The use of anti-TNF therapy for ankylosing spondylitis in everyday rheumatology practice and the relationship to disease activity, work disability and diagnostic delay.

BACKGROUND: Ankylosing spondylitis (AS) is characterised by insidious onset lower back pain. Poor symptom recognition results in delays in diagnosis of up to 11 years. Despite the widespread use of anti-tumour necrosis factor alpha (anti-TNFα) therapy, work disability remains a challenging problem in AS. METHODS: A retrospective review of AS patients attending our physiotherapy service was carried out. Data regarding patient demographics, delay in diagnosis, treatment and disease activity were recorded. RESULTS: Ninety-two patients were identified of which 80 % were male. Just over 60 % of patients were on treatment with a TNF inhibitor and the average delay in diagnosis was 6 years. Clinically relevant changes in disease activity after 3 months of anti-TNFα therapy were demonstrated with a reduction in Bath AS Metrology Index, Bath AS Functional Index and Bath AS Disease Activity Index of 1, 1.99 and 2.39, respectively. In patients under the age of 65 years only 55.4 % of patients were employed. There was no relationship identified between diagnostic delay, employment status and treatment with an anti-TNF agent. CONCLUSIONS: Delays in diagnosis of AS remain unacceptably high; however, delays of 6 years compare favourably to reported data. Despite this and the appropriate use of anti-TNFα agents, we continue to see high rates of unemployment in this patient group which can impact both on the person and society and bears further consideration.

Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein.

OBJECTIVES: Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin's B-box domain is necessary for interactions with proline serine threonine phosphatase interacting protein 1 (PSTPIP1). The aim was to characterise the phenotype of patients with these substitutions and to determine their functional significance. METHODS: A database of genetic tests undertaken at the US National Institutes of Health was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Coimmunoprecipitation techniques were employed to determine the variants' effects on pyrin/PSTPIP1 interactions. RESULTS: A total of 40 symptomatic and 4 asymptomatic family members with these substitutions were identified. P369S and R408Q were found in cis, and cosegregated in all patients sequenced. Clinical details were available on 22 patients. In all, 5 patients had symptoms and signs fulfilling a clinical diagnosis of FMF, and 15 received colchicine. In patients not achieving the criteria, trials of anti-tumour necrosis factor (TNF) agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Coimmunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. CONCLUSIONS: P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modelling studies suggest that these substitutions do not significantly affect pyrin's interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms.

Fevers, genes, and innate immunity.

The characterization of patients with recurrent inflammatory syndromes into distinct clinical phenotypes provided early clues to the mode of inheritance of these conditions and facilitated the subsequent identification of causative gene mutations. The prototype autoinflammatory syndrome, familial Mediterranean fever, is characterized by self-limiting episodes of localized inflammation. Hallmarks of the classical autoimmune response are largely absent. The use of positional cloning techniques led to the identification of the causative gene, MEFV, and its product pyrin. This previously unrecognized protein plays an important role in modulating the innate immune response. Cryopyrin, the protein encoded by CIAS1, is mutated in a spectrum of autoinflammatory conditions, the cryopyrinopathies. In response to a wide range of potential pathogens, it forms a macromolecular complex termed the "inflammasome," resulting in caspase-1 activation and subsequent release of the active proinflammatory cytokine interleukin-1beta (IL-1beta). The role of an established biochemical pathway in regulating inflammation was uncovered by the discovery that the hyperimmunoglobulin D with periodic fever syndrome (HIDS) results from mutations in MVK, which encodes an enzyme in the isoprenoid pathway. The discovery that mutations in the gene encoding tumor necrosis factor (TNF) receptor 1 (TNFR1) cause a proinflammatory phenotype was unanticipated, as it seemed more likely that such mutations would instead have resulted in an immunodeficiency pattern. This review describes the clinical phenotypes of autoinflammatory syndromes, the underlying gene mutations, and current concepts regarding their pathophysiology.

Improving trends in glucocorticoid-induced osteoporosis management: 2002 to 2006.

