Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, improves patient-reported outcomes in a phase 2b, randomized, double-blind, placebo-controlled study in patients with moderate-to-severe psoriasis.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease with a significant impact on health-related quality of life (HRQoL). Tofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator. OBJECTIVE: This Phase 2b study assessed three tofacitinib dosage regimens vs. placebo to characterize the efficacy and safety of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis. We report the patient-reported outcome (PRO) data. METHODS: A total of 197 patients were randomized to tofacitinib 2, 5, 15 mg twice daily or placebo for 12 weeks. Six PRO questionnaires were completed during the study: Dermatology Life Quality Index, Itch Severity Score (ISS), Short Form-36 questionnaire, version 2 (SF-36), Pain/Discomfort Assessment (PDA), Patient Satisfaction with Study Medication (PSSM) item and Patient Global Assessment of psoriasis. RESULTS: Treatment with tofacitinib resulted in significant, dose-dependent improvements in several PROs vs. placebo from week 2 onwards. At week 12, least squares mean changes from baseline for Dermatology life quality index, ISS and SF-36 mental component scores were significantly greater for all active drug arms vs. placebo (P < 0.05), and significantly greater for tofacitinib 5 and 15 mg for SF-36 physical component scores vs. placebo (P < 0.05). At week 12, all dose groups had significantly greater numbers of patients reporting 'Clear' or 'Almost clear' on the PtGA vs. placebo. CONCLUSION: In patients with moderate-to-severe chronic plaque psoriasis, short-term (12-week) treatment with oral twice-daily tofacitinib improves HRQoL outcomes and patient assessment of disease severity and symptoms, with an early onset noted.

Effect of tofacitinib, a Janus kinase inhibitor, on haematological parameters during 12 weeks of psoriasis treatment.

BACKGROUND: The Janus kinase (JAK) inhibitor, tofacitinib, has shown efficacy for the treatment of psoriasis in a phase IIb trial (A3921047; NCT00678210). OBJECTIVES: To report haematology data from the phase IIb trial, given the importance of JAK-dependent signalling in haematopoiesis. METHODS: Patients with moderate-to-severe chronic plaque psoriasis were randomized to receive tofacitinib 2, 5 or 15 mg, or placebo, twice daily over 12 weeks. Blood samples were collected at screening, baseline, weeks 2, 4, 8 and 12 during treatment, and weeks 14 and 16 during off-treatment follow-up. RESULTS: Baseline haematology was similar across patients receiving tofacitinib 2 mg (n = 49), 5 mg (n = 49) or 15 mg (n = 49), or placebo (n = 50). Tofacitinib conferred dose-dependent decreases in haemoglobin, haematocrit and red blood cell counts, while reticulocyte counts initially declined, before recovering by week 8, and exceeding baseline levels after treatment cessation. With regard to white blood cells, tofacitinib had no clear dose-dependent effects on basophils or monocytes, but appeared to be associated with transient or reversible dose-dependent decreases in neutrophil and eosinophil counts and transient increases in lymphocyte counts, which were primarily attributable to increases in B-cell counts. Natural killer cell counts declined with tofacitinib. CONCLUSIONS: Tofacitinib conferred tolerable, dose-dependent changes in haematological parameters during short-term administration in patients with psoriasis. The effects did not appear to be progressive, and were often transient or reversible.

Psychometric validation of the physician global assessment scale for assessing severity of psoriasis disease activity.

PURPOSE: The Physician Global Assessment (PGA) is a key measure of psoriasis frequently used in clinical trials. A psychometric validation of a three-item (erythema, induration, and scaling) PGA scale was performed using Phase 2 data. METHODS: Confirmatory factor analysis (CFA) tested the PGA measurement model and appropriateness of equal weighting of the items. PGA test-retest reliability was assessed by estimating the intraclass correlation coefficient (ICC). Internal consistency reliability was gauged by calculating Cronbach's coefficient α (CCα). Clinically important difference (CID) was defined using the repeated measures model to estimate the relationship between PGA and Patient Global Assessment (PtGA). Known-group, convergent, and divergent validity for the PGA were also assessed. RESULTS: 197 patients with psoriasis were randomized to tofacitinib 2, 5, 15 mg twice daily, or placebo. CFA demonstrated that the PGA measurement model fitted the data using equal weighting of the PGA items. The PGA scale demonstrated good test-retest reliability (ICC > 0.7) and internal consistency reliability (CCα > 0.8). The CID for PGA was estimated at 0.52 (95 % confidence interval: 0.47, 0.56). A robust monotonic relationship between PGA and Psoriasis Area and Severity Index (PASI) data substantiated known-group validity. Relatively high correlations of PGA with PASI and PtGA data (all correlations >0.5 except at baseline) supported convergent validity; relatively low correlations of PGA with the Pain/Discomfort Assessment and the Ocular Comfort Index supported divergent validity. CONCLUSIONS: The three-item PGA scale has sound psychometric properties with respect to reliability and validity, with equal weighting of the items being appropriate.

Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study.

BACKGROUND: Tofacitinib is a novel, oral Janus kinase inhibitor under investigation as a potential treatment for plaque psoriasis. OBJECTIVES: This Phase 2b, 12-week, dose-ranging study (A3921047, NCT00678210) aimed to characterize the exposure-response, efficacy and safety of tofacitinib vs. placebo in patients with moderate-to-severe chronic plaque psoriasis. METHODS: One hundred and ninety-seven patients were randomized. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI 75) score at week 12. RESULTS: At week 12, PASI 75 response rates were significantly higher for all tofacitinib twice-daily groups: 25·0% (2 mg; P < 0·001), 40·8% (5 mg; P < 0·0001) and 66·7% (15 mg; P < 0·0001), compared with placebo (2·0%). Significant increases in the proportion of PASI 75 responses were seen by week 4 and were maintained at week 12. Exposure-response over the 0-15 mg tofacitinib twice-daily dose range was successfully characterized. PASI 50, PASI 90 and Physician's Global Assessment response rates were also higher for tofacitinib vs. placebo. The most frequently reported adverse events (AEs) were infections and infestations: 22·4% (2 mg twice daily), 20·4% (5 mg twice daily), 36·7% (15 mg twice daily) and 32·0% (placebo). Discontinuations due to AEs were 6·0%, 2·0%, 4·1% and 6·1% of patients in the placebo, and 2, 5 and 15 mg twice-daily tofacitinib groups, respectively. Dose-dependent increases from baseline in mean serum high-density lipoprotein, low-density lipoprotein and total cholesterol, and decreases in haemoglobin and neutrophils were observed. CONCLUSION: Short-term treatment with oral tofacitinib results in significant clinical improvement in patients with moderate-to-severe plaque psoriasis and is generally well tolerated.

Can sebum reduction predict acne outcome?

Sebum excretion has generally been accepted as an important factor in the development of acne vulgaris. However, the relationship of sebum excretion and acne outcome has not yet been clearly demonstrated quantitatively. The objective of this analysis was to explore the correlation of sebum and acne by combining data from studies of various acne treatments that have demonstrated effects on both sebum excretion and acne outcome. Acne measures included total lesion count, inflammatory lesion count and acne severity grade. For each acne measure, data were pooled and analysed at the 3- and 4-month endpoints, when sebum reduction has generally equilibrated and efficacy in acne is approaching the maximum effect for most treatments. A linear model was used to describe the percentage reduction in each acne measure as a function of percentage reduction in sebum excretion. Slope values were similar for the three acne parameters and all were significantly different from zero (P < 0·025), suggesting a significant correlation of sebum and acne. The projected sebum reduction required to achieve 50% reduction in acne measures ranged from 30% to 50%. The results shown here suggest that the collective data across multiple studies may provide a useful generalization of the association of sebum reduction and acne outcome. As the relationship apparently remains consistent regardless of the treatment, it can be inferred that extrapolation to novel exploratory treatments may be valid.

Increased levels of activated T-cells and reduced levels of CD4/CD25+ cells in peripheral blood of Guillain-Barré syndrome patients compared to controls.

Guillain-Barré syndrome (GBS) is a severe, self-limiting, autoimmune motor neuropathy. This study was performed to investigate the numbers of activated T-cells and regulatory T-cells, and CD95 and bcl-2 expression in GBS patients compared to controls. The percentage of cells expressing CD69 (activated T-cells) was increased in the blood of both patients with GBS and those with other neuropathies compared to healthy controls. GBS patients displayed significant decreases in the percentage of T-lymphocytes (CD3) and CD4/CD25+ cells (T regulatory cells) compared to patients with other neuropathies and a reduction in the percentage of cytotoxic/suppressor T-lymphocytes (CD8) compared to healthy controls. CD95 expression was reduced in GBS compared to patients with other neuropathies and expression of Bcl-2 was increased in GBS compared to healthy controls. We therefore suggest that in GBS there are increased activated T-cells and disturbances in regulatory T-cells and T-cell apoptosis.

