Factors Affecting Resident Satisfaction in Continuity Clinic-a Systematic Review.

PURPOSE: In recent years, with an increasing emphasis on time spent in ambulatory training, educators have focused attention on improving the residents' experience in continuity clinic. The authors sought to review the factors associated with physician trainee satisfaction with outpatient ambulatory training. METHODS: A systematic literature review was conducted for all English language articles published between January 1980 and December 2016 in relevant databases, including Medline (medicine), CINAHL (nursing), PSYCHinfo (psychology), and the Cochrane Central Register of Controlled Clinical Trials. Search terms included internship and residency, satisfaction, quality of life, continuity of care, ambulatory care, and medical education. We included studies that directly addressed resident satisfaction in the ambulatory setting through interventions that we considered reproducible. RESULTS: Three hundred fifty-seven studies were reviewed; 346 studies were removed based on exclusion criteria with 11 papers included in the final review. Seven studies emphasized aspects of organizational structure such as block schedules, working in teams, and impact on resident-patient continuity (continuity between resident provider and patient as viewed from the provider's perspective). Four studies emphasized the importance of a dedicated faculty for satisfaction. The heterogeneity of the studies precluded aggregate analysis. CONCLUSIONS: Clinic structures that limit inpatient and outpatient conflict and enhance continuity, along with a dedicated outpatient faculty, are associated with greater resident satisfaction. Implications for further research are discussed.

Fibroblast growth factor control of cartilage homeostasis.

Osteoarthritis (OA) and degenerative disc disease (DDD) are similar diseases involving the breakdown of cartilage tissue, and a better understanding of the underlying biochemical processes involved in cartilage degeneration may allow for the development of novel biologic therapies aimed at slowing the disease process. Three members of the fibroblast growth factor (FGF) family, FGF-2, FGF-18, and FGF-8, have been implicated as contributing factors in cartilage homeostasis. The role of FGF-2 is controversial in both articular and intervertebral disc (IVD) cartilage as it has been associated with species- and age-dependent anabolic or catabolic events. Recent evidence suggests that FGF-2 selectively activates FGF receptor 1 (FGFR1) to exert catabolic effects in human articular chondrocytes and IVD tissue via upregulation of matrix-degrading enzyme production, inhibition of extracellular matrix (ECM) accumulation and proteoglycan synthesis, and clustering of cells characteristic of arthritic states. FGF-18, on the other hand, most likely exerts anabolic effects in human articular chondrocytes by activating the FGFR3 pathway, inducing ECM formation and chondrogenic cell differentiation, and inhibiting cell proliferation. These changes result in dispersed chondrocytes or disc cells surrounded by abundant matrix. The role of FGF-8 has recently been identified as a catabolic mediator in rat and rabbit articular cartilage, but its precise biological impact on human adult articular cartilage or IVD tissue remains unknown. The available evidence reveals the promise of FGF-2/FGFR1 antagonists, FGF-18/FGFR3 agonists, and FGF-8 antagonists (i.e., anti-FGF-8 antibody) as potential therapies to prevent cartilage degeneration and/or promote cartilage regeneration and repair in the future.

In vitro metabolism and in vivo pharmacokinetics of quinoline 3-carboxamide derivatives in various species.

The metabolism of a group of quinoline 3-carboxamide derivatives was evaluated in liver microsomes from various species. In addition, metabolism data were compared with in vivo pharmacokinetics in the mouse. The studied compounds were metabolized by cytochrome P450 enzymes. Microsomal clearance was low and seemed independent of a substituent in the quinoline moiety, whereas clearance was enhanced when an ethyl group replaced the methyl group at the carboxamide position. A similar metabolism with hydroxylated and dealkylated metabolites was found in the various species, with quantitative differences due to substituent. As predicted from the in vitro studies, in vivo pharmacokinetics showed low clearance and thus high exposure of the parent compounds in the mouse. The therapeutic effect seen in the acute EAE mouse model for these related compounds seems dependent on the high exposure of parent compound rather than formation of any potentially active metabolites.

A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma.

OBJECTIVE: Early diffuse scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early diffuse SSc. METHODS: Seventy-one patients with diffuse SSc of <3 years' duration were enrolled in a multicenter, randomized, placebo-controlled, double-blind trial. Thirty-five patients were treated with MTX and 36 with placebo. Treatment was administered for 12 months. The primary outcome measures were skin score (as determined with 2 different indices) and physician global assessment. RESULTS: At baseline, there were no statistically significant differences in skin scores, carbon monoxide diffusing capacity (DLco), physician global assessment, or other secondary outcome measurements between the 2 treatment groups. At study completion, results slightly favored the MTX group (mean +/- SEM modified Rodnan skin score 21.4+/-2.8 in the MTX group versus 26.3+/-2.1 in the placebo group [P < 0.17]; UCLA skin score 8.8+/-1.2 in the MTX group versus 11.0+/-0.9 in the placebo group [P < 0.15]; DLco in the MTX group 75.7+/-4.6 versus 61.8+/-3.4 in the placebo group [P < 0.2]). In addition, physician global assessment results favored MTX (P < 0.035), whereas patient global assessment did not differ significantly between groups. When between-group differences for changes in scores from baseline to 12 months were examined using intent-to-treat methodology, MTX appeared to have a favorable effect on skin scores (modified Rodnan score -4.3 in the MTX group versus 1.8 in the placebo group [P < 0.009]; UCLA score -1.2 in the MTX group versus 1.2 in the placebo group [P < 0.02]), but differences in the degree of change in the DLco and physician global assessment were not significant. For the UCLA skin score, these differences in results were not statistically significant after adjustment for baseline differences in sex distribution and steroid use. Dropout rates were similar in the 2 groups. CONCLUSION: Although results of this trial demonstrated a trend in favor of MTX versus placebo in the treatment of early diffuse SSc, the between-group differences were small and the power to rule out false-negative results was only 50%. Our findings do not provide evidence that MTX is significantly effective in the treatment of early diffuse SSc.

