Quantifying the burden of emotional ill-health amongst patients referred to a specialist rheumatology service.

OBJECTIVES: (1) To determine the prevalence of emotional disorders (DSM IV depression, anxiety and panic disorders) amongst patients referred to a rheumatology out-patient service and the proportion of these detected by the rheumatologist. (2) To test the hypotheses that emotional disorders are associated with (i) broad categories of rheumatological diagnosis (systemic, inflammatory vs non-systemic, non-inflammatory), (ii) female gender, (iii) greater symptom burden and disability and (iv) markers of socio-economic deprivation. METHODS: A cross-sectional study was made of consecutive newly referred attenders at a hospital-based, regional rheumatology service. Emotional disorders, pain, health status and socio-economic factors were assessed by questionnaire. The letter to the referrer was scrutinized for the rheumatological diagnosis and mention of emotional disorder. RESULTS: A total of 256 patients were eligible and 203 (79%) participated. The sample was 69% female, had a mean age of 50 yr and 68 patients (33.5%) had one or more emotional disorders. Only a minority were detected. There was no association with type of rheumatological diagnosis. Patients with an emotional disorder were more likely to be female (81 vs 62%; P<0.007), to report more pain (mean Visual Analogue Score 70 vs 50 mm, P<0.001), a greater number of somatic symptoms (median 3 vs 1, P<0.001) and greater disability (median Health Assessment Questionnaire 1.1 vs 0.5, P<0.001). Emotional disorders were also associated with some, but not all, measures of lower social and economic status and life dissatisfaction. CONCLUSIONS: Emotional disorder is present in one-third of new rheumatology referrals. The course, causation and management of this important component of rheumatological illness merit further attention.

Medically unexplained symptoms in patients referred to a specialist rheumatology service: prevalence and associations.

OBJECTIVES: To determine the prevalence of medically unexplained rheumatic symptoms amongst patients newly referred to a rheumatology out-patient service and to examine their relationship with pain, disability, socioeconomic factors and the presence of emotional disorders (anxiety, depression and panic). METHODS: A sample of newly referred consecutive patients to a hospital-based, regional rheumatology service was administered a questionnaire for assessment of emotional disorders, pain, health status and socioeconomic factors. Rheumatologists rated the degree to which patients' symptoms were explained by organic disease (organicity rating). RESULTS: Two hundred and fifty-six patients were eligible and 203 (79%) participated. The sample included 69% females and mean age was 50 yr. Ninety-three (46%) had symptoms that were completely explained, 52 (26%) largely explained, 41 (20%) somewhat explained and 17 (8%) not at all explained by organic disease. Patients whose symptoms were of "low organicity" (somewhat or not at all explained) were more likely to be female [relative risk (RR) 1.8, 95% confidence interval (CI) 1.0-3.1], younger (mean age 44 vs 52 yr, P<0.001) and to report more somatic symptoms (median 2 vs 1, P=0.021). On univariate analysis they were more likely to be experiencing financial hardship (RR 1.7, 95% CI 1.1-2.6) and work dissatisfaction (RR 1.6, 95% CI 1.0-2.4) and to live in rented housing (RR 1.8, 95% CI 1.2-2.8) or with dependent relatives (RR 1.6, 95% CI 1.0-2.5). Logistic regression showed that female gender and living in rented housing were the significant independent predictors of low organicity. Organicity ratings were not associated with pain severity, disability, physical and mental health status or the presence of emotional disorders. CONCLUSIONS: Twenty-nine per cent of patients newly referred to rheumatology clinics had symptoms that were poorly explained by identifiable rheumatic disease. Having unexplained symptoms was associated with socioeconomic factors but not levels of pain, disability or emotional disorders.

Does waiting matter? A randomized controlled trial of new non-urgent rheumatology out-patient referrals.

