'I've never drunk very much water and I still don't, and I see no reason to do so': a qualitative study of the views of community-dwelling older people and carers on hydration in later life.

BACKGROUND: dehydration is associated with significant adverse outcomes in older people despite being largely preventable and treatable. Little research has focused on the views of community-dwelling older people on hydration, healthy drinking and the perceived importance of drinking well in later life. OBJECTIVES: to understand community-dwelling older people and informal carers' views on hydration in later life and how older people can be supported to drink well. METHODS: qualitative study using interviews and a focus group exploring hydration and nutrition in later life (24 older people at risk of malnutrition and dehydration, 9 informal carers) and thematic analysis. RESULTS: this article presents the findings on hydration alone. Four themes are presented: perceptions of healthy drinking, barriers to and facilitators of drinking in later life and supporting older people to drink well. The perceived importance of adequate hydration in later life was polarised. Concerns about urinary incontinence and knowledge gaps were significant barriers. Consideration of individual taste preference and functional capacity acted as facilitators. Distinct habitual drinking patterns with medications and meals exist within individuals. Many relied on thirst at other times or when fluid demands are greater (such as hot weather), a known unreliable prompt in later life. CONCLUSIONS: older people could be supported to drink well by building upon existing habitual drinking patterns. Primary care and public health should consider individual barriers, facilitators and tailored education. A multidisciplinary approach to promote hydration should be incorporated into care for older people with more complex needs.

Genes and life-style factors in BELFAST nonagenarians: Nature, Nurture and Narrative.

Understanding how to 'Age Longer and Age Well' is a priority for people personally, for populations globally and for government policy. Nonagenarians are the oldest members of our societies and survivors of their generation. Approximately 10 % of nonagenarians reach 90 years and beyond in good condition and seem to have a combination of both age-span and health-span. But what are the factors which help people reach their ninetieth birthday and beyond in good condition? Are they genetics, as in 'nature', or do they depend on 'nurture' and are related to environment, or are both factors inextricably intertwined within the concept of behavioural genetics? Nonagenarians have rich life experiences that can teach us much about ageing well; they are reservoirs of genetic, life-style and behavioural information which can help dissect out how to live not only longer but better. Personal family history and narrative are powerful tools that help to determine familial traits, beliefs and social behaviours and when used in parallel with new biotechnology methods inform and elaborate causality. Here we present themes and insights from personal narrative enquiry from nonagenarian participants from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST) about factors they consider important for good quality ageing and relate these insights to the emerging genetics and life-style evidence associated with healthy longevity.

Stability of ranibizumab during continuous delivery from the Port Delivery Platform.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system that has the potential to reduce treatment burden in patients with retinovascular diseases. The Port Delivery Platform (PD-P) implant is a permanent, indwelling device that can be refilled in situ through a self-sealing septum and is designed to continuously deliver ranibizumab by passive diffusion through a porous titanium release control element. We present results for the studies carried out to characterize the stability of ranibizumab for use with the PD-P. Simulated administration, in vitro release studies, and modeling studies were performed to evaluate the compatibility of ranibizumab with the PD-P administration components, and degradation and photostability in the implant. Simulated administration studies demonstrated that ranibizumab was highly compatible with the PD-P administration components (initial fill and refill needles) and commercially available administration components (syringe, transfer needle, syringe closure). Subsequent simulated in vitro release studies examining continuous delivery for up to 12 months in phosphate buffered saline, a surrogate for human vitreous, showed that the primary degradation products of ranibizumab were acidic variants. The presence of these variants increased over time and potency remained high. The stability attributes of ranibizumab were consistent across multiple implant refill-exchanges. Despite some degradation within the implant, the absolute mass of variants released daily from the implant was low due to the continuous release mechanism of the implant. Simulated light exposure within the implant resulted in small increases in the relative amount of ranibizumab degradants compared with those seen over 6 months.

In-vitro characterization of ranibizumab release from the Port Delivery System.

The Port Delivery System with ranibizumab (PDS) consists of an implant that is a permanent, indwelling drug delivery device that can be refilled through a self-sealing septum and is designed to continuously release a customized formulation of ranibizumab into the vitreous by passive diffusion through a porous titanium release control element. Target release rates of ranibizumab via the implant used in studies of the PDS in patients with neovascular age-related macular degeneration were selected based on clinical and pharmacokinetic (PK) data from previously conducted intravitreal ranibizumab injection studies. In-vitro testing was performed to verify release rates with a range of ranibizumab concentrations before the phase II Ladder (NCT02510794) and phase III Archway (NCT03677934) trials of the PDS. Implants were filled with ranibizumab and were regularly transferred to new buffer-containing tubes to represent ocular ranibizumab clearance and release kinetics. Ranibizumab concentrations were measured and release rates calculated. Release rate data were fit to an exponential model and compared with expected release kinetics of diffusion. Release profiles of the implant releasing ranibizumab at concentrations of 10 mg/mL, 40 mg/mL, and 100 mg/mL were determined in the pre-phase II in-vitro studies. At day 3.5, mean (SD) ranibizumab release rates were 1.75 (0.07), 6.42 (0.35), and 16.69 (0.67) µg/d for PDS 10 mg/mL, 40 mg/mL, and 100 mg/mL, respectively. At month 6, mean (SD) release rates were 1.68 (0.05) and 4.16 (0.05) µg/d for PDS 40 mg/mL and 100 mg/mL, respectively. Measured release rates were within 90% of theoretical release rates during the course of drug release. PDS 100 mg/mL released 73% (SD, 1.92) of drug by month 6. In the pre-phase III in-vitro studies, mean (SD) release rates with PDS 100 mg/mL were 17.97 (0.90), 4.44 (0.11), and 2.45 (0.08) µg/d at 3.5 days, 6 months, and 9 months, respectively. Cumulative release (SD) was 73% (1.92) by month 6 and 87% (1.88) by month 9. The sustained, continuous, and reproducible release from the PDS observed in the in-vitro studies was also observed in Ladder and Archway. In conclusion, in-vitro studies were a powerful tool for characterizing and verifying ranibizumab release from the PDS implant and supported clinical evaluation of the PDS. PDS 100 mg/mL, which was associated with the longest therapeutic-level delivery of ranibizumab among the concentrations tested, was selected for evaluation in the pivotal phase III Archway trial.

Insights Into Sibling Relationships and Longevity From Genetics of Healthy Ageing Nonagenarians: The Importance of Optimisation, Resilience and Social Networks.

Understanding how to "Age Longer and Age Well" is a priority for people personally, for populations and for government policy. Approximately ten percent of nonagenarians reach 90 years and beyond in good condition and seem to have a combination of both age-span and health-span. However, the factors which contribute to human longevity remain challenging. Culture is a shared system of learning ideas, feelings, and survival strategies. It has a strong influence on each person's psychological development, behavior, values and beliefs. Nonagenarians have rich life experiences that can teach us much about aging well; they are rich reservoirs of genetic, lifestyle and psychological information which can help understanding about how to live longer and better. Sibling or trio nonagenarians are important sources of family beliefs and behaviors upon which individual personalities may have been built. Their personal family histories and narratives are powerful tools that help to determine familial traits, beliefs and social behaviors which may help establish factors important in the siblings' longevity. Using purposefully selected subjects, recruited to the Genetics of Healthy Ageing (GeHA) project in four European countries, this research used the simple life story and qualitative research methods to analyze contrasting and distinctive questions about the interface between the psychological and social worlds as presented in the nonagenarian siblings' insights about their longevity. Their stories aimed to give better understanding about which psychological aspects of their common life journey and the degree of emotional support in their sibling relationships may have supported their paths to longevity. The most universal finding in each of the four European countries was that nonagenarians demonstrated high positivity, resilience and coping skills and were supported in social networks. Around this theme, nonagenarians reported "being happy," "always cheerful," "never melancholy" and having a contentment with a "rich life" and family relationships which fits with accumulating evidence that life satisfaction comes from a perceived self-efficacy and optimism. Most sibling relationships in this study, when analyzed according to the Gold classification, fit the "congenial" or "loyal" relationship type - demonstrating a healthy respect for the others' opinion without overt dependence, which may help individual coping and survival mechanisms.

