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1.
Anesth Analg ; 134(2): 269-275, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34403379

ABSTRACT

BACKGROUND: The pattern of perioperative use of personal electronic devices (PEDs) among anesthesia providers in the United States is unknown. METHODS: We developed a 31-question anonymous survey of perioperative PED use that was sent to 813 anesthesiologists, anesthesiology residents, and certified registered nurse anesthetists at 3 sites within one health system. The electronic survey assessed patterns of PED use inside the operating room (OR), outside the OR, and observed in others. Questions were designed to explore the various purposes for PED use, the potential impact of specific hospital policies or awareness of medicolegal risk on PED use, and whether PED was a source of perioperative distraction. RESULTS: The overall survey response rate was 36.8% (n = 299). With regard to often/frequent PED activity inside the OR, 24% reported texting, 5% reported talking on the phone, and 11% reported browsing on the Internet. With regard to often/frequent PED activity outside the OR, 88% reported texting, 26% reported talking on the phone, and 63% reported browsing the Internet. With regard to often/frequent PED activity observed in others, 52% reported others texting, 14% reported others talking on the phone, and 34% reported others browsing the Internet. Two percent of respondents self-reported a distraction compared to 15% who had observed a distraction in others. Eighty percent of respondents recognized PED as a potential distraction for patient safety. CONCLUSIONS: Our data reinforce that PED use is prevalent among anesthesia providers.


Subject(s)
Anesthesia/trends , Anesthesiologists/trends , Nurse Anesthetists/trends , Smartphone/trends , Surveys and Questionnaires/standards , Adult , Anesthesia/psychology , Anesthesiologists/psychology , Female , Humans , Male , Middle Aged , Nurse Anesthetists/psychology , Reproducibility of Results
3.
BMC Med Inform Decis Mak ; 19(1): 196, 2019 10 21.
Article in English | MEDLINE | ID: mdl-31638964

ABSTRACT

BACKGROUND: Every case of breast cancer is unique, and treatment must be personalized to incorporate a woman's values and preferences. We developed an individually-tailored mobile patient education application for women with breast cancer. METHODS: Pre-post surveys were completed by 255 women who used the tool. RESULTS: Patients thought the application included helpful information (N = 184, 72%) and was easy to navigate (N = 156, 61%). Most patients thought the amount of information in the tool was "about right" (N = 193, 87%). Decision making confidence increased by an average of 0.8 points (10-point scale) following a consultation and use of the tool (p < 0.001). CONCLUSIONS: Tailored mobile applications may optimize care by facilitating shared decision making and knowledge transfer, and they may also enhance the experience of patients as they navigate through their breast cancer journey.


Subject(s)
Breast Neoplasms/psychology , Breast Neoplasms/therapy , Decision Making , Internet , Adult , Aged , Breast Neoplasms/diagnosis , Computers, Handheld , Female , Humans , Middle Aged , Patient Education as Topic , Patient Participation , Referral and Consultation , Surveys and Questionnaires
4.
ASAIO J ; 65(5): 443-448, 2019 07.
Article in English | MEDLINE | ID: mdl-29768282

ABSTRACT

Left ventricular assist device (LVAD) pump thrombosis occurs in up to 8.4% of patients within 3-months postimplantation. Thromboelastography (TEG) could be used to signal hypercoagulability at LVAD implantation to predict patients at high risk for thrombosis. We sought to evaluate whether TEG maximum amplitude (MA) hypercoagulability (MA ≥69 mm) at the time of LVAD implantation predicts pump thrombosis. A single center, retrospective, nested case-control study was conducted using patients from January 1, 2005, to March 31, 2015. Each pump thrombosis case was matched to two control subjects based on age ± 5 years, sex, and duration of follow-up. A multivariable logistic regression analysis was performed on the matched sets; the odds ratio with 95% confidence interval (CI) was calculated to estimate the relative risk. Thirty-seven age- and sex-matched case-control sets were included for a total of 111 study participants. TEG-MA hypercoagulability occurred in 10.8% of the case group versus 6.8% of controls. There was no association between TEG-MA hypercoagulability and device thrombosis (odds ratio 1.71, 95% confidence interval 0.42-7.05, p = 0.46). Utilization of baseline TEG-MA hypercoagulability to detect individuals at risk for LVAD thrombosis is a novel concept. This study found no significant association between TEG-MA and LVAD thrombosis.


Subject(s)
Heart-Assist Devices/adverse effects , Thrombelastography/methods , Thrombophilia , Thrombosis , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk , Thrombophilia/etiology , Thrombosis/etiology
5.
Am J Hematol ; 91(11): 1113-1117, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27472910

ABSTRACT

Recent literature has demonstrated concern over the risk of Pneumocystis jirovecii pneumonia (PJP) when administering rituximab with combination chemotherapy such as in R-CHOP; however, the exact risk and potential need for prophylaxis is unknown. We sought to determine the incidence of PJP infection following R-CHOP administration in patients with B-cell lymphoma. Consecutive patients diagnosed with B-cell lymphoma receiving R-CHOP were evaluated from chemotherapy initiation until 180 days after the last administration. The primary outcome was cumulative incidence of PJP infection. Secondary endpoints included the association of rituximab, prednisone and subsequent chemotherapy with PJP infection risk. A total of 689 patients (53% male, median age 66 years) were included. Seventy-three percent of patients completed at least 6 cycles of R-CHOP treatment. Median rituximab and prednisone cumulative doses were 3950 mg and 5325 mg, respectively. Median daily prednisone dose through end of treatment was 45 mg (range 7.6 mg to 119 mg). The cumulative incidence of PJP was 1.51% (95% CI 0.57-2.43, at maximum follow-up of 330 days), below 3.5%, the conventional threshold for prophylaxis. Univariate analysis did not detect a statistically significant association between PJP and rituximab, steroids, or receipt of additional chemotherapy in this patient population. Our results demonstrate a low occurrence of Pneumocystis pneumonia during R-CHOP treatment of B-cell lymphoma and argue against universal anti-Pneumocystis prophylaxis in this setting. Further investigations should focus on targeted anti-Pneumocystis prophylaxis for patients presenting with high-risk baseline characteristics or when receiving rituximab-inclusive intensive combination chemotherapy regimens as treatment for other aggressive lymphoma subtypes. Am. J. Hematol. 91:1113-1117, 2016. © 2016 Wiley Periodicals, Inc.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/drug therapy , Pneumonia, Pneumocystis/drug therapy , Rituximab/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemoprevention/methods , Cohort Studies , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Incidence , Male , Middle Aged , Molecular Diagnostic Techniques/methods , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/etiology , Pneumonia, Pneumocystis/prevention & control , Polymerase Chain Reaction , Prednisone/administration & dosage , Retrospective Studies , Vincristine/administration & dosage , Young Adult
6.
Clin Pharmacokinet ; 55(8): 971-6, 2016 08.
Article in English | MEDLINE | ID: mdl-26873228

ABSTRACT

INTRODUCTION: Quetiapine is an oral atypical antipsychotic drug commonly used to treat a large number of neuropsychiatric disorders and conditions. However, a substantial number of patients who may benefit from treatment with quetiapine are unable to ingest quetiapine or other medications by mouth and thus require alternative routes of administration. There are currently no studies evaluating non-oral compounded dosage forms of quetiapine. METHODS: We conducted a single-dose open-label crossover pharmacokinetic study in 10 healthy adults to determine whether quetiapine compounded as a rectal suppository or a topical cream achieved absorption similar to that achieved by a commercially available oral formulation. RESULTS: Rectal quetiapine produced an area under the plasma concentration-time curve from time zero to infinity (AUC∞) approximately 90 % greater than that produced by an equal (milligram per milligram) dose of oral quetiapine (15,333 ng/mL versus 8118.8 ng/mL, p = 0.005). However, only two of ten subjects who received topical quetiapine had detectable serum levels. When detected, serum levels achieved with topical quetiapine were delayed and low in comparison with those produced by the oral and rectal dosage forms. CONCLUSION: Our results suggest that rectal, but not topical, quetiapine may be useful in clinical settings. Clinical outcome studies of rectal quetiapine are needed.


