Patients' and clinicians' perspectives towards primary care consultations for shoulder pain: qualitative findings from the Prognostic and Diagnostic Assessment of the Shoulder (PANDA-S) programme.

BACKGROUND: Clinical management of musculoskeletal shoulder pain can be challenging due to diagnostic uncertainty, variable prognosis and limited evidence for long-term treatment benefits. The UK-based PANDA-S programme (Prognostic And Diagnostic Assessment of the Shoulder) is investigating short and long-term shoulder pain outcomes. This paper reports linked qualitative research exploring patients' and clinicians' views towards primary care consultations for shoulder pain. METHODS: Semi-structured interviews were conducted with 24 patients and 15 primary care clinicians. Twenty-two interviews (11 patients, 11 clinicians) were conducted as matched patient-clinician 'dyads'. Data were analysed thematically. RESULTS: Clinicians reported attempts to involve patients in management decisions; however, there was variation in whether patients preferred treatment choice, or for decisions to be clinician-led. Some patients felt uncertain about the decisions made, due to a lack of discussion about available management options. Many General Practitioners expressed a lack of confidence in diagnosing the underlying cause of shoulder pain. Patients reported either not being given a diagnosis, or receiving different diagnoses from different professionals, resulting in confusion. Whilst clinicians reported routinely discussing prognosis of shoulder pain, patients reported that prognosis was not raised. Patients also expressed concern that their shoulder pain could be caused by serious pathology; however, clinicians felt that this was not a common concern for patients. CONCLUSIONS: Findings showed disparities between patients' and clinicians' views towards shoulder pain consultations, indicating a need for improved patient-clinician communication. Findings will inform the design of an intervention to support treatment and referral decisions for shoulder pain that will be tested in a randomised controlled trial.

Metabolic risk factors and the incidence and progression of radiographic hand osteoarthritis: a population-based cohort study.

OBJECTIVE: To determine whether selected metabolic factors are associated with greater amounts of radiographic hand osteoarthritis (OA) incidence and progression. METHODS: The study identified 706 adults, aged 50-69 years, with hand pain and hand radiographs at baseline, from two population-based cohorts. Metabolic factors (body mass index, hypertension, dyslipidaemia, and diabetes) were ascertained at baseline by direct measurement and medical records. Analyses were undertaken following multiple imputation of missing data, and in complete cases (sensitivity analyses). Multivariable regression models estimated associations between metabolic factors and two measures of radiographic change at 7 years for all participants, individuals free of baseline radiographic OA, and in baseline hand OA subsets. Estimates were adjusted for baseline values and other covariates. RESULTS: The most consistent and strong associations observed were between the presence of diabetes and the amount of radiographic progression in individuals with nodal OA [adjusted mean differences in Kellgren-Lawrence summed score of 4.50 (-0.26, 9.25)], generalized OA [3.27 (-2.89, 9.42)], and erosive OA [3.05 (-13.56, 19.67)]. The remaining associations were generally weak or inconsistent, although numbers were limited for analyses of incident radiographic OA and erosive OA in particular. CONCLUSION: Overall metabolic risk factors were not independently or collectively associated with greater amounts of radiographic hand OA incidence or progression over 7 years, but diabetes was associated with radiographic progression in nodal, and possibly generalized and erosive OA. Diabetes has previously been associated with prevalent but not incident hand OA. Further investigation in hand OA subsets using objective measures accounting for disease duration and control is warranted.

Demographic and clinical factors associated with radiographic severity of first metatarsophalangeal joint osteoarthritis: cross-sectional findings from the Clinical Assessment Study of the Foot.

OBJECTIVE: To explore demographic and clinical factors associated with radiographic severity of first metatarsophalangeal joint osteoarthritis (OA) (First MTPJ OA). DESIGN: Adults aged ≥50 years registered with four general practices were mailed a Health Survey. Responders reporting foot pain within the last 12 months were invited to undergo a clinical assessment and weight-bearing dorso-plantar and lateral radiographs of both feet. Radiographic first MTPJ OA in the most severely affected foot was graded into four categories using a validated atlas. Differences in selected demographic and clinical factors were explored across the four radiographic severity subgroups using analysis of variance (ANOVA) and ordinal regression. RESULTS: Clinical and radiographic data were available from 517 participants, categorised as having no (n = 105), mild (n = 228), moderate (n = 122) or severe (n = 62) first MTPJ OA. Increased radiographic severity was associated with older age and lower educational attainment. After adjusting for age, increased radiographic first MTPJ OA severity was significantly associated with an increased prevalence of dorsal hallux and first MTPJ pain, hallux valgus, first interphalangeal joint (IPJ) hyperextension, keratotic lesions on the dorsal aspect of the hallux and first MTPJ, decreased first MTPJ dorsiflexion, ankle/subtalar joint eversion and ankle joint dorsiflexion range of motion, and a trend towards a more pronated foot posture. CONCLUSIONS: This cross-sectional study has identified several dose-response associations between radiographic severity of first MTPJ OA and a range of demographic and clinical factors. These findings highlight the progressive nature of first MTPJ OA and provide insights into the spectrum of presentation of the condition in clinical practice.