Solvation mechanisms of nedocromil sodium from activation energy and reaction enthalpy measurements of dehydration and dealcoholation.

Two independent athermal methods of analysis have been used to determine the activation energies associated with the dehydration of nedocromil sodium hydrates. For the highest temperature reaction, monohydrate to the anhydrate, the differences in the measured activation energies indicate a three-dimensional nucleation mechanism in the bulk of the crystal with subsequent three-dimensional anhydrate crystal growth. The number of critical nuclei varies inversely with heating rate. Measured enthalpy values for successive removal of water molecules at 31.7 +/- 1.0, 91.3 +/- 0.8, and 193 +/- 0.6 degrees C are the same, within experimental error, at 21.6 +/- 2.6 kJ (mol H(2)O)(-1), as determined from differential thermal analysis traces. This result implies that an earlier concept of "strong" and "weak" water binding is not relevant and temperatures at which H(2)O molecules are removed is related to nucleation effects and not bond energies. The low temperature shoulder on the 91.3 degrees C peak is identified as an effect arising from open pan analysis conditions. The appearance of "transient" peaks in the conditioning stage of nedocromil sodium trihydrate thermal analysis experiments have been investigated and an explanation based on the presence of alcoholates [(NS)(4) small middle dot 5CH(3)OH, (NS)(5) small middle dot 9C(2)H(5)OH, and (NS)(2) small middle dot C(3)H(7)OH] in the preparations is proposed.

Cyclosporin A treatment modulates cytokine mRNA expression by inflammatory cells extracted from the spinal cord of rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein.

In Lewis rats, treatment with high doses of cyclosporin A (CsA) suppresses clinical signs of experimental autoimmune encephalomyelitis (EAE), although disease occurs when treatment is ceased. Treatment with low doses of CsA causes EAE to take a chronic relapsing course. We have previously shown that CsA treatment causes a decline in the number of T cells and increased inflammatory cell apoptosis in the spinal cord. The present study was undertaken to assess whether CsA therapy also modulates cytokine mRNA expression by inflammatory cells in the spinal cord of rats with EAE, looking for changes that might contribute to the observed effects of CsA on the course of EAE. EAE was induced in Lewis rats by inoculation with myelin basic protein and adjuvants. At the peak of neurological signs, on day 14 after inoculation, rats were given a single intraperitoneal injection of saline, or CsA at a dose of 8, 16, 32 or 64 mg/kg. The next day, rats were sacrificed, the spinal cords removed, inflammatory cells were extracted from the cords, and mRNA isolated from these cells. Expression of cytokine mRNA was assessed by semi-quantitative reverse transcription polymerase chain reaction (PCR) and by quantitative real-time PCR. With both techniques, we found that CsA suppressed the expression of interferon-gamma mRNA and interleukin-2 (IL-2) mRNA. With real-time PCR, we found that CsA caused significantly increased expression of transforming growth factor-beta mRNA. With the different techniques, we observed no consistent pattern of alteration of expression of interleukin-10 or interleukin-4 mRNA. It is possible that these changes in cytokine mRNA expression contribute to the modulation of the clinical course of EAE that is produced by CsA treatment.

Sonographically guided directional vacuum-assisted breast biopsy using a handheld device.

OBJECTIVE: The goal of this study was to show that one can safely remove all sonographic evidence of masses in the breast less than or equal to 1.5 cm in greatest dimension using the 11-gauge handheld Mammotome, thereby reducing the possibility of a false-negative diagnosis and other shortcomings of the automated core biopsy device. SUBJECTS AND METHODS: Over a 12-week period (May 3--July 31, 2000), 124 sonographically guided breast biopsies were performed in 113 patients, using a new handheld directional vacuum-assisted biopsy device. All lesions that were less than or equal to 1.5 cm were biopsied using a handheld Mammotome; an attempt was made to continue the biopsy until no sonographic evidence of the lesion remained. RESULTS: Of these 124 lesions, 14 had infiltrating ductal carcinomas, four had infiltrating ductal carcinomas with associated ductal carcinoma in situ, one had infiltrating lobular carcinoma, one had ductal carcinoma in situ, three had atypical ductal hyperplasias, one had atypical lobular hyperplasia, and one had phyllodes tumor. Only one infiltrating ductal carcinoma was entirely removed histologically at Mammotome biopsy. There were no underestimates of disease. No cases of epithelial displacement were observed in any of the surgical excisions of malignancies. The remaining 99 lesions were benign. CONCLUSION: The handheld Mammotome diminishes the shortcomings of the automated core biopsy device. It reduces the possibility of false-negatives and underestimation of disease. It eliminates the need for multiple insertions and reduces the likelihood of epithelial displacement. As a result, we now use this device for all sonographically guided biopsies of breast masses smaller than 1.5 cm and recommend that others consider it for such use.

