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1.
Osteoporos Int ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38922398

ABSTRACT

Oslo in Norway has had the highest incidence of hip fractures in the world. The incidence in Oslo has been thoroughly described every decade since the late 1970s. The incidence in Oslo has previously been higher compared to the rest of Norway but has now decreased to a level below the country average. PURPOSE: The purpose of this study was to report the incidence of hip fractures in Oslo in 2019 and compare it with the incidence rates from the previous four decades. METHODS: Patients residing in Oslo in 2019 with a new hip fracture identified by searching the Oslo hospital's patient administrative systems and protocols from the operating theaters. The diagnosis was verified through medical records and/or radiographs. To compare with previous studies, the direct standardization method was used with the population of Oslo in 2019 as the standard. RESULTS: A total of 758 hip fractures, 70% women, were identified in 2019. The age-standardized incidence rates per 10,000 person-years in 2019 (95% CI) were 45 (41.1-48.8) for women and 30 (25.8-33.8) for men. In women, there has been a continuous decline in age-standardized rates the last three decades and in men the last two decades. The most pronounced decline was seen in the oldest age groups over 70 years. There has been a secular decline in both cervical and trochanteric fractures; however, the decrease in trochanteric fractures was most distinct for males, with more than two times higher risk in 1996/1997 compared to 2019. CONCLUSION: Incidence rates for hip fractures in Oslo in 2019 were the lowest rate reported since 1978. The decrease was significant for both men and women. For the first time, the incidence rates are below the national rates of Norway. However, the rates are still among the highest worldwide.

2.
Arch Osteoporos ; 19(1): 28, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602605

ABSTRACT

This study reported the incidence of validated adult distal radius fractures in Oslo, Norway, in 2019. The incidence has been reduced over the last 20 years. However, it is still high compared to other regions in Norway and some of the other Nordic countries. PURPOSE: We aimed to report the incidence of distal radius fractures in Oslo in 2019 and compare it to the incidence rates in 1998/1999. METHODS: Patients aged ≥ 20 years resident in Oslo sustaining a distal radius fracture in 2019 were identified by electronic diagnosis registers, patient protocols, and/or radiology registers. The diagnosis was verified using medical records and/or radiology descriptions. We used the same method as the previous study from Oslo, making the comparison over time more accurate. The age-adjusted incidence rates and the age-standardized incidence rate ratio (IRR) were calculated. RESULTS: The absolute number of fractures decreased from 1490 in 1998/1999 to 1395 in 2019. The IRR for women and men in the age group ≥ 20 years in 2019 compared to 1998/1999 was 0.77 (95% CI 0.71-0.84) and 0.77 (95% CI 0.66-0.90), respectively. The IRR for women and men in the age group ≥ 50 years in 2019 compared to 1998/1999 was 0.78 (95% CI 0.71-0.86) and 0.78 (95% CI 0.63-0.97), respectively. For the population in Oslo with Asian background compared to Norwegian background in the age group ≥ 50 years, the IRR in 2019 was 0.57 (95% CI 0.40-0.80) for women and 0.77 (95% CI 0.44-1.37) for men. CONCLUSIONS: The incidence of distal radius fractures in Oslo has decreased over the last 20 years. It is still, however, higher than in other areas of Norway and in some of the other Nordic countries.


Subject(s)
Fractures, Bone , Wrist Fractures , Adult , Male , Humans , Female , Incidence , Norway/epidemiology
3.
Osteoporos Int ; 32(5): 873-881, 2021 May.
Article in English | MEDLINE | ID: mdl-33201249

