Review of the cost-effectiveness of surveillance for hereditary pancreatic cancer.

Individuals with hereditary pancreatic cancer risk include high risk individuals (HRIs) with germline genetic susceptibility to pancreatic cancer (PC) and/or a strong family history of PC. Previously, studies have shown that PC surveillance in HRIs can downstage PC diagnosis and extend survival leading to pancreatic surveillance being recommended for certain HRIs. However, the optimal surveillance strategy remains uncertain, including which modalities should be used for surveillance, how frequently should surveillance be performed, and which sub-groups of HRIs should undergo surveillance. Additionally, in the ideal world PC surveillance should also be cost-effective. Cost-effectiveness analysis is a valuable tool that can consider the costs, potential health benefits, and risks among various PC surveillance strategies. In this review, we summarize the cost-effectiveness of various PC surveillance strategies for HRIs for hereditary pancreatic cancer and provide potential avenues for future work in this field. Additionally, we include cost-effectiveness studies among individuals with new-onset diabetes (NoD), a high-risk group for sporadic PC, as a comparison.

Patient reported outcomes of emergency general surgery procedures.

BACKGROUND: Emergency general surgery (EGS) involves care of a patient's often previously unknown disease in the setting of an unplanned interaction with the healthcare system. This leads to challenges collecting and interpreting patient reported outcome measures (PROMs). METHODS: We performed a qualitative and mixed methods study using semi-structured interviews during the index hospitalization and at 6-12 months to capture peri-operative patient experiences. We compared interview findings to clinical characteristics. RESULTS: Among 30 patients, two-thirds reported feeling no choice but to pursue emergency surgery with many reporting exclusion from decision-making. Females reported these themes more commonly. Patients with minor complications less frequently reported trust in their team and discussed communication issues and delays in care (all p â€‹< â€‹0.05). Patients with major complications more frequently reported confidence in their team and gratefulness, but also communication limitations (all p â€‹< â€‹0.05). Patients not admitted to the ICU more frequently discussed good communication and expeditious treatment. CONCLUSIONS: PROMs developed for EGS patients should consider patient outcomes and reflections that they felt excluded from decision-making. Severity of complications may also differentially impact PROMs.

The experience of using a hospital bed alternative at home among individuals with spinal cord injury: A case series.

OBJECTIVE: To inform clinicians' equipment recommendations by characterizing the experiences, skin integrity, and interface pressures in a series of recently discharged individuals with spinal cord injury (SCI) who chose to use an alternative adjustable bed system at home rather than a standard of care hospital bed with mattress overlay. DESIGN: Mixed methods, observational case series. SETTING: Community based. METHODS: Four individuals with cervical SCIs and one partner of a participant with SCI completed interviews about their experiences using an alternative adjustable bed system and their skin health. Participants also underwent pressure mapping on their alternative adjustable bed system and on a standard of care hospital bed with mattress overlay. Interview themes were identified using a consensus qualitative approach. Pressure readings at the sacrum and ischial tuberosities in supine and at the greater trochanter in side lying were compared between surfaces. OUTCOME MEASURES: Semi-structured interview, questionnaire, and pressure mapping. RESULTS: All participants reported positive experiences utilizing an alternative adjustable bed system and no episodes of bed-related skin breakdown. Reasons for wanting an alternative adjustable bed included a greater sense of normalcy and larger size. Participants perceived their alternative beds to be comfortable, and to have features that aided their function and assisted their caregivers. Features used included head of bed elevation, height elevation, and bed rails. All participants had clinically acceptable pressure mapping patterns on the alternative adjustable bed system. CONCLUSION: An adjustable bed system, combined with other skin protection strategies, may be appropriate for certain individuals with spinal cord injury.

Inherited L1 Retrotransposon Insertions Associated With Risk for Schizophrenia and Bipolar Disorder.