Subsets of symptomatic hand osteoarthritis in community-dwelling older adults in the United Kingdom: prevalence, inter-relationships, risk factor profiles and clinical characteristics at baseline and 3-years.

OBJECTIVE: To compare the population prevalence, inter-relationships, risk factor profiles and clinical characteristics of subsets of symptomatic hand osteoarthritis (OA) with a view to understanding their relative frequency and distinctiveness. METHOD: 1076 community-dwelling adults with hand symptoms (60% women, mean age 64.7 years) were recruited and classified into pre-defined subsets using physical examination and standardised hand radiographs, scored with the Kellgren & Lawrence (K&L) and Verbruggen-Veys grading systems. Detailed information on selected risk factors was obtained from direct measurement (Body Mass Index (BMI)), self-complete questionnaires (excessive use of hands, previous hand injury) and medical record review (hypertension, dyslipidaemia, type 2 diabetes). Hand pain and disability were self-reported at baseline and 3-year follow-up using Australian/Canadian Osteoarthritis Hand Index (AUSCAN). RESULTS: Crude population prevalence estimates for symptomatic hand OA subsets in the adult population aged 50 years and over were: thumb base OA (22.4%), nodal interphalangeal joint (IPJ) OA (15.5%), generalised hand OA (10.4%), non-nodal IPJ OA (4.9%), erosive OA (1.0%). Apart from thumb base OA, there was considerable overlap between the subsets. Erosive OA appeared the most distinctive with the highest female: male ratio, and the most disability at baseline and 3-years. A higher frequency of obesity, hypertension, dyslipidaemia, and metabolic syndrome was observed in this subset. CONCLUSION: Overlap in the occurrence of hand OA subsets poses conceptual and practical challenges to the pursuit of distinct phenotypes. Erosive OA may nevertheless provide particular insight into the role of metabolic and cardiovascular risk factors in the pathogenesis of OA.

Alternatively spliced tissue factor induces angiogenesis through integrin ligation.

The initiator of coagulation, full-length tissue factor (flTF), in complex with factor VIIa, influences angiogenesis through PAR-2. Recently, an alternatively spliced variant of TF (asTF) was discovered, in which part of the TF extracellular domain, the transmembrane, and cytoplasmic domains are replaced by a unique C terminus. Subcutaneous tumors produced by asTF-secreting cells revealed increased angiogenesis, but it remained unclear if and how angiogenesis is regulated by asTF. Here, we show that asTF enhances angiogenesis in matrigel plugs in mice, whereas a soluble form of flTF only modestly enhances angiogenesis. asTF dose-dependently upregulates angiogenesis ex vivo independent of either PAR-2 or VIIa. Rather, asTF was found to ligate integrins, resulting in downstream signaling. asTF-alphaVbeta3 integrin interaction induces endothelial cell migration, whereas asTF-dependent formation of capillaries in vitro is dependent on alpha6beta1 integrin. Finally, asTF-dependent aortic sprouting is sensitive to beta1 and beta3 integrin blockade and a TF-antibody that disrupts asTF-integrin interaction. We conclude that asTF, unlike flTF, does not affect angiogenesis via PAR-dependent pathways but relies on integrin ligation. These findings indicate that asTF may serve as a target to prevent pathological angiogenesis.

Determining sample size for progression criteria for pragmatic pilot RCTs: the hypothesis test strikes back!