Crohn's disease arthritis treated with infliximab: an open trial in four patients.

Four patients with Crohn's disease arthritis, who were unresponsive to conventional treatment, improved very rapidly and safely with the use of infliximab, the chimeric antibody directed against tumor necrosis factor alpha. The patients were able to stop or significantly decrease other antirheumatic medications after the infliximab infusions. It is likely that tumor necrosis factor plays a major role in the arthritis as well as the bowel involvement that is seen in Crohn's disease. Suppression of this cytokine may effectively ameliorate Crohn's disease arthritis in some patients.

Therapeutic plasma exchange for the acute management of the catastrophic antiphospholipid syndrome: beta(2)-glycoprotein I antibodies as a marker of response to therapy.

We describe two patients with the catastrophic antiphospholipid syndrome associated with elevation of beta(2)-glycoprotein I antibodies and fulminant thrombotic diatheses. Both patients were treated with therapeutic plasma exchange (TPE), which resulted in a marked decrease in antibody titer accompanied by an improved clinical outcome in one patient (IgG antibody). In the second patient, the outcome was poor despite TPE (IgA antibody). There were no significant complications of TPE in either case. Because of the fulminant nature of the catastrophic antiphospholipid syndrome, we conclude that a trial of TPE is warranted for the acute management. Further studies are needed to clarify which patients may benefit from this treatment.

Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma). METHODS: A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary. RESULTS: Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION: Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

A new index of prognostic severity for chronic asthma.

OBJECTIVE: To develop a prognostic clinical index for adults with chronic stable asthma. DESIGN: Analysis of data from a 48-week randomized, crossover trial of regular vs as-needed inhaled beta-agonist therapy. PATIENTS: Eligible patients included 70 men and women between the ages of 15 and 64 years with asthma for > 1 year. OUTCOME MEASURE: Asthma deterioration within 20 weeks, defined as either a marked decline in FEV1 (> or = 1.0 L or > or = 30% from baseline) or initiation of systemic corticosteroid therapy for asthma exacerbation. RESULTS: Three baseline factors independently predicted asthma deterioration: frequent symptoms on waking in the 4 weeks before baseline, past hospitalization for asthma, and age 35 years or older. Based on cross-stratification and consolidation of these prognostic factors, an index was developed that stratified subjects into four risk groups with distinctive deterioration rates of 9%, 21%, 39%, and 67% (p<0.001). CONCLUSION: For adults with chronic stable asthma, three simple clinical factors can be combined to stratify effectively for risk of subsequent asthma deterioration.

Leukocyte colony stimulating factors for rheumatologists.

The leukocyte colony stimulating factors (recombinant granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor) have become widely used in hematology and oncology to raise neutrophil levels in patients with neutropenia. They have been used primarily by rheumatologists to treat neutropenia accompanying infections in patients with Felty's syndrome or systemic lupus erythematosus and in infected patients made neutropenic with drug therapy. These factors have been lifesaving. The drugs generally are well tolerated and adverse effects usually are easily treated. Some of the adverse effects of the agents may mimic de novo rheumatic conditions such as vasculitis and Sweet's syndrome. There may be important future roles for these growth factors in treatment protocols for patients with rheumatic disease using more aggressive chemotherapy regimens.

Calcium pyrophosphate dihydrate deposition disease presenting as tumoral calcinosis (periarticular pseudogout).

It has been considered unusual for periarticular calcifications to consist of calcium pyrophosphate dihydrate (CPPD). We describe a patient presenting with pain and inflammation adjacent to the site of tumoral calcifications and extending to the first metatarsophalangeal joint. Aspiration of the material revealed weakly positive birefringent rhomboid shaped crystals that proved to be CPPD by atomic force microscopy. The patient had no metabolic abnormalities or radiographic chondrocalcinosis. We believe other cases similar to ours represent another clinical form of CPPD deposition disease-periarticular pseudogout.

Chromosome aberrations and pharmacokinetics in patients receiving tauromustine as either a single or a repeated dose.

Tauromustine (TCNU) is an exploratory drug that has demonstrated activity in various solid tumors. We examined chromosome aberrations and plasma levels of the drug in two groups of patients receiving either a single dose of 130 mg/m2 or 40 mg/m2 on 3 consecutive days. Peak plasma concentrations (mean +/- SD) were obtained at a similar time after both treatments, i.e., at 38 +/- 25, 32 +/- 24, 28 +/- 14, and 40 +/- 26 min after administration of 130 mg/m2 on day 1 and after that of 40 mg/m2 on days 1, 2, and 3, respectively. In addition, the cumulative area under the curve (AUC value) determined after administration of 40 mg/m2 x 3 was similar to that noted after treatment with a single dose of 130 mg/m2, i.e., 180 and 179 micrograms min ml-1, respectively. Both treatments induced chromosome aberrations (CAs) in peripheral blood lymphocytes. A dose-dependent increase in the number of CAs was found, with 40 mg/m2 producing 5.5% CAs and 130 mg/m2 yielding 20.9% CAs at 24 h after treatment. In addition, although the drug concentration declined to a level under the detection limit between the daily treatments, drug-induced chromosome damage was cumulative, with the 90-min values increasing from 4.8% on day 1 to 14.3% CAs on day 3. In individual patients, no correlation was found between CAs and kinetic parameters; however, the total mean CA yield was in agreement with the total drug exposure (CAs, 14.3% and 14.6%, AUC 180 +/- 62.8 and 179 +/- 115 micrograms min ml-1, respectively.

The increase in death and disease under "katstroika".

The author describes recent trends in mortality and morbidity in the successor states to the former Soviet Union. Separate consideration is given to mortality under late perestroika (1987-1991) and subsequent mortality trends. The author concludes that "the collapse of the USSR and the problems of the successor states have had severe adverse affects not only on macroeconomic indices but also on the mortality and morbidity of the population.... Since the collapse of the USSR, the mortality situation in the successor states has rapidly and significantly worsened. Between 1991 and 1993 the crude death rate in Russia rose by 26%. As a result, by 1993 the life expectancy at birth of Russian men had fallen to about 59, which is about 6 years below the level of 1987.... By 1993, male life expectancy at birth in Russia had fallen below the level of the medium income countries and had probably fallen to a level about that of Indonesia in the second half of the 1980s. Ukraine has also experienced an increase in mortality since the collapse of the USSR. In other successor states, experiencing serious military conflicts, such as Tadjikstan and Armenia, the proportionate increase in mortality was even larger than in Russia."

Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis. DESIGN: Multicenter, randomized, parallel placebo-controlled, double-blind study. SETTING: University medical centers. PATIENTS: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years. INTERVENTION: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo. MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing. RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo. CONCLUSION: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

Soviet deaths in the Great Patriotic War: a note.

PIP: The authors attempt a synthesis of recent research in the USSR and post-Soviet Russia on Soviet mortality during World War II. They conclude that the official estimate adopted since 1990 of 26 to 27 million deaths is probably accurate, and note that most of the Soviet citizens who died were civilians.^ieng

Clinical reasoning and the new "non-" nosology.

Although seemingly odd, the designations prefixed with "non-" have become a familiar feature of clinical terminology. A common structure of these designations is the partition of a single clinical category into two contrasting ones. Despite the similar "non-" designations, the partitions can have four different functions: dividing one disease into two, aggregating multiple diseases, distinguishing etiologic uncertainty, and negating "legitimate" disease. The "non-" terminology may seem peculiar, but it is based on clinically pertinent distinctions and similarities in disease, reflecting prudent clinical reasoning.

Acute lymphatic filariasis in an American traveler.

Acute lymphatic filariasis developed in an American traveling recreationally to Asia. The illness was characterized by fatigue, eosinophilia, and lymphedema of the arm and chest wall, but no lymphangitis, lymphadenitis, or pain. Complete resolution occurred over 1-2 years. We discuss this syndrome and describe the use of new diagnostic tests in its diagnosis and management.

Neurologic testing with somatosensory evoked potentials in idiopathic scoliosis.

A study was undertaken to determine if a somatosensory conduction delay is present in the posterior columns of adolescents with idiopathic scoliosis. Somatosensory evoked potentials were recorded after median and posterior tibial nerve stimulation in 12 adolescent subjects being followed for idiopathic scoliosis with an average age of 14.6 years (range, 12.0-16.6 years). Twelve normal controls matched for age, sex, race, and height underwent identical testing. Evoked potential peak latencies were measured and conduction velocities calculated. Results showed no difference between scoliotics and normal controls. Comparable posterior column conduction velocities were recorded in both groups. If a defect in posterior column function does exist in adolescent idiopathic scoliosis, as previously postulated, it is not reflected by a conduction delay as measured by somatosensory evoked potential testing.

Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotrexate.

We describe the occurrence of a lymphoma in a patient with rheumatoid arthritis (RA) taking weekly oral pulse methotrexate (MTX) in low doses for 33 months. This occurrence may be coincidental. There may be an increased incidence of lymphoma in RA not treated with immunosuppressive medications. However, the increasing use of MTX warrants reporting unusual events, especially malignancy. It is possible that even the mild immunosuppression that occurs with MTX therapy places patients with RA at added risk for developing lymphoproliferative diseases.