OBJECTIVE: In 2002 we undertook an audit of GIO (glucocorticoid-induced osteoporosis) management in the outpatient clinics of our university teaching hospital and found a wide variation in practice and considerable under-treatment of patients. We re-audited our practice in 2006. METHODS: A retrospective chart audit was undertaken over a 4-month period of 3,475 patients attending the 3 medical specialty outpatient clinics that were originally audited in 2002. All glucocorticoid (GC) users over the past 6 months were identified. Demographic data and treatment details were extracted, and findings were compared with the previous audit. RESULTS: Two hundred and fifty-three (7%) patients were identified to be taking GC vs. 104 (2%) in 2002. GIO risk was documented in 71% (179) (p < 0.001) of the charts vs. 13% (19) in the previous audit. In 2002, 56% (58) were on some form of bone protection [53% (55) on Ca/vitamin D and 29% (30) on a bisphosphonate] whereas in 2006 the figures were 86% (219), 82% (207) and 57% (144), respectively. DXA scanning was performed in 32% (82) of our patients in 2006. Nonetheless, considerable variation in practice was still seen, with prescription rates for anti-resorptive therapy varying from 24%-70% and those for Ca/vitamin D supplements ranging from 15%-95% for different services. For the highest risk patients, the prescription rates by specialty ranged from 36%-72% for anti-resorptive therapy and 76%-95% for Ca/vitamin D supplements. CONCLUSION: Over 4 years, major improvements in GIO management have taken place in our institution, with almost a doubling of the prescription of bone protectants. However, there still remains a considerable variation in individual practices and an under-utilisation of DXA scanning. We believe that these overall, encouraging findings can be generalized to similar institutions elsewhere.

AA amyloidosis in psoriatic arthritis.

BACKGROUND: Amyloidosis is an extremely rare complication of psoriatic arthritis (PsA) and is associated with a poor prognosis. We report a case of amyloidosis secondary to severe PsA in a young patient and the course of his disease over a 13-year period of aggressive immunosuppression. METHODS: Diagnosis of renal amyloidosis was made on biopsy: multi-agent immunosuppressive therapy was continued with stabilisation of renal function. RESULTS: Marked deterioration in renal function subsequently occurred following a reduction in cyclosporin A (CyA) dose and repeat biopsy confirmed worsening amyloidosis. CONCLUSION: This case report emphasises the need for aggressive control of the inflammatory response in secondary amyloidosis.

An unusual case of Behçet's syndrome: triggered by typhoid vaccination?

A case of Behçet's syndrome in a 32-year-old woman occurring shortly after her third vaccination against typhoid fever is described. Scleritis and pyoderma gangrenosum were unusual manifestations of BS that occurred in this case. Treatment benefit was provided by mycophenolate mofetil and etanercept. As bacterial antigens have been proposed as potential triggers for the onset of BS, it is possible that the syndrome was precipitated by typhoid vaccination in this patient.

Current management of corticosteroid-induced osteoporosis: variations in awareness and management.

BACKGROUND: Guidelines for the prevention of corticosteroid-induced osteoporosis (CIO) have been widely published. There are no guidelines on the use of gastro-protectants with corticosteroids (CS). AIMS: To determine whether patients receiving CS therapy are evaluated and treated for osteoporosis risk, how management varied by steroid dose and diagnosis, and how many patients received gastro-protection. METHODS: A retrospective audit of 4,350 patients presenting to four medical specialities. RESULTS: One hundred and fifty-one patients prescribed CS were identified. Indications for CS therapy included renal transplantation (32%) and asthma/respiratory diseases (23%), inflammatory arthritis/vasculitis (32%) and inflammatory bowel disease/auto-immune hepatitis/other (13%). Risk of osteoporosis was mentioned in 13% of charts. The prescription rates for bone protection agents varied from 69% to 4% according to the medical speciality attended. Gastro-protectants were prescribed for 44% of patients. CONCLUSION: There are large variations among medical specialties both in the prescription of gastro-protectant agents and in the use of measures to prevent CIO. Simpler guidelines could facilitate rational prescribing in these patients.

Geochemical evidence for magmatic water within Mars from pyroxenes in the Shergotty meteorite.

