Continuity, Coordination, and Transitions of Care for Patients with Serious and Advanced Illness: A Systematic Review of Interventions

Objectives: Continuity, coordination, and transitions of care are key to high-quality medical care for patients with serious and advanced illness. We conducted a systematic review to evaluate the impact of interventions targeting these areas in this population. Methods: We searched PubMed, CINAHL, PsycINFO, Cochrane, and DARE from 2000 through 2011. We included prospective controlled studies targeting continuity, coordination, and transitions for patients with advanced illness that reported patient centered outcomes. Of 13,014 citations, 23 studies met inclusion criteria. Two investigators extracted and checked data on population, interventions, methods, outcomes, and methodological quality. Results: Four of the six studies evaluating patient satisfaction (67%) and four of the six studies evaluating caregiver satisfaction (67%) showed statistically significant improvements in these outcomes in the intervention compared to the control group. Only three of the nine studies (33%) measuring quality of life and five of the 16 (31%) measuring health care utilization showed improvement. Results were similar across different types of interventions. Conclusions: Many studies were limited by methodologic issues such as use of measurement tools not developed for patients with advanced disease and small sample size. Interventions and outcomes were too heterogeneous for meta-analysis. We found moderate evidence that interventions targeting continuity, coordination, and transitions in patients with advanced and serious illness improve patient and caregiver satisfaction, but low evidence for other outcomes. Further research is needed on how to target these domains for outcomes such as health care utilization.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140114/1/jpm.2012.0317.pd

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

Hospital admissions and deaths relating to deliberate self-harm and accidents within 5 years of a cancer diagnosis: a national study in Scotland, UK

The risk of suicide in cancer patients has been reported as elevated in several countries. These patients are exposed to many medicines that may confuse or provide a means for harm, potentially also increasing their risk from accidents. Ratios of observed/expected numbers of hospital admission and death events relating to deliberate self-harm (DSH) and accidents were calculated in the 5 years from a cancer diagnosis in Scotland 1981–1995, compared to the matched general population. The relative risk (RR) of suicide was 1.51 (95% confidence interval (CI): 1.29–1.76). The RR of hospital admissions for DSH was not significantly increased, suggesting a strong suicidal intent in DSH acts in cancer patients. Accidental poisonings and all other accidents were both increased (RR death=3.69, 95% CI: 2.10–6.00; and 1.58, 95% CI: 1.48–1.69, respectively) (RR hospital admissions=1.32, 95% CI: 1.19–1.47; and 1.55, 95% CI: 1.53–1.57, respectively). The association of only certain tumour types (e.g. respiratory) with suicide and accidental poisoning, and a broad range of tumour types with an elevated risk of all other accidents, suggests accidental poisoning categories may be a common destination for code shifting of some DSH events. A previous history of DSH or accidents, significantly increased the RR of suicide or fatal accidents, respectively (RR suicide=14.86 (95% CI: 4.69–34.97) vs 1.16 (95% CI: 0.84–1.55)) (RR accidental death=3.37 (95% CI: 2.53–4.41) vs 1.29 (95% CI: 1.12–1.49)). Within 5 years of a cancer diagnosis, Scottish patients are at increased RR of suicide and fatal accidents, and increased RR of hospital admissions for accidents. Some of these accidents, particularly accidental poisonings, may contain hidden deliberate acts. Previous DSH or accidents are potential markers for those most at risk, in whom to target interventional techniques

Suicide in cancer patients in South East England from 1996 to 2005: a population-based study

BACKGROUND: Studies from around the world have shown that suicide risk is increased in cancer patients, but no previous detailed analysis has been carried out in England

Suicides among Danish cancer patients 1971–1999

Compared to the general population, the suicide risk among Danish cancer patients diagnosed in 1971–1986 was increased by 50% for men and 30% for women. We updated the earlier study to evaluate both long-term and recent trends in the suicide risk. Cancer patients with a first cancer diagnosed between 1971 and 1999 in Denmark were followed-up for completed suicide through 1999. Excluding nonmelanoma skin cancer, 564 508 cancer patients were included and 1241 suicides observed. Both the standardised mortality ratio (SMR) of suicide relative to the general population and the suicide rates were analysed with Poisson regression methods. The overall SMR was increased to 1.7 (95% CI. 1.6–1.9) for men and 1.4 (95% CI: 1.3–1.5) for women. Following the cancer diagnosis, the suicide risk was highest in the first 3 months for men and between months 3 and 12 for women. The risk was higher for nonlocalised cancer and for cancers with perceived poor prognosis. Breast cancer patients had a higher risk than other cancer patients with similar good prognosis. The suicide rates among cancer patients decreased with calendar time, but less so than the rates in the general population. The suicide risk among cancer patients has not decreased as much as in the Danish population and reasons for this should be explored. Breast cancer might be believed by patients to be more life threatening than it is. Assessment and treatment of depression could improve the quality of life for cancer patients who suffer from unrecognised depressions and in turn reduce the risk of suicide in cancer patients

Factors Associated with Colposcopy-Histopathology Confirmed Cervical Intraepithelial Neoplasia among HIV-Infected Women from Rio De Janeiro, Brazil

Introduction: Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods:Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+diagnosis. Results:The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+was 6.0%. Factors associated with CIN2+diagnosis in the multivariate model were age,years compared to$35 years (aPR = 3.22 95CD4 T-cell count,350 cells/mm3 when compared to$350 cells/mm3 (aPR = 6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR = 2.68 95%CI 0.99–7.24). Discussion:Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of wome

Purging Deleterious Mutations under Self Fertilization: Paradoxical Recovery in Fitness with Increasing Mutation Rate in Caenorhabditis elegans

Background: The accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci. Methodology/Principal Findings: We tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase. Conclusions: Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. Th

Positive Selection Shaped the Convergent Evolution of Independently Expanded Kallikrein Subfamilies Expressed in Mouse and Rat Saliva Proteomes

We performed proteomics studies of salivas from the genome mouse (C57BL/6 strain) and the genome rat (BN/SsNHsd/Mcwi strain). Our goal was to identify salivary proteins with one or more of three characteristics that may indicate that they have been involved in adaptation: 1) rapid expansion of their gene families; 2) footprints of positive selection; and/or 3) sex-limited expression. The results of our proteomics studies allow direct comparison of the proteins expressed and their levels between the sexes of the two rodent species. Twelve members of the Mus musculus species-specific kallikrein subfamily Klk1b showed sex-limited expression in the mouse saliva proteomes. By contrast, we did not find any of the Rattus norvegicus species-specific kallikrein subfamily Klk1c proteins in male or female genome rat, nor transcripts in their submandibular glands. On the other hand, we detected expression of this family as transcripts in the submandibular glands of both sexes of Sprague-Dawley rats. Using the CODEML program in the PAML package, we demonstrate that the two rodent kallikrein subfamilies have apparently evolved rapidly under the influence of positive selection that continually remodeled the amino acid sites on the same face in the members of the subfamilies. Thus, although their kallikrein subfamily expansions were independent, this evolutionary pattern has occurred in parallel in the two rodent species, suggesting a form of convergent evolution at the molecular level. On the basis of this new data, we suggest that the previous speculative function of the species-specific rodent kallikreins as important solely in wound healing in males be investigated further. In addition to or instead of that function, we propose that their sex-limited expression, coupled with their rapid evolution may be clues to an as-yet-undetermined interaction between the sexes

Zoonotic Viruses Associated with Illegally Imported Wildlife Products

The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence