Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial.

PURPOSE: According to preclinical evidence, GLP-1 receptor may be an actionable target in neurodegenerative disorders, including Alzheimer's disease (AD). Previous clinical trials of GLP-1 receptor agonists were conducted in patients with early AD, yielding mixed results. The aim was to assess in a proof-of-concept study whether slow-release exenatide, a long-acting GLP-1 agonist, can benefit the cognitive performance of people with mild cognitive impairment (MCI). METHODS: Thirty-two (16 females) patients were randomized to either slow-release exenatide (n = 17; 2 mg s.c. once a week) or no treatment (n = 15) for 32 weeks. The primary endpoint was the change in ADAS-Cog11 cognitive test score at 32 weeks vs baseline. Secondary endpoints herein reported included additional cognitive tests and plasma readouts of GLP-1 receptor engagement. Statistical analysis was conducted by intention to treat. RESULTS: No significant between-group effects of exenatide on ADAS-Cog11 score (p = 0.17) were detected. A gender interaction with treatment was observed (p = 0.04), due to worsening of the ADAS-Cog11 score in women randomized to exenatide (p = 0.018), after correction for age, scholar level, dysglycemia, and ADAS-Cog score baseline value. Fasting plasma glucose (p = 0.02) and body weight (p = 0.03) decreased in patients randomized to exenatide. CONCLUSION: In patients with MCI, a 32-week trial with slow-release exenatide had no beneficial effect on cognitive performance. TRIAL REGISTRATION NUMBER: NCT03881371, registered on 21 July, 2016.

Can risk rating increase the ability of voluntary deductibles to reduce moral hazard?

Several regulated health insurance markets include the option for consumers to choose a voluntary deductible. An important motive for this option is to reduce moral hazard. In return for a voluntary deductible, consumers receive a premium rebate, which is typically community rated. Under community rating, voluntary deductibles are particularly attractive for low-risk consumers. Since these people use relatively little medical care, the total moral hazard reduction might be relatively small compared to the total healthcare spending. This paper examines the potential moral hazard reduction under risk-rated premiums. We use Chile as a case study due to institutional features that make it a valid benchmark for other countries. Our simulations show that in the presence of self-selection and under a uniform percentage moral hazard reduction across risk types, the absolute moral hazard reduction from a voluntary deductible is indeed expected to be larger in a system with risk-rated premiums than in a system with community-rated premiums. Nevertheless, sensitivity checks show that this conclusion might no longer hold as the percentage moral hazard reduction is lower for high-risk individuals compared to low-risk individuals.

Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization.

DISCLAIMER: This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.

Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers.

Disclaimer: The Extracorporeal Life Support Organization (ELSO) Coronavirus Disease 2019 (COVID-19) Guidelines have been developed to assist existing extracorporeal membrane oxygenation (ECMO) centers to prepare and plan provision of ECMO during the ongoing pandemic. The recommendations have been put together by a team of interdisciplinary ECMO providers from around the world. Recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. This is a living document and will be regularly updated when new information becomes available. ELSO is not liable for the accuracy or completeness of the information in this document. These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic.

Rapid prototyping and clinical testing of a reusable face shield for health care workers responding to the COVID-19 pandemic.

Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment (PPE) for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of simple products such as protective face shields. As a consequence, many public domain designs for face shields have become available. No clear path exists, however, for introducing a locally fabricated and unapproved product into a clinical setting. In a US health care setting, face shields are regulated by the Food and Drug Administration (FDA); similar policies exist in other countries. We describe a research protocol under which rapid iteration on an existing design, coupled with clinical feedback and real-world testing in an emergency department, allowed a face shield to be adopted by the incident command team at a major academic medical center. We describe our design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of face shields and related products. All designs, materials used, testing protocols, and survey results are reported in full to facilitate the execution of similar face shield efforts in other clinical settings. Our work serves as a case study for development of a robust local response to pandemics and other health care emergencies, with implications for healthcare professionals, hospital administrators, regulatory agencies and concerned citizens.

