)) and area under the curve (AUC(0-1 h)) of each of the endpoints. Tolerability to the technique was addressed by recording adverse events. Reproducibility of the i.d. capsaicin model was demonstrated for each type of capsaicin-induced pain. Following each dose, the magnitude and profile of response and overall AUC values were similar for each parameter although some decrease in pinprick hyperalgesia was observed over time. For spontaneous pain, evidence of a period effect was observed in mean AUC data, with values increasing following the second dose of each trial day. This effect was confounded by the possibility of an arm effect, with the non-dominant arm appearing to be more sensitive to pain than the dominant arm. The data were not sufficient to confirm the existence of these effects. Between-subject variability and within-day, within-subject variability accounted for most of the variability observed in the trial. By optimising study design to eliminate these sources of variability, it was estimated that spontaneous pain and the area of allodynia would be the least variable endpoints. A positive correlation was found between the area of allodynia and area of pinprick hyperalgesia (r(2) = 0.835). Overall, the model was well tolerated with no reports of adverse events. We conclude that the tolerability profile, and variability of i.d. capsaicin-induced pain is acceptable for pharmacological profiling of novel anti-nociceptive agents, with limited number of subjects.