Abnormal Laboratory Test Results Research Articles

Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five long-term extensions

We present safety and efficacy data from Japanese clinical studies on monotherapy with tocilizumab (TCZ), a humanized anti-interleukin 6 receptor monoclonal antibody, in which 601 patients with moderate to severe rheumatoid arthritis, with a total of 2188 patient-years (pt-yr) exposure, were enrolled. The median treatment duration was 3.8 years. The incidence of adverse events (AEs), including abnormal laboratory test results, was calculated as 465.1 per 100 pt-yr. The most common serious adverse events (SAEs) were infections (6.22 per 100 pt-yr). There was no increase in the frequency of AEs or SAEs with long-term treatment. Abnormalities in the laboratory test results, such as increases in lipid parameters or abnormal liver function parameters, were common, but most were mild and there were no SAEs related to them. At baseline, 546 patients (90.8%) were taking corticosteroids; of these, 77.8% were able to decrease their corticosteroid dose during the study period, while 35.2% discontinued corticosteroids altogether. In the patients treated longer than 5 years, 91.3, 73.0, and 51.3% met the ACR20, ACR50, and ACR70 response criteria, respectively, and 59.7% met the DAS remission criterion (DAS28 <2.6) at 5 years. In conclusion, based on these results, TCZ has shown good tolerability and high efficacy during long-term treatment.

Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five long-term extensions

We present safety and efficacy data from Japanese clinical studies on monotherapy with tocilizumab (TCZ), a humanized anti-interleukin 6 receptor monoclonal antibody, in which 601 patients with moderate to severe rheumatoid arthritis, with a total of 2188 patient-years (pt-yr) exposure, were enrolled. The median treatment duration was 3.8 years. The incidence of adverse events (AEs), including abnormal laboratory test results, was calculated as 465.1 per 100 pt-yr. The most common serious adverse events (SAEs) were infections (6.22 per 100 pt-yr). There was no increase in the frequency of AEs or SAEs with long-term treatment. Abnormalities in the laboratory test results, such as increases in lipid parameters or abnormal liver function parameters, were common, but most were mild and there were no SAEs related to them. At baseline, 546 patients (90.8%) were taking corticosteroids; of these, 77.8% were able to decrease their corticosteroid dose during the study period, while 35.2% discontinued corticosteroids altogether. In the patients treated longer than 5 years, 91.3, 73.0, and 51.3% met the ACR20, ACR50, and ACR70 response criteria, respectively, and 59.7% met the DAS remission criterion (DAS28 <2.6) at 5 years. In conclusion, based on these results, TCZ has shown good tolerability and high efficacy during long-term treatment.

Notification of Abnormal Lab Test Results in an Electronic Medical Record: Do Any Safety Concerns Remain?

Background Follow-up of abnormal outpatient laboratory test results is a major patient safety concern. Electronic medical records can potentially address this concern through automated notification. We examined whether automated notifications of abnormal laboratory results (alerts) in an integrated electronic medical record resulted in timely follow-up actions. Methods We studied 4 alerts: hemoglobin A1c ≥15%, positive hepatitis C antibody, prostate-specific antigen ≥15 ng/mL, and thyroid-stimulating hormone ≥15 mIU/L. An alert tracking system determined whether the alert was acknowledged (ie, provider clicked on and opened the message) within 2 weeks of transmission; acknowledged alerts were considered read. Within 30 days of result transmission, record review and provider contact determined follow-up actions (eg, patient contact, treatment). Multivariable logistic regression models analyzed predictors for lack of timely follow-up. Results Between May and December 2008, 78,158 tests (hemoglobin A1c, hepatitis C antibody, thyroid-stimulating hormone, and prostate-specific antigen) were performed, of which 1163 (1.48%) were transmitted as alerts; 10.2% of these (119/1163) were unacknowledged. Timely follow-up was lacking in 79 (6.8%), and was statistically not different for acknowledged and unacknowledged alerts (6.4% vs 10.1%; P =.13). Of 1163 alerts, 202 (17.4%) arose from unnecessarily ordered (redundant) tests. Alerts for a new versus known diagnosis were more likely to lack timely follow-up (odds ratio 7.35; 95% confidence interval, 4.16-12.97), whereas alerts related to redundant tests were less likely to lack timely follow-up (odds ratio 0.24; 95% confidence interval, 0.07-0.84). Conclusions Safety concerns related to timely patient follow-up remain despite automated notification of non-life-threatening abnormal laboratory results in the outpatient setting.