Subject(s)
Administration, Oral , Administration, Rectal , Administration, Topical , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/pharmacokinetics , Quetiapine Fumarate/administration & dosage , Quetiapine Fumarate/pharmacokinetics , Adult , Antipsychotic Agents/blood , Biological Availability , Chemistry, Pharmaceutical , Cross-Over Studies , Drug Administration Routes , Drug Compounding , Female , Healthy People Programs , Humans , Male , Middle Aged , Quetiapine Fumarate/blood
7.
Curr Ther Res Clin Exp ; 76: 104-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25408788

ABSTRACT

OBJECTIVES: Trimethoprim (TMP)/sulfamethoxazole (SMX) has consistently demonstrated great interindividual variability. Therapeutic drug monitoring may be used to optimize dosing. Optimal peak SMX concentration has been proposed as 100 to 150 µg/mL. The objective of our work was to determine the success rate of a TMP/SMX dosing guideline in achieving a targeted serum peak SMX concentration range. METHODS: Our retrospective cohort study enrolled 305 adult hospitalized patients who received treatment with TMP/SMX and underwent serum peak SMX concentration monitoring from January 2003 to November 2011. Patients receiving low-dose TMP/SMX therapy (TMP <15 mg/kg/d) were compared with those receiving high-dose therapy (TMP >15 mg/kg/d). RESULTS: Patients were classified into peak and modified peak SMX concentration cohorts based on time between TMP/SMX dose and SMX quantification. The association between dosing group and the outcome of the SMX level within the goal range was measured using logistic regression models. The primary outcome measured was serum peak SMX concentration 100 to 150 µg/mL. Serum peak SMX concentrations were attained within range for the peak and modified peak cohort 29% and 26% of the time, respectively. The median peak SMX concentration was 144 µg/mL (range 25-471 µg/mL). The low daily dose cohort demonstrated a trend toward improvement in the odds of target peak concentration range attainment. The results were similar regardless of the method used to adjust for baseline characteristics. The pure peak and modified peak cohorts had 44% and 46% of patients with above-target SMX peak concentrations, respectively. CONCLUSIONS: Attainment of the intended target concentration range was low with no difference in attainment between the low-dose and high-dose cohorts. Higher proportions of patients had an above-target SMX peak, which may indicate that the dosing algorithm is overly aggressive in obtaining the therapeutic goal.

8.
Mayo Clin Proc ; 84(8): 685-93, 2009 08.
Article in English | MEDLINE | ID: mdl-19648385

ABSTRACT

OBJECTIVE: To systematically study the association of monoclonal gammopathy of undetermined significance (MGUS) with all diseases in a population-based cohort of 17,398 patients, all of whom were uniformly tested for the presence or absence of MGUS. PATIENTS AND METHODS: Serum samples were obtained from 77% (21,463) of the 28,038 enumerated residents in Olmsted County, Minnesota. Informed consent was obtained from patients to study 17,398 samples. Among 17,398 samples tested, 605 cases of MGUS and 16,793 negative controls were identified. The computerized Mayo Medical Index was used to obtain information on all diagnoses entered between January 1, 1975, and May 31, 2006, for a total of 422,663 person-years of observations. To identify and confirm previously reported associations, these diagnostic codes were analyzed using stratified Poisson regression, adjusting for age, sex, and total person-years of observation. RESULTS: We confirmed a significant association in 14 (19%) of 75 previously reported disease associations with MGUS, including vertebral and hip fractures and osteoporosis. Systematic analysis of all 16,062 diagnostic disease codes found additional previously unreported associations, including mycobacterium infection and superficial thrombophlebitis. CONCLUSION: These results have major implications both for confirmed associations and for 61 diseases in which the association with MGUS is likely coincidental.


