Persistence, reproducibility, and cost-effectiveness of an intervention to improve the quality of osteoporosis care after a fracture of the wrist: results of a controlled trial

INTRODUCTION: Older patients with fragility fractures are not commonly tested or treated for osteoporosis. Compared to usual care, a previously reported intervention led to 30% absolute increases in osteoporosis treatment within 6 months of wrist fracture. Our objective was to examine longer-term outcomes, reproducibility, and cost-effectiveness of this intervention. METHODS: We conducted an extended analysis of a non-randomized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls. Patients >50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta, Canada were included; those already treated for osteoporosis were excluded. Overall, 102 patients participated in this study (55 intervention and 47 controls; median age: 66 years; 78% were women). The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling. Controls received usual care; at 6-months post-fracture, when the original trial was completed, all controls were crossed-over to intervention. The main outcomes were rates of osteoporosis testing and treatment within 6 months (original study) and 1 year (delayed intervention) of fracture, and 1-year persistence with treatments started. From the perspective of the healthcare payer, the cost-effectiveness (using a Markov decision-analytic model) of the intervention was compared with usual care over a lifetime horizon. RESULTS: Overall, 40% of the intervention patients (vs. 10% of the controls) started treatment within 6 months post-fracture, and 82% (95%CI: 67-96%) had persisted with it at 1-year post-fracture. Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density (BMD) testing (64 vs. 60% in the original study; p = 0.72) and osteoporosis treatment (43 vs. 40%; p = 0.77) as previously reported. Compared with usual care, the intervention strategy was dominant - per patient, it led to a $13 Canadian (U.S. $9) cost savings and a gain of 0.012 quality-adjusted life years. Base-case results were most sensitive to assumptions about treatment cost; for example, a 50% increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $24,250 Canadian (U.S. $17,218) per quality-adjusted life year gained. CONCLUSIONS: A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment, even when delivered 6-months post-fracture. From the healthcare payer's perspective, the intervention appears to have led to both cost-savings and gains in life expectancy.     

Factor structure of the geriatric depression scale in a cohort of depressed nursing home residents

We examined factor structures of the 30-item Geriatric Depression Scale in a sample of depressed nursing home residents at various levels of cognitive functioning (N=917; observation-to-variable ratio 30.6:1). Using principal components analysis and orthogonal varimax rotation, a six-factor structure involving 26 of the 30 items was derived. This solution, which explained 55.1% of the variance, consisted of the following factors: life dissatisfaction, dysphoria, hopelessness/decreased self-attitude, rumination/anxiety, social withdrawal/decreased motivation and decreased cognition. This factor solution shows that a screening test for depression like the GDS may be able to make stable and independent distinctions between various dimensions associated with depressed mood in nursing home residents. The factors derived map well onto commonly recognized dimensions of depressed mood in frail older adults residing in long-term care facilities. The proposed six-factor solution offers a stable, intuitively sound and statistically supported framework for differentiation of depressive screening data into independent dimensions. This, in turn, offers opportunities for clinical differentiation in both practice and research efforts using the GDS.     

Cocaine-associated dissection of the thoracic aorta

Patients present to emergency departments with a variety of complications related to cocaine abuse. Emergency physicians must be aware of the life- and limb-threatening complications to avoid undue mortality and morbidity. We present the case of a patient with aortic dissection who developed the acute onset of abdominal pain 5 minutes after subcutaneous cocaine use. Four previous reports of cocaine-associated aortic dissection are reported in the literature. These cases and other reports of intra-abdominal vascular injuries related to cocaine use are reviewed. Cocaine's mechanism of action as it relates to aortic dissection and some of the pharmacologic agents available for treatment are discussed.     

Visual hallucinations in patients with macular degeneration.

OBJECTIVE: This study was undertaken to determine the prevalence of visual hallucinations in patients with macular degeneration, describe such hallucinations phenomenologically, and possibly determine factors predisposing to their development. METHOD: Using a case-control design, the authors screened 100 consecutive patients with age-related macular degeneration for visual hallucinations. Each patient with visual hallucinations was matched to the next three patients without hallucinations. The patients and comparison subjects were compared in terms of scores on the Beck Depression Inventory, Eysenck Personality Questionnaire, Telephone Interview for Cognitive Status, and a structured questionnaire including demographic characteristics, family history, and medical and psychiatric history. Ophthalmologic data were obtained by chart review. RESULTS: Of the 100 patients, 13 experienced visual hallucinations. Four variables were significantly associated with having hallucinations: living alone, lower cognition score, history of stroke, and bilaterally worse visual acuity. Hallucinations were not associated with family or personal history of psychiatric disorder or with personality traits. In 11 (84.6%) of the 13 patients, the hallucinations had begun in association with an acute change in vision. CONCLUSION: These results indicate that visual hallucinations are prevalent among patients with macular degeneration. They appear unrelated to primary psychiatric disorder. The predisposing factors of bilaterally worse vision and living alone support an association with sensory deprivation, while history of stroke and worse cognition support a decreased cortical inhibition theory.     

