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See related article by Moore et al., p. 821.Cancer modeling has become an accepted method for generating evidence about comparative effectiveness and cost-effectiveness of candidate cancer control policies across the continuum of care. Models of early detection policies require inputs concerning disease natural history and screening test performance, which are often subject to considerable uncertainty. Model validation against an external data source can increase confidence in the reliability of assumed or calibrated inputs. read more When a model fails to validate, this presents an opportunity to revise these inputs, thereby learning new information about disease natural history or diagnostic performance that could both enhance the model results and inform real-world practices. We discuss the conditions necessary for validly drawing conclusions about specific inputs such as diagnostic performance from model validation studies. Doing so requires being able to faithfully replicate the validation study in terms of its design and implementation and being alert to the problem of non-identifiability, which could lead to explanations for failure to validate other than those identified. See related article by Rutter et al., p. 775.The role of aspirin in cancer prevention has been well described for multiple cancers, with strong data for gastrointestinal cancers. Studies, primarily conducted in colorectal cancer, suggest that aspirin exerts its cancer-preventive effects through the inhibition of gastrointestinal inflammation. Compared with colorectal cancer, the role of aspirin in gastric cancer prevention is less well described, however it stands to reason that aspirin and/or other nonsteroidal anti-inflammatory drugs may inhibit gastric cancer progression through the inhibition of COX-2. As discussed in this issue of Cancer Prevention Research, aspirin may prevent gastric cancer, albeit it appears to exert a disparate effect in men and women, the reason for which remain unclear. These results expand upon prior studies by prospectively examining aspirin use at a wider range of doses and durations in non-Asian participants and lend support to observations from previously conducted studies in Asian populations. See related article, p. 265.In this issue of Cancer Prevention Research, Cecil and colleagues show that nonsteroidal anti-inflammatory drugs (NSAID), celecoxib and naproxen, decrease the expression of programmed death-ligand 1 (PD-L1) and increase the influx of Type I tumor-infiltrating lymphocytes in colonic tumors. Importantly, both decrease of PD-L1 expression and increase of CD8+ T cells were associated with the inhibition of COX-2/PGE2 pathway in vitro and syngeneic colonic tumor xenograft models. This study clearly suggests that NSAIDs regulate the intratumoral immunity multiple ways, including suppression of expression of immune checkpoint blockade. Thus, NSAIDs should be considered as chemopreventive for patients with PD-L1-positive colonic polyp. See related article, p. 225.Celecoxib is among the more potent and better clinically studied, nonsteroidal anti-inflammatory drugs (NSAID) for use as a chemoprevention agent for colorectal cancer. Its use is associated with a 40% to 50% response rate for reduction in adenomatous polyps. However, rare serious cardiovascular effects and even death with celecoxib and other NSAIDs make it important to understand why some patients respond and others do not. Celecoxib is a selective inhibitor of COX-2. Its anticancer mechanism has largely been attributed to the inhibition of COX-2. Celecoxib also shows activity to induce apoptosis in cancer cells not expressing COX-2. This includes activity to upregulate 15-lipoxygenase-1 (15-LOX-1) independent of COX-2 and increase the synthesis of 13-S-hydroxyoctadecadienoic acid (13-S-HODE) from linoleic acid (LA) to downregulate PPAR-δ and induce apoptosis in colorectal cancer models. In examining the effect of celecoxib on 15-LOX-1 for reducing adenomatous polyps in patients with familial adenomatous polyposis (FAP), Yang and colleagues point out the potential importance of drug bioavailability in blood, normal, and neoplastic colorectal tissue in patient response. See related article, p. 217.

Most rural hospitals and general practices in New Zealand (NZ) are reliant on point-of-care troponin. A rural accelerated chest pain pathway (RACPP), combining an electrocardiogram (ECG), a structured risk score (Emergency Department Assessment of Chest Pain Score), and serial point-of-care troponin, was designed for use in rural hospital and primary care settings across NZ. The aim of this study was to evaluate the safety and effectiveness of the RACPP.

A prospective multi-centre evaluation following implementation of the RACPP was undertaken from 1 July 2018 to 31 December 2020 in rural hospitals, rural and urban general practices, and urgent care clinics. The primary outcome measure was the presence of 30-day major adverse cardiac events (MACEs) in low-risk patients. The secondary outcome was the percentage of patients classified as low-risk that avoided transfer or were eligible for early discharge. There were 1205 patients enrolled in the study. 132 patients were excluded. Of the 1073 patients included in the primary analysis, 474 (44.0%) patients were identified as low-risk. There were no [95% confidence interval (CI) 0-0.3%] MACE within 30 days of the presentation among low-risk patients. Most of these patients (91.8%) were discharged without admission to hospital. Almost all patients who presented to general practice (99%) and urgent care clinics (97.6%) were discharged to home directly.

The RACPP is safe and effective at excluding MACEs in NZ rural hospital and primary care settings, where it can identify a group of low-risk patients who can be safely discharged home without transfer to hospital.

The RACPP is safe and effective at excluding MACEs in NZ rural hospital and primary care settings, where it can identify a group of low-risk patients who can be safely discharged home without transfer to hospital.

Low response rates in health surveys may affect the representativeness and generalizability of results if non-response is systematically related to the indicator of interest. To account for such potential bias, weighting procedures are widely used with an overall aim to obtain less biased estimates. The aim of this study was to assess the impact of applying calibrated weights on prevalence estimates of primary health care utilization among respondents compared to the entire sample of a representative Danish survey of adults aged ≥16 years.

Registry-based 1-year prevalence data on health care utilization of chiropractor/physiotherapist, dentist and psychologist in 2016 were linked to the entire sample (n = 312349), including respondents (n = 183372), from the Danish National Health Survey in 2017. Calibrated weights, which applied information on e.g. sex, age, ethnic background, education and overall health service use were used to assess their impact on prevalence estimates among respondents.

Across all included types of health care, weighting for non-response decreased prevalence estimates among respondents, which resulted in less biased estimates. For example, the overall 1-year prevalence of chiropractor/physiotherapist, dentist and psychologist utilization decreased from 19.1% to 16.9%, 68.4% to 62.5% and 1.9% to 1.8%, respectively. The corresponding prevalence in the entire sample was 16.5%, 59.4% and 1.7%.

Applying calibrated weights to survey data to account for non-response reduces bias in primary health care utilization estimates. Future studies are needed to explore the possible impact of weighting on other health estimates.

Applying calibrated weights to survey data to account for non-response reduces bias in primary health care utilization estimates. Future studies are needed to explore the possible impact of weighting on other health estimates.Trypanosoma theileri, a non-pathogenic parasite of bovines, has a predicted surface protein architecture that likely aids survival in its mammalian host. Their surface proteins are encoded by genes which account for ∼10% of their genome. A non-pathogenic parasite of sheep, Trypanosoma melophagium, is transmitted by the sheep ked and is closely related to T. theileri. To explore host and vector specificity between these species, we sequenced the T. melophagium genome and transcriptome and an annotated draft genome was assembled. T. melophagium was compared to 43 kinetoplastid genomes, including T. theileri. T. melophagium and T. theileri have an AT biased genome, the greatest bias of publicly available trypanosomatids. This trend may result from selection acting to decrease the genomic nucleotide cost. The T. melophagium genome is 6.3Mb smaller than T. theileri and large families of proteins, characteristic of the predicted surface of T. theileri, were found to be absent or greatly reduced in T. melophagium. Instead, T. melophagium has modestly expanded protein families associated with the avoidance of complement-mediated lysis. We propose that the contrasting genomic features of these species is linked to their mode of transmission from their insect vector to their mammalian host. This article has an associated First Person interview with the first author of the paper.

We provide new evidence on the profiles of social isolation, social support, and loneliness before and after spousal death for older widows. We also examine the moderating effects of gender and financial resources on changes in social health before and after widowhood.

We use 19 waves of data from the Household, Income and Labour Dynamics in Australia Survey, including 749 widowed individuals and a comparison group of around 8,000 married individuals. We apply coarsened exact matching weights and control for age and time trends. Local polynomial smoothed plots show the profiles of social health from 3 years pre- to 3 years postspousal death. All analyses were stratified by gender.

Spousal death was strongly associated with increased loneliness for women and men, but also an increase in interactions with friends and family not living with the bereaved. For men, financial resources (both income and asset wealth) provided some protection against loneliness. Spousal death was not associated with changes in ackling loneliness, particularly for women. Alternative strategies, such as helping the bereaved form a new sense of identity and screening for loneliness around widowhood by health care workers, could be beneficial.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Our organization implemented a health-system pharmacy/community pharmacy transitions of care (TOC) program, developing a scalable model to improve care transitions from the health system to the community setting for shared patients.

In this report, we describe our organization's experiences in taking a purposeful approach to building and pilot testing a partnership between our department of pharmacy and 14 community pharmacies within a larger statewide network to improve TOC across care settings. We have been successful in partnering with our electronic health record (EHR) vendor to enhance access capabilities to allow for documentation by community pharmacists (external to the organization) to be included in the patient record as a note.