Subject(s)
Comorbidity , Monoclonal Gammopathy of Undetermined Significance/epidemiology , Paraproteinemias/epidemiology , Age Distribution , Aged , Blood Chemical Analysis , Cohort Studies , Female , Follow-Up Studies , Hip Fractures/diagnosis , Hip Fractures/epidemiology , Humans , Male , Middle Aged , Minnesota/epidemiology , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Paraproteinemias/diagnosis , Population Surveillance , Prevalence , Probability , Reference Values , Risk Assessment , Severity of Illness Index , Sex Distribution , Spinal Fractures/diagnosis , Spinal Fractures/epidemiology
9.
N Engl J Med ; 356(25): 2582-90, 2007 Jun 21.
Article in English | MEDLINE | ID: mdl-17582068

ABSTRACT

BACKGROUND: Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder associated with a high risk of progression to symptomatic multiple myeloma or amyloidosis. Prognostic factors for the progression and outcome of this disease are unclear. METHODS: We searched a computerized database and reviewed the medical records of all patients at Mayo Clinic who fulfilled the criteria of the International Myeloma Working Group for the diagnosis of smoldering multiple myeloma between 1970 and 1995. Bone marrow aspirate and biopsy specimens were studied, and patients were followed throughout the course of disease. RESULTS: During the 26-year period, 276 patients fulfilled the criteria for smoldering multiple myeloma. During 2131 cumulative person-years of follow-up, symptomatic multiple myeloma or amyloidosis developed in 163 persons (59%). The overall risk of progression was 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% per year for the last 10 years; the cumulative probability of progression was 73% at 15 years. At diagnosis, significant risk factors for progression included the serum level and type of monoclonal protein, the presence of urinary light chain, the extent and pattern of bone marrow involvement, and the reduction in uninvolved immunoglobulins. The proportion of plasma cells in the bone marrow and the serum monoclonal protein level were combined to create a risk-stratification model with three distinct prognostic groups. CONCLUSIONS: The risk of progression from smoldering multiple myeloma to symptomatic disease is related to the proportion of bone marrow plasma cells and the serum monoclonal protein level at diagnosis.


Subject(s)
Antibodies, Monoclonal/blood , Bone Marrow Cells/immunology , Multiple Myeloma , Plasma Cells , Adult , Aged , Aged, 80 and over , Amyloidosis , Biopsy , Bone Marrow Cells/pathology , Bone Marrow Examination , Cohort Studies , Disease Progression , Female , Humans , Lymphocyte Count , Male , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/immunology , Multiple Myeloma/pathology , Prognosis , Risk Factors
10.
Mayo Clin Proc ; 81(12): 1575-8, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17165636

ABSTRACT

OBJECTIVE: To determine the relative diagnostic contribution of urine assays as part of the screening algorithm for monoclonal gammopathies. PATIENTS AND METHODS: We identified 428 patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis. The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. RESULTS: The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. All 428 had a monoclonal urine protein, 85.7% had an abnormal serum free light chain kappa/lambda ratio, 80.8% had an abnormal serum protein electrophoresis, and 93.5% had an abnormal serum immunofixation result. All 3 serum assays were normal in only 2 patients, 1 of whom had monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria) and 1 whose urine sample contained an intact monoclonal immunoglobulin but whose serum and subsequent urine samples showed no evidence of a monoclonal gammopathy. CONCLUSION: Discontinuation of urine studies and reliance on a diagnostic algorithm using only serum studies (protein electrophoresis, immunofixation, and free light chain quantitation) missed 2 (0.5%) of the 428 monoclonal gammopathies with urinary monoclonal proteins, and these 2 cases required no medical intervention.


Subject(s)
Immunoglobulin Light Chains/blood , Paraproteinemias/diagnosis , Urinalysis , Algorithms , Diagnosis, Differential , Diagnostic Errors , Electrophoresis , Humans , Immunoglobulin Light Chains/urine , Paraproteinemias/blood , Paraproteinemias/urine , Proteinuria , Urinalysis/statistics & numerical data
11.
Br J Haematol ; 133(2): 158-64, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16611306

ABSTRACT

We sought to define prognostic factors for survival in Waldenstrom macroglobulinaemia (WM). Of 585 patients diagnosed with WM and seen at Mayo Clinic between 1960 and 2001, 337 symptomatic patients met the inclusion criteria and were analysed for overall and disease-specific survival. The median survival from the time of diagnosis was 6.4 years. The median disease-specific survival was 11.2 years. Univariate analysis for overall survival identified the following adverse prognostic factors: age >65 years (P < 0.001), organomegaly (P < 0.001), elevated beta2-microglobulin (<0.001), anaemia (Hb < 10.0 g/dl) (P = 0.01), leucopenia (<4.0 x 10(9)/l) (P = 0.03), thrombocytopenia (<150 x 10(9)/l) (P = 0.01), serum albumin <40 g/l (P = 0.001), and quantitative IgM < 0.4 g/l (P = 0.04). On multivariate analysis, age >65 years and organomegaly were associated with poor prognosis. A prognostic model was built based on these two variables. Patients at high risk (1-2 risk factors, median survival 4.2 years) experienced worse survival than patients at low risk (0 risk factors, median survival 10.6 years), P < 0.001. The prognostic model was validated in 204 patients who were not included in the analysis cohort. Beta2-microglobulin > or =4 mg/l was associated with a threefold increase in the risk of death when added to the prognostic model. We describe a simple prognostic model for overall survival for newly diagnosed patients with WM.


Subject(s)
Waldenstrom Macroglobulinemia/diagnosis , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Minnesota/epidemiology , Prognosis , Waldenstrom Macroglobulinemia/mortality , beta 2-Microglobulin/blood
12.
N Engl J Med ; 354(13): 1362-9, 2006 Mar 30.
Article in English | MEDLINE | ID: mdl-16571879

ABSTRACT

BACKGROUND: The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area. METHODS: We identified all living residents of Olmsted County, Minnesota, as of January 1, 1995. We obtained serum that remained after the performance of routine clinical tests at Mayo Clinic or asked subjects for whom such serum was unavailable to provide a sample. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation. RESULTS: Serum samples were obtained from 21,463 of the 28,038 enumerated residents 50 years of age or older (76.6 percent). MGUS was identified in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older. The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain. CONCLUSIONS: Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.


Subject(s)
Paraproteinemias/epidemiology , Age Distribution , Aged , Aged, 80 and over , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Minnesota/epidemiology , Paraproteinemias/blood , Prevalence , Sex Distribution
13.
Am J Kidney Dis ; 46(2): 278-82, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16112046

ABSTRACT

BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) is a common histological finding in patients with proteinuria. The natural history of the condition varies, and although it may be responsive to therapy, FSGS is an important cause of end-stage renal disease. FSGS can be caused by a variety of conditions, but it has been reported rarely in association with a plasma cell disorder. METHODS: Mayo Clinic databases were queried and cross-referenced for FSGS and plasma cell disorders. The diagnoses were confirmed, and relevant clinical and laboratory data were abstracted. RESULTS: A cohort of 13 patients with "idiopathic" FSGS and a monoclonal plasma cell disorder were identified. Four patients had myeloma, and 9 patients had monoclonal gammopathy of undetermined significance. Patients treated for myeloma experienced improvement in their renal lesion, and the latter relapsed when the myeloma relapsed. CONCLUSION: We show that FSGS and plasma cell disorders are temporally and epidemiologically linked. Therapy for the underlying plasma cell disorder can lead to resolution of FSGS. The emerging molecular pathogenesis of both FSGS and myeloma also provides potential mechanisms that link the 2 conditions together. Thus, physicians must rule out a plasma cell proliferative disorder in patients with FSGS before concluding that the renal lesion is idiopathic. Moreover, FSGS may respond favorably after the underlying plasma cell disorder is controlled.