Pretest expectations strongly influence interpretation of abnormal laboratory results and further management

BackgroundAbnormal results of diagnostic laboratory tests can be difficult to interpret when disease probability is very low. Although most physicians generally do not use Bayesian calculations to interpret abnormal results, their estimates of pretest disease probability and reasons for ordering diagnostic tests may - in a more implicit manner - influence test interpretation and further management. A better understanding of this influence may help to improve test interpretation and management. Therefore, the objective of this study was to examine the influence of physicians' pretest disease probability estimates, and their reasons for ordering diagnostic tests, on test result interpretation, posttest probability estimates and further management.MethodsProspective study among 87 primary care physicians in the Netherlands who each ordered laboratory tests for 25 patients. They recorded their reasons for ordering the tests (to exclude or confirm disease or to reassure patients) and their pretest disease probability estimates. Upon receiving the results they recorded how they interpreted the tests, their posttest probability estimates and further management. Logistic regression was used to analyse whether the pretest probability and the reasons for ordering tests influenced the interpretation, the posttest probability estimates and the decisions on further management.ResultsThe physicians ordered tests for diagnostic purposes for 1253 patients; 742 patients had an abnormal result (64%). Physicians' pretest probability estimates and their reasons for ordering diagnostic tests influenced test interpretation, posttest probability estimates and further management. Abnormal results of tests ordered for reasons of reassurance were significantly more likely to be interpreted as normal (65.8%) compared to tests ordered to confirm a diagnosis or exclude a disease (27.7% and 50.9%, respectively). The odds for abnormal results to be interpreted as normal were much lower when the physician estimated a high pretest disease probability, compared to a low pretest probability estimate (OR = 0.18, 95% CI = 0.07-0.52, p < 0.001).ConclusionsInterpretation and management of abnormal test results were strongly influenced by physicians' estimation of pretest disease probability and by the reason for ordering the test. By relating abnormal laboratory results to their pretest expectations, physicians may seek a balance between over- and under-reacting to laboratory test results.

Reasons for ordering laboratory tests and relationship with frequency of abnormal results

Objective. Laboratory tests are ordered on a daily basis, even though disease probability is often very low. Abnormal results, especially mildly abnormal results, can be difficult to interpret in these circumstances. Further insights into the occurrence of abnormalities can help improve rational test ordering and test interpretation. The objective was therefore to examine the frequency of mildly and markedly abnormal results and their relationship with physicians' reasons for ordering tests. Design. Prospective study. Participants. A total of 87 primary care physicians in the Netherlands collected data on 1775 patients. Main outcome measures. The physicians recorded the reason for ordering the tests, the most probable diagnosis and the pretest probability. The laboratories' reference values and specified “action limits” were used to assess the number of abnormal results and markedly abnormal results, respectively. Results. Laboratory results were received for 1621 patients and 15,603 tests were reported (mean 9.6). The proportion of abnormal test results increased with increasing pretest probability (from 13.9% to 34.7%) and was 13.4% for tests ordered to reassure the patient and 13.3% for psychosocial diagnoses. The proportion of patients with at least one abnormal test result was high: 53.1% for tests ordered to reassure and 57.7% in patients with low pretest probability. Corresponding values for a marked abnormality were 11.1% and 12.4%, respectively. Conclusion. Abnormal laboratory test results were frequent, even when pretest probability was low. Physicians should therefore carefully consider when tests are necessary. Future research could explore physicians' interpretation of test results and its impact on diagnosis and management.