The effects of pregnancy on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats: suppression of clinical disease, modulation of cytokine expression in the spinal cord inflammatory infiltrate and suppression of lymphocyte proliferation by pregnancy sera.

PROBLEM: The present study was performed to explore the effects of pregnancy on experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats by inoculation with myelin basic protein (MBP) (MBP-EAE). METHOD OF STUDY: MBP-EAE was induced in pregnant and non-pregnant rats and severity of disease evaluated. Serum from pregnant and non-pregnant rats was used in standard lymphocyte proliferation assays. Real-time polymerase chain reaction (PCR) was used to investigate the expression of cytokine mRNA in the inflammatory cells obtained from the spinal cord of rats on day 15 after inoculation. RESULTS: Pregnant rats developed less severe disease than non-pregnant rats. Serum from pregnant rats suppressed the proliferation of T lymphocytes in response to MBP. There was significantly increased expression of IL-4, IL-10 and TNF-alpha mRNA in the spinal cord infiltrate of pregnant rats. CONCLUSION: Circulating humoral factors and alteration in cytokine production by inflammatory cells may contribute to the suppression of EAE in pregnant rats.

Early pregnancy factor suppresses experimental autoimmune encephalomyelitis induced in Lewis rats with myelin basic protein and in SJL/J mice with myelin proteolipid protein peptide 139-151.

Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties. During pregnancy, it appears in maternal serum within 6-24 h of fertilization, is present for at least the first two-thirds of pregnancy in all species studied and is essential for embryonic survival. It is a homologue of chaperonin 10, a heat shock protein, but, unlike other members of this family, EPF has an extracellular role. As it has the ability to modulate CD4+ T cell-dependent immune responses, its role in treatment of experimental autoimmune encephalomyelitis (EAE) was investigated. EAE is a CD4+ T cell-mediated disease, the best available animal model of multiple sclerosis (MS). Two models of EAE were investigated, acute EAE induced in Lewis rats by inoculation with myelin basic protein (MBP-EAE) and chronic relapsing EAE induced in SJL/J mice by inoculation with myelin proteolipid protein peptide (residues 139-151) (PLP-EAE). EPF, delivered intraperitoneally or orally to rats or intraperitoneally to mice, suppressed clinical signs of disease. Mice with PLP-EAE were also treated with interferon-beta, with and without EPF. Both EPF and IFN-beta suppressed clinical signs of EAE and, when administered together, gave greater suppression than when given separately. These findings suggest that EPF may be a potential candidate for use in treatment of MS and may be of use in combined therapy with IFN-beta.

The change of the rate-controlling processes with temperature in the hydration of anhydrous nedocromil sodium by water vapor.

A six-stage model is proposed to describe the overall process of sorption of water vapor on and into anhydrous nedocromil sodium. The way in which temperature, pressure, and time affect the rate of reaction for each of the stages has been analyzed. Experimental data for the measured rates, where temperature, pressure, and time are variables, are compared with the predictions obtained from each of the six stages. The most useful comparator is a graphical representation of reduced time versus hydration rate. The theoretical equations presented as a shape analysis of the experimental curves show the process to have different controlling mechanisms in three temperature regions: up to 27 degrees C, hydration is controlled by a nucleation and growth mechanism; between 27 and 31 degrees C, the process is dominated by diffusion of water molecules into the crystal; and >31 degrees C, neither nucleation nor diffusion are controlling but some, as yet, undetermined physical processes.

Future of thyroid surgery and training surgeons to meet the expectations of 2000 and beyond.