BACKGROUND: The current CONSORT guidelines for reporting pilot trials do not recommend hypothesis testing of clinical outcomes on the basis that a pilot trial is under-powered to detect such differences and this is the aim of the main trial. It states that primary evaluation should focus on descriptive analysis of feasibility/process outcomes (e.g. recruitment, adherence, treatment fidelity). Whilst the argument for not testing clinical outcomes is justifiable, the same does not necessarily apply to feasibility/process outcomes, where differences may be large and detectable with small samples. Moreover, there remains much ambiguity around sample size for pilot trials. METHODS: Many pilot trials adopt a 'traffic light' system for evaluating progression to the main trial determined by a set of criteria set up a priori. We construct a hypothesis testing approach for binary feasibility outcomes focused around this system that tests against being in the RED zone (unacceptable outcome) based on an expectation of being in the GREEN zone (acceptable outcome) and choose the sample size to give high power to reject being in the RED zone if the GREEN zone holds true. Pilot point estimates falling in the RED zone will be statistically non-significant and in the GREEN zone will be significant; the AMBER zone designates potentially acceptable outcome and statistical tests may be significant or non-significant. RESULTS: For example, in relation to treatment fidelity, if we assume the upper boundary of the RED zone is 50% and the lower boundary of the GREEN zone is 75% (designating unacceptable and acceptable treatment fidelity, respectively), the sample size required for analysis given 90% power and one-sided 5% alpha would be around n = 34 (intervention group alone). Observed treatment fidelity in the range of 0-17 participants (0-50%) will fall into the RED zone and be statistically non-significant, 18-25 (51-74%) fall into AMBER and may or may not be significant and 26-34 (75-100%) fall into GREEN and will be significant indicating acceptable fidelity. DISCUSSION: In general, several key process outcomes are assessed for progression to a main trial; a composite approach would require appraising the rules of progression across all these outcomes. This methodology provides a formal framework for hypothesis testing and sample size indication around process outcome evaluation for pilot RCTs.

Hall effect measurements on Bridgman-grown CuInSe2 with sodium.

The presence of sodium, either in the substrate or as a co-evaporant during absorber deposition, has been shown to improve the performance of polycrystalline photovoltaic devices made with Cu(In, Ga)Se(2), as well as the ternary CuInSe(2). Investigations have shown Na or Na compounds deposited on the grain boundaries, but none have been found within intact crystal grains, leading to suggestions that grain boundaries may play a role in the improved performance of the cells. Therefore, in this study, ingots containing large monocrystals of CuInSe(2) have been grown, using a vertical-Bridgman method, from melts that also include a varying quantity of sodium. In order to simulate the conditions under which cells are constructed, a proportion of Se above stoichiometry has been added to some of the melts. Resistivity and Hall effect measurements were then performed on the material after growth. The results show no large change in either resistivity or majority hole concentration in either set of samples, although a slight decrease in the latter value was apparent in the excess Se samples with 0.2 and 0.3 at.% Na additions. No clear trend in hole mobility could be discerned, although an increase was seen with 0.2 at.% Na addition for both samples.

Radiographic hand osteoarthritis: patterns and associations with hand pain and function in a community-dwelling sample.

OBJECTIVE: Patterns of radiographic osteoarthritis (ROA) of the hand are often examined by row, with the four joints of the thumb studied inconsistently. The objectives of this study were to determine relationships of ROA at different hand joints, use the findings to define radiographic sub-groups and investigate their associations with pain and function. METHODS: Sixteen joints in each hand were scored for the presence of ROA in a community-dwelling cohort of adults, 50-years-and-over, with self-reported hand pain or problems. Principal components analysis (PCA) with varimax rotation was used to study patterns of ROA in the hand joints and identify distinct sub-groups. Differences in pain and function between these sub-groups were assessed using Australian/Canadian Osteoarthritis Index (AUSCAN), Grip Ability Test (GAT) and grip and pinch strength. RESULTS: PCA was undertaken on data from 592 participants and identified four components: distal interphalangeal joints (DIPs), proximal interphalangeal joints (PIPs), metacarpophalangeal joints (MCPs), thumb joints. However, the left thumb interphalangeal (IP) joint cross-loaded with the PIP and thumb groups. On this basis, participants were categorised into four radiographic sub-groups: no osteoarthritis (OA), finger only OA, thumb only OA and combined thumb and finger OA. Statistically significant differences were found between the sub-groups for AUSCAN function, and in women alone for grip and pinch strength. Participants with combined thumb and finger OA had the worst scores. CONCLUSION: Individual thumb joints can be clustered together as a joint group in ROA. Four radiographic sub-groups of hand OA can be distinguished. Pain and functional difficulties were highest in participants with both thumb and finger OA.

Discrepancies between self-report and objective measures for stimulant drug use in HIV: cognitive, medication adherence and psychological correlates.

While it has long been recognized that self-reported drug use may be at variance with objectively obtained evidence such as urine toxicology assays, few studies have explored the behavioral correlates of such discrepancies. Here we compared self-reported and objective measures of stimulant drug use for 162 HIV infected individuals and identified a sub-group with discrepancies between data obtained via the two methods. Results showed poorer neurocognitive performance (attention, learning/memory) and lower medication adherence rates for the discrepant group as compared to those who either acknowledged their drug use or accurately denied recent stimulant use. Using the Millon Clinical Multiaxial Inventory-III, it was also found that those in the discrepant group were more hesitant to reveal psychopathology. Comparisons of self-reported and objectively measured medication adherence data are also discussed.