Constipación en la Unidad de Terapia Intensiva Un trastorno de motilidad inadvertido / GUIDELINES FOR THE MANAGEMENT OF CONSTIPATION IN INTENSIVE CARE UNITS. AN UNNOTICIED DISORDER OF MOTILITY

This article discusses the incidence of constipation in an intensive care unit. Disorders of the gastrointestinal motility are frequent among critically ill patients. Nevertheless, constipation has received less importance in this matter. Several alimentary factors and of the clinical treatment have been associated to this event. Constipation is the condition in which bowel movements are infrequent or incomplete during three, six or nine consecutive days, or otherwise because of the necessity to assist to the treatment with evacuating measures. The authors conducted a descriptive, quali-quantitative, transversal and prospective design of the incidence of constipation and its implications on the progress of critically ill patients, in patients 18 years old or older, assisted at the Intensive Care Unit from the Hospital "Juan Fernandez", from Buenos Aires. It is concluded that constipation is a frequent complication among critically ill patients and thus the administration of early enteral nutrition with insoluble fiber should be considered, as a protector support against constipation. Accelerating gastrointestinal recovery during intensive care stay could increase patient comfort, decrease the average hospital stay and reduce costs and readmission rates.

Hanging of the hepatic veins septa: a safe control prior and during outflow anastomosis in liver transplantation.

Inferior vena cava (IVC) preservation during orthotopic liver transplantation (OLT) is known as the "piggyback" technique. The end-to-side anastomosis is constructed between the graft's IVC and recipient's hepatic veins using a Satinsky side clamp applied in a transverse position. To stabilize the large Satinsky clamp and preserve a sufficient vascular stump after hepatectomy and before graft implantation, we propose a technical innovation consisting of hanging the septa between the left and middle hepatic vein and between the middle and right hepatic vein using 2 tapes. This technique showed some advantages when performing the caval outflow anastomosis, representing a further technical refinement of the piggyback end-to-side technique for the implantation on the 3 hepatic veins. From November 2001 to September 2012, we performed 272 consecutive OLT at our institution with the piggyback technique using the hanging of the hepatic veins septa in all cases. In conclusion, the hanging of the 3 hepatic veins septa presented in this study represents a simple, safe and reproducible technique for the outflow anastomosis using the piggyback technique.

Effects of a home-based walking training program on cardiorespiratory fitness in breast cancer patients receiving adjuvant chemotherapy: a pilot study.

BACKGROUND: Breast cancer treatment is associated with a decline in measured cardiorespiratory fitness and increased fatigue. There is accumulating evidence that exercise training during adjuvant chemotherapy may contribute to prevent these changes. Additional studies are needed to explore the effectiveness of home-based walking interventions among this population. AIM: The aim of this study was to investigate the effects of a 12-week adapted home-based walking training program (WTP) on clinical rehabilitation in breast cancer patients receiving adjuvant chemotherapy. DESIGN: This was a pilot study using a single-group design. SETTING: Unit Department of Physiology and Medical Oncology, Limoges University Hospital, France. POPULATION: Thirty-nine outpatients predominantly with stage II breast cancer. METHODS: Participants performed 3 home ambulatory aerobic walking sessions per week at 50-60% of their maximum heart rate for 12 weeks. Functional capacity was assessed with an incremental cardiopulmonary exercise test during which peak oxygen consumption (VO(2peak)) was measured. A six-minute walking test (6 MWT) was performed to evaluate physical function. The revised Piper Fatigue Scale (PFS-R) was used to measure self-reported fatigue. RESULTS: Thirty-four patients (87%) completed all study procedures. Per Protocol (PP) analysis indicated that VO(2peak) recorded both before and after a 12-week adapted home-based WTP increased significantly by 2.21 mL.kg-1.min-1 (P=0.008) and 6 MWT distance increased significantly by 42 m (P=0.04). PFS-R score increased by 0.4 points, but not significantly. CONCLUSION: In breast cancer patients receiving adjuvant chemotherapy, home-based WTP is feasible and associated with significant improvements in VO(2peak), with no significant effect on fatigue score. Larger randomized trials are necessary to confirm these findings.

Neurosensory and functional evaluation in distraction osteogenesis of the anterior mandibular alveolar process.

Neurosensory status and craniomandibular function of 19 patients (mean age 35.2 years, range 17.8-58.8 years) treated by combined surgical orthodontic treatment with distraction osteogenesis of the mandibular anterior alveolar process (DO group) was compared with that in 41 orthodontically treated patients (mean age 22.9 years, range 15.1-49.0 years; control group). Clinical examination took place on average 5.9 years (DO group) and 5.4 years (control group) after treatment ended. Neurosensory status was determined by two-point discrimination (2-pd) and the pointed and blunt test. Lateral cephalograms evaluated advancement of the mandibular alveolar process and possible relapse. There was no significant difference in craniomandibular function and neurosensory status between the groups. Age was significantly correlated with 2-pd at the lips (DO: p=0.01, R=0.575; control group: p=0.039, R=0.324) and chin (DO: p=0.029, R=0.501; control group: p=0.008, R=0.410). Younger patients had smaller 2-pd values. Gender, age, the amount of advancement, and relapse at point B or incision inferior show no correlation with craniomandibular function and neurosensory impairment. DO of the mandibular anterior alveolar process is a valuable and safe method with minor side effects regarding neurosensory impairment.

Skeletal and dental stability of segmental distraction of the anterior mandibular alveolar process. A 5.5-year follow-up.

17 patients (14 female; 3 male) were analysed retrospectively for skeletal and dental relapse before distraction osteogenesis (DO) of the mandibular anterior alveolar process at T1 (17.0 days), after DO at T2 (mean 6.5 days), at T3 (mean 24.4 days), at T4 (mean 2.0 years), and at T5 (mean 5.5 years). Lateral cephalograms were traced by hand, digitized, superimposed, and evaluated. Skeletal correction (T5-T1) was mainly achieved through the distraction of the anterior alveolar segment in a rotational manner where the incisors were more proclined. The horizontal backward relapse (T5-T3) measured -0.3mm or 8.3% at point B (non-significant) and -1.8mm or 29.0% at incision inferior (p<0.01). Age, gender, amount and type (rotational vs. translational) of advancement were not correlated with the amount of relapse. High angle patients (NL/ML'; p<0.01) showed significant smaller relapse rates at point B. Overcorrection of the overjet achieved by the distraction could be a reason for dental relapse. Considering the amount of long-term skeletal relapse the DO could be an alternative to bilateral sagittal split osteotomy for mandibular advancement in selected cases.

Soft tissue stability after segmental distraction of the anterior mandibular alveolar process: a 5.5 year follow-up.

Soft tissue changes were analysed retrospectively in 17 patients following distraction osteogenesis (DO) of the mandibular anterior alveolar process. Lateral cephalograms were traced by hand, digitized, superimposed, and evaluated at T1 (17.0 days), after DO at T2 (mean 6.5 days), at T3 (mean 24.4 days), at T4 (mean 2.0 years), and at T5 (mean 5.5 years). Statistical analysis was carried out using Kolmogorov-Smirnov test, paired t-test, Pearson's correlation coefficient, and linear backward regression analysis. 5.5 years postoperatively, the net effect for the soft tissue at point B' was 88% of the advancement at point B while the lower lip (labrale inferior) followed the advancement of incision inferior to 24%. Increased preoperative age was correlated (p<0.05) with more horizontal backward movement (T5-T3) for labrale inferior and pogonion'. Higher NL/ML' angles were significantly correlated (p<0.05) to smaller horizontal soft tissue change at labrale inferior (T5-T3). The amount of advancement at point B was significantly correlated with an upward movement (T5-T3) of labrale inferior (p<0.01) and stomion inferior (p<0.05). It can be concluded that further change in soft tissues occurred between 2.0 and 5.5 years postoperatively. The physiological process of ageing and loss of soft tissue elasticity should be considered as possible reasons.

Skeletal and dental stability of segmental distraction of the anterior mandibular alveolar process. A 2-year follow-up.

33 patients (27 females; 6 males) were retrospectively analysed for skeletal and dental relapse before distraction osteogenesis (DOG) of the mandibular anterior alveolar process at T1 (17.0 days), after DOG at T2 (mean 6.5 days), at T3 (mean 24.4 days), and at T4 (mean 2.0 years). Lateral cephalograms were traced by hand, digitized, superimposed, and evaluated. Skeletal correction (T3-T1) was mainly achieved through the distraction of the anterior alveolar segment in a rotational manner where the incisors were more proclined. The horizontal backward relapse (T4-T3) measured -0.8mm or 19.0% at point B (p<0.001) and -1.6mm or 25.0% at incision inferior (p<0.001). Age, gender, amount and type (rotational versus translational) of advancement were not correlated with the amount of relapse. High angle patients (NL/ML'; p<0.01) and patients with large gonial angle (p<0.05) showed significantly smaller relapse rates at point B. Overcorrection of the overjet achieved by the distraction was seen in a third of the patients and could be a reason for relapse. Considering the amount of skeletal relapse the DOG could be an alternative to bilateral sagittal split osteotomy for mandibular advancement in selected cases.

Soft tissue stability in segmental distraction of the anterior mandibular alveolar process. A 2-year follow-up.

This study evaluated soft tissue changes in adult patients treated with distraction osteogenesis (DOG) of the anterior mandibular alveolar process and related it to different parameters. 33 patients (27 females; 6 males) were analysed retrospectively before surgery at T1 (17.0 days), after surgery at T2 (mean 6.5 days), at T3 (mean 24.4 days), and at T4 (mean 2.0 years). Lateral cephalograms were traced by hand, digitized, superimposed, and evaluated. Statistical analysis was carried out using Kolmogorov-Smirnov test, paired t test, Pearson's correlation coefficient, and linear backward regression analysis. 2 years postoperatively (T4), the net effect of the soft tissue at point B' was 100% of the advancement at point B whilst the lower lip (labrale inferior) followed the advancement of incision inferior to 46%. Increased preoperative age was correlated (p<0.05) with more horizontal backward movement (T4-T3) for labrale superior and pogonion'. Higher NL/ML' angles were significantly correlated (p<0.05) with smaller horizontal soft tissue change at point B'. Gender and the amount of skeletal and dental advancement were not correlated with postoperative soft tissue changes (T4-T3). DOG of the anterior mandibular alveolar process is a valuable alternative for mandibular advancement regarding soft tissue change and predictability.

A case of dengue type 3 virus infection imported from Africa to Italy, October 2009.

In October 2009, a traveller returning from Africa to Italy was hospitalised with symptoms suggestive of a haemorrhagic fever of unknown origin. The patient was immediately placed in a special biocontainment unit until laboratory investigations confirmed the infection to be caused by a dengue serotype 3 virus. This case reasserts the importance of returning travellers as sentinels of unknown outbreaks occurring in other countries, and highlights how the initial symptoms of dengue fever resemble those of other haemorrhagic fevers, hence the importance of prompt isolation of patients until a final diagnosis is reached.

Hair follicle characteristics and fibre production in South American camelids.

Hair follicle and fibre characteristics of Peruvian alpaca and llama and Bolivian llama were analysed in three experimental studies. The first experiment was designed to determine the age at which all the secondary follicles reach maturity, as well as to compare the skin follicular structure and activity among these different types of Peruvian camelids. It is concluded that the South American camelids investigated in this study gained a complete and mature skin follicle apparatus at an early age, and hence producers should practise an early first shearing. A second Peruvian experiment investigated comparative fibre cuticular structure on twenty Peruvian domestic camelids comprising huacaya, suri and llama (woolly) 'chacos' genotypes. The results showed that the number of cuticular scales per 100 µm fibre length proved to be strongly affected by both the fleece type and the fibre diameter. The suri fleece was clearly differentiated from those of both huacaya and llama by possessing the highest percentage of fibres with a number of scales less than eight, the lowest percentage of fibres with more than nine scales, along with the lowest percentage of fibres with a diameter of more than 35 µm. It is concluded that, with the exception of the scale height, the cuticular parameters investigated in this study can be utilised in textile fibre analyses for distinguishing among these three types of fleece, as well as in selection projects designed to produce homogeneous fibres from Peruvian domestic camelids. A further study was conducted to determine the age at which the hair follicles in Bolivian llamas reach maturity as well as for comparing the skin follicular structure and activity between the two distinct genotypes. Thirty-one llama kids were chosen. They were born between January and April 1998 and were of different sex and of 'Q'aras' (or Carguera) or 'T'amphullis' type. Skin biopsies were taken from the right mid-costal region at 2, 4, 6, 8,10,12 and 14 months of age in order to monitor four follicular parameters. In this experiment, secondary to primary (S/P) data show that the Bolivian llama population analysed possessed a complete and mature skin follicle apparatus at birth that remained essentially constant throughout the investigation period. Due to the variation of these traits inside the same genetic population, the present results showed that T and Q types could only be subjective on the basis of S/P ratio.

Alcohol and coffee drinking and smoking habit among subjects with HCV infection.

BACKGROUND/AIMS: The aims were to estimate among patients with hepatitis C virus (HCV) infection the prevalence of alcohol and coffee intake and smoking habit, the reliability of these self-reported data and the possible change of patients' habit after their first contact with a Viral Hepatitis Service. METHODS: 229 patients were initially interviewed personally at the Viral Hepatitis Service and after 6 months they were re-interviewed by phone in regard to their alcohol, coffee drinking and smoking habits. RESULTS: Alcohol drinkers were 55.5% of males and 35.3% of females. Most subjects drank coffee daily, both men (90.0%) and women (84.9%). The proportion of current smokers was higher in males (43.6%) than females (26.9%). We found a fair to good reliability of self-reported data regarding patients' habits, alcohol and coffee intake, and number of cigarettes smoked daily. We observed a statistically significant decrease in alcohol and coffee intake and cigarettes smoked between baseline and follow-up interviews. CONCLUSION: We found a fairly high proportion of HCV-infected patients who regularly drink alcohol and coffee beverages and smoke cigarettes, especially among males. The reliability of self-reported data on these habits seems satisfactory. More decisive action to modify these habits, especially alcohol intake, is required in these patients.

Effects of field bean (Vicia faba L. var. minor) dietary supplementation on plasma thyroid hormones, insulin, insulin-like growth factor-1 concentrations and mohair characteristics in growing Angora goat kids.

Twenty-two Angora kids were used to study the effect of a dietary supplementation with field bean (Vicia faba L. var. minor) on hair follicle activity, mohair characteristics and plasma total thyroxine (T4), triiodothyronine (T3), insulin (INS) and insulin-like growth factor-1 (IGF-1) concentrations. At birth, their mothers were divided in two groups (S: supplemented, C: control), the S group being supplemented with 300 g/head/day of whole field bean. At weaning, diet of kids from S group was supplemented with 80 g/head/day of whole field bean. At weaning, secondary hair follicle activity (S: 0.91 ± 0.01, C: 0.84 ± 0.02, p < 0.01) and staple length (S: 5.82 ± 0.13 cm, C: 5.16 ± 0.14 cm, p < 0.001) were greater in the S group. At 155 days of age, secondary fibre diameter (S: 16.54 ± 0.35 µm, C: 18.09 ± 0.31 µm, p < 0.01) was higher in the C kids. Concentrations of total plasma T4 and T3 were higher (p < 0.001) in S (120 ± 12 and 4.87 ± 0.92 ng/ml respectively) than in C kids (92 ± 8 and 2.97 ± 0.77 ng/ml respectively). At weaning, T4 values were negatively correlated (p < 0.05) with the secondary fibre diameter and the T3/T4 ratio was positively correlated (p < 0.05) with the secondary to primary hair follicle ratio. At 155 days of age, both T3 and T3/T4 values were positively correlated (p < 0.01) with staple length. Plasma INS (0.11 ± 0.03 ng/ml) and total IGF-1 concentrations (232 ± 13 ng/ml) were not affected by diet. Improvements of diet quality in kids positively affected fibre diameter and length and follicle activity rate. We suggest that increased circulating thyroid hormones concentrations, but not those of INS and IGF-1, may contribute to the beneficial actions of nutritional supplementation on anatomical growth and mohair production of kids.

Incidence of neutropenia and infections during combination treatment of chronic hepatitis C with pegylated interferon alfa-2a or alfa-2b plus ribavirin.

BACKGROUND: Combination therapy with pegylated interferon (peginterferon) plus ribavirin is associated with several side effects, including neutropenia and infection. AIMS: To evaluate the incidence of neutropenia and infection between all consecutive patients with hepatitis C who were treated in two centers with peginterferon-alfa-2a and peginterferon-alfa-2b, in combination with ribavirin and actively monitored for occurrence of any infection. METHODS: A total of 319 consecutive patients with chronic hepatitis C received once-weekly peginterferon alfa-2b at a weight-adjusted dose (n=162) or peginterferon alfa-2a at a flat dose (n=157), plus ribavirin. RESULTS: Neutropenia was observed in 53 patients overall (17%). There were 73 infections in 73 subjects (23% of the treated population); 4/73 required hospitalization. Infections included respiratory infections (n=23), cellulitis (n=17), dental abscesses (n=13), gastroenteric infections (n=2), and other types of infections (n=18). The incidence of all infections was significantly associated with age, especially over 60 years (p<0.01) but not with neutropenia or type of pegylated interferon. CONCLUSIONS: During the treatment with pegylated interferons and ribavirin, we did not find a correlation between neutropenia and infections. This result provides a support for the notion that current guidelines for pegylated interferons dose reduction in the treatment of chronic hepatitis C for hematologic toxicity could be overly strict.