OBJECTIVE: To examine the effect of waiting times on the health status of patients referred for a non-urgent rheumatology opinion. METHODS: The study was a randomized controlled clinical study evaluating a 'fast track' appointment with a 6-week target waiting time against an 'ordinary' appointment in the main city out-patient clinic of the rheumatology service for the Lothian and Borders region (population approximately 1 million). Health status was measured using the SF12 physical and mental summary component T-scores and pain was measured with a 100 mm visual analogue pain scale. Secondary outcomes were health utility and perceived health both measured with the EuroQol instrument, mental health measured with the Hospital Anxiety and Depression scale, disability with the modified Health Assessment Questionnaire and economic costs measured from a societal perspective. RESULTS: Mean waiting times were 43 days (sigma = +/-16) and 105 days (sigma = +/-51) for 'fast track' and 'ordinary' appointments, respectively. Both groups showed significant improvements in mean [95% confidence interval (CI)] scores for pain: 11 (7, 16)(P < 0.001); physical health status: 4 (2, 5) (P < 0.001); mental health status: 2 (0.1, 4) (P < 0.02); and health utility: 0.11 (0.07, 0.16) (P < 0.001) by the end of the 15-month period of the study, but there was no significant difference between either arm of the study. CONCLUSIONS: Rationing by delay was not detrimental to either mental or physical health and patients in both arms of the study showed significant and similar improvement in health by 15 months. Expenditure of resources on waiting times without regard to clinical outcomes is likely to be wasteful and additional resources should be directed at achieving the greatest clinical benefit. More research into effective methods of controlling demand and better identification of those who would benefit from access to specialist care is needed.

DNA-Flow cytometric analysis of bladder TCC using paraffin-embedded tissues.

A retrospective study of DNA flow cytometry (FCM) in paraffin-embedded tissues of urinary bladder transitional cell carcinoma (TCC) was performed on 239 biopsy samples taken from 81 patients in the period from 1984 to 1994. 210 (87%) were analysable. Of these samples 21 patients had multiple biopsies taken from large tumours and/or bladder mucosa showing an endoscopically normal appearance. DNA-FCM results have been evaluated comparing ploidy and histopathological grade, clinical stage and different clinical status, i.e., first diagnosis, recurrence and patients who died from bladder cancer. Our results indicate that 'diploid' FCM correlated with a better prognosis, whilst DNA aneuploid correlated with malignancy and a poorer prognosis. There was a trend to an increasing incidence of DNA aneuploidy as the grade of the tumour rose and the proportion of biopsies with aneuploidy was significantly higher in malignant tissue samples, recurrences and in biopsies from patients who died from TCC than in other groups. In 12 patients from whom several biopsies were obtained, samples from recurrences had significantly higher DNA aneuploidy than those from the first diagnosis.

The gamma-subunit of the rod photoreceptor cGMP-binding cGMP-specific PDE is expressed in mouse lung.

The type 6 phosphodiesterase (PDE-6) from retinal rod photoreceptors is an alpha beta gamma 2 heterotetramer. The alpha- and beta-subunits contain catalytic sites for cGMP hydrolysis, whereas the gamma-subunits (P gamma) serve as a protein inhibitor of the enzyme. P gamma is believed to be expressed only in photoreceptors. Using RT-PCR, we have amplified the complete coding sequence for P gamma from mouse lung RNA. The expression of P gamma in this tissue may be related to its ability to interact the type 5 phosphodiesterase (PDE-5), which is the predominant cGMP binding protein in lung. We therefore suggest that P gamma may have a wider signaling role in mammalian cells than previously appreciated.

Is day care equivalent to inpatient care for active rheumatoid arthritis? Randomised controlled clinical and economic evaluation.

OBJECTIVE: To test the clinical equivalence and resource consequences of day care with inpatient care for active rheumatoid arthritis. DESIGN: Randomised controlled clinical trial with integrated cost minimisation economic evaluation. SETTING: Rheumatic diseases unit at a teaching hospital between 1994 and 1996. SUBJECTS: 118 consecutive patients with active rheumatoid arthritis randomised to receive either day care or inpatient care. MAIN OUTCOME MEASURES: Clinical assessments recorded on admission, discharge, and follow up at 12 months comprised: the health assessment questionnaire, Ritchie articular index, erythrocyte sedimentation rate, hospital anxiety and depression scale, and Steinbrocker functional class. Resource estimates were of the direct and indirect costs relating to treatment for rheumatoid arthritis. Secondary outcome measures (health utility) were ascertained by time trade off and with the quality of well being scale. RESULTS: Both groups had improvement in scores on the health assessment questionnaire and Ritchie index and erythrocyte sedimentation rate after hospital treatment (P < 0.0001) but clinical outcome did not differ significantly between the groups either at discharge or follow up. The mean hospital cost per patient for day care, 798 Pounds (95% confidence interval 705 Pounds to 888 Pounds), was lower than for inpatient care, 1253 Pounds (1155 Pounds to 1370 Pounds), but this difference was offset by higher community, travel, and readmission costs. The difference in total cost per patient between day care and inpatient care was small (1789 Pounds (1539 Pounds to 2027 Pounds) v 2021 Pounds (1834 Pounds to 2230 Pounds)). Quantile regression analysis showed a cost difference in favour of day care up to the 50th centile (374 Pounds; 639 Pounds to 109 Pounds). CONCLUSIONS: Day care and inpatient care for patients with uncomplicated active rheumatoid arthritis have equivalent clinical outcome with a small difference in overall resource cost in favour of day care. The choice of management strategy may depend increasingly on convenience, satisfaction, or more comprehensive health measures reflecting the preferences of patients, providers, and service commissioners.

Concurrent colonic adenocarcinoma and two ileal carcinoids in a 72-year-old male.

A case of synchronous rectal cancer and two small-bowel carcinoid tumours was recently encountered in a 72-year-old man. This will be presented and discussed with a literature review. It emphasizes the importance of the concept of synchronous malignancy within the gastrointestinal tract and that patients presenting with any gastrointestinal neoplasm, especially colonic cancer and carcinoids, should undergo thorough exploration of the peritoneal cavity and its organs at initial surgery.

The regulation of the cGMP-binding cGMP phosphodiesterase by proteins that are immunologically related to gamma subunit of the photoreceptor cGMP phosphodiesterase.

The cGMP phosphodiesterase from retinal rods (PDE-6) is an alphabetagamma2 heterotetramer. The alpha and beta subunits contain catalytic sites for cGMP hydrolysis, whereas the gamma subunits serve as a protein inhibitor of the enzyme. Visual excitation of photoreceptors enables the activated GTP-bound form of the G-protein transducin to remove the inhibitory action of the gamma subunit, thereby triggering PDE-6 activation. The type 5 phosphodiesterase (PDE-5) isoform shares a number of similar characteristics with PDE-6, including binding of cGMP to noncatalytic sites, the cyclic nucleotide specificity, and inhibitor sensitivities. Although the functional role of PDE-5 remains unclear, it has been shown to be activated by protein kinase A (PKA) (Burns, F., Rodger, I. W. & Pyne, N. J. (1992) Biochem. J. 283, 487-491). Here we report that both the recombinant gamma subunit and a peptide corresponding to amino acids 24-46 in this protein inhibited the activation of PDE-5 by PKA. Furthermore, immunoblotting airway smooth muscle membranes with a specific antibody against amino acids 24-46 of the PDE-6 gamma subunit identified two major immunoreactive small molecular mass proteins of 14 and 18 kDa (p14 and p18). These appear to form a complex with PDE-5, because PDE activity was immunoprecipitated using antibody against the PDE-6 gamma subunit. p14 and p18 were also substrates for phosphorylation by a unidentified kinase that was stimulated by a pertussis toxin-sensitive G-protein. Phosphorylation of p14/p18 in membranes treated with guanine nucleotides correlated with a concurrent reduction in the activation of PDE-5 by PKA. We suggest that p14 and p18 share an epitope common to PDE-6 gamma and that this region may interact with PDE-5 to prevent its activation by PKA.

The prognostic significance of tumor-associated markers p53, HER-2/neu, c-myc, v-H-ras, PCNA and EGFr of local and distant recurrence in localized human prostatic adenocarcinoma.