Subject(s)
Glomerulosclerosis, Focal Segmental/etiology , Paraneoplastic Syndromes/etiology , Paraproteinemias/complications , Aged , Amyloidosis/etiology , Amyloidosis/pathology , Antibodies, Monoclonal/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Cohort Studies , Combined Modality Therapy , Comorbidity , Cytokines/physiology , Databases, Factual , Dexamethasone/administration & dosage , Female , Glomerulosclerosis, Focal Segmental/epidemiology , Glomerulosclerosis, Focal Segmental/physiopathology , Humans , Immunoglobulin Light Chains/metabolism , Kidney/metabolism , Kidney/pathology , Male , Melphalan/administration & dosage , Metabolic Clearance Rate , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/physiopathology , Multiple Myeloma/therapy , Myeloma Proteins/metabolism , Paraneoplastic Syndromes/epidemiology , Paraneoplastic Syndromes/physiopathology , Paraproteinemias/epidemiology , Paraproteinemias/physiopathology , Peripheral Blood Stem Cell Transplantation , Prednisone/administration & dosage , Prevalence , Proteinuria/etiology , Recurrence , Remission Induction , Retrospective Studies , Time Factors , Vasculitis/complications , Vasculitis/pathology
14.
Blood ; 106(3): 812-7, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-15855274

ABSTRACT

We hypothesized that the presence of monoclonal free kappa or lambda immunoglobulin light chains in monoclonal gammopathy of undetermined significance (MGUS), as detected by the serum free light chain (FLC) assay increases the risk of progression to malignancy. Of 1384 patients with MGUS from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 1148. At a median follow-up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An abnormal FLC ratio (kappa-lambda ratio < 0.26 or > 1.65) was detected in 379 (33%) patients. The risk of progression in patients with an abnormal FLC ratio was significantly higher compared with patients with a normal ratio (hazard ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P < .001) and was independent of the size and type of the serum monoclonal (M) protein. Patients with an abnormal serum FLC ratio, non-immunoglobulin G (non-IgG) MGUS, and a high serum M protein level (> or = 15 g/L) had a risk of progression at 20 years of 58% (high-risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk), 21% with one risk factor (low-intermediate risk), and 5% when none of the risk factors were present (low risk).


Subject(s)
Immunoglobulin Light Chains/blood , Paraproteinemias/blood , Predictive Value of Tests , Aged , Cell Transformation, Neoplastic , Disease Progression , Female , Follow-Up Studies , Humans , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Male , Middle Aged , Paraproteinemias/diagnosis , Paraproteinemias/pathology , Risk Factors
15.
Clin Lymphoma ; 5(4): 257-60, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15794860

ABSTRACT

Monoclonal gammopathy of undetermined significance (MGUS) of the immunoglobulin M (IgM) class was diagnosed at our institution in 213 patients who resided in the 11 counties of southeastern Minnesota from 1960 to 1994. The median age at diagnosis was 74 years and the median concentration of serum M-protein was 1.2 g/dL. The 213 patients were monitored for 1567 person-years (median, 6.3 years), during which 71% died. During follow-up, non-Hodgkin's lymphoma (n = 17), Waldenstrom's macroglobulinemia (n = 6), primary amyloidosis (n = 3), and chronic lymphocytic leukemia (n = 3) developed in 29 patients (14%). The number of patients with progression to lymphoid neoplasms was 15.9 times that expected in the general population. The cumulative probabilities of progression to one of these disorders were 10% at 5 years, 18% at 10 years, and 24% at 15 years. The overall average risks for progression were approximately 1.5% per year. Rates of death resulting from other diseases (cardiovascular, cerebrovascular, etc.) were 31% at 5 years, 52% at 10 years, and 65% at 15 years. Multivariate analysis revealed that only the concentration of serum M-protein at diagnosis and the serum albumin value were independent predictors of progression. It was concluded that the patients with IgM MGUS should be followed indefinitely.