Alitretinoin in Severe Chronic Hand Eczema†

m Alitretinoin is an endogenous retinoid and acts as a pan-agonist at retinoid receptors, binding with high affinity to both retinoic acid receptors and retinoid X receptors (RXR). Oral alitretinoin once daily is approved for use in patients with severe chronic hand eczema unresponsive to treatment with potent topical corticosteroids. m In a large (n = 1032), randomized, double-blind, placebo-controlled, multicentre study (BACH) of up to 24 weeks’ duration in adults with severe chronic hand eczema, significantly more patients in the alitretinoin 10 or 30 mg/day groups than in the placebo group responded to treatment with clear/ almost clear hands, as assessed by the Physician Global Assessment (PGA) [primary endpoint]. m In an extension phase of the BACH study, alitretinoin was effective in patients who relapsed after responding to initial treatment with the drug. Of patients who had responded to initial treatment with alitretinoin 30 mg/day, significantly more alitretinoin 30 mg/day than placebo recipients responded on the PGA with clear/almost clear hands during the extension phase (primary endpoint; 80% vs 8%). Of those who had responded to initial treatment with alitretinoin 10 mg/day, 48% of alitretinoin 10 mg/day and 10% of placebo recipients responded during the extension phase. m Alitretinoin was generally well tolerated in clinical trials excluding pregnant women. The most common treatment-emergent adverse events and abnormal laboratory test results were consistent with those previously observed with other oral retinoids and RXR agonists. Features and properties of alitretinoin cis(9- retinoic acid; Toctino®)

Alitretinoin

Alitretinoin is an endogenous retinoid and acts as a pan-agonist at retinoid receptors, binding with high affinity to both retinoic acid receptors and retinoid X receptors (RXR). Oral alitretinoin once daily is approved for use in patients with severe chronic hand eczema unresponsive to treatment with potent topical corticosteroids. In a large (n = 1032), randomized, double-blind, placebo-controlled, multicentre study (BACH) of up to 24 weeks' duration in adults with severe chronic hand eczema, significantly more patients in the alitretinoin 10 or 30 mg/day groups than in the placebo group responded to treatment with clear/almost clear hands, as assessed by the Physician Global Assessment (PGA) [primary endpoint]. In an extension phase of the BACH study, alitretinoin was effective in patients who relapsed after responding to initial treatment with the drug. Of patients who had responded to initial treatment with alitretinoin 30 mg/day, significantly more alitretinoin 30 mg/day than placebo recipients responded on the PGA with clear/almost clear hands during the extension phase (primary endpoint; 80% vs 8%). Of those who had responded to initial treatment with alitretinoin 10 mg/day, 48% of alitretinoin 10 mg/day and 10% of placebo recipients responded during the extension phase. Alitretinoin was generally well tolerated in clinical trials excluding pregnant women. The most common treatment-emergent adverse events and abnormal laboratory test results were consistent with those previously observed with other oral retinoids and RXR agonists.

DOUBLE-BLIND, PLACEBO-CONTROLLED, PILOT TRIAL OF BOTULINUM TOXIN A IN RESTLESS LEGS SYNDROME

The hallmarks of restless legs syndrome (RLS) are a desire to move the limbs due to sensory discomfort, motor restlessness, and worsening of symptoms during rest or at night.1 Sensory symptoms cause the greatest discomfort,2 and are commonly localized to muscle. Sensory and motor symptoms can be improved with dopaminergic medications, some anticonvulsants, opioids, and to a lesser extent with GABA-active hypnotics. Botulinum toxin has been suggested as a potential therapy for refractory RLS, based on its ability to reduce peripheral and central sensitization to pain.3 In an unblinded observational study by Rotenberg and colleagues, IM injections of 70–320 mouse units (mU) of botulinum toxin type A (BTX-A; Botox, Irvine, CA) were injected into the legs of three patients with RLS and demonstrated symptom improvement, reduced medication use, and a reduction in daytime sleepiness.4 Based on these findings, we conducted a randomized, placebo-controlled, double-blind, crossover study. ### Methods. #### Patients. We enrolled six patients from June to July 2007 who were age 18 or older, had a diagnosis of primary RLS based on International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria,1 had a minimum score of 11 (at least moderate severity) on the IRLSSG rating scale (IRLS),5 and were stable on medications for greater than 6 weeks prior to enrollment. Patients were excluded for an abnormal neurologic examination, abnormal laboratory test results, a dermatologic disorder precluding leg injections, pregnancy/lactation, incapacity for informed consent, taking medications which could interact with BTX-A, …