The intracellular expression of the gene products of tumor-associated markers p53, proliferative cell nuclear antigen (PCNA), HER-2/neu, c-myc, H-ras, and epidermal growth factor receptor (EGFr) in 86 cases of localized prostatic adenocarcinoma was investigated immunohistochemically in formalin-fixed paraffin-embedded tissue sections after pretreatment with a novel antigen retrieval buffer. A scoring system was devised to assess strength, pattern, and combined strength/pattern of immunostainings in the nucleus and cytoplasm for each immunomarker. The results were evaluated to determine whether overexpression of the gene products in the nucleus and cytoplasm was predictive of local and/or distant tumor recurrence and whether their expression was associated with known clinical prognostic factors. There was no significant relation between p53, PCNA, HER-2/neu, c-myc, and H-ras protein expression with risk of recurrence. EGFr expression showed a trend of increasing risk of tumor recurrence with higher composite score. Analysis of the association with other known prognostic factors in prostatic adenocarcinoma showed that PCNA was significantly correlated with tumor stage while H-ras and HER-2/neu were marginally correlated with prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) pretreatment serum levels, respectively. Together our findings suggest that overexpression of these intracellular oncoproteins in the tumor cells may not play an important role in determining whether prostatic tumors are likely to recur in localized prostatic adenocarcinoma.

Validity of Euroqol--a generic health status instrument--in patients with rheumatoid arthritis. Economic and Health Outcomes Research Group.

The main aim of this pilot study was to test the 'construct' validity of Euroqol, a new generic health status instrument which consists of a questionnaire and visual analogue scale. Its ability to measure both current health status and change in health status was assessed in 55 patients with RA. The Euroqol questionnaire and visual analogue scales showed significant and clinically relevant correlations with other condition-specific instruments measuring loss of function, joint pain, joint tenderness and mood; change in these symptoms as measured by the condition-specific instruments was also predictive of change in Euroqol scores. Either component of the Euroqol instrument provide an index of current clinical status and these data provide preliminary evidence for the 'construct' validity of Euroqol in RA. Further work is needed to evaluate more fully the sensitivity of Euroqol to change over time.

A pilot study of the economic cost and clinical outcome of day patient vs inpatient management of active rheumatoid arthritis.

The aims of this pilot study, which compares day patient with inpatient care for management of active RA were (i) to test the feasibility of a trial protocol design including the method of randomization and the practicality of data collection, and (ii) to obtain preliminary information on economic cost and clinical outcome of these two methods of management. Twenty consecutive patients requiring admission for management of active RA were randomized to receive either day patient or inpatient care. All hospital, transport, community and indirect costs incurred over a 6-month period from recruitment were collected for each patient. Disease activity and clinical outcome were assessed using the Ritchie articular index, ESR, Health Assessment Questionnaire, Functional Independence Measure and Hospital Anxiety and Depression Scale. The trial protocol was found to be feasible and no patient allocated to the day patient group requested or required to be transferred to inpatient care. Day care was significantly cheaper than inpatient care despite higher transport costs; the total cost of treating 10 day patients was UK 10,272 pounds compared with 14,528 pounds for 10 inpatients. Clinical outcome was comparable in both groups for all parameters studied and there was no obvious detrimental effect on patients receiving day care. This pilot study demonstrates that day care is feasible and acceptable to patients with active RA. The preliminary data suggest that day care is substantially cheaper than inpatient care and does not apparently compromise clinical outcome.

Balanitis xerotica obliterans in children.

Balanitis xerotica obliterans was studied in 48 fully developed and 6 early cases in children aged 2-15 years. It occurred in 9% of 100 consecutive circumcisions for all, including religious, reasons and in 19% of 232 other circumcisions for disease of the prepuce and penis. Seven cases developed after surgery for hypospadias. The boys nearly always presented with inability to retract the prepuce; half also had discomfort after micturition, and a quarter had obstructive signs, usually minor. At surgery, half had involvement of glans or meatus, previously considered rare in childhood, 3 requiring meatotomy. The condition, once seen, was easily recognized clinically as well as microscopically. The early cases, characterized by focal narrow hyaline edematous zones in severe diffuse chronic balanitis, suggest that the condition may be an inflammation in which the usual increased permeability of small vessels in inflammatory reaction is accentuated in a loose vascular region.