What is the future of thyroid surgery in the new millennium? How can surgeons keep abreast of advances in thyroid endocrinology, genetics, surgical therapy, and other aspects of thyroid disease management? How should surgeons be trained to become highly competent in thyroid disease and to perform safe, effective thyroid operative procedures? Nine internationally recognized endocrine surgeons were asked to express their views on these and related subjects. They noted that advances in molecular biology, pathology, and genetics of thyroid disease should allow more tailored surgical approaches during the twenty-first century. Current training of general surgical residents in thyroid and other types of endocrine surgery is highly variable, which may contribute to increased complication rates and number of second operations. The leadership for addressing these deficiencies and promoting a more organized approach to thyroid disease management should come from national endocrine surgery associations and their leaders. It is incumbent upon endocrine surgeons to maintain their central role in the management of many aspects of thyroid disease. Organizing teams of specialists into thyroid centers (centers of excellence) can (1) increase efficiency; (2) increase quality of care; (3) decrease costs; (4) encourage a more individualized approach to surgery; (5) lower complication rates; and (6) foster innovation in technology and disease management. Two years of additional fellowship training in thyroid and endocrine surgery is now being advocated by increasing numbers of national endocrine surgical associations as the best way to prepare surgeons for society's needs for highly skilled, competent thyroid surgeons of the future.

Ziprasidone and the pharmacokinetics of a combined oral contraceptive.

AIMS: To determine whether multiple doses of ziprasidone alter the steady-state pharmacokinetics of the component steroids, ethinyloestradiol and levonorgestrel, of an oral contraceptive; to evaluate the tolerability of a co-administered combined oral contraceptive and ziprasidone; and to compare plasma concentrations of prolactin in subjects taking a combined oral contraceptive with placebo or ziprasidone. METHODS: Nineteen women taking a combined oral contraceptive (ethinyloestradiol 30 microg day(-1) and levonorgestrel 150 microg day(-1)) were enrolled into a double-blind, placebo-controlled, two-way crossover study. They received ziprasidone 40 mg day- 1 in two divided daily doses or placebo for 8 days (days 8-15) in one of two 21 day treatment periods separated by a 7 day washout period. Venous blood samples were collected immediately before and up to 24 h after the morning dose of oral contraceptive and ziprasidone or placebo on day 15 of each 21 day treatment period. These were assayed for ethinyloestradiol and levonorgestrel and the resulting data used to derive pharmacokinetic data for these steroids. Additional samples were collected immediately before and 4 h after the morning dose of oral contraceptive and ziprasidone or placebo on day 15 of each 21 day treatment period for prolactin assay. All observed and volunteered adverse events were recorded throughout the study. RESULTS: The mean AUC(0,24 h), Cmax and tmax for ethinyloestradiol and the mean AUC(0, 24 h) and Cmax for levonorgestrel during ziprasidone co-administration were not statistically significantly different from corresponding values occurring during placebo co-administration. The tmax for levonorgestrel was approximately 0.5 h longer. Concomitant therapy with a combined oral contraceptive and ziprasidone did not result in adverse events not previously seen with either preparation alone. CONCLUSIONS: The findings of this study suggest that, based on pharmacokinetic and tolerability data, ziprasidone may be co-administered with ethinyloestradiol and levonorgestrel without loss of contraceptive efficacy or increased risk of adverse events.

Adsorption of water by anhydrous nedocromil sodium from 20 to 40 degrees C.

Three different powder preparations of the drug disodium 9-ethyl-4, 6-dioxo-10-propyl-4H,6H pyrano[3,2-g]quinoline-2,8-dicarboxylic trihydrate, Nedocromil sodium (trade name Tilade), have been fully dehydrated in a vacuum and their water vapor adsorption characteristics quantitatively assessed at different water vapor pressures over a temperature range 20 to 40 degrees C. At saturated vapor pressures, 100% RH, rates of adsorption are around 0.1 s(-1/2). Graphs of square root of time against reduced mass during uptake of water vapor at vapor pressures in the range 20 to 47 mm of Hg, all equivalent to 100% RH, indicate control by a diffusion mechanism with activation energies in the range 8 to 24 kJ mol(-1), dependent on the powder preparation method. In two of the powders nonlinear Arrhenius-type plots are interpreted as showing that control of the process is dependent on the surface's ability to hold water molecules at the experimental temperature. The variation in activation energies and the calculated values for diffusivities, around 1 x 10(-13) m(2) s(-1), are used to explore structural involvement in the overall water adsorption process. The measured values of water vapor diffusivity into the structure have been used to predict the water solubility of nedocromil sodium trihydrate, and the results show good agreement to reported solubilities. This approach to solubility prediction is an alternative to the Noyes and Whitney method where ions leaving the surface are monitored.

Effects of cyclosporin A treatment on clinical course and inflammatory cell apoptosis in experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein.