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility. Controlled release is achieved via passive diffusion through the porous release control element, which is tuned to specific drug characteristics to accomplish a therapeutic level of ranibizumab in the vitreous. To characterize drug release from the implant, release rate was measured in vitro with starting concentrations of ranibizumab 10, 40, and 100 mg/mL, with release of ranibizumab 40 and 100 mg/mL found to remain quantifiable after 6 months. Using a starting concentration of 100 mg/mL, active release rate at approximately 6 months was consistent after the initial fill and first, second, and third refills, demonstrating reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single 100-µL stroke using the refill needle was shown to replace over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.

Utilization of laparoscopic colectomy in the United States before and after the clinical outcomes of surgical therapy study group trial.

OBJECTIVE: To evaluate the utilization of laparoscopic colectomy (LC) in the United States before and after prospective data supported its use for the treatment of colon cancer. METHODS: The Nationwide Inpatient Sample 2001-2003 [before Clinical Outcomes of Surgical Therapy (COST)] and 2005-2007 (after COST) was queried for elective colectomies for both benign and malignant disease. The COST trial was published in 2004; therefore, 2004 data were excluded. Univariate analyses including patient-specific, hospital-specific, and outcome variables were performed. Multivariate logistic regression models and subset analyses were used to evaluate these variables and operative approach by time frame. RESULTS: The query yielded 741,817 elective colectomies (684,969 open and 56,848 laparoscopic). The percentage of elective colectomies performed laparoscopically has increased over time. Laparoscopic colectomy for benign disease increased from 6.2% in 2001-2003 to 11.8% in 2005-2007, while those for colon cancer have increased by a larger percentage, 2.3% to 8.9%. In a multivariate model of patients with colon cancer, the odds ratio (OR) for having a laparoscopic approach after COST was 4.55 (confidence interval 3.81-5.44) compared with before COST. In contrast, for benign disease, the OR was 2.10 (confidence interval 1.79-2.46). Factors predictive of having a laparoscopic approach for cancer have changed very little over time: Patients are more likely to be male, insured, live in areas with the highest incomes, and undergo resection at urban teaching hospitals. CONCLUSIONS: Within 3 years after publication of the COST trial, the use of laparoscopic resection for colon cancer approached that of benign disease. However, almost 90% of cases are still performed open and utilization remains influenced by socioeconomic factors.

Specialized practice reduces inpatient mortality, length of stay, and cost in the care of colorectal patients.

OBJECTIVE: This study aimed to determine whether specialized surgeon practice improves clinical outcomes for major inpatient adult colorectal resections. DESIGN: The Nationwide Inpatient Sample was queried for elective colorectal resections performed from 2001 through 2007. Specialization was determined by first identifying surgeons' procedures as either colorectal or noncolorectal. Surgeons were then stratified as either a specialized surgeon, if colorectal cases comprised more than 75% of their caseload, or a nonspecialized surgeon if colorectal cases comprised less than 75%. MAIN OUTCOME MEASURES: The data points collected for these cases were: cost, length of stay, mortality, demographics, comorbidities, acuity of admission, hospital region, hospital location and teaching status, and primary payer information. Cost and length of stay were analyzed using a linear regression model with a log transformation for length of stay. A logistic regression analysis was performed for mortality. These models were adjusted for all other covariates including surgeon volume. RESULTS: A total of 13,925 surgeons performing 115,540 procedures were analyzed. Specialized surgeons comprised 4.6% of surgeons and performed 17.0% of resections. In multivariate analysis, specialized surgeons had a lower risk of mortality (OR 0.72; CI 0.57-0.90, P = .0044), decreased length of stay (absolute difference in days 0.23; CI 0.11-0.49, P = .0022), and similar hospital cost (absolute cost difference $420 less; CI $238 more to $1079 less, P = .211) compared with nonspecialized surgeons. Although cost was not significant at a 75% specialization cutoff, a relationship exists between lower hospitalization cost and increased surgeon specialization even when controlled for surgeon volume. CONCLUSIONS: Surgical specialization leads to reductions in mortality, hospital days, and cost for inpatient colorectal care.

Laparoscopic proctectomy after neoadjuvant therapy: safety and long-term follow-up.

PURPOSE: The oncologic value of laparoscopic proctectomy for rectal adenocarcinoma is uncertain. Long-term data, particularly in tumors at higher risk of recurrence, is lacking. This study evaluated short- and long-term outcomes in patients who underwent laparoscopic proctectomy for locally advanced cancer (transmural and/or node positive) after neoadjuvant chemoradiotherapy (CRT). METHODS: This is a retrospective cohort study of 50 consecutive patients with transmural and/or node-positive rectal cancer, from a single surgeon's practice, from 2001 to 2009. All patients were treated with neoadjuvant CRT. All cases were started laparoscopic or hand-assist. RESULTS: Of 50 patients, 58% were men, mean age was 60.9 years, and mean body mass index (BMI) was 26.3. The average distance of the tumor from the anal verge was 5.7 cm. All patients completed CRT, and the subsequent mean time to operation was 7.8 weeks. The conversion to open rate was 26%. Thirty-day mortality was 2%. Twenty-two percent had a complete response to CRT. Two patients had positive margins: one developed distant recurrence only, and the other died 2 years later without evidence of local recurrence. The average distal margin was 3.26 cm. The average lymph nodes resected was 11.9. Seven patients had an ileus that delayed discharge and one had a pelvic abscess. Median length of stay was 6 days. Three patients were readmitted within 30 days; all for dehydration. Mean follow-up was 2.72 years. According to Kaplan-Meier analysis, the 5-year local recurrence rate was 9.6%, and the distant recurrence rate was 31%. Five-year disease-specific survival was 80% and overall survival was 68%. CONCLUSIONS: Patients with locally advanced rectal cancer treated with neoadjuvant therapy can safely undergo laparoscopic proctectomy with a low rate of complications. Oncologic outcomes, including 5-year disease-free survival and local recurrence rates, are comparable to published reports of open proctectomy.

Endoscopic ultrasound may be unnecessary in the preoperative evaluation of intraductal papillary mucinous neoplasm.

OBJECTIVES: Several imaging modalities are commonly performed during work-up of intraductal papillary mucinous neoplasm (IPMN), but guidelines do not suggest any one technique. The aim of this study was to evaluate tumour and duct measurements by computed tomography (CT) and endoscopic ultrasound (EUS) and their ability to predict high-grade dysplasia (HGD) and cancer within pancreatic IPMN. METHODS: Patients with IPMN who underwent preoperative CT and EUS between 2001 and 2009 were selected. Data were gathered retrospectively from medical records. RESULTS: The study group was comprised of 52 patients, 33% (17/52) of whom had HGD or cancer. On fine needle aspirate (FNA), neither carcinoembryonic antigen (CEA) >200 nor cytological analysis correlated with malignancy. In multivariate analysis, duct size ≥ 1.0 cm (P= 0.034) was a significant predictor of HGD or cancer, and diameter on CT scan (P= 0.056) approached significance. Lesion diameter of ≥ 2.5 cm on CT scan identified malignancy in 71% (12/17) of patients (P= 0.037). When analysed, all patients with HGD or cancer had a lesion diameter ≥ 2.5 cm and/or a duct diameter ≥ 1.0 cm by CT scan. CONCLUSIONS: The use of radiographic criteria on CT including lesion size ≥ 2.5 cm and/or pancreatic duct diameter ≥ 1.0 cm appears to reliably identify patients with either HGD or invasive cancer. High-resolution CT scanning may obviate the need for EUS and FNA in patients with suspected IPMN.

Supporting nutrition in frail older people: a qualitative study exploring views of primary care and community health professionals.

BACKGROUND: Malnutrition is associated with increased morbidity and mortality, and is very common in frail older people. However, little is known about how weight loss in frail older people can be managed in primary care. AIMS: To explore the views and practices of primary care and community professionals on the management of malnutrition in frail older people; identify components of potential primary care-based interventions for this group; and identify training and support required to deliver such interventions. DESIGN AND SETTING: Qualitative study in primary care and community settings. METHOD: Seven focus groups and an additional interview were conducted with general practice teams, frailty multidisciplinary teams (MDTs), and community dietitians in London and Hertfordshire, UK (n = 60 participants). Data were analysed using thematic analysis. RESULTS: Primary care and community health professionals perceived malnutrition as a multifaceted problem. There was an agreement that there is a gap in care provided for malnutrition in the community. However, there were conflicting views regarding professional accountability. Challenges commonly reported by primary care professionals included overwhelming workload and lack of training in nutrition. Community MDT professionals and dietitians thought that an intervention to tackle malnutrition would be best placed in primary care and suggested opportunistic screening interventions. Education was an essential part of any intervention, complemented by social, emotional, and/or practical support for frailer or socially isolated older people. CONCLUSIONS: Future interventions should include a multifaceted approach. Education tailored to the needs of older people, carers, and healthcare professionals is a necessary component of any intervention.

Efficacy of immobilized polyplexes and lipoplexes for substrate-mediated gene delivery.

Non-viral gene delivery by immobilization of complexes to cell-adhesive biomaterials, a process termed substrate-mediated delivery, has many in vitro research applications such as transfected cell arrays or models of tissue growth. In this report, we quantitatively investigate the efficiency of gene delivery by surface immobilization, and compare this efficiency to the more typical bolus delivery. The ability to immobilize vectors while allowing cellular internalization is impacted by the biomaterial and vector properties. Thus, to compare this efficiency between vector types and delivery methods, transfection conditions were initially identified that maximized transgene expression. For surface delivery from tissue culture polystyrene, DNA complexes were immobilized to pre-adsorbed serum proteins prior to cell seeding, while for bolus delivery, complexes were added to the media above adherent cells. Mathematical modeling of vector binding, release, and cell association using a two-site model indicated that the kinetics of polyplex binding to cells was faster than for lipoplexes, yet both vectors have a half-life on the surface of approximately 17 min. For bolus and surface delivery, the majority of the DNA in the system remained in solution or on the surface, respectively. For polyplexes, the efficiency of trafficking of cell-associated polyplexes to the nucleus for surface delivery is similar or less than bolus delivery, suggesting that surface immobilization may decrease the activity of the complex. The efficiency of nuclear association for cell-associated lipoplexes is similar or greater for surface delivery relative to bolus. These studies suggest that strategies to enhance surface delivery for polyplexes should target the vector design to enhance its potency, whereas enhancing lipoplex delivery should target the material design to increase internalization.

Engineering surfaces for substrate-mediated gene delivery using recombinant proteins.

Immobilized fibronectin and other natural proteins have been utilized to enhance substrate-mediated gene delivery, with apparent contributions from the intrinsic bioactivity and also physical properties of the immobilized proteins. In this report, we investigated the use of recombinant proteins, compared to the full-length fibronectin protein, as surface coatings for gene delivery to investigate the mechanisms by which fibronectin enhances gene transfer. The recombinant fibronectin fragment FNIII(7-10) (FNIII) contains the alpha(5)beta(1) binding domain of fibronectin and supports cell adhesion, whereas the recombinant protein polymer PP-12 is also negatively charged and has a molecular weight similar to FNIII, but lacks cell binding domains. Transfection was compared on surfaces modified with FNIII, full-length fibronectin, or PP-12. The full-length fibronectin provided the greatest extent of transgene expression relative to FNIII or PP-12, which was consistent with the amount of DNA that associated with cells. FNIII had 4.2-fold or 4.7-fold lower expression levels relative to fibronectin for polyplexes and lipoplexes, respectively. PP-12 produced expression levels that were 317-fold and 12.0-fold less than fibronectin for polyplexes and lipoplexes, respectively. Although expression was greater on FNIII relative to PP-12, the levels of DNA associated per cell with FNIII were similar to or less than those with PP-12, suggesting that the bioactive sequences may contribute to an enhanced intracellular trafficking. For lipoplexes delivered on FNIII, the efficiency of intracellular trafficking and levels of caveolar DNA were greater than that observed with either the full-length fibronectin or PP-12. For polyplexes, fibronectin fragment resulted in greater intracellular trafficking efficiency compared to PP-12 protein polymer. Recombinant proteins can be employed in place of full-length extracellular matrix proteins for substrate-mediated gene delivery, and bioactive sequences can influence one or more steps in the gene delivery process to maximize transfection.

How effective is nutrition education aiming to prevent or treat malnutrition in community-dwelling older adults? A systematic review.

BACKGROUND: While malnutrition is associated with adverse health outcomes in older adults, little is known about the effectiveness of nutrition education. This systematic review examines the evidence for educational interventions to improve nutritional and other health-related outcomes in community-dwelling older people. METHODS: Systematic searches of three databases (Embase, Medline and CINAHL) were conducted. Studies testing educational interventions targeting older adults (mean age ≥ 60 years) or their caregivers were eligible for inclusion. Two authors independently assessed trial eligibility, risk of bias and extracted data. Study heterogeneity was high precluding meta-analysis, therefore a narrative synthesis was conducted. RESULTS: Nine articles reporting on eight studies (n = 7 trials; 1 pre-post-intervention study) met inclusion criteria. There was considerable variability in the format of educational interventions. Nutrition education was either generic or personalised and the intensity was variable (1-6 sessions). We found some evidence (in five out of eight studies) that nutrition education may improve nutrition-related outcomes. Nutrition education involving caregivers was found to reduce nutritional risk in one study, and nutritional counselling following discharge from hospital was found to reduce the risk of readmission in another study. However, the overall quality of the studies was hampered by poor methodology, low sample size and attrition bias, and results need to be interpreted with caution. CONCLUSIONS: Educational interventions may have potential to improve malnutrition-related outcomes in older people, but the strength of evidence is poor. More robust, larger studies are needed to ascertain the effectiveness of nutritional education interventions in this population.

Prompting medical students to self-assess their learning needs during the ageing and health module: a mixed methods study.

Understanding our learning needs is fundamental for safe, effective and knowledge-based medical practice and facilitates life-long learning. A mixed methods study investigated fourth-year medical students' self-perceived understanding of their learning needs using 1] a visual scale, before and after a four-week module in Ageing and Health (A&H) and 2] through focus group discussions. During 2013-14 academic year, all students (252) were invited to use a Visual Analogue Scale (VAS) tool to self-assess their learning needs that were linked to Ageing and Health curriculum learning outcomes. Assenting students (197 at pre-self-assessment, 201 at post-assessment) returned anonymous Visual Analogue Scales, self-assessing history-taking skills, examination skills, knowledge of medication use, co-morbidity, nutritional and swallowing assessment responses, before and after the A&H module. Three student focus groups explored whether completion of the VAS self-assessment had prompted improved self-awareness of their learning needs. The VAS responses increased for each curriculum domain with significant differences between the pre-and post responses - for the student-year-group. Nutritional and swallowing knowledge showed the greatest improvement from a self-assessed low baseline at entry. Focus-group students generally viewed the VAS tool positively, and as an aid for prompting consideration of current and future clinical practice. Some students recognised that 'a need to be ready-for-work' focused engaged learning; others demonstrated self-regulated learning through self-motivation and an action plan. The Visual Analogue Scale quantitative responses showed increased student-self-perceived learning for each curriculum domain at fourth-year completion of the A&H module, suggesting that prompting self-assessment had increased students' knowledge and skills. Focus group students saw the VAS tool as useful for prompting awareness of their current and future learning needs. Additional educational strategies should be explored to enable all students to self-reflect and engage effectively on their learning needs, to gain the skills for the maintenance of professional medical competence. Abbreviations: A&H: Ageing and Health Module; e-portfolio: an electronic version of an evidence portfolio, which allows medical students and graduates to reflect and document learning and competencies; F1: year1 of post-graduate medical clinical training; GMC: General Medical Council-the regulation organisation for maintaining standards for doctors in UK; Logbook: usually a written document which can be used to record procedures and attendance at clinics or case-based discussions and can be used to set learning outcomes and to structure teaching in clinical settings for medical students and doctors; PDP: personal development plan is used to plan future learning and skills needs for work and education with an plan for action/s outcome; SPSS: Statistical Package for the Social Sciences; VAS: Visual Analogue Scale is a visual method of describing an experience.

Exploring the Views and Dietary Practices of Older People at Risk of Malnutrition and Their Carers: A Qualitative Study.

BACKGROUND: While malnutrition is an important cause of morbidity and mortality in older people, it is commonly under-recognised. We know little on the views of community-dwelling older people and their carers regarding the management of malnutrition. The aim of the study was: (a) to explore views and dietary practices of older people at risk of malnutrition and their carers; (b) to identify gaps in knowledge, barriers and facilitators to healthy eating in later life; (c) to explore potential interventions for malnutrition in primary care. METHODS: A qualitative study was performed using semi-structured interviews with participants recruited from four general practices and a carers' focus group in London. Community-dwelling people aged ≥75, identified as malnourished or at risk of malnutrition (n = 24), and informal carers of older people (n = 9) were interviewed. Data were analysed using thematic analysis. RESULTS: Older people at risk of malnutrition rarely recognise appetite or weight loss as a problem. Commonly held perceptions include that being thin is healthy and 'snacking' is unhealthy. Changes in household composition, physical or mental health conditions and cognitive impairment can lead to inadequate food intake. Most carers demonstrate an awareness of malnutrition, but also a lack of knowledge of what constitutes a nutritious diet. Although older people rarely seek any help, most would value advice from their GP/practice nurse, a dietitian or another trained professional. CONCLUSION: Older people at risk of malnutrition and their carers lack knowledge on nutritional requirements in later life but are receptive to intervention. Training for health professionals in delivering tailored dietary advice should be considered.

Approach to management of intussusception in adults: a new paradigm in the computed tomography era.

Intussusception has been considered an operative indication in adults as a result of the risk of ischemia and the possibility of a malignant lead point. Computed tomographic (CT) scans can reveal unsuspected intussusception. All CT reports from July 1999 to December 2005 were scanned electronically for letter strings to include the keyword intussusception. Identified CT scans were analyzed to characterize the intussusception and associated findings. Clinical, laboratory, pathological, and follow-up variables were gleaned from medical records. Findings were analyzed by treatment and findings at operation. Review of 380,999 CT reports yielded 170 (0.04%) adult patients (mean age, 41 years) with intussusceptions described as enteroenteric in 149 (87.6%), ileocecal in eight (4.7%), colocolonic in 10 (5.9%), and gastroenteric in three (1.8%). Radiological features included mean length of 4.4 cm (range, 0.8-20.5 cm) and diameter of 3.2 cm (range, 1.6-11.5 cm). Twenty-nine (17.1%) had a lead point, and 12 (7.1%) had bowel obstruction. Clinically, 88 (48.2%) patients reported abdominal pain, 52 (30.6%) had nausea and/or vomiting, and 74 (43.5%) had objective findings on abdominal examination. Thirty of 170 (17.6%) patients underwent operation, but only 15 (8.8%) patients had pathologic findings that correlated with CT findings. Seven had,enteroenteric intussusceptions from benign neoplasms (two), adhesions (one), local inflammation (one), previous anastomosis (one), Crohn's disease (one), and idiopathic (one). Three had ileocolic disease, including cecal cancer (one), metastatic melanoma (one) and idiopathic (one; whereas five patients had colocolonic intussusception from colon cancer (three), tubulovillous adenoma (one), and local inflammation (one). Of the 15 without intussusception at exploration, five had pathology related to trauma, four had nonincarcerated internal hernia after Roux-en-Y gastric bypass, four had negative explorations, one had adhesions, and one had appendicitis that did not correlate with CT findings. No patient in the observation group required subsequent operative exploration for intussusception at mean 14.1 months (range, 0.25-67.5 months) follow up. All operative patients demonstrated gastrointestinal symptoms versus 55.3 per cent of the observation group (P < 0.006). Analysis of CT features demonstrated differences among patients observed without operation, those without intussusception at exploration, and confirmed intussusception with regard to mean intussusception length 3.8 versus 3.8 versus 9.6 cm, diameter 3.0 versus 3.2 versus 4.8 cm, lead point 12.1 per cent versus 30 per cent versus 53.3 per cent, and proximal obstruction 3.8 per cent versus 0 per cent versus 46.7 per cent, respectively. Intussusceptions in adults discovered by CT scanning do not always mandate exploration. Most cases can be treated expectantly despite the presence of gastrointestinal symptoms. Close follow up is recommended with imaging and/or endoscopic surveillance. Length and diameter of the intussusception, presence of a lead point, or bowel obstruction on CT are predictive of findings that warrant exploration.