Subject(s)
Immunoglobulin M/analysis , Paraproteinemias/mortality , Paraproteinemias/pathology , SEER Program/statistics & numerical data , Adult , Age of Onset , Aged , Aged, 80 and over , Disease Progression , Female , Follow-Up Studies , Humans , Lymphoma/pathology , Male , Middle Aged , Multivariate Analysis , Paraproteinemias/complications , Prognosis , Risk Factors , Survival Analysis
16.
Br J Haematol ; 127(3): 308-10, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15491291

ABSTRACT

We hypothesized that the presence of monoclonal free light chains (FLC) in the serum of patients with monoclonal gammopathy of undetermined significance (MGUS) is a marker of clonal evolution and a risk factor for progression. Forty-seven patients with MGUS and documented progression to myeloma or related malignancy were compared with 50 age- and gender-matched patients with MGUS and no evidence of progression after 5 or more years of follow-up. The presence of an abnormal kappa/lambda FLC ratio in the serum was associated with a higher risk of MGUS progression (relative risk 2.5; 95% confidence interval: 1.6-4.0; P < 0.001).


Subject(s)
Biomarkers, Tumor/blood , Immunoglobulin Light Chains/blood , Paraproteinemias/blood , Case-Control Studies , Disease Progression , Humans , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Prognosis
17.
Cancer ; 101(11): 2667-74, 2004 Dec 01.
Article in English | MEDLINE | ID: mdl-15481060

ABSTRACT

BACKGROUND: Previous studies have indicated that the incidence and mortality rates for multiple myeloma have increased in the United States. The authors reported on the incidence of multiple myeloma in Olmsted County, Minnesota, between 1991 and 2001 and on trends in multiple myeloma incidence over the last 56 years. METHODS: Using the files of the Mayo Clinic and the Olmsted Medical Center (Rochester, MN), the authors identified all residents of Olmsted County who had multiple myeloma, suspected myeloma, or a related disorder. Reports of all laboratory determinations, in addition to autopsy findings and death certificates, were obtained. The criteria for the diagnosis of multiple myeloma have not changed during the last 6 decades. RESULTS: All but 1 of the 47 residents with multiple myeloma first diagnosed between 1991 and 2001 were recognized antemortem. Fifty-five percent had a previous monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma before multiple myeloma was diagnosed. From 1991 to 2001, the overall annual incidence rate, age-adjusted to the 2000 U.S. population, was 4.3 per 100,000 (95% confidence interval, 3.0-5.5 per 100,000). Poisson regression analysis showed no statistically significant trend in Olmsted County incidence rates over 56 years. In similar fashion, the authors adjusted multiple myeloma incidence rates from nine other studies worldwide for which adequate data were available and documented similar findings in each case, except for one study that included patients with smoldering multiple myeloma. CONCLUSIONS: The overall incidence of multiple myeloma in Olmsted County, Minnesota, has not changed in almost 6 decades. The apparent increase in incidence elsewhere is unexplained but probably is attributable to improvements in diagnostic techniques, particularly in older patients.


Subject(s)
Multiple Myeloma/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Epidemiologic Studies , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Minnesota/epidemiology , Retrospective Studies
18.
Cancer Res ; 64(19): 7073-7, 2004 Oct 01.
Article in English | MEDLINE | ID: mdl-15466202