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by inoculation with myelin basic protein (MBP) and adjuvants. Rats were treated with second daily injections of saline or cyclosporin A (CsA) from the day of inoculation. Saline-treated rats had an acute episode of disease followed by clinical recovery. Rats treated with CsA 16 or 32 mg/kg had minimal signs of EAE at the usual time after inoculation, but developed signs of disease after treatment was ceased. Rats treated with CsA 8 mg/kg had a delayed first episode of disease and then developed a relapsing or a chronic persistent course of disease. CsA 4 mg/kg delayed the onset of disease. To study the effects of CsA on the inflammatory infiltrate, cells were extracted from the spinal cords of rats with EAE, 16 h after a single injection of CsA or saline. Extracted cells were labelled with antibodies to T cells, CD11b/c (macrophages/microglia), CD95 (Fas) and Fas ligand. CsA 4 mg/kg did not alter the composition of the inflammatory infiltrate. Treatment with higher single doses of CsA caused a dose-dependent decline in the percentage of T cell receptor (TCR) alphabeta+ cells in the inflammatory infiltrate. All doses of CsA caused a significant increase in the number and percentage of cells that were apoptotic. CsA treatment caused an increase in the percentages of CD5+ and TCR alphabeta+ cells that were apoptotic. There was a decline in the percentage of apoptotic T cells that were Vbeta8.2+, compared to the percentage of non-apoptotic T cells that were Vbeta8.2+, in CsA treated rats compared to saline-treated controls. This suggests that, while CsA treatment caused a non-specific increase in the overall level of T cell apoptosis in the spinal cord, it abrogated the selective apoptosis of Vbeta8.2+ encephalitogenic T cells that normally occurs during spontaneous recovery from acute EAE.

Immunolymphoscintigraphy in breast cancer: evaluation using 131I-labeled monoclonal antibody B72.3.

Noninvasive axillary lymph node staging was investigated using [131I]murine monoclonal antibody B72.3 in 16 patients with breast cancer scheduled for axillary dissection. [131I]B72.3 was injected into ipsilateral finger webs or around the breast biopsy. Scintigraphy to 72 h and gamma-counting/immunohistochemistry of nodes were performed. Specific antibody uptake (%ID/g) and the ratio of specific:nonspecific antibody uptake were not significantly different in tumor-positive versus tumor-negative nodes, suggesting that [131I]B72.3 is unsuitable to discriminate axillary node tumor involvement.

Operative experience of U.S. general surgery residents with diseases of the adrenal glands, endocrine pancreas, and other less common endocrine organs.

The aim of this study was to determine if the experience of general surgery residents is adequate and effective. The Resident Statistic Summaries (Report C) of the Residence Review Committee (Surgery) for eight academic years from 1986 to 1994 were analyzed. The main outcome measurements were total number of residents and programs, average number of operations performed, maximum number of operations performed, standard deviation, and the most common number of operations performed. For adrenalectomy, the average per resident was 0.98. The maximum range was from 7 to 15. The standard deviations ranged from 1.12 to 2.00. For pancreatic endocrine operations the average per resident was 0.15 with maximums of 3 to 10. For other endocrine procedures (nonthyroid and nonparathyroid) the average per resident was 0.14, with the maximums ranging from 7 to 19. The most common number of any of these procedures performed by U.S. graduates was 0. The number of adrenal, endocrine pancreas, and other less common endocrine procedures available for graduates of U.S. residency training programs is limited. As a consequence, most U.S. resident graduates have little or no experience with any of these procedures. Our findings suggest a strong need for fellowship training for any surgeon hoping to develop expertise in the management of these unusual and infrequent endocrine surgical diseases.

Operative experience of U.S. general surgery residents in thyroid and parathyroid disease.

BACKGROUND: We wanted to determine whether the experience of general surgery residents is adequate and effective. METHODS: The Resident Statistic Summaries (Report C) of the Residency Review Committee (Surgery) for 8 academic years from 1986 through 1994 were analyzed. The main outcome measurements were total number of residents and programs, average number of operations performed, maximum number of operations performed, standard deviation, and the most common number of operations performed. RESULTS: For thyroidectomy the average per resident ranged from 10.3 to 12.6. The maximum ranged from 52 to 102. The standard deviations ranged from 6.96 to 8. The most common number of thyroidectomies performed ranged from 7 to 10 per graduating resident. For parathyroidectomy the average ranged from 4.1 to 5.1, the standard deviations were 3.44 to 4, the maximum ranged from 25 to 60, and the most common number performed was 2. CONCLUSIONS: U.S. graduates have highly variable experience in thyroid and parathyroid surgery. Most residents have inadequate experience in parathyroid surgery and marginal experience in thyroid surgery.