Cocarcinogenic activity of peroxy compounds.

Peracetic acid was a potent tumor promoter and a weak complete carcinogen on the skin of female ICR Swiss mice. "Decomposed peracetic acid" was inactive as a tumor promoter, as were 3% [hydrogen peroxide and 5%] urea peroxide; 1% perbenzoic acid and m-chloroperbenzoic acid were active tumor prototers.

The combined action of two thyroidal proteases releases T4 from the dominant hormone-forming site of thyroglobulin.

Thyroid hormones are synthesized within the thyroglobulin (Tg) molecule and must be released to reach the circulation and exert their metabolic effect. We have previously shown that three lysosomal endopeptidases, cathepsin B, D, and L, are active in the early stages of intrathyroidal degradation of Tg but do not themselves release free hormone. The current study examines the role of exopeptidases as the next step in thyroid hormone release. Human thyroidal cathepsin B and two partially purified exopeptidases, dipeptidyl peptidase II (DP-PII) and lysosomal dipeptidase I (LDPI), were used to digest the 20-kDa N-terminal peptide of rabbit Tg, which contains the dominant T4 site of Tg at residue 5. Cathepsin B acted as an endopeptidase initially, producing small T4-containing peptides. After more extended digestion, it also acted as an exopeptidase, producing the dipeptide T4-Gln, corresponding to residues 5 and 6 of Tg. Lysosomal dipeptidase I alone had no effect on 20 kDa but acted in combination with cathepsin B to release T4 from the T4-Gln dipeptide. Although addition of DPPII increased the release of hormone from 125I-Tg by an extract of DPPII-deficient lysosomes, it had no apparent effect on the degradation of the 20-kDa peptide, either alone or in combination with cathepsin B or LDPI. Thus DPPII may act in synergy with some other endopeptidase, or alternatively, may play a role in the release of hormone from other sites in Tg. We conclude that the N-terminus of Tg, which contains its major hormonogenic site, is particularly susceptible to hydrolysis by the endopeptidase cathepsin B and that cathepsin B additionally has an important exopeptidase action that allows it to release a T4 dipeptide that is then further degraded by LDPI to release free T4.

Thyroids from siblings with Pendred's syndrome contain thyroglobulin messenger ribonucleic acid variants.

We studied thyroid tissue from two siblings with Pendred's syndrome (familial goiter and congenital deafness), both with the Mondini-type inner ear malformation, goiter, and hypothyroidism. Iodine trapping and peroxidase levels were grossly normal. Thyroglobulin (Tg), the only iodoprotein found, had a normal monomer size (330 kilodaltons), but low content of hormone and iodine. Tg's expected N-terminal peptides of 26 and 18 kilodaltons, usually formed in association with iodination and thyroid hormone synthesis, were absent, but appeared after iodination in vitro. Reverse transcription of ribonucleic acid from Pendred thyroid tissue and amplification by polymerase chain reaction of specific regions encoding the most important hormonogenic sites of Tg revealed a normal complementary DNA sequence corresponding to the first 100 amino acid residues in Tg's N-terminus. However, 3 of 35 clones of the 3'-region corresponding to the Tg C-terminus exhibited a deletion of nucleotides 7860-7994; this deletion was not present in any of the 150 clones from 7 other thyroids we examined. Four Pendred clones had a 2-nucleotide deletion at positions 7870-7871, a change that would result in a premature stop codon and was found in thyroids from several other subjects as well. We conclude that the messenger ribonucleic acid encoding the 3'-region of Tg can be abnormal in Pendred's syndrome. Some, but not all, of these changes also occur in other human thyroids. Further work is necessary to show if and how these alterations relate to defective hormone synthesis and goiter.

Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study.

Cocaine can cause a variety of neuropsychiatric and neurobehavioral complications; however, it is uncertain whether cocaine causes persistent cerebral structural and neurochemical abnormalities in asymptomatic users. We studied 52 African-American men (26 human immunodeficiency virus-negative asymptomatic heavy cocaine users and 26 normal subjects). Ventricle-to-brain ratio (VBR) and white matter lesions (WML) were quantified on magnetic resonance imaging. N-acetyl-containing compounds (NA), total creatine, choline-containing compounds, myo-inositol, and glutamate + glutamine were measured with in vivo proton magnetic resonance spectroscopy, VBR and WML were not significantly different in the cocaine users compared to the normal controls. Elevated creatine (+7%; p = .05) and myo-inositol (+18%; p = .01) in the white matter were associated with cocaine use. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal. Normal NA suggest no neuronal loss or damage in the brain regions examined in these cocaine users. Therefore, we conclude that neurochemical abnormalities observed might result from alterations in nonneuronal brain tissue.

Hypertension in blacks: psychosocial and biological perspectives.

The extraordinarily high rate of hypertension in blacks remains a significant public health issue in most industrialized societies. Research has focused on the investigation of racial differences in biological, nutritional, behavioural and psychological, and social factors in an effort to identify the causes of this high morbidity rate. Thus far, research suggests important racial differences in renal functioning, particularly in sodium metabolism and plasma renin activity, as well as potassium intake and sodium:potassium ratio. Behavioral factors such as anger-coping style and John Henryism, and social factors such as socioeconomic status, socioecological stress, social support, urban-rural residence, and family interaction patterns have also been identified as potential contributors. Finally, emerging research paradigms such as laboratory stress reactivity and 24-h ambulatory monitoring of blood pressure may provide promising leads about the interaction between these effects and hypertension in black populations.

American Academy of Pediatrics. Committee on Practice and Ambulatory Medicine and Committee on Medical Liability. Pediatric physician profiling.

Employers, insurers, and other purchasers of health care services collect data to profile the practice habits of pediatricians and other physicians. This policy statement delineates a series of recommendations that should be adopted by health care purchasers to guide the development and implementation of physician profiling systems.

A computer-assisted, interactive radiology learning program.

A computer-assisted adjunct to traditional radiology teaching files is described. The student is presented with an image and questions with multiple choice answers. The student's choice leads to additional presentations that reinforce correct responses and provide a critique of incorrect answers. The process is under the control of a teaching script. Requirements for the system included the ability to present high-resolution radiology images along with text; high capacity for storing teaching scripts and images; ease of use by students and authors of teaching scripts; and reasonable cost. A prototype program was written in C-language and run on an IBM PS/2 (IBM Corp., Armonk, NY) with DOS. The hardware also included a 30 megabyte disk drive, an IBM Image Adapter/A and a 14 inch IBM 8514 monitor operating at a 1024 X 768 X 8 bit resolution. Image acquisition was accomplished with a high resolution Pulnix video camera (Pulnix Corp., Tokyo, Japan), with an Imaging Technology (Imaging Technology Corp., Weston, MA) frame grabber, attached to an IBM PC/AT. All hardware is available commercially. A sample teaching file was constructed using a case of ischemic colon after a cecal volvulus. Students used the system and provided a critique. Results indicate that computer-assisted teaching programs can be a valuable addition to traditional teaching methods in radiology.

Natural bioburden levels detected on rigid lumened medical devices before and after cleaning.

Controversy exists concerning the degree of microbial contamination associated with the use of rigid lumened medical devices, the efficacy of standard cleaning techniques used to remove pathogenic microorganisms from lumen channels, and whether patients are placed at risk of cross infection because of microbial contamination. In this study the level and types of microorganisms found on rigid lumened medical devices before and after cleaning in a hospital environment were investigated. The bioburden level after clinical use was found to be relatively low, ranging from 10(1) to 10(4) colony forming units (CFU) per device. After the instruments were cleaned, none of the devices studied contained bioburden levels greater than 10(4) CFU and 83% had bioburden levels less than or equal to 10(2) CFU. The bioburden present before cleaning was comprised of organisms derived from the handling of the device, from the hospital environment, and from the patient. The bioburden present after cleaning was comprised of organisms typically derived from the handling of the device and from the hospital environment. The level of bioburden per device was also related to the anatomic site where the device was used, with lower numbers of organisms found on devices exposed to sterile body sites and the respiratory tract.

Levels of naturally occurring microorganisms on surgical instruments after clinical use and after washing.

Surgical instruments exposed to sterile body sites should be contaminated with relatively low levels of microbial contamination or bioburden; however, few studies in the literature have determined the quantitative level and types of contamination. A study was conducted at 2 clinical sites to determine the level of microbial contamination of surgical instruments after clinical use and after washing. Quantitative assays showed that bioburden levels were in the range of 0 to 4415 colony forming units per instrument after clinical use, and 88% of the instruments had bioburden levels lower than 1000. As expected, a reduction in counts occurred after washing; however, in some cases, higher counts were found on the instruments after the washing process. Although the washing procedure is effective in reducing the microbial levels deposited on the surgical instruments during use, a recontamination process occurs that results in increased counts after washing. The low bioburden level after washing consists of predominantly vegetative microorganisms that present a relatively low challenge to sterilization and disinfection systems.