ABSTRACT

Celiac disease is associated with an increased risk of small bowel adenocarcinoma. The aims of this study were to investigate the molecular basis, assess outcomes, and identify clinicopathologic characteristics of small bowel adenocarcinoma in celiac disease. Retrospective case control cohort study of all celiac disease patients treated at our institution for small bowel adenocarcinoma and matched control patients with sporadic small bowel adenocarcinoma from July 1960 to November 2002. Mismatch repair (MMR) status was accessed by testing tissue for microsatellite instability (MSI) and for hMLH1 and hMSH2 protein expression. Over a 40-year time period, 18 patients with small bowel adenocarcinoma and celiac disease were treated at the Mayo Clinic. One celiac disease patient was excluded. High-frequency MSI (MSI-H) was identified in 8 of 11 (73%) and 2 of 22 (9%) available small bowel adenocarcinoma specimens in the celiac disease and control groups, respectively. In the celiac disease group, MSI-H was associated with loss of hMLH1 and hMSH2 in 6 and 1 specimens, respectively. Loss of hMLH1 occurred in both control tumors. Stage was associated with celiac disease status (P = 0.018), and 78% of controls were stage III or IV compared with 47% of celiac disease patients. Overall, survival was better (P = 0.025) in the celiac disease group compared with stage-matched controls. Celiac disease patients with small bowel adenocarcinoma had a high incidence defective MMR (73%) compared with controls and had better survival compared with stage-matched controls. In addition, celiac disease patients presented more frequently with early-stage small bowel adenocarcinoma. The better survival and earlier presentation of small bowel adenocarcinoma in celiac disease appears to be biologically associated with defective MMR.


Subject(s)
Adenocarcinoma/genetics , Base Pair Mismatch , Celiac Disease/complications , DNA Repair/physiology , Intestinal Neoplasms/genetics , Adaptor Proteins, Signal Transducing , Adenocarcinoma/complications , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carrier Proteins , Celiac Disease/genetics , Celiac Disease/metabolism , Celiac Disease/pathology , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Female , Humans , Intestinal Neoplasms/complications , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/pathology , Male , Middle Aged , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Nuclear Proteins , Proto-Oncogene Proteins/biosynthesis , Proto-Oncogene Proteins/genetics , Survival Rate
19.
Mayo Clin Proc ; 79(7): 859-66, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15244381

ABSTRACT

OBJECTIVE: To determine the long-term outcome of patients with monoclonal gammopathy of undetermined significance (MGUS). PATIENTS AND METHODS: We reviewed the medical records of 241 patients with MGUS who were examined at the Mayo Clinic in Rochester, Minn, between January 1, 1956, and December 31, 1970. RESULTS: Follow-up was 3579 person-years (median, 13.7 years; range, 0-39 years). Only 14 patients (6%) were alive and had no substantial increase of M protein at last follow-up; 138 patients (57%) died without evidence of multiple myeloma or a related disorder; a malignant lymphoplasma cell proliferative disorder developed in 64 patients (27%). The interval from diagnosis of MGUS to diagnosis of multiple myeloma or related disorder ranged from 1 to 32 years (median, 10.4 years). CONCLUSIONS: The median survival rate of study patients with MGUS was only slightly shorter than that of a comparable US population. Risk of progression of MGUS to lymphoplasma cell malignancy is indefinite and persists even after more than 30 years of follow-up, with no reliable predictors of malignant evolution.


Subject(s)
Monoclonal Gammopathy of Undetermined Significance/complications , Monoclonal Gammopathy of Undetermined Significance/mortality , Disease Progression , Follow-Up Studies , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M , Multiple Myeloma/etiology , Myeloma Proteins/analysis , Time Factors
20.
Haematologica ; 89(5): 626-8, 2004 May.
Article in English | MEDLINE | ID: mdl-15136236

ABSTRACT

Interleukin-6 (IL-6) and C-reactive protein (CRP, a surrogate marker for IL-6) are important in monoclonal gammopathy of undetermined significance (MGUS) and myeloma. Smoking and obesity may elevate CRP levels, while statins decrease CRP levels. A case-control study in 200 MGUS patients found that statin use, smoking history and obesity do not affect MGUS progression.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Obesity/complications , Paraproteinemias/physiopathology , Smoking/adverse effects , Adult , Aged , Aged, 80 and over , Body Mass Index , Case-Control Studies , Disease Progression , Humans , Middle Aged
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