Investigation of Intragam® P Haemolysis Adverse Events

Aim To understand the underlying cause of a cluster of haemolysis-type adverse event (AE) reports received by CSL/ARCBS in patients receiving Intragam® P. Method The cluster of AE reports were analysed with respect to patient factors (clinical indication, dose, blood group, concomitant medications and blood products, bone marrow reserve), product factors (batch results, production records) and changes in clinical practice (administration protocols, infusion kits). All Intragam P haemolysis related AEs from clinical trials and post-marketing exposure were reviewed, as well as international literature on this subject. Result Sixteen haemolysis type cases were reported to ARCBS/CSL over a 3 month period, ranging from abnormal laboratory test results (positive Coombs test) to clinical symptoms requiring transfusion. Ten of these reports were received in 4 days from 2 Victorian hospitals following the detection of 2 cases, which precipitated a retrospective review that identified additional similar cases. All patients received high dose (doses exceeding 400–600 mg/kg given every 3–4 weeks either in frequency or quantity) and all but one (where evidence suggested an underlying disorder) were of blood group A or AB. Eight patients were recipients of bone marrow transplants. No product or batch related factors or processes likely to have contributed to the haemolysis type AEs were identified. Anti-A and Anti-B titres of all Intragam P batches were investigated and confirmed to be within regulatory approved release specifications and pharmacopoeial limits. Conclusion Haemolysis type adverse events are a recognised consequence of IVIG administration and are widely discussed in the literature. This investigation has confirmed the association of high dose IVIG in recipients of blood group A or AB and increased risk of haemolysis type adverse events. It also highlighted the possibility of accentuating any consequent anaemia in patients with diminished bone marrow reserve (eg post bone marrow transplant patients). Pre-infusion ABO blood groups should be determined in patients receiving high dose IVIG and their haemoglobin levels monitored in the days following therapy.

Sitafloxacin hydrate for bacterial infections

Sitafloxacin hydrate (DU-6859a, Gracevit), a new-generation, broad-spectrum oral fluoroquinolone that is very active against many Gram-positive, Gram-negative and anaerobic clinical isolates, including strains resistant to other fluoroquinolones, was recently approved in Japan for the treatment of respiratory and urinary tract infections. Sitafloxacin is active against methicillin-resistant staphylococci, Streptococcus pneumoniae and other streptococci with reduced susceptibility to levofloxacin and other quinolones and enterococci. Sitafloxacin has also demonstrated activity against clinical isolates of Klebsiella pneumoniae (including about 67% of strains producing extended-spectrum, beta-lactamases and resistant to ciprofloxacin), Enterobacter cloacae, Pseudomonas aeruginosa with some activity against quinolone-resistant strains and Acinetobacter baumannii. The in vitro activity against anaerobes is comparable to imipenem or metronidazole. In a published phase II randomized, open-label, multicenter study of patients hospitalized with pneumonia, sitafloxacin (400 mg once daily) was comparable to imipenem/cilastatin (500 mg three times a day). Results of the phase III trials of sitafloxacin are not available in English. The clinical safety profile of sitafloxacin has been characterized from 1,059 patients who participated in 10 clinical trials. The most common events with 50 or 100 mg twice daily were gastrointestinal disorders (17.2%), mostly diarrhea, and abnormal laboratory test results (16.2%), mostly liver enzyme elevations. For Japanese patients, sitafloxacin provides the broad-spectrum coverage promised by clinafloxacin and trovafloxacin and comparable to carbapenems. While it is currently limited by its potential for phototoxicity in Caucasians, phototoxicity is essentially irrelevant if sitafloxacin is used in hospitals and especially in intensive care units.