Observations of martian surface morphology have been used to argue that an ancient ocean once existed on Mars. It has been thought that significant quantities of such water could have been supplied to the martian surface through volcanic outgassing, but this suggestion is contradicted by the low magmatic water content that is generally inferred from chemical analyses of igneous martian meteorites. Here, however, we report the distributions of trace elements within pyroxenes of the Shergotty meteorite--a basalt body ejected 175 million years ago from Mars--as well as hydrous and anhydrous crystallization experiments that, together, imply that water contents of pre-eruptive magma on Mars could have been up to 1.8%. We found that in the Shergotty meteorite, the inner cores of pyroxene minerals (which formed at depth in the martian crust) are enriched in soluble trace elements when compared to the outer rims (which crystallized on or near to the martian surface). This implies that water was present in pyroxenes at depth but was largely lost as pyroxenes were carried to the surface during magma ascent. We conclude that ascending magmas possibly delivered significant quantities of water to the martian surface in recent times, reconciling geologic and petrologic constraints on the outgassing history of Mars.

Why don't emergency department patients have advance directives?

OBJECTIVES: In 1997 the authors determined that only 27% of their adult ED patients had advance directives (ADs). The purpose of this follow-up study was to determine the reasons why their adult ED patients do not have ADs. METHODS: This prospective study enrolled patients from a convenience sample of representative shifts in the ED selected over a three-month period. Survey questions included demographic information, whether the patients had a life-threatening medical problem, whether they had an AD, with whom they had discussed their ADs, and the reasons why they did not have an AD. We excluded those who refused participation or who were incapacitated (i.e., any patient with a condition that precluded him or her from answering the questionnaire himself or herself, such as an altered level of consciousness, dementia, mental retardation, or inability to understand English). RESULTS: Four hundred seventy-six subjects were enrolled during the study period from an ED census of 816 adult patients. Three hundred forty patients were not included in the study for the following reasons: inability to complete the survey, refusal to participate, or not being approached by the interviewers. Of those enrolled, 77% of the patients did not have an AD (females, 73%; males, 80%). The most frequent reasons given for not having an AD were: 40% never thought about it, 24% preferred family to make the decision, and 23% were procrastinating. Factors jointly predictive of having an AD were older age, having a specialist, having a life-threatening medical problem, and not being Catholic. Patients who had ADs were discussing their ADs with their primary care physicians (PCPs) only 5% of the time. CONCLUSION: Many patients, even when they have life-threatening medical problems, do not have an AD, and several reasons for this have been identified. Few of these ED patients who had ADs had discussed them with their physicians. Further studies should assess whether more physician intervention would increase the percentage of patients who have ADs.

Health outcomes of women exposed to household alcohol abuse: a Family Practice Training Site Research Network (FPTSRN) study.

BACKGROUND: There is a paucity of knowledge about the effects of exposure to alcohol abuse in the household on women who do not abuse alcohol. The purpose of this study was to determine whether women who did not abuse alcohol demonstrated any health-related adverse effects because they lived with family members who did abuse alcohol. METHODS: This study was a historical prospective survey of female patients at five primary care practices. Survey instruments included the CAGE questionnaire, a five-item screening test for exposure to alcoholism, and the Medical Outcomes Study 36-item Short Form Health Survey (MOS SF-36). Patient records were examined for specific diagnoses. RESULTS: A total of 267 patients completed the questionnaires and had complete medical records available for analysis. Forty-two (15.7%) potential alcohol abusers were excluded from the sample leaving a working total of 225; 70 (31.1%) were potentially exposed to alcoholism in the household. Women exposed to alcohol abuse in the home did not experience an increased risk for the medical diagnoses studied, but they did demonstrate decreased health-related quality of life as measured by the MOS-SF-36 for the following scales: role physical (P = .025), role emotional (P = .038), social functioning (P = .001), bodily pain (P = .016), and mental health (P = .040). CONCLUSIONS: Women exposed to alcohol abuse in the household are more likely to perceive themselves as less healthy. Although they may not have received a clinical diagnosis of depression, they are more likely to feel depressed. The extent to which subjects' health-related quality of life is influenced by exposure to alcohol abuse suggests that the medical diagnosis may be insensitive as a description of health status in this population.

Are emergency department patients thinking about advance directives?

