Friendly visiting by a volunteer for reducing loneliness or social isolation in older adults: A systematic review.

Background: Loneliness and social isolation are currently among the most challenging social issues. Given their detrimental impact on physical and mental health, identifying feasible and sustainable interventions to alleviate them is highly important. Friendly visiting, a befriending intervention whereby older persons are matched with someone who visits them on a regular basis, seems promising. However, it is unclear if face-to-face (F2F) friendly visiting by a volunteer (FVV) is effective at reducing loneliness or social isolation, or both. Objectives: To assess the effect of F2F FVV on feelings of loneliness, social isolation (primary outcomes) and wellbeing (i.e., life satisfaction, depressive symptom experiencing and mental health; secondary outcomes) in older adults. Search Methods: We searched six electronic databases up until 11 August 2021. We also consulted 15 other resources, including grey literature sources and websites of organizations devoted to loneliness and ageing, between 25 October and 29 November 2021. Selection Criteria: We included experimental and observational studies that quantitatively measured the effect of F2F FVV, compared to no friendly visiting, on at least one of following outcomes in older adults (≥60 years of age): loneliness, social isolation or wellbeing. Data Collection and Analysis: Two reviewers independently performed study selection, data extraction and synthesis, risk of bias and GRADE assessment. If outcomes were measured multiple times, we extracted data for one short-term (≤1 month after the intervention had ended), one intermediate-term (>1 and ≤6 months), and one long-term time point (>6 months). Data from randomized controlled trials (RCTs) and non-RCTs were presented and synthesized separately. Synthesis was done using vote counting based on the direction of effect. Main Results: Nine RCTs and four non-RCTs, conducted primarily in the United States and involving a total of 470 older adults (mean or median ages: 72-83 years), were included. All studies were limited in size (20-88 participants each). Programmes lasted 6-12 weeks and mostly involved weekly visits by undergraduate students to community-dwelling older adults. Visits consisted mainly of casual conversation, but sometimes involved gameplaying and TV-watching. All studies had major shortcomings in design and execution. The current evidence about the effect of F2F FVV on loneliness in older adults is very uncertain, both in the short (one RCT in 88, and one non-RCT in 35 participants) and intermediate term (one RCT in 86 participants) (both very low-certainty evidence). The same goes for the effects on social isolation, again both in the short (one RCT in 88, and two non-RCTs in 46 participants) and intermediate term (two non-RCTs in 99 participants) (both very low-certainty evidence). Similarly, there is a lot of uncertainty about the effect of F2F FVV on outcomes related to wellbeing (all very low-certainty evidence). Authors' Conclusions: Due to the very low-certainty evidence, we are unsure about the effectiveness of F2F FVV with regard to improving loneliness, social isolation, or wellbeing in older adults. Decision-makers considering implementing FVV should take into account this uncertainty. More and larger high-quality studies that are better designed and executed, and preferably conducted in various settings, are needed.

Cost Effectiveness of Different Platelet Preparation, Storage, Selection and Dosing Methods in Platelet Transfusion: A Systematic Review.

BACKGROUND AND OBJECTIVE: Evidence-based guidelines on platelet transfusion therapy assist clinicians to optimize patient care, but currently do not take into account costs associated with different methods used during the preparation, storage, selection and dosing of platelets for transfusion. This systematic review aimed to summarize the available literature regarding the cost effectiveness (CE) of these methods. METHODS: Eight databases and registries, as well as 58 grey literature sources, were searched up to 29 October 2021 for full economic evaluations comparing the CE of methods for preparation, storage, selection and dosing of allogeneic platelets intended for transfusion in adults. Incremental CE ratios, expressed as standardized cost (in 2022 EUR) per quality-adjusted life-year (QALY) or per health outcome, were synthesized narratively. Studies were critically appraised using the Philips checklist. RESULTS: Fifteen full economic evaluations were identified. Eight investigated the costs and health consequences (transfusion-related events, bacterial and viral infections or illnesses) of pathogen reduction. The estimated incremental cost per QALY varied widely from EUR 259,614 to EUR 36,688,323. For other methods, such as pathogen testing/culturing, use of apheresis instead of whole blood-derived platelets, and storage in platelet additive solution, evidence was sparse. Overall, the quality and applicability of the included studies was limited. CONCLUSIONS: Our findings are of interest to decision makers who consider implementing pathogen reduction. For other preparation, storage, selection and dosing methods in platelet transfusion, CE remains unclear due to insufficient and outdated evaluations. Future high-quality research is needed to expand the evidence base and increase our confidence in the findings.

Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.

BACKGROUND: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs. METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence. RESULTS: Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting. CONCLUSIONS: It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.