ABSTRACT

Low vitamin D in patients with hip fracture is common. In the present study, 407 of 872 (47%) patients had serum calcidiol less than 50 nmol/L. Patients with low vitamin D had more delirium, more new hip fractures, and more medical readmissions, but not more orthopedic complications after 1 year. INTRODUCTION: We wanted to study the relation between vitamin D level and postoperative orthopedic and medical complications in patients with hip fracture. In addition, we investigated the effect of giving a single-dose cholecalciferol 100.000 IU. METHODS: Data were taken from the local hip fracture register. Logistic regression analyses including vitamin D level and potentially confounding variables were performed for complications and readmissions. RESULTS: A total of 407 (47%) of 872 included hip fractures had low vitamin D at baseline. A total of 155 (18%) developed delirium, and the risk was higher in vitamin D-deficient patients (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.04 to 2.12; p = 0.03). A total of 261 (30%) were readmitted for non-hip-related conditions. Low vitamin D was associated with a higher risk of medical readmissions within 30 days (OR 1.64 (1.03 to 2.61); p = 0.036) and 12 weeks (OR 1.47 (95% CI 1.02 to 2.12); p = 0.039). There was a higher risk of a new hip fracture (OR 2.84 (95% CI 1.15 to 7.03) p = 0.024) in vitamin D-deficient patients. A total of 105 (12%) developed at least one orthopedic complication, with no correlation to baseline vitamin D. Among vitamin D-deficient patients, those receiving a single-dose of 100.000 IU cholecalciferol had fewer orthopedic complications (OR 0.32 (95% CI 0.11 to 0.97) p = 0.044) the first 30 days after surgery. CONCLUSION: Low vitamin D at admission for hip fracture increased the risk of delirium, a new hip fracture, and medical readmissions, but not orthopedic complications. The role of vitamin D supplementation to prevent orthopedic complications requires further study.


Subject(s)
Hip Fractures , Vitamin D Deficiency , Cholecalciferol , Hip Fractures/epidemiology , Hip Fractures/surgery , Humans , Patient Readmission , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Vitamins
4.
Osteoporos Int ; 31(3): 505-514, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31754755

ABSTRACT

Determinants of trabecular bone score (TBS) and vertebral fractures assessed semiquantitatively (SQ1-SQ3) were studied in 496 women with fragility fractures. TBS was associated with age, parental hip fracture, alcohol intake and BMD, not SQ1-SQ3 fractures. SQ1-SQ3 fractures were associated with age, prior fractures, and lumbar spine BMD, but not TBS. INTRODUCTION: Trabecular bone score (TBS) and vertebral fractures assessed by semiquantitative method (SQ1-SQ3) seem to reflect different aspects of bone strength. We therefore sought to explore the determinants of and the associations between TBS and SQ1-SQ3 fractures. METHODS: This cross-sectional sub-study of the Norwegian Capture the Fracture Initiative included 496 women aged ≥ 50 years with fragility fractures. All responded to a questionnaire about risk factors for fracture, had bone mineral density (BMD) of femoral neck and/or lumbar spine assessed, TBS calculated, and 423 had SQ1-SQ3 fracture assessed. RESULTS: Mean (SD) age was 65.6 years (8.6), mean TBS 1.27 (0.10), and 33.3% exhibited SQ1-SQ3 fractures. In multiple variable analysis, higher age (ßper SD = - 0.26, 95% CI: - 0.36,- 0.15), parental hip fracture (ß = - 0.29, 95% CI: - 0.54,- 0.05), and daily alcohol intake (ß = - 0.43, 95% CI - 0.79, - 0.08) were associated with lower TBS. Higher BMD of femoral neck (ßper SD = 0.34, 95% CI 0.25-0.43) and lumbar spine (ßper SD = 0.40, 95% CI 0.31-0.48) were associated with higher TBS. In multivariable logistic regression analyses, age (ORper SD = 1.94, 95% CI 1.51-2.46) and prior fragility fractures (OR = 1.71, 95% CI 1.09-2.71) were positively associated with SQ1-SQ3 fractures, while lumbar spine BMD (ORper SD = 0.75 95% CI 0.60-0.95) was negatively associated with SQ1-SQ3 fractures. No association between TBS and SQ1-SQ3 fractures was found. CONCLUSION: Since TBS and SQ1-SQ3 fractures were not associated, they may act as independent risk factors, justifying the use of both in post-fracture risk assessment.


Subject(s)
Diabetes Mellitus, Type 2 , Osteoporotic Fractures , Spinal Fractures , Absorptiometry, Photon , Aged , Bone Density , Cancellous Bone/diagnostic imaging , Child , Cross-Sectional Studies , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Norway/epidemiology , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Spinal Fractures/diagnostic imaging , Spinal Fractures/epidemiology , Spinal Fractures/etiology
5.
Histochem Cell Biol ; 143(2): 195-207, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25201349

ABSTRACT

Tartrate-resistant acid phosphatase (TRAP) is well known as an osteoclast marker; however, a recent study from our group demonstrated enhanced number of TRAP + osteocytes as well as enhanced levels of TRAP located to intracellular vesicles in osteoblasts and osteocytes in experimental osteoporosis in rats. Such vesicles were especially abundant in osteoblasts and osteocytes in cancellous bone as well as close to bone surface and intracortical remodeling sites. To further investigate TRAP in osteoblasts and osteocytes, long bones from young, growing rats were examined. Immunofluorescence confocal microscopy displayed co-localization of TRAP with receptor activator of NF-KB ligand (RANKL) and osteoprotegerin (OPG) in hypertrophic chondrocytes and diaphyseal osteocytes with Pearson's correlation coefficient ≥0.8. Transmission electron microscopy showed co-localization of TRAP and RANKL in lysosomal-associated membrane protein 1 (LAMP1) + vesicles in osteoblasts and osteocytes supporting the results obtained by confocal microscopy. Recent in vitro data have demonstrated OPG as a traffic regulator for RANKL to LAMP1 + secretory lysosomes in osteoblasts and osteocytes, which seem to serve as temporary storage compartments for RANKL. Our in situ observations indicate that TRAP is located to RANKL-/OPG-positive secretory lysosomes in osteoblasts and osteocytes, which may have implications for osteocyte regulation of osteoclastogenesis.


Subject(s)
Acid Phosphatase/metabolism , Isoenzymes/metabolism , Lysosomal-Associated Membrane Protein 1/metabolism , Osteoblasts , Osteocytes , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Animals , Fluorescent Antibody Technique , Microscopy, Electron, Transmission , Osteoblasts/enzymology , Osteoblasts/microbiology , Osteocytes/enzymology , Osteocytes/metabolism , Protein Transport , Rats , Tartrate-Resistant Acid Phosphatase
6.
Bone Joint Res ; 1(6): 125-30, 2012 Jun.
Article in English | MEDLINE | ID: mdl-23610682

ABSTRACT

OBJECTIVES: An experimental rabbit model was used to test the null hypothesis, that there is no difference in new bone formation around uncoated titanium discs compared with coated titanium discs when implanted into the muscles of rabbits. METHODS: A total of three titanium discs with different surface and coating (1, porous coating; 2, porous coating + Bonemaster (Biomet); and 3, porous coating + plasma-sprayed hydroxyapatite) were implanted in 12 female rabbits. Six animals were killed after six weeks and the remaining six were killed after 12 weeks. The implants with surrounding tissues were embedded in methyl methacrylate and grinded sections were stained with Masson-Goldners trichrome and examined by light microscopy of coded sections. RESULTS: Small amounts of bone were observed scattered along the surface of five of the 12 implants coated with porous titanium, and around one out of 12 porous coated surfaces with Bonemaster. No bone formation could be detected around porous coated implants with plasma-sprayed hydroxyapatite. CONCLUSION: Porous titanium coating is to some degree osteoinductive in muscles.

8.
Leuk Res ; 28(9): 979-85, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15234576

ABSTRACT

This meeting was convened by Richard T. Silver, M.D. and co-chaired by Jerry L. Spivak, M.D. It was held from 16 to 18 October 2003 in New York City, New York, USA. Thirty-nine invited speakers from nine different countries participated in the conference. There were more than 350 attendees. There were formal presentations and discussions on biology, clinical aspects, and management of patients with these diverse bone marrow stem cell disorders linked by a variable progression to acute myeloid leukemia. Of considerable interest, a clinical symposium exclusively for patients was held the day preceding the meeting at which John Bennett, Tiziano Barbui, Richard Silver, Jerry Spivak, and Ayalew Tefferi spoke on various topics pertaining to these diseases. This proved to be highly informative to the patients who reported that they enjoyed the program immensely. This was sponsored by the Cancer Research & Treatment Fund, Inc. Representatives of the Myelodysplasia Foundation were also present. This meeting report provides a summary of five different sections prepared by one or more of the session chairs. The keynote address was given by Shahin Rafii (Cornell Medical Center). Most appropriately, this talk focused on the expression and activation of angiogenic factors which play a crucial role in the progression of both myeloproliferative disorders and myelodysplastic syndromes (MDS). Among the known factors, vascular endothelial growth tyrosine kinase receptors (VEGF-R1, R2, and R3) support proliferation, survival, and mobility. Rafii's team has demonstrated that these receptors are expressed on subsets of primary hematopoietic cells as well as leukemic cells. Some leukemic cells express both VEGF-A and VEGF-R2, resulting in the generation of an autocrine loop that supports survival and within the osteoblastic zone translocating these cells to the vascular enriched niche for receipt of molecular instructions required for proliferation and differentiation. A pathologic correlation can be seen in some patients with the identification of abnormal localization of immature precursors (ALIP) in the central portions of the medullary cavity. Misplaced megakaryocytes can release pro-fibrotic factors, including platelet derived growth factors and transforming growth factor-beta. Collectively, these data suggest that chronic disregulation of angiogenic factors alter the microenvironment dislocating marrow stem cells that force both proliferation and differentiation in varying degrees, contributing to these hematological disorders.


Subject(s)
Myelodysplastic Syndromes , Myeloproliferative Disorders , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/etiology , Myelodysplastic Syndromes/genetics , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/etiology , Myeloproliferative Disorders/genetics , Polycythemia , Primary Myelofibrosis , Thrombocytosis
9.
Mol Psychiatry ; 8(4): 423-33, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12740600

ABSTRACT

Depression is a heritable disorder that is often precipitated by stress. Abnormalities of the stress-reactive hypothalamic-pituitary-adrenal (HPA) axis are also common in depressed patients. In animal models, the forced swim test (FST) is the most frequently used test of depressive-like behavior. We have used a proposed animal model of depression, the Wistar Kyoto (WKY) rat, to investigate the relationship as well as the mode of inheritance of FST behaviors and HPA measures. Through reciprocal breeding of WKY and F344 parent strains and brother-sister breeding of the F1 generation, we obtained 486 F2 animals. Parent, F1 and F2 animals were tested in the FST. Blood samples were collected for determination of basal and stress (10-min restraint) plasma corticosterone (CORT) levels, and adrenal weights were measured. We found that all measures were heritable to some extent and that this heritability was highly sex dependent. Both correlation and factor analyses of the F2 generation data demonstrate that FST behavior and HPA axis measures are not directly related. Thus, the underlying genetic components of depressive-like behavior and HPA axis abnormalities are likely to be disparate in the segregating F2 generation of a WKY x F344 cross.


Subject(s)
Depression/genetics , Hypothalamo-Hypophyseal System/physiology , Pituitary-Adrenal System/physiology , Stress, Psychological/genetics , Animals , Chromosome Mapping , Crosses, Genetic , Female , Hydrocortisone/blood , Male , Rats , Rats, Inbred F344 , Rats, Inbred WKY , Sex Characteristics , Species Specificity
10.
Brain Res ; 913(2): 224-33, 2001 Sep 21.
Article in English | MEDLINE | ID: mdl-11549391

ABSTRACT

The rat prepro-thyrotropin releasing hormone (TRH) 178-199 is derived from prepro-TRH by the actions of the endopeptidases, prohormone convertase 1 (PC1) and PC2. PPTRH 178-199 attenuates the synthesis and secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary both in vitro and in vivo, suggesting an inhibitory action on hypothalamic-pituitary-adrenal (HPA) axis function. This peptide also acts centrally to increase activity and decrease anxiety related behaviors. To elucidate the involvement of this peptide in these functions, we have compared the expression of PPTRH 178-199, PPTRH mRNA, and PC1 and PC2 mRNAs in the Wistar-Kyoto (WKY) and Wistar strains of rat. WKY rats have been shown to possess neuroendocrine abnormalities (HPA hyper-activity) and hyper-emotional behavioral characteristics. Immunohistochemical analysis of PPTRH 178-199 demonstrated significant strain differences in the paraventricular nucleus (PVN) of the hypothalamus and the parastrial nucleus (PSN). WKY rats had significantly greater numbers of immunoreactive (IR) cell body profiles (P<0.0005) than Wistar rats in the PVN and a significantly lower fiber density (P<0.002) in the PSN. Levels of PPTRH, PC1, and PC2 mRNA were not different between strains in any brain region examined. These data suggest that altered levels of PPTRH 178-199 in WKY rats could cause, at least in part, the hyper-activity of the HPA axis and the hyper-emotional behavioral characteristics seen in this rat strain. Such data fit with the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior.


Subject(s)
Adrenocorticotropic Hormone/metabolism , Aspartic Acid Endopeptidases/genetics , Hypothalamo-Hypophyseal System/metabolism , Peptide Fragments/metabolism , Protein Precursors/metabolism , Stress, Physiological/metabolism , Subtilisins/genetics , Thyrotropin-Releasing Hormone/metabolism , Adrenocorticotropic Hormone/biosynthesis , Animals , Axons/metabolism , Axons/ultrastructure , Depression/genetics , Depression/metabolism , Depression/physiopathology , Hypothalamo-Hypophyseal System/cytology , Immunohistochemistry , Male , Paraventricular Hypothalamic Nucleus/cytology , Paraventricular Hypothalamic Nucleus/metabolism , Proprotein Convertase 2 , Proprotein Convertases , Protein Precursors/genetics , RNA, Messenger/metabolism , Rats , Rats, Inbred WKY , Rats, Wistar/anatomy & histology , Rats, Wistar/genetics , Rats, Wistar/metabolism , Stress, Physiological/genetics , Stress, Physiological/physiopathology , Thyrotropin-Releasing Hormone/genetics
11.
Am J Physiol Regul Integr Comp Physiol ; 281(3): R786-94, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11506993

ABSTRACT

The Wistar Kyoto (WKY) rat is hyperreactive to stress and exhibits depressive-like behavior in several standard behavioral tests. Because patients with depressive disorders often exhibit disruptions in the circadian rhythm of activity, as well as altered secretory patterns of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid hormones, we tested the hypothesis that these phenomena occur in the WKY rat. Plasma ACTH and corticosterone levels remained significantly higher after the diurnal peak for several hours in WKY rats relative to Wistar rats. Also, plasma levels of thyroid-stimulating hormone were significantly higher in WKY relative to Wistar rats across the 24-h period, despite normal or slightly higher levels of 3,5,3'-triiodothyronine. In addition, under constant darkness conditions, WKY rats exhibited a shorter free running period and a decreased response to a phase-delaying light pulse compared with Wistar rats. In several ways these results are similar to those seen in other animal models of depression as well as in depressed humans, suggesting that the WKY rat could be used to investigate the genetic basis for these abnormalities.


Subject(s)
Adrenocorticotropic Hormone/blood , Chronobiology Disorders/physiopathology , Corticosterone/blood , Depression/physiopathology , Thyrotropin/blood , Activity Cycles , Animals , Behavior, Animal , Chronobiology Disorders/complications , Darkness , Depression/complications , Disease Models, Animal , Male , Motor Activity , Photic Stimulation , Photoperiod , Rats , Rats, Inbred WKY , Rats, Wistar , Triiodothyronine/blood
12.
Prev Med ; 33(1): 53-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11482996

ABSTRACT

BACKGROUND: Although there is good evidence that several pharmacotherapies and counseling can effectively facilitate smoking cessation, there is little information about the use or effectiveness of these or any other quit aids outside of controlled trials. METHODS: A mailed survey with phone follow-up documented the use of various quit aids among 3,122 health plan members who smoke. A multilevel statistical modeling technique controlled for potentially confounding variables. RESULTS: Nearly half (1,513) of these smokers reported a quit attempt during the preceding 6 months. Although 1,036 (33.2%) reported using some type of aid to quitting, primarily nicotine products or bupropion, 10-26% of these "users" did not report an actual quit attempt. Ninety percent of the medication users had a personal cost, averaging $53-$87. Fully 26.9% of those reporting a quit without any type of aid quit for at least 7 days. This rate equals that of users of all types of aids except for nicotine patches and bupropion, both of which had associated 7 or more day quit rates of about 46% (95% CI 39.3-52.2). CONCLUSIONS: Pharmacotherapeutic quit aids are being widely used, even in the absence of significant insurance coverage.


Subject(s)
Bupropion/therapeutic use , Nicotine/therapeutic use , Smoking Prevention , Smoking/epidemiology , Female , Humans , Male , Middle Aged , Minnesota/epidemiology , Randomized Controlled Trials as Topic , Smoking Cessation/statistics & numerical data , Surveys and Questionnaires
13.
Eff Clin Pract ; 4(3): 121-6, 2001.
Article in English | MEDLINE | ID: mdl-11434075

ABSTRACT

CONTEXT: Preventive services are not delivered at optimal rates in primary care settings, and the literature suggests that a systems approach is key to improvement. Studying variation among clinics could help us to understand the extent of system use in practice. PRACTICE PATTERN EXAMINED: The proportion of patients who are up-to-date for preventive services in 44 primary care practices in the Midwest. PREVENTIVE SERVICES EXAMINED: Papanicolaou (Pap) smear, cholesterol testing, mammography, clinical breast examination, blood pressure measurement, influenza and pneumococcal vaccinations, and advice on tobacco use. DATA SOURCE: 6830 patients surveyed after their clinic visit (response rate, 85%). RESULTS: The proportion of patients up-to-date for preventive services varied widely among clinics. For example, up-to-date rates for Pap smear testing ranged from 70% to 93% and 45% to 88% for cholesterol screening. There was little correlation between a clinic's performance on one preventive service (relative to the other 43 clinics) and its performance on others. When correlations between pairs of up-to-date rates within clinics were examined, only 4 of 28 service pairs were positive and statistically significant and only 1 had a correlation coefficient that exceeded 0.5 (for mammography and clinical breast examination). CONCLUSION: There is wide variation in the rates at which various preventive services are performed, both between and within clinics. This variation, which is probably due to a lack of organized prevention systems that cover multiple services, provides a clear target for improvement efforts.


Subject(s)
Diagnostic Tests, Routine/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Preventive Health Services/statistics & numerical data , Primary Health Care/standards , Blood Pressure Determination/statistics & numerical data , Cholesterol/blood , Female , Health Care Surveys , Humans , Influenza Vaccines/administration & dosage , Male , Mammography/statistics & numerical data , Minnesota , Papanicolaou Test , Pneumococcal Vaccines/administration & dosage , Preventive Health Services/standards , Smoking/adverse effects , Utilization Review , Vaginal Smears/statistics & numerical data
15.
Neuropsychopharmacology ; 24(6): 632-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11331143

ABSTRACT

Wistar-Kyoto (WKY) rats show endogenous depressive behavior that can be reversed by antidepressants. Given that WKYs exhibit decreased sensitivity to some antidepressants and treatment-resistant depressed patients often show hypothalamic-pituitary-thyroid (HPT) dysregulation, we examined the behavioral and HPT hormonal responses of WKYs to altered thyroid status. "Euthyroid" WKYs had elevated basal plasma TSH and T(3) levels as compared to Wistars. Hypothyroidism increased TSH levels more in WKYs than in Wistars and increased response latency in the open field test (OFT) of WKYs only. Administration of T(4) and T(3) suppressed plasma TSH equally in both strains. Wistars responded to increased T(3) levels with decreased response latency and increased activity in the OFT, but increased immobility in the forced swim test. In contrast, WKYs responded only to the high T(3) levels with decreased response latency in the OFT. These results suggest the existence of a decreased central nervous system sensitivity to thyroid hormones in WKYs that could be related to their depressive behavior.


Subject(s)
Depression/blood , Hyperthyroidism/metabolism , Hypothalamo-Hypophyseal System/metabolism , Hypothyroidism/metabolism , Rats, Inbred WKY/metabolism , Thyroid Gland/metabolism , Animals , Antidepressive Agents/pharmacology , Behavior, Animal/physiology , Depression/drug therapy , Depression/physiopathology , Hormones/metabolism , Hyperthyroidism/physiopathology , Hypothalamo-Hypophyseal System/physiopathology , Hypothyroidism/physiopathology , Male , Rats , Reaction Time/physiology , Swimming/physiology , Thyroid Gland/physiopathology , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/blood
16.
Semin Hematol ; 38(1 Suppl 2): 5-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11242596

ABSTRACT

The current dogma about polycythemia vera (PV) is that one or more genetic mutations in a hematopoietic stem cell (HSC) cause abnormal proliferation and differentiation of the progeny of that stem cell. This model ignores two fundamental characteristics of biologic systems that must be considered if regulation is to be understood: first, at a molecular level, biochemical processes are intrinsically stochastic; and second, ontogeny and hematopoiesis are branching processes-with one cell dividing into two cells, and so on. Why is it important to add an understanding of the stochastic, branching nature of HSC function to a description of the genes and gene products only? Why not just say one understands the regulation of normal hematopoiesis, or PV, when all the genes and gene products actively transcribed have been identified? The answer is that within a branching, stochastic process, one mutation can cause more than one outcome (phenotype) in the future. There will be one or more related outcomes that will be highly likely and others that will be less likely. Although most patients will have similar phenotypes, some will differ, but not because they have different underlying mutations. Mathematics will probably play an increasingly important role in describing and analyzing the regulation that occurs as the genetic program of HSC is expressed within a clone over time. Semin Hematol 38(suppl 2):5-9.


Subject(s)
Hematopoiesis/physiology , Clone Cells/pathology , Hematopoietic Stem Cells/pathology , Humans , Models, Biological , Polycythemia Vera/etiology , Polycythemia Vera/pathology , Polycythemia Vera/physiopathology
17.
Semin Clin Neuropsychiatry ; 6(1): 43-67, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11172532

ABSTRACT

Is there an appropriate animal model for human affective disorders? The traditional difficulties in accepting animal models for psychopathology stem from the argument that there is no evidence for concluding that what occurs in the brain of the animal is equivalent to what occurs in the brain of a human. However, if one models any or some core aspects of affective disorder, this model can become an invaluable tool in the analysis of the multitude of causes, genetic, environmental, or pharmacological, that can bring about symptoms homologous to those of patients with affective disorders. Animal models can also allow the study of the mechanisms of specific behaviors, their pathophysiology, and can aid in developing and predicting therapeutic responses to pharmacologic agents. Although animals exhibit complex and varied social and emotional behaviors for which well-validated and standardized measures exist, an understanding that a precise replica of human affective disorders cannot be expected in a single animal model is crucial. Instead, a good animal model of a human disorder should fulfill as many of the four main criteria as possible: (1) strong behavioral similarities, (2) common cause, (3) similar pathophysiology, and (4) common treatment. An animal model fulfilling any or most of these criteria can be used to elucidate the mechanisms of the specific aspect of the model that is homologous to the human disorder. A wide range of animal models of affective disorders, primarily depression, has been developed to date. They include models in which "depressive behavior" is the result of genetic selection or manipulation, environmental stressors during development or in adulthood, or pharmacologic treatments. The assessment of these animal models is based either on behavioral tests measuring traits that are homologous to symptoms of the human disorder they model, or behavioral tests responsive to appropriate pharmacologic treatments. The goal of this review is to focus on relatively recent developments of selected models, to aid in understanding their strengths and weaknesses, and to help those choosing the difficult task of developing novel animal models of affective disorders. The ideal animal model of affective disorders of the future would be an endogenous, genetic model that reiterates the essential, core aspects of the human disease and responds to the standard regimens of therapy. Because complex diseases have been approached from the genetic startpoint by using rodent models, a genetic model of affective disorder would open up possibilities for genetic analysis of polygenic traits that seem to underlie these disorders.


Subject(s)
Disease Models, Animal , Genetic Predisposition to Disease , Mood Disorders/genetics , Mood Disorders/physiopathology , Stress, Psychological/physiopathology , Animals , Animals, Genetically Modified , Depression/chemically induced , Humans , Mood Disorders/psychology , Rodentia , Stress, Psychological/genetics
18.
Mayo Clin Proc ; 76(2): 138-43, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11213301

ABSTRACT

OBJECTIVE: To learn whether patients who smoke and who receive smoking cessation information during medical office visits were less likely to be satisfied with the smoking cessation help they received than patients who smoke but who did not receive such information. PATIENTS AND METHODS: A total of 3703 current cigarette smokers were identified by a mailing in November 1998 to 163,596 members of 2 Minnesota health plans, and 2714 (77.3%) responses to a 44-item questionnaire were available for analysis. Using hierarchical analysis to control confounding variables, we assessed the relationship between patient-reported smoking cessation support actions at the last physician visit and satisfaction "with the help received from your doctor about quitting smoking." RESULTS: Smokers were very satisfied (12.0%), satisfied (25.3%), neutral (48.6%), and dissatisfied or very dissatisfied (13.5%) with physician help. After controlling for other characteristics, the 1898 patients who reported that they had been asked about tobacco use or advised to quit during the latest visit had 10 percentage point greater satisfaction ratings and 5 percentage point less dissatisfaction than those not reporting such discussions (P<.001). Smokers reporting no interest in quitting at the time of the latest visit also demonstrated greater satisfaction in association with these actions. CONCLUSION: Smoking cessation interventions during physician visits were associated with increased patient satisfaction with their care among those who smoke. This information should reduce concerns of physicians or nurses about providing tobacco cessation assistance to patients during office visits.


Subject(s)
Counseling , Patient Satisfaction , Smoking Cessation , Adult , Female , Health Behavior , Humans , Male , Middle Aged , Nurse-Patient Relations , Physician-Patient Relations
19.
Jt Comm J Qual Improv ; 27(12): 639-50, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11765381

ABSTRACT

BACKGROUND: The DIAMOND Project (Depression Is A MANageable Disorder), a nonrandomized controlled effectiveness trial, was intended to improve the long-term management of depression in primary care medical clinics. The project tested whether a quality improvement (QI) intervention could implement a systems approach-so that there would be more reliable and effective monitoring of patients with depression, leading to better outcomes. THE QUALITATIVE STUDY: A study was conducted in 1998-2000 to determine why a quality improvement intervention to improve depression care did not have a significant impact. Data consisted of detailed notes from observations of 12 project-related events (for example, team meetings and presentations) and open-ended interviews with a purposive sampling of 17 key informants. Thematic analytic methods were used to identify themes in the contextual data. PRINCIPAL FINDINGS: Overall, the project implementation was very limited. Five themes emerged: (1) The project received only lukewarm support from clinic and medical group leadership. (2) Clinicians did not perceive an urgent need for the new care system, and therefore there was a lack of impetus to change. (3) The improvement initiative was perceived as too complex by the physicians. (4) There was an inherent disconnect between the commitment of the improvement team and the unresponsiveness of most other clinic staff. (5) The doctor focus in clinic culture created a catch-22 dilemma-the involvement and noninvolvement of physicians were both problematic. CONCLUSION: Problems in both predisposing and enabling factors accounted for the ultimate failure of the DIAMOND quality improvement effort.


Subject(s)
Case Management , Continuity of Patient Care/standards , Depressive Disorder/therapy , Primary Health Care/standards , Total Quality Management , Chronic Disease/therapy , Continuity of Patient Care/organization & administration , Depressive Disorder/nursing , Health Services Research , Humans , Organizational Culture , Outcome and Process Assessment, Health Care/methods , Patient Care Team , Pilot Projects , Primary Health Care/organization & administration , Program Evaluation
20.
Eff Clin Pract ; 4(6): 239-49, 2001.
Article in English | MEDLINE | ID: mdl-11769296

ABSTRACT

CONTEXT: Although new strategies for managing depression in primary care (e.g., nurse telephone calls, collaborative care) have been shown to be effective, no models are available for their systematic implementation in the "real world." OBJECTIVE: To test whether a continuous quality improvement (CQI) intervention could be used to implement systems in primary care clinics to improve the care and outcomes for patients diagnosed with depression. DESIGN: Before-after study with concurrent controls. INTERVENTION: A multidisciplinary team from the three intervention clinics developed and implemented a graded set of five care management options, ranging from watchful waiting (nurse telephone call in 4 to 6 weeks) to mental health management, which clinicians could order for their patients with depression. SETTING: 9 primary care clinics in greater Minneapolis-St. Paul, Minnesota. PATIENTS: Outpatients 18 years of age and older whose primary care clinic visit included an International Classification of Diseases, 9th revision, code for depression and who completed baseline and 3-month follow-up surveys before and after the intervention. MAIN OUTCOME MEASURES: Measures of process of care (follow-up depression visits to physician, mental health visits, follow-up telephone calls) and outcomes of care (improved depression symptoms over 3 months, satisfaction with care). RESULTS: Although the CQI team appeared to function well, only 30 of the 257 patients identified from depression-coded visits for this study were referred to the new system during the 3-month evaluation period. In both the intervention and control clinics, follow-up visits, mental health referrals, and follow-up telephone calls did not improve significantly from the preintervention levels of about 0.5 for a primary care visit, 0.4 for a mental health visit, or 0.1 for a follow-up phone call per person. The same was true of patient outcomes: The proportion of patients in the intervention and control clinics who had improved depression symptoms and those who were very satisfied with their depression care did not change significantly from the preintervention levels of 43% and 26%, respectively. CONCLUSIONS: Our attempt to improve the primary care management of depression failed because physicians used the new order system so infrequently. Whether a greater leadership commitment to change or a different improvement process would alter our findings is an open question.


Subject(s)
Depressive Disorder/therapy , Practice Patterns, Physicians' , Primary Health Care/standards , Total Quality Management , Adolescent , Adult , Continuity of Patient Care , Depressive Disorder/classification , Female , Humans , Male , Middle Aged , Minnesota , Outcome and Process Assessment, Health Care , Patient Care Team , Referral and Consultation , Treatment Outcome
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