Routine Laboratory Screening Among Newly Admitted Psychiatric Patients: Is It Worthwhile?

This study compared the prevalence of abnormal results of laboratory tests routinely performed among newly hospitalized psychiatric patients in Spain and the cost-effectiveness of such tests. Routine biochemical tests were performed for 510 newly hospitalized psychiatric patients. For all tests, this study examined the prevalence of values outside the normal range and compared the number needed to screen to find one abnormal result (NNSAR=1/prevalence of abnormal results in the studied population) with the direct cost spent to find one abnormal result (DCSAR=NNSAR x direct cost per test). The prevalence of values outside the normal range ranged from 1% for free thyroxine (FT4) to 36% for total cholesterol. The NNSAR ranged from 2.8 for total cholesterol to 127.3 for FT4. The DCSAR ranged from .38 international dollars of 2000 (I$) for chloride to 402.27 I$ for FT4. There were large differences in the prevalence of abnormal results (NNSAR) and cost-effectiveness (DCSAR) for the laboratory tests routinely performed among newly admitted psychiatric patients.

Routine Laboratory Screening Among Newly Admitted Psychiatric Patients: Is It Worthwhile?

Routine Laboratory Screening Among Newly Admitted Psychiatric Patients: Is It Worthwhile?

Efficacy of Atorvastatin Therapy in Ischaemic Heart Disease – Effects on Oxidized Low-density Lipoprotein and Adiponectin

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels > 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 +/- 148.6 to 286.9 +/- 88.5 nmol/l, and adiponectin increased from 9.7 +/- 7.4 to 13.9 +/- 9.98 microg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.

Coinfections acquired from ixodes ticks.

The pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis can coexist in Ixodes ticks and cause human coinfections. Although the risk of human coinfection differs by geographic location, the true prevalence of coinfecting pathogens among Ixodes ticks remains largely unknown for the majority of geographic locations. The prevalence of dually infected Ixodes ticks appears highest among ticks from regions of North America and Europe where LD is endemic, with reported prevalences of < or =28%. In North America and Europe, the majority of tick-borne coinfections occur among humans with diagnosed LD. Humans coinfected with LD and babesiosis appear to have more intense, prolonged symptoms than those with LD alone. Coinfected persons can also manifest diverse, influenza-like symptoms, and abnormal laboratory test results are frequently observed. Coinfecting pathogens might alter the efficiency of transmission, cause cooperative or competitive pathogen interactions, and alter disease severity among hosts. No prospective studies to assess the immunologic effects of coinfection among humans have been conducted, but animal models demonstrate that certain coinfections can modulate the immune response. Clinicians should consider the likelihood of coinfection when pursuing laboratory testing or selecting therapy for patients with tick-borne illness.

Liver Failure Is Uncommon in Adults Receiving Long‐Term Parenteral Nutrition

Abnormal liver enzymes and endstage liver disease are reported to occur in 25%-100% and 15%-40% of adult patients receiving long-term parenteral nutrition (PN), respectively. The purpose of this historic cohort study was to investigate the incidence of and possible factors leading to the development of liver disease in our large home PN population. All patients on home PN for at least 6 months from July 1991 through June 2002 were eligible. Patients were excluded if they had active malignancy, underlying liver disease, or exposure to a hepatotoxin. The presence of PN-associated liver disease was only considered if test results were elevated on more than 1 occasion over at least 6 or more months. The severity of liver-associated enzymes was based on the degree of elevation and was stratified as mild (<2 times normal), moderate (2-5 times normal), and severe (>5 times normal). Severe liver dysfunction was defined as having all of the following criteria: total bilirubin >3 mg/dL; albumin <3.2 g/dL; and prothrombin time >3 seconds prolonged. A cumulative logit model was used to compare age, gender, underlying disease, PN indication, and PN formulas in patients with normal vs abnormal laboratory test results. Two hundred eight patients received PN for more than 6 months, 36 had exclusion criteria, and 10 could not be analyzed, because of incomplete laboratory test results, leaving 162 in the study group. The average PN duration was 2.14 +/- 2.19 years (maximum, 10.28 years). Abnormal liver tests occurred in 154 patients, with most having a moderate elevation of alkaline phosphatase or aspartate aminotransferase; severe liver dysfunction occurred in 7 patients; 1 patient had completely normal liver enzymes. On average, patients received a PN formula that was high in amino acids (1.45 +/- 0.65 g/kg/d), modest in energy (24.7 +/- 13.4 kcal/kg/d), and in most cases with enough lipid emulsion to meet essential fatty acid requirements (0.28 +/- 0.25 g/kg/d). Only female gender was found to be associated with a greater likelihood of liver failure (p = .02). There was a trend toward a greater amount of total calories, dextrose calories, and duration of PN exposure leading to the development of severe liver dysfunction. When long-term PN is given with a modest amount of total energy and a minimal amount of lipid emulsion, abnormal liver enzymes are common, but severe liver dysfunction is unusual.

Herbal Remedies: Effects on Clinical Laboratory Tests

Complementary and alternative medicine (herbal medicines) can affect laboratory test results by several mechanisms. In this review, published reports on effects of herbal remedies on abnormal laboratory test results are summarized and commented on. All published reports between 1980 and 2005 with the key words herbal remedies or alternative medicine and clinical laboratory test, clinical chemistry test, or drug-herb interaction were searched through Medline. The authors' own publications were also included. Important results were then synthesized. Falsely elevated or falsely lowered digoxin levels may be encountered in a patient taking digoxin and the Chinese medicine Chan Su or Dan Shen, owing to direct interference of a component of Chinese medicine with the antibody used in an immunoassay. St John's wort, a popular herbal antidepressant, increases clearance of many drugs, and abnormally low cyclosporine, digoxin, theophylline, or protease inhibitor concentrations may be observed in a patient taking any of these drugs in combination with St John's wort. Abnormal laboratory results may also be encountered owing to altered pathophysiology. Kava-kava, chaparral, and germander cause liver toxicity, and elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin concentrations may be observed in a healthy individual taking such herbal products. An herbal product may be contaminated with a Western drug, and an unexpected drug level (such as phenytoin in a patient who never took phenytoin but took a Chinese herb) may confuse the laboratory staff and the clinician. Use of alternative medicines may significantly alter laboratory results, and communication among pathologists, clinical laboratory scientists, and physicians providing care to the patient is important in interpreting these results.

Review of abnormal laboratory test results and toxic effects due to use of herbal medicines.

Herbal medicines are used widely in the United States, and according to a recent survey, the majority of people who use herbal medicines do not inform their physicians about their use. Herbal medicines can cause abnormal test results and confusion in proper diagnosis. Herbal medicines can alter test results by direct interference with certain immunoassays. Drugherb interactions can result in unexpected concentrations of therapeutic drugs. For example, low concentrations of several drugs (e.g., cyclosporine, theophylline, digoxin) can be observed in patients who initiated self-medication with St John's wort. Herbal medicines can alter physiology, and these changes can be reflected in abnormal test results. For example, kavakava can cause drug-induced hepatitis, leading to unexpected high concentrations of liver enzymes. Use of toxic herbal products such as ma huang (an ephedra-containing herbal product), Chan Su, and comfrey may cause death. Other toxic effects of herbal medicines include cardiovascular toxic effects, hematologic toxic effects, neurotoxic effects, nephrotoxic effects, carcinogenic effects, and allergic reactions.

Review of Abnormal Laboratory Test Results and Toxic Effects Due to Use of Herbal Medicines

Review of Abnormal Laboratory Test Results and Toxic Effects Due to Use of Herbal Medicines

Does continuity of care matter? No: discontinuity can improve patient care.