Impact of disasters on blood donation rates and blood safety: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Timely and adequate access to safe blood forms an integral part of universal health coverage, but it may be compromised by natural or man-made disasters. This systematic review provides an overview of the best available scientific evidence on the impact of disasters on blood donation rates and safety outcomes. MATERIALS AND METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Web of Science and CINAHL) were searched until 27 March 2020 for (un)controlled studies investigating the impact of disasters on blood donation rates and/or safety. Risk of bias and overall certainty of the evidence were assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Eighteen observational studies were identified, providing very low certainty of evidence (due to high risk of bias, inconsistency and/or imprecision) on the impact of natural (12 studies) and man-made/technological (6 studies) disasters. The available evidence did not enable us to form any generalizable conclusions on the impact on blood donation rates. Meta-analyses could not detect any statistically significant changes in transfusion-transmissible infection (TTI) rates [hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2, human T-lymphotropic virus I and II (HTLV-I/II) and syphilis] in donated blood after a disaster, either in first-time or repeat donors, although the evidence is very uncertain. CONCLUSION: The very low certainty of evidence synthetized in this systematic review indicates that it is very uncertain whether there is an association between disaster occurrence and changes in TTI rates in donated blood. The currently available evidence did not allow us to draw generalizable conclusions on the impact of disasters on blood donation rates.

Lack of Cost-Effectiveness of Preoperative Erythropoiesis-Stimulating Agents and/or Iron Therapy in Anaemic, Elective Surgery Patients: A Systematic Review and Updated Analysis.

OBJECTIVES: For anaemic elective surgery patients, current clinical practice guidelines weakly recommend the routine use of iron, but not erythrocyte-stimulating agents (ESAs), except for short-acting ESAs in major orthopaedic surgery. This recommendation is, however, not based on any cost-effectiveness studies. The aim of this research was to (1) systematically review the literature regarding cost effectiveness of preoperative iron and/or ESAs in anaemic, elective surgery patients and (2) update existing economic evaluations (EEs) with recent data. METHODS: Eight databases and registries were searched for EEs and randomized controlled trials (RCTs) reporting cost-effectiveness data on November 11, 2020. Data were extracted, narratively synthesized and critically appraised using the Philips reporting checklist. Pre-existing full EEs were updated with effectiveness data from a recent systematic review and current cost data. Incremental cost-effectiveness ratios were expressed as cost per (quality-adjusted) life-year [(QA)LY] gained. RESULTS: Only five studies (4 EEs and 1 RCT) were included, one on intravenous iron and four on ESAs + oral iron. The EE on intravenous iron only had an in-hospital time horizon. Therefore, cost effectiveness of preoperative iron remains uncertain. The three EEs on ESAs had a lifetime time horizon, but reported cost per (QA)LY gained of 20-65 million (GBP or CAD). Updating these analyses with current data confirmed ESAs to have a cost per (QA)LY gained of 3.5-120 million (GBP or CAD). CONCLUSIONS: Cost effectiveness of preoperative iron is unproven, whereas routine preoperative ESA therapy cannot be considered cost effective in elective surgery, based on the limited available data. Future guidelines should reflect these findings.

Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis.

Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence).

An educational pathway and teaching materials for first aid training of children in sub-Saharan Africa based on the best available evidence.

BACKGROUND: First aid training is a cost-effective way to decrease the burden of disease and injury in low- and middle-income countries (LMIC). Since evidence from Western countries has shown that children are able to learn first aid, first aid training of children in LMIC may be a promising way forward. Hence, our project aim was to develop contextualized materials to train sub-Saharan African children in first aid, based on the best available evidence. METHODS: Systematic literature searches were conducted to identify studies on first aid education to children up to 18 years old (research question one), and studies investigating different teaching approaches (broader than first aid) in LMIC (research question two). A multidisciplinary expert panel translated the evidence to the context of sub-Saharan Africa, and evidence and expert input were used to develop teaching materials. RESULTS: For question one, we identified 58 studies, measuring the effect of training children in resuscitation, first aid for skin wounds, poisoning etc. For question two, two systematic reviews were included from which we selected 36 studies, revealing the effectiveness of several pedagogical methods, such as problem-solving instruction and small-group instruction. However, the certainty of the evidence was low to very low. Hence expert input was necessary to formulate training objectives and age ranges based on "good practice" whenever the quantity or quality of the evidence was limited. The experts also placed the available evidence against the African context. CONCLUSIONS: The above approach resulted in an educational pathway (i.e. a scheme with educational goals concerning first aid for different age groups), a list of recommended educational approaches, and first aid teaching materials for children, based on the best available evidence and adapted to the African context.

PROTOCOL: Friendly visiting by a volunteer for reducing loneliness and social isolation in older adults.