Novel mutation in the KCNJ10 gene in three siblings with seizures,ataxia and no electrolyte abnormalities

We report a consanguineous family with three affected siblings with novel mutation in the KCNJ10 gene. All three presented with central nervous system symptoms in the form of infantile focal seizures, ataxia, slurred speech with early developmental delay and intellectual disability in two siblings. None had any associated electrolyte abnormalities and no symptomatic hearing deficits were observed.     

Exteroceptive suppression periods and pericranial muscle tenderness in chronic tension-type headache: effects of psychopathology, chronicity and disability

We examined pericranial muscle tenderness and abnormalities in the second exteroceptive suppression period (ES2) of the temporalis muscle in chronic tension-type headache (CTTH; n = 245) utilizing a blind design and methods to standardize the elicitation and scoring of these variables. No ES2 variable differed significantly between CTTH sufferers and controls (all tests, P>0.05). We found no evidence that CTTH sufferers with daily or near daily headaches, a mood or an anxiety disorder, or high levels of disability exhibit abnormal ES2 responses (all tests, P>0.05). CTTH sufferers were significantly more likely than controls to exhibit pervasive tenderness in pericranial muscles examined with standardized (500 g force) manual palpation (P<0.005). Female CTTH sufferers exhibited higher levels of pericranial muscle tenderness than male CTTH sufferers at the same level of headache activity (P<0.0001). Elevated pericranial muscle tenderness was associated with a comorbid anxiety disorder. These findings provide further evidence of pericranial hyperalgesia in CTTH and suggest this phenomenon deserves further study. Basic research that better elucidates the biological significance of the ES2 response and the factors that influence ES2 assessments appears necessary before this measure can be of use in clinical research.     

Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens

We have analyzed the expression of late differentiation antigens during terminal in vitro maturation of human macrophages (M phi) from blood monocytes (MO) in comparison to their distribution among mature M phi residing in various tissue sites. By immunizing mice with M phi derived from blood MO by culture on hydrophobic Teflon foils, monoclonal antibodies (mAbs) were developed (MAX.1, MAX.2, MAX.3, MAX.11) that reacted with lineage-restricted differentiation antigens. These antigens were expressed exclusively on M phi or were markedly increased after in vitro differentiation. The only overlap to another hemopoietic cell lineage was observed with MAX.3, which is shared by platelets and megakaryocytes. In the course of M phi maturation in vitro, the MAX.1 and MAX.3 antigens are detected within the cytoplasm two days before they appear on the cell surface. In contrast, the MAX.11 antigen is expressed simultaneously in the cytoplasm and at the cell surface, is found in varying degrees on a minor portion of blood MO and U937 cells, and is expressed rapidly at high density during early M phi differentiation in vitro. Among conventional mAbs that do not react with MO we found those against the transferrin (TF)-receptor, the BA-2, and the PCA1 antigen to label M phi. M phi matured in vivo and isolated from body fluids were positive with some but not all MAX mAbs. Distinctive patterns were observed with pulmonary M phi, exudate M phi from pleural and peritoneal effusions, synovial fluids, and early lactation milk. M phi from the alveolar space, for example, constantly expressed the MAX.2 antigen but not the MAX.3 antigen. Pleural effusion M phi, however, did not react with the MAX.1 mAb, but in most cases, it did react with the MAX.3 mAb. The detection of novel differentiation antigens, all expressed on monocyte-derived M phi but differently expressed on site-specific M phi in situ, underlines the remarkable heterogeneity among human M phi. The expression of these antigens is flexible because those MAX antigens that were not expressed in situ could be induced if cells from distinct tissue sites were cultured in vitro for several days. MAX mAbs may be of potential value to study both the sequential stages of maturation within the M phi lineage as well as differential developments induced by various culture conditions in parallel to environmental factors in vivo.     

Ca2+ and phospholipid-dependent protein kinase (protein kinase C) activity is not necessarily required for secretion by human neutrophils

Ca2+-dependent and phospholipid-dependent protein kinase (PKC) is a receptor for and is activated by phorbol esters. This enzyme is reportedly involved in the mechanism of superoxide anion (O2-) production and the release of intracellular granule contents from human neutrophils. As previously reported by others, we found that greater than 75% of the total cellular PKC activity existed in a soluble form in untreated neutrophils and that this activity was enhanced in a dose- dependent manner by phorbol 12-myristate 13-acetate (PMA) and by phorbol 12,13-dibutyrate (PDBu). Furthermore, mezerein, an analogue of PMA that is thought to be a competitive inhibitor, did not activate PKC, and on the contrary, inhibited PMA-stimulated activity in a dose- dependent manner. Pretreatment of intact neutrophils with PMA or PDBu caused the "translocation" of PKC activity to the insoluble cell fraction; PKC translocation was not detected after mezerein stimulation at any of the tested concentrations. Neither did mezerein cause an increase in intracellular Ca2+, as monitored by Quin 2 fluorescence. Both phorbol esters and mezerein stimulated intact neutrophils to generate O2- and release lysosomal enzymes into the extracellular medium. Finally sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis demonstrated key differences in the patterns of endogenous phosphoproteins of neutrophils stimulated with phorbol as compared with mezerein. We therefore suggest that PKC activation may not be the only pathway required to elicit neutrophil responses.