The Decision to Accept Treatment for Osteoporosis Following Hip Fracture: Exploring the Woman’s Perspective Using a Stage-of-Change Model

Despite the availability of medications that reduce fracture risk, most women who sustain a hip fracture are not evaluated or treated for osteoporosis. While a number of studies have attributed this to a lack of physician awareness, no studies have evaluated this problem from the patient’s perspective. To explore the process a woman negotiates when deciding to accept pharmacologic treatment for osteoporosis after hip fracture, we used a stage-of-change model to characterize a consecutive series of 70 postmenopausal women (mean age 85 years) admitted to a tertiary care hospital with an acute low-impact hip fracture between May 2000 and August 2000. We measured stage-of-change using a modified form of the Weinstein Precaution Adoption Process Model (PAPM). The majority of patients (65%) were ineligible because of dementia or delirium; only 29 were eligible and 21 were enrolled. Most women (62%) were in stages 1 or 2 of the PAPM, indicating that they were unaware of osteoporosis or had never considered pharmacologic treatment for it. The only factors associated with a more advanced PAPM stage (indicating active consideration or currently taking treatment) were a previous bone mineral density (BMD) evaluation (p= 0.007) and a diagnosis of osteoporosis (p= 0.001). Although 48% of women had a previous fragility fracture and osteoporosis knowledge was poor overall (mean score 52% correct), neither was associated with a more advanced PAPM stage in this sample. In conclusion, women evaluated after hip fracture were not ready to accept pharmacologic treatment for osteoporosis; they were unaware that they had osteoporosis or had never considered treatment for it. For a woman to advance through the behavior change process, she must first be made aware of the problem that requires a change in behavior. Physicians play a crucial role in promoting awareness of the diagnosis of osteoporosis after fracture, which in turn is associated with patient advancement through the behavior change process and the decision to accept pharmacologic intervention. The large number of cognitively impaired patients in this population, however, will certainly make efforts to improve osteoporosis awareness, diagnosis and intervention more challenging. Received: 20 August 2001 / Accepted: 12 December 2001     

The transformation of the meaning of death in complicated grief group therapy for survivors of suicide: A treatment process analysis using the meaning of loss codebook

We examined the therapeutic process of grief change in survivors of suicide participating in complicated grief group therapy (CGGT) using the meaning of loss codebook (MLC). Complicated grief group therapy is a multimodal group psychotherapy designed to restore normal grieving in persons with complicated grief. Using video data, we evaluated transition points in psychotherapy associated with meaning reconstruction: retelling the narrative of the death, having an imaginal conversation with the deceased, and memory integration. The MLC codes captured most of the voiced statements of participants, provided a valuable lens for articulating the therapeutic process, and affirmed that CGGT facilitated effective grief.     

RESEARCH AND THE PROBLEMS OF LITTER AND MEDICAL WASTES ON THE UK COASTLINE

Recent research has shown that recreational water and bathing beach quality are associated with injury, infection and personal well-being. Continued surveillance is essential to audit the environmental and associated health trends. In the Coastwatch UK project and since 1989, annual surveys each autumn have been undertaken during a two-week study period, into the extent of littering of the UK coastline. The Public Health Laboratory Service also collects data on the use of hepatitis B immunoglobulin. In these studies it is now possible to examine time trends. The findings are not reassuring. They help to justify present concern about the health effects of discarded litter and medical waste and fears that environmental degradation could lead to loss of income from tourism. In response, some health and local authorities have started public education programmes, supplying litter bins on or near bathing beaches, emptying them regularly and undertaking beach cleansing during the summer months. The UK government is also introducing new legislation that will require 6 mm fine mesh wire screens on all shore-based sewage outlets around the UK coastline. Continued monitoring is needed to assess the effectiveness of these interventions. The need for greater personal responsibility is particularly identified.     

Fetal organ response to maternal protein deprivation during pregnancy in swine.