Studies of the genetic heritability of schizophrenia and bipolar disorder examining single nucleotide polymorphisms (SNPs) and copy number variations have failed to explain a large portion of the genetic liability, resulting in substantial missing heritability. Long interspersed element 1 (L1) retrotransposons are a type of inherited polymorphic variant that may be associated with risk for schizophrenia and bipolar disorder. We performed REBELseq, a genome wide assay for L1 sequences, on DNA from male and female persons with schizophrenia and controls (n = 63 each) to identify inherited L1 insertions and validated priority insertions. L1 insertions of interest were genotyped in DNA from a replication cohort of persons with schizophrenia, bipolar disorder, and controls (n = 2268 each) to examine differences in carrier frequencies. We identified an inherited L1 insertion in ARHGAP24 and a quadallelic SNP (rs74169643) inside an L1 insertion in SNTG2 that are associated with risk for developing schizophrenia and bipolar disorder (all odds ratios ~1.2). Pathway analysis identified 15 gene ontologies that were differentially affected by L1 burden, including multiple ontologies related to glutamatergic signaling and immune function, which have been previously associated with schizophrenia. These findings provide further evidence supporting the role of inherited repetitive genetic elements in the heritability of psychiatric disorders.

Investigation of long interspersed element-1 retrotransposons as potential risk factors for idiopathic temporal lobe epilepsy.

OBJECTIVE: To determine if long interspersed element-1 (L1) retrotransposons convey risk for idiopathic temporal lobe epilepsy (TLE). METHODS: Surgically resected temporal cortex from individuals with TLE (N = 33) and postmortem temporal cortex from individuals with no known neurological disease (N = 33) were analyzed for L1 content by Restriction Enzyme Based Enriched L1Hs sequencing (REBELseq). Expression of three KCNIP4 splice variants was assessed by droplet digital PCR (ddPCR). Protein ANalysis THrough Evolutionary Relationships (PANTHER) was used to determine ontologies and pathways for lists of genes harboring L1 insertions. RESULTS: We identified novel L1 insertions specific to individuals with TLE, and others specific to controls. Although there were no statistically significant differences between cases and controls in the numbers of known and novel L1 insertions, PANTHER analyses of intragenic L1 insertions showed statistically significant enrichments for epilepsy-relevant gene ontologies in both cases and controls. Gene ontologies "neuron projection development" and "calcium ion transmembrane transport" were among those found only in individuals with TLE. We confirmed novel L1 insertions in several genes associated with seizures/epilepsy, including a de novo somatic L1 retrotransposition in KCNIP4 that occurred after neural crest formation in one patient. However, ddPCR results suggest this de novo L1 did not alter KCNIP4 mRNA expression. SIGNIFICANCE: Given current data from this small cohort, we conclude that L1 elements, either rare heritable germline insertions or de novo somatic retrotranspositions, may contribute only minimally to overall genetic risk for idiopathic TLE. We suggest that further studies in additional patients and additional brain regions are warranted.

Restriction Enzyme Based Enriched L1Hs Sequencing (REBELseq): A Scalable Technique for Detection of Ta Subfamily L1Hs in the Human Genome.

Long interspersed element-1 retrotransposons (LINE-1 or L1) are ∼6 kb mobile DNA elements implicated in the origins of many Mendelian and complex diseases. The actively retrotransposing L1s are mostly limited to the L1 human specific (L1Hs) transcriptional active (Ta) subfamily. In this manuscript, we present REBELseq as a method for the construction of Ta subfamily L1Hs-enriched next-generation sequencing libraries and bioinformatic identification. REBELseq was performed on DNA isolated from NeuN+ neuronal nuclei from postmortem brain samples of 177 individuals and empirically-driven bioinformatic and experimental cutoffs were established. Putative L1Hs insertions passing bioinformatics cutoffs were experimentally validated. REBELseq reliably identified both known and novel Ta subfamily L1Hs insertions distributed throughout the genome. Differences in the proportion of individuals possessing a given reference or non-reference retrotransposon insertion were identified. We conclude that REBELseq is an unbiased, whole genome approach to the amplification and detection of Ta subfamily L1Hs retrotransposons.