OBJECTIVES: To assess the percentage of adult patients presenting to an urban ED who have a written advance directive (AD) and to determine whether age, sex, a patient's perception of his or her health status, and having a regular physician are associated with the patient's having an AD. METHODS: This was a cross-sectional patient survey performed at a community teaching hospital ED. Surveys were completed by 511 adult ED patients during representative shifts over a 3-month period. The questions included age, sex, "self-reported" health status, whether the patient had a "regular" physician, a patient-generated list of medical problems, and whether the patient had a written AD. For this study, ADs included health care proxies, living wills, and do-not-attempt-resuscitation (DNAR) orders. RESULTS: Of the patients surveyed, 27% reported having an AD. Males and females were equally likely to have an AD. Factors associated with an increased likelihood of having an AD were older age, having a "regular" physician, and the patient's perception of his or her health status as ill. Most patients who had an AD (82%) discussed it with their families, but only 48% discussed it with their physicians. CONCLUSION: Only 27% of the adult patients presenting to the ED had an AD. Older age, the patient's perception of his or her health status as ill, and having a "regular" physician increased the likelihood of having an AD.

Reliability of faculty clinical evaluations of non-emergency medicine residents during emergency department rotations.

OBJECTIVES: To assess the reliability of faculty evaluations of non-emergency medicine (non-EM) residents during clinical ED rotations and to determine the effect that the "leniency" of grading by these evaluators had on the residents' final evaluations. METHODS: A prospective, observational study of the evaluation patterns of EM faculty was performed in an academic ED (50,000 visits yearly census). Each resident was evaluated on a daily basis by a board-certified or board-prepared emergency physician. The evaluation form rated 7 characteristics, but only the rating for overall clinical competence was used for data analysis. If an attending evaluated the same resident more than once, only the first evaluation was used to avoid bias from prior exposure. The scoring patterns of the evaluators, both individually and in groups, were analyzed using 1-way analysis of variance. Evaluator leniency was estimated using the mean evaluator score across all residents. Since each resident was evaluated by a different combination of evaluators, evaluator leniency for each resident was estimated from the mean leniency of the evaluators who specifically assessed that resident. RESULTS: During the period of the study, 66 residents rotated through the ED, yielding a total of 401 evaluations. When the scoring patterns of individual evaluators were analyzed, a high degree of variability was found in the mean scores (range 5.23-8.09) and SDs (range 0.45-1.55) across evaluators; p = 0.0001. There was a moderate correlation between the mean overall competence score received by each resident and that resident's evaluators' leniency, r = 0.52; p = 0.0001. CONCLUSIONS: There is significant variability in the scoring patterns of individual evaluators. The evaluators in this study showed large variations in both leniency (as measured by their mean score) and range restriction (as measured by their SD). The differences in evaluator scoring leniency have a moderate correlation with the overall score received by the resident.

Effects of incarceration on HIV-infected individuals.

Human immunodeficiency virus (HIV) infection is a critical problem among the incarcerated population, with rates as high as 17% being reported for prison systems in New York. The literature suggests that stressful living conditions and inherent defects in the immune system associated with HIV infection make prison populations more susceptible to a disproportionate decrease in their CD4 counts. To determine the effects of incarceration on HIV-infected individuals, the charts of 800 inmates were reviewed. Baseline (draw 1), 2- to 5-month (draw 2), and 6- to 12-month (draw 3) CD4 cell counts were obtained. Mean cell counts were calculated, and paired t-tests were used to identify differences. The group receiving antiretrovirals throughout showed no difference in mean CD4 cell count between draws 1 and 2 or between draws 1 and 3. The group not receiving HIV medications did not show a significant difference in CD4 cell counts between draws 1 and 2, but did show a significant difference between draws 1 and 3. For this group, the rate of decline in CD4 cells was greater than among an outpatient setting. The subsample of subjects initiating therapy prior to the second blood draw showed a significant increase in mean CD4 cell counts at draw 1 versus draw 2, but did not show a significant change when comparing draw 1 to draw 3. When examining subjects based on their antiviral status, the mean CD4 cell count at each of the draws was statistically associated with subjects' antiviral status. We conclude that incarceration causes a more rapid decrease in CD4 cells compared with an outpatient population, causing clinical significance on the normal course of HIV disease.

The female role in the transmission of HIV infection.

Women are increasingly recognized as a significant population at risk for human immunodeficiency virus (HIV) infection. In major cities in Africa, the Americas, and Europe, HIV infection is the leading cause of death in women aged 25 through 29 years. New patterns have emerged in the epidemic, the most dramatic of which is the increased rate of transmission for heterosexuals, directly associated with an increase in seropositivity among women and children. Between 1989 and 1990, the number of women diagnosed with the acquired immunodeficiency syndrome rose 34% compared with a 22% rise in men. The Centers for Disease Control and Prevention have increased support for studies related to prevention of HIV infection in response to these trends. Health professionals should demonstrate an understanding of the complex nature of sexuality, femininity, and the female role in society when educating female patients about virus avoidance, so that preventive behavior will be perceived as consistent with a woman's personal standards for sexual relationships.

Family physicians' support for school-based HIV prevention education programs.

OBJECTIVE: To identify the extent to which family physicians support school-based education programs regarding the human immunodeficiency virus (HIV). Sexually active adolescents are at risk for infection with HIV. Education programs on HIV that target this vulnerable group effectively prevent infection, yet family physicians are often not directly involved in the design and implementation of such programs. DESIGN: A systematic random sample of 2660 members of the American Academy of Family Physicians was surveyed using a mailed questionnaire to assess clinical experiences with HIV disease, willingness to provide HIV treatment, and support for school-based HIV education programs. The response rate was 63.7%. Poststratification weights were applied to adjust for the slight under-representation of non-board-certified physicians in the study sample. RESULTS: Support for school-based HIV counseling programs was overwhelmingly positive. The mean level of support was 1.28 (with 1 indicating strong approval and 4 strong disapproval). Physicians' attitudes toward programs that include condom availability were marginally less favorable (1.92). Residency trained (P = .009) and female physicians (P = .010) expressed the greatest support for school-based programs. Physicians with fewer professional concerns about providing direct HIV patient care (P = .030) and who believed that communication with their patients about sexuality was an acceptable component of clinical care (P < .001) were most likely to support school-based programs. CONCLUSIONS: Family physicians can play an important role in designing and implementing HIV education programs. The results of these analyses suggest family physicians may be relied on to endorse school-based HIV prevention programs, including programs that make condoms available to adolescents. School and public health authorities should enlist family physicians' assistance when planning and implementing these or related community-based HIV education activities.

Family physician attitudes about HIV screening.

This study examined why and for whom family physicians are likely to require HIV screening according to general policies or procedures, based on a national survey of 2,660 family practice physicians. Of those contacted, 1,678 responded, yielding a response rate of 63.7%. The study also examined whether attitudes toward screening differed for physicians in different types of practices, of varying educational backgrounds, and with differing opinions regarding treating persons with AIDS (PWAs). The results showed that required screening was most strongly endorsed for pregnant women who had other risk factors and for i.v. drug users. Those physicians who most favored mandatory screening were also most likely to favor the mandatory reporting of AIDS cases to public health officials. They also had the least formal medical training (were not residency trained or board certified) and expressed the greatest apprehension regarding their own and their staff's preparedness and willingness to treat PWAs. A major implication of the findings is that family physicians and others who do mandatory testing should be provided opportunities, through residency training, board-certification preparation, or continuing medical education, to learn how to care for those patients they test who turn out to be seropositive.

Ectoparasites and endoparasites in sexually transmitted diseases.

A number of protozoan organisms, both ectoparasitic and endoparasitic, may be related to sexual activity. The broad range of clinical presentations makes this group of diseases challenging to diagnose. Patients may present with skin, genital, gastroenterologic, pulmonary, or neurologic symptoms, or may be asymptomatic. A careful history, including specific sexual history, with appropriate laboratory evaluation will aid the primary care physician in making the correct diagnosis and thus supply the correct treatment. Awareness that infection with multiple organisms is frequent in some populations is important. Prevention of reinfection or further transmission of the disease must be aggressively pursued by patient education about the means of transmission of the disease and avoidance of high-risk sexual practices.