Intracellular biomass flocculation as a key mechanism of rapid bacterial killing by cationic, amphipathic antimicrobial peptides and peptoids.

Many organisms rely on antimicrobial peptides (AMPs) as a first line of defense against pathogens. In general, most AMPs are thought to kill bacteria by binding to and disrupting cell membranes. However, certain AMPs instead appear to inhibit biomacromolecule synthesis, while causing less membrane damage. Despite an unclear understanding of mechanism(s), there is considerable interest in mimicking AMPs with stable, synthetic molecules. Antimicrobial N-substituted glycine (peptoid) oligomers ("ampetoids") are structural, functional and mechanistic analogs of helical, cationic AMPs, which offer broad-spectrum antibacterial activity and better therapeutic potential than peptides. Here, we show through quantitative studies of membrane permeabilization, electron microscopy, and soft X-ray tomography that both AMPs and ampetoids trigger extensive and rapid non-specific aggregation of intracellular biomacromolecules that correlates with microbial death. We present data demonstrating that ampetoids are "fast killers", which rapidly aggregate bacterial ribosomes in vitro and in vivo. We suggest intracellular biomass flocculation is a key mechanism of killing for cationic, amphipathic AMPs, which may explain why most AMPs require micromolar concentrations for activity, show significant selectivity for killing bacteria over mammalian cells, and finally, why development of resistance to AMPs is less prevalent than developed resistance to conventional antibiotics.

Design of modular non-viral gene therapy vectors.

Gene delivery has numerous potential applications both clinically and for basic science research. Non-viral vectors represent the long-term future of gene therapy and biomaterials are a critical component for the development of efficient delivery systems. Biomaterial development combined with fundamental studies of virus function and cellular processes will enable the molecular level design of modular vectors. Vectors are being developed based on cationic polymers or lipids that contain functional groups to mediate appropriate interactions with the extracellular environment or to interface with specific cellular processes. This review describes recent progress on the development of biomaterials for non-viral vectors and highlights opportunities for future development. Ultimately, efficient vectors will expand the traditional applications of gene therapy within the clinic and may enable numerous other opportunities within diagnostics, biotechnology, and basic science research.

Capillary ion-exchange chromatography with nanogram sensitivity for the analysis of monoclonal antibodies.

Ion-exchange chromatography (IEC) is widely used for profiling the charge heterogeneity of proteins, including monoclonal antibodies (mAbs). Despite good resolving power and robustness, ionic strength-based ion-exchange separations are generally product specific and can be time consuming to develop. In addition, conventional analytical scale ion-exchange separations require tens of micrograms of mAbs for each injection, amounts that are often unavailable in sample-limited applications. We report the development of a capillary IEC (c-IEC) methodology for the analysis of nanogram amounts of mAb charge variants. Several key modifications were made to a commercially available liquid chromatography system to perform c-IEC for charge variant analysis of mAbs with nanogram sensitivity. We demonstrate the method for multiple monoclonal antibodies, including antibody fragments, on different columns from different manufacturers. Relative standard deviations of <10% were achieved for relative peak areas of main peak, acidic and basic regions, which are common regions of interest for quantifying monoclonal antibody charge variants using IEC. The results herein demonstrate the excellent sensitivity of this c-IEC characterization method, which can be used for analyzing charge variants in sample-limited applications, such as early-stage candidate screening and in vivo studies.