Loneliness and social isolation are reaching epidemic proportions in both children and adults, despite the increasing connectedness in our twenty-first century world. As a growing number of studies reveal their detrimental impact on physical and mental health, identifying and investing in feasible and sustainable interventions to alleviate social isolation and feelings of loneliness is of prime importance. Friendly visiting, a befriending intervention whereby older persons are matched with someone who visits them on a regular basis, seems to be a realistic and sustainable option for providing social support. However, until this day, it remains unclear if friendly visiting by a volunteer is effective at reducing loneliness and social isolation. Therefore, this systematic review aims to answer the following research question: what is the effect of friendly visiting by a volunteer on feelings of loneliness and social isolation (primary outcomes) and wellbeing (i.e. life satisfaction, depressive symptom experiencing and mental health; secondary outcomes) in older adults? The results of this review may provide useful information to policy-makers that are preparing to take on one the most challenging social issues facing our ageing society.

The role of nutrient sensing in the metabolic changes after gastric bypass surgery.

Taste receptors coupled to the gustatory G-protein, gustducin, on enteroendocrine cells sense nutrients to regulate gut hormone release. During Roux-en-Y gastric bypass (RYGB) surgery, the altered nutrient flow to more distal regions can affect gustducin-mediated gut hormone release and hence energy and glucose homeostasis. We studied the role of gustducin-mediated signaling in the metabolic improvements and intestinal adaptations along the gut after RYGB surgery in wild-type (WT) and α-gustducin-/- (α-gust-/-) mice. RYGB surgery decreased body weight in WT and α-gust-/- mice, whereas food intake was only decreased in WT mice. Pair-feeding to the RYGB group improved glucose homeostasis to a similar extent in WT mice. GLP1 levels were increased in both genotypes, PYY levels in α-gust-/- mice and octanoyl ghrelin levels were not affected after RYGB surgery. In WT mice, nutrients act via α-gustducin to increase L-cell differentiation (foregut) and L-cell number (foregut and hindgut) in a region-dependent manner. In α-gust-/- mice, the effect on gut hormone levels is probably tuned via increased peptide sensor and glucose transporter expression in the Roux limb and increased caecal butyrate and propionate levels in the hindgut that activate free fatty acid receptors. Finally, signaling via α-gustducin plays a role in the increased ion transport of the foregut but not in the improvement in colonic barrier function. In conclusion, RYGB surgery decreased body weight in both WT and α-gust-/- mice. Elevated plasma GLP1 and PYY levels might mediate this effect, although α-gustducin differentially affects several regulatory systems in the foregut and hindgut, tuning gut hormone release.

The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice.

Intestinal chemosensory signaling pathways involving the gustatory G-protein, gustducin, and bitter taste receptors (TAS2R) have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gustducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a high-fat diet (HFD). White adipose tissue (WAT) mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT) thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obese WT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB) or quinine (Q) during 4 weeks resulted in an α-gustducin-dependent decrease in body weight gain associated with a decrease in food intake (DB), but not involving major changes in gut peptide release. Both WAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipocytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obesity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism.

Shifting the circadian rhythm of feeding in mice induces gastrointestinal, metabolic and immune alterations which are influenced by ghrelin and the core clock gene Bmal1.

BACKGROUND: In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF), a paradigm in which food availability is limited to short and unusual times of day. RF induces a food-anticipatory increase in the levels of the hunger hormone ghrelin. We aimed to investigate whether ghrelin triggers the changes in body weight and gastric emptying that occur during RF. Moreover, the effect of genetic deletion of the core clock gene Bmal1 on these physiological adaptations was studied. METHODS: Wild-type, ghrelin receptor knockout and Bmal1 knockout mice were fed ad libitum or put on RF with a normal or high-fat diet (HFD). Plasma ghrelin levels were measured by radioimmunoassay. Gastric contractility was studied in vitro in muscle strips and in vivo (13C breath test). Cytokine mRNA expression was quantified and infiltration of immune cells was assessed histologically. RESULTS: The food-anticipatory increase in plasma ghrelin levels induced by RF with normal chow was abolished in HFD-fed mice. During RF, body weight restoration was facilitated by ghrelin and Bmal1. RF altered cytokine mRNA expression levels and triggered contractility changes resulting in an accelerated gastric emptying, independent from ghrelin signaling. During RF with a HFD, Bmal1 enhanced neutrophil recruitment to the stomach, increased gastric IL-1α expression and promoted gastric contractility changes. CONCLUSIONS: This is the first study demonstrating that ghrelin and Bmal1 regulate the extent of body weight restoration during RF, whereas Bmal1 controls the type of inflammatory infiltrate and contractility changes in the stomach. Disrupting the circadian rhythm of feeding induces a variety of diet-dependent metabolic, immune and gastrointestinal alterations, which may explain the higher prevalence of obesity and immune-related gastrointestinal disorders among shift workers.

Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein.

BACKGROUND: Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell. METHODS: Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo. RESULTS: Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels. CONCLUSION: This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell.

Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying.

Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust(-/-) mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust(-/-) and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust(-/-) mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders.