Liver structure and function following small bowel resection

The observation that patients with extensive small bowel resection have impaired hepatocellular function with reduced BSP clearance and fatty change in biopsies from the liver led to a systematic study of liver structure and function following proximal and distal small bowel resection in the rat.While anaesthesia and surgery impaired BSP clearance per se, small bowel resection further reduced BSP clearance with impairment of both uptake and excretion phases of BSP excretion.The increased BSP retention was more marked after distal than after proximal small bowel resection, but in both experimental groups the abnormalities of BSP excretion spontaneously returned to normal three to four weeks after surgery.Circulating liver enzymes were normal but serum alkaline phosphatase was significantly depressed, particularly after distal resection. Isoenzyme studies showed that the depression of serum AP was due to a reduced intestinal isoenzyme. While serum levels remained consistently depressed up to eight weeks after proximal resection, in parallel with mucosal regeneration, serum AP returned to normal two to four weeks after ileectomy.While these minor changes in hepatic structure and function would normally be of little clinical importance, the additional insult of hepatic dysfunction may well be important in malnourished patients after extensive small bowel resection.     

Genetic and Environmental Risk Factors for Illicit Substance Use and Use Disorders: Joint Analysis of Self and Co-twin Ratings

The specificity of genetic and environmental risk factors for illicit substance use and substance use disorders (SUD) was investigated by utilizing self and co-twin reports in 1,791 male twins. There was a high rate of comorbidity between both use of, and SUD from, different classes of illicit substances. For substance use, the model that included one common genetic, one shared environmental, and one individual-specific (i.e., unique) environmental factor, along with substance-specific effects that were attributed entirely to genetic factors fit the data best. For illicit SUD, one common genetic and one common unique environmental risk factor, and substance specific shared environmental and unique environmental risk factors were identified. Risk factors for illicit substance use and SUD are mainly non-specific to substance class. Co-twin rating of illicit substance use and SUD was a reliable source of information, and by taking account of random and systematic measurement error, environmental exposures unique to the individual were of lesser importance than found in earlier studies.     

Autism spectrum disorder severity reflects the average contribution of de novo and familial influences

Autism spectrum disorders (ASDs) are a highly heterogeneous group of conditions—phenotypically and genetically—although the link between phenotypic variation and differences in genetic architecture is unclear. This study aimed to determine whether differences in cognitive impairment and symptom severity reflect variation in the degree to which ASD cases reflect de novo or familial influences. Using data from more than 2,000 simplex cases of ASD, we examined the relationship between intelligence quotient (IQ), behavior and language assessments, and rate of de novo loss of function (LOF) mutations and family history of broadly defined psychiatric disease (depressive disorders, bipolar disorder, and schizophrenia; history of psychiatric hospitalization). Proband IQ was negatively associated with de novo LOF rate (P = 0.03) and positively associated with family history of psychiatric disease (P = 0.003). Female cases had a higher frequency of sporadic genetic events across the severity distribution (P = 0.01). High rates of LOF mutation and low frequencies of family history of psychiatric illness were seen in individuals who were unable to complete a traditional IQ test, a group with the greatest degree of language and behavioral impairment. These analyses provide strong evidence that familial risk for neuropsychiatric disease becomes more relevant to ASD etiology as cases become higher functioning. The findings of this study reinforce that there are many routes to the diagnostic category of autism and could lead to genetic studies with more specific insights into individual cases.The set of conditions diagnosed as autism spectrum disorders (ASDs) vary enormously in their presentation (1). The most severely impaired individuals—often those with intellectual disabilities, limited speech, and severe behavioral problems—can require lifelong care. At the other end of the functional spectrum, people diagnosed with ASDs can be verbally fluent and academically gifted and can achieve independence in adulthood (2, 3). The broad range of cognitive and behavioral profiles seen in diagnosed ASDs has been long viewed as a challenge by the research community (4). Although it is well established that (i) the cognitive/behavioral profile of people diagnosed with ASDs varies widely and (ii) the set of genetic factors related to ASDs varies widely (5, 6), the degree to which phenotype can be used to predict patterns in disease architecture remains unclear.Recent insights into the genetic influences on ASDs offer an opportunity to investigate this question through the lens of de novo vs. familial effects. On average, ASDs run in families. The siblings of children with ASDs are 10–20 times more likely to receive a diagnosis of ASD themselves (7, 8); the parents of children with ASDs are more likely to manifest autistic features, as well as a variety of other neuropsychiatric conditions, such as schizophrenia and bipolar disorder (9, 10). These epidemiologic observations are consistent with analyses suggesting that ASDs are influenced by thousands of common genetic variants transmitted between generations. It has been estimated that common, genotyped SNPs account for 20–60% of variation in ASD risk, although the effect of any individual SNP is likely very small (11–13). Many of these influences are shared with other psychiatric disorders (12, 14), which at least in part explains the familial clustering of different types of behavior problems.However, statistics about ASD heritability reflect an average. For example, there are likely many affected families for whom sibling recurrence risk is less than 10–20%. The strongest evidence toward this claim comes from studies of rare, severely deleterious genetic events that are associated with ASDs (15–20). Events of this type, for example copy number variants and loss of function (LOF) mutations, are often de novo (not seen in an affected individual’s parents). Although cases of ASDs involving a de novo mutation could reflect a concert of spontaneous and inherited genetic events, de novo events of large effect may reduce the likelihood of seeing psychiatric problems in an affected individual’s family members.     

Association between anxiety,health-related quality of life and functional impairment in primary care patients with chronic pain

Objective

Anxiety and chronic pain are prevalent and frequently co-occur. Our purpose was to examine the association between anxiety, health-related quality of life (HRQL) and functional impairment in primary care patients with chronic musculoskeletal pain.

Methods

Data were drawn from baseline interviews of the 250 primary care patients enrolled in the Stepped Care to Optimize Pain care Effectiveness trial. Validated measures were used to determine the proportion of patients screening positive for five common anxiety disorders: generalized anxiety, panic, social anxiety, posttraumatic stress and obsessive–compulsive disorder. Bivariate analyses examined associations between the type and number of anxiety disorders for which patients screened positive and representative pain, psychological and other HRQL outcomes. Multivariable models controlling for major depression and other covariates examined the association between the number of screen-positive anxiety conditions and functional impairment in psychological [SF-12 mental component summary (MCS) score], pain [Brief Pain Inventory (BPI) interference score] and work (disability days) domains.

Results

One hundred fourteen (45%) patients screened positive for at least one anxiety disorder and, compared to the 136 screen-negative patients, had significantly worse scores across multiple pain, psychological and other HRQL domains. Substantial impairment was seen for each of the five screen-positive anxiety conditions and progressively worsened as the number of conditions increased from one (n= 54) to two (n= 26) to ≥ 3 (n= 34). The number of screen-positive anxiety conditions was strongly associated (P< .0001) with worse BPI interference and MCS scores and more disability days in models adjusting for age, sex and medical comorbidity. After further adjusting for major depression, associations were attenuated but remained significant for BPI interference (P< .0001) and MCS (P= .018) and marginally significant for disability days (P= .062).

Conclusion

Nearly half of primary care patients with chronic pain screen positive for one or more anxiety disorders, which in turn are adversely associated with impairment across multiple domains of HRQL. Detecting and treating anxiety may be an important component of pain management.     

Variation in Networks and Forms of Support for Care‐Seeking Across the HIV Care Continuum in the Rural Southeastern United States

Purpose

In spite of progress in understanding the importance of social support for health outcomes in Persons Living with HIV (PLWH), more remains to be known about mechanisms of support most beneficial at each stage of HIV treatment. In this study, we use a qualitative analytic approach to investigate the forms and sources of social support deemed most integral to the diagnosis, care engagement, and medication adherence behaviors of a diverse sample of PLWH in a mostly rural health district in the Southeastern United States.

Methods

In‐depth interviews (N = 18) were collected during the qualitative phase of a larger mixed methods needs assessment for the Northeast Georgia Health District. A deductive‐inductive analysis of participant narratives revealed variation in the perceived importance of particular forms and sources of social support during the initial versus advanced stages of HIV care.

Findings

PLWH identified the emotional, informational, and appraisal support provided by family as especially critical for emotional stability, coping, and care linkage during the initial stages of diagnosis and treatment. However, once in care, PLWH emphasized informational and instrumental forms of support from care providers and appraisal support from peers as key influences in care engagement and retention behaviors.

Conclusion

Increased understanding of the social support mechanisms that contribute to the HIV treatment behaviors of PLWH can fill knowledge gaps in research and inform the efforts of health care providers seeking to leverage various aspects of the social support toward improving the care retention, health, and wellness outcomes of PLWH.     

Adverse Tumor Biology Associated with Mesenterico-Portal Vein Resection Influences Survival in Patients with Pancreatic Ductal Adenocarcinoma

Background

Although pancreatoduodenectomy (PD) with mesenterico-portal vein resection (VR) can be performed safely in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the impact of this approach on long-term survival is controversial.

Patients and Methods

Analyses of a prospectively collected database revealed 122 consecutive patients with PDAC who underwent PD with (PD+VR) or without (PD?VR) VR between January 2004 and May 2012. Clinical data, operative results, and survival outcomes were analysed.

Results

Sixty-four (53 %) patients underwent PD+VR. The majority (84 %) of the venous reconstructions were performed with a primary end-to-end anastomosis. Demographic and postoperative outcomes were similar between the two groups. American Society of Anesthesiologists (ASA) score, duration of operation, intraoperative blood loss, and blood transfusion requirement were significantly greater in the PD+VR group compared with the PD?VR group. Furthermore, the tumor size was larger, and the rates of periuncinate neural invasion and positive resection margin were higher in the PD+VR group compared with the PD?VR group. Histological venous involvement occurred in 47 of 62 (76 %) patients in the PD+VR group. At a median follow-up of 29 months, the median overall survival (OS) was 18 months for the PD+VR group, and 31 months for the PD?VR group (p = 0.016). ASA score, lymph node metastasis, neurovascular invasion, and tumor differentiation were predictive of survival. The need for VR in itself was not prognostic of survival.

Conclusions

PD with VR has similar morbidity but worse OS compared with a PD?VR. Although VR is not predictive of survival, tumors requiring a PD+VR have more adverse biological features.     

How should we measure addiction recovery? Analysis of service provider perspectives using online Delphi groups

Aims: To explore ways of measuring addiction recovery and the extent of agreement/disagreement between diverse service providers on potential recovery indicators.

Methods: Separate online Delphi groups with (i) addiction psychiatrists (n?=?10); (ii) senior residential rehabilitation staff (n?=?9); and (iii) senior inpatient detoxification unit staff (n?=?6). Each group was conducted by email and followed the same structured format involving three iterative rounds of data collection. Content analyses were undertaken and the results from each group were compared and contrasted.

Findings: Indicators of recovery spanned 15 broad domains: substance use, treatment/support, psychological health, physical health, use of time, education/training/employment, income, housing, relationships, social functioning, offending/anti-social behaviour, well-being, identity/self-awareness, goals/aspirations, and spirituality. Identification of domains was very consistent across the three groups, but there was some disparity between, and considerable disparity within, groups on the relative importance of specific indicators.

Conclusions: Whilst there is general consensus that recovery involves making changes in a number of broad life areas and not just substance use, there is substantial disagreement on particular measures of progress. Further studies involving other stakeholder groups, particularly people who have personally experienced drug or alcohol dependence, are needed to assess how transferable the 15 identified domains of recovery are.