To test the hypothesis that maternal protein deprivation in early pregnancy retards body and organ growth of 63-d (midterm) pig fetuses, 16 primiparous domestic four-way crossbred swine were fed a diet adequate in protein (13% protein) (A) or a protein-restricted (0.7% protein) diet (PR) from d 1 to 63 of pregnancy or to parturition. Maternal body weight, plasma protein, hematocrit, and heart and spleen weights were reduced, and indices of body fatness were increased by the PR diet. Fetal body weights were reduced and fetal placental weights were increased at d 63 by protein restriction. Length from crown to rump and weights of liver, kidney, gastrointestinal tract, and cerebrum were lower in PR than in A fetuses. Concentrations of protein, RNA and DNA in liver, cerebrum and longissimus muscle were unaffected by maternal diet, but total amounts of all three constituents in liver and cerebrum were lower in PR than in A. Relative organ weights were similar in A and PR fetuses except that kidneys and gastrointestinal tract were greater in A fetuses. Newborn body weights and absolute organ weights were generally lower in PR than in A, but relative weights were similar. The observed reduction in body and organ weights and amounts of protein, RNA and DNA in 63-d fetuses and newborn progeny of PR swine establishes that the stunting effect of maternal protein restriction can be initiated by midterm, preceding the period of most rapid accretion of body tissues during prenatal life in the pig.     

Clinical Application of Whole-Genome Sequencing To Inform Treatment for Multidrug-Resistant Tuberculosis Cases

The treatment of drug-resistant tuberculosis cases is challenging, as drug options are limited, and the existing diagnostics are inadequate. Whole-genome sequencing (WGS) has been used in a clinical setting to investigate six cases of suspected extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) encountered at a London teaching hospital between 2008 and 2014. Sixteen isolates from six suspected XDR-TB cases were sequenced; five cases were analyzed in a clinically relevant time frame, with one case sequenced retrospectively. WGS identified mutations in the M. tuberculosis genes associated with antibiotic resistance that are likely to be responsible for the phenotypic resistance. Thus, an evidence base was developed to inform the clinical decisions made around antibiotic treatment over prolonged periods. All strains in this study belonged to the East Asian (Beijing) lineage, and the strain relatedness was consistent with the expectations from the case histories, confirming one contact transmission event. We demonstrate that WGS data can be produced in a clinically relevant time scale some weeks before drug sensitivity testing (DST) data are available, and they actively help clinical decision-making through the assessment of whether an isolate (i) has a particular resistance mutation where there are absent or contradictory DST results, (ii) has no further resistance markers and therefore is unlikely to be XDR, or (iii) is identical to an isolate of known resistance (i.e., a likely transmission event). A small number of discrepancies between the genotypic predictions and phenotypic DST results are discussed in the wider context of the interpretation and reporting of WGS results.     

Gemcitabine resistant pancreatic cancer cell lines acquire an invasive phenotype with collateral hypersensitivity to histone deacetylase inhibitors

Gemcitabine based treatment is currently a standard first line treatment for patients with advanced pancreatic cancer, however overall survival remains poor, and few options are available for patients that fail gemcitabine based therapy. To identify potential molecular targets in gemcitabine refractory pancreatic cancer, we developed a series of gemcitabine resistant (GR) cell lines. Initial drug exposure selected for an early resistant phenotype that was independent of drug metabolic pathways. Prolonged drug selection pressure after 16 weeks, led to an induction of cytidine deaminase (CDA) and enhanced drug detoxification. Cross resistance profiles demonstrate approximately 100-fold cross resistance to the pyrimidine nucleoside cytarabine, but no resistance to the same in class agents, azacytidine and decitabine. GR cell lines demonstrated a dose dependent collateral hypersensitivity to class I and II histone deacetylase (HDAC) inhibitors and decreased expression of 3 different global heterochromatin marks, as detected by H4K20me3, H3K9me3 and H3K27me3. Cell morphology of the drug resistant cell lines demonstrated a fibroblastic type appearance with loss of cell-cell junctions and an altered microarray expression pattern, using Gene Ontology (GO) annotation, consistent with progression to an invasive phenotype. Of particular note, the gemcitabine resistant cell lines displayed up to a 15 fold increase in invasive potential that directly correlates with the level of gemcitabine resistance. These findings suggest a mechanistic relationship between chemoresistance and metastatic potential in pancreatic carcinoma and provide evidence for molecular pathways that may be exploited to develop therapeutic strategies for refractory pancreatic cancer.