At first blush, there are few values in health care that seem more self-evidently important than preserving continuity. Only a masochist could possibly take the “continuity doesn't matter” side of this debate! But things are not so simple. Assume that you have found the perfect primary care physician—someone who cares about not just your health care but your health, not just your protoplasm but your values. She knows your family and understands what makes you tick. She is a terrific clinician. Is this the person you want operating on your cerebral aneurysm? Will you wait for her to arrive when you are hypotensive in the emergency department? Of course not. We decided long ago that there were fundamental advantages to having a single primary care physician whose job was to oversee your care during childhood (pediatrician) or adult life (general internist or family physician). But we also recognized that having this person provide all your specialized health care needs made no more sense than having a single professor teach all your college courses. There are simply some practices whose cognitive or technical complexity and time sensitivity render a single provider not just impractical but downright dangerous. Several recent trends have added to the importance of what I will call “advantageous and purposeful discontinuities.” First, a burgeoning literature confirms that practice often does make perfect in caring for patients across a wide array of diseases and procedures.1 Second, the increasing computerization of information flow means that we can more easily transfer patient data without significant “voltage drops.” Finally, the growing scope and complexity of primary care practice—now encompassing disease management, health promotion, genetic counseling, and more—has left primary physicians with less time and inclination to care for patients across the continuum. Perhaps the most prominent recent challenge to continuity in American medicine is the hospitalist movement, in which a separate physician assumes the role of providing general hospital care in place of primary care physicians.2 Although some have critiqued the new model because of its inpatient-outpatient discontinuity, increasingly persuasive evidence demonstrates that the model improves the efficiency and possibly the quality of inpatient care.3,4 Moreover, I would argue that within-hospital continuity improves when hospitalists are involved. By creating an advantageous and purposeful discontinuity at hospital admission and discharge, the hospitalist can do things between dawn and dusk that are logistically impossible for busy primary care physicians: see patients twice, meet with families, react to abnormal laboratory test results and changes in patient status, and meet with consultants. Effective hospitalist programs find ways to make certain that primary care physicians remain informed about and appropriately involved in the key events of the hospitalization and that as little information as possible is lost in the transitions. Finally, discontinuities can provide an opportunity for a beneficial second look. Tandeter and Vinson recently described 2 cases in which a second physician's examination revealed findings that the primary care physician had overlooked.5 “Continuity of care,” they wrote, “... may keep us from seeing gradual changes in our patients and may leave us with the illusion of a lack of change. When the overlooked changes are those of an insidious new disease developing on top of previous pathologies, the failure to diagnose a significant problem can result.”5(p423) Let us continue to value continuity, but let us not be its slaves when an advantageous and purposeful discontinuity will improve the care of our patients.

Arthritis related to ileal pouchitis following total proctocolectomy for ulcerative colitis

Objective: To draw attention to arthritis that developed in patients who underwent total proctocolectomy with ileal pouch construction for ulcerative colitis (UC). Methods: The course of 4 patients who developed arthritis for the first time after ileal-anal pouch anastomosis is described. In addition, the relationship to the chronic inflammation of the pouch–pouchitis–is discussed. Results: The clinical manifestations were very similar to seronegative arthritis affecting mainly the joints of the lower extremities. It was accompanied by enthesopathy (2 patients) and by sacroiliitis (2 patients). All had active pouchitis. The abnormal laboratory test results were nonspecific, indicating chronic inflammation. All 4 patients tested negative for human leukocyte antigen (HLA) B27, and none had other concomitant extraintestinal manifestations. Steroids rapidly improved both the arthritis and pouchitis; however, disease-modifying antirheumatic drugs were required to maintain remission with minimal daily steroids. Flares of the arthritis were always associated with active pouchitis, but the opposite was not necessarily true. Conclusions: Arthritis related to ileal pouchitis after total colectomy for UC has many similarities to the arthritis associated with inflammatory bowel disease and should be added to the list of enteropathic arthropathies. Semin Arthritis Rheum 30:242-248. Copyright © 2001 by W.B. Saunders Company