Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska natives and non-natives residing in rural settings: a randomized controlled trial

Background: Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the μ‐opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians. Methods: Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence. Results: Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking‐related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response. Conclusions: Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism.     

Profiling of Patients with Temporomandibular Disorders: Experience of One Tertiary Care Center

ObjectivesThe aim of this study was to assess typical and most prevalent characteristics of patients suffering from temporomandibular disorders (TMD) by a retrospective assessment of their medical records.Material and MethodsDemographic data and data on the characteristics of TMD were collected from the existing medical documentation of 304 TMD patients (250 females and 54 males) who had been referred to the Department of Dentistry, Clinical Hospital Center Zagreb from October 2016 to October 2020 due to temporomandibular pain. For the purpose of analysis, three age groups were formed: i) “children and adolescents” (up to 19 years of age); ii) “middle age” (from 20 to 50 years of age); iii) “older age” (>50 year- olds). A two-step cluster analysis was performed with the aim of classifying TMD patients into homogenous groups.ResultsThe mean age of patients whose data were included in the study was 33.8 ± 16.66, with a significantly higher age in the group of women (p<0.001). Most of the patients had chronic pain (67.4%), with the ratio in favor of chronic patients being significantly higher in women than in men (p=0.001). Data on parafunctional behavior were confirmed in 14.5% of patients. Data on the onset of symptoms during/just after orthodontic treatment were present in 14.5% of patients. Data on spontaneous pain, assessed with a visual analogue scale, were recorded in 87 patients, with a mean of 6.14 ± 1.79 and with the highest pain in the “older age” group. Physical therapy was the most common therapeutic modality (56.3%) followed by an occlusal splint (40.5%). The analysis revealed 5 different clusters in the TMD patient data set.ConclusionsOur results are largely in line with current epidemiological knowledge on TMD. Women predominated in all age groups and most of the patients experienced chronic pain. Classifying patients into homogeneous groups using the clustering method could provide better identification of subgroups of conditions that mainly occur together in these patients, thus providing the basis for more specific management.     

Genetic epidemiology and genome-wide linkage analysis of carotid artery ultrasound traits in multigenerational African ancestry families

Objective

Intima-media thickness, adventitial diameter and lumen diameter are indicators of cardiovascular disease risk. The influence of genetic factors on these measures in African ancestry populations is not well defined. Therefore, we estimated heritability and performed genome-wide linkage analysis of carotid ultrasound traits in 7 multigenerational families of African ancestry.

Methods

A total of 395 individuals (7 pedigrees; mean family size = 56; 2392 relative pairs) aged ≥18 years had a common carotid artery ultrasound scan. Statistical analyses were conducted using pedigree-based maximum likelihood methods.

Results

Significant covariates included age, sex, body mass index or height and waist, and systolic blood pressure. Residual heritabilities ranged from 0.35 ± 0.10 to 0.64 ± 0.12 (P < 0.0001). We identified a novel quantitative trait locus for adventitial and lumen diameters on chromosome 11 (max LOD = 4.09, 133 cm).

Conclusion

Further fine mapping of this region may identify specific mutations predisposing to subclinical vascular disease among African ancestry individuals.     

Lipid profile and atherogenic indices in patients with stable chronic obstructive pulmonary disease

Background and aimsLimited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy.Methods and resultsThe study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated.HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742–0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases.ConclusionLipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.     

Age-specific associations between underlying health conditions and hospitalisation,death and in-hospital death among confirmed COVID-19 cases: a multi-country study based on surveillance data,June to December 2020

BackgroundUnderlying conditions are risk factors for severe COVID-19 outcomes but evidence is limited about how risks differ with age.AimWe sought to estimate age-specific associations between underlying conditions and hospitalisation, death and in-hospital death among COVID-19 cases.MethodsWe analysed case-based COVID-19 data submitted to The European Surveillance System between 2 June and 13 December 2020 by nine European countries. Eleven underlying conditions among cases with only one condition and the number of underlying conditions among multimorbid cases were used as exposures. Adjusted odds ratios (aOR) were estimated using 39 different age-adjusted and age-interaction multivariable logistic regression models, with marginal means from the latter used to estimate probabilities of severe outcome for each condition–age group combination.ResultsCancer, cardiac disorder, diabetes, immunodeficiency, kidney, liver and lung disease, neurological disorders and obesity were associated with elevated risk (aOR: 1.5–5.6) of hospitalisation and death, after controlling for age, sex, reporting period and country. As age increased, age-specific aOR were lower and predicted probabilities higher. However, for some conditions, predicted probabilities were at least as high in younger individuals with the condition as in older cases without it. In multimorbid patients, the aOR for severe disease increased with number of conditions for all outcomes and in all age groups.ConclusionWhile supporting age-based vaccine roll-out, our findings could inform a more nuanced, age- and condition-specific approach to vaccine prioritisation. This is relevant as countries consider vaccination of younger people, boosters and dosing intervals in response to vaccine escape variants.     

Comparison of the effectiveness of two combinations of antibiotic used for perioperative prophylactic therapy during radical cystectomy: A retrospective cohort study

IntroductionThis retrospective cohort study aimed to compare primary and secondary outcomes of patients undergoing radical cystectomy according to two different perioperative antimicrobial therapy protocols in 2016.MethodsIn this single-center, retrospective cohort study, we investigated data of 104 patients undergoing radical cystectomy due to bladder cancer from January 1, 2016, to December 31, 2016. According to perioperative antimicrobial prophylaxis, patients were divided into two groups: 48 patients received piperacillin/tazobactam 3x4.5 g intravenously (IV) combined with metronidazole 3x500 mg IV, and 56 patients received ceftriaxone 1x2 g IV combined with metronidazole 3x500 mg IV. All patients received the first dose of antibiotics 24 hours prior to the operative procedure, and it continued over the next 48 hours after the procedure. We analyzed and compared data from various primary and secondary outcomes for both groups of patients.ResultsIn the group of patients receiving the combination of the piperacillin/tazobactam with metronidazole, the length of postoperative hospitalization was shorter (14 vs. 16 days, Z=2.24957 p=0.02383), leukocyte blood count on the first postoperative day was lower (9.80 vs. 11.15, p=0.01384), and hospital-acquired pneumonia was less common (2.08% vs. 12.5%, p=0.04688) than in the group receiving a combination of ceftriaxone and metronidazole.ConclusionsIn radical cystectomy, perioperative antimicrobial prophylaxis protocol using piperacillin/tazobactam combined with metronidazole proved to be more effective than the combination of ceftriaxone with metronidazole.     

Redefining the Koizumi model of mouse cerebral ischemia: A comparative longitudinal study of cerebral and retinal ischemia in the Koizumi and Longa middle cerebral artery occlusion models

Cerebral and retinal ischemia share similar pathogenesis and epidemiology, each carrying both acute and prolonged risk of the other and often co-occurring. The most used preclinical stroke models, the Koizumi and Longa middle cerebral artery occlusion (MCAO) methods, have reported retinal damage with great variability, leaving the disruption of retinal blood supply via MCAO poorly investigated, even providing conflicting assumptions on the origin of the ophthalmic artery in rodents. The aim of our study was to use longitudinal in vivo magnetic resonance assessment of cerebral and retinal vascular perfusion after the ischemic injury to clarify whether and how the Koizumi and Longa methods induce retinal ischemia and how they differ in terms of cerebral and retinal lesion evolution. We provided anatomical evidence of the origin of the ophthalmic artery in mice from the pterygopalatine artery. Following the Koizumi surgery, retinal responses to ischemia overlapped with those in the brain, resulting in permanent damage. In contrast, the Longa method produced only extensive cerebral lesions, with greater tissue loss than in the Koizumi method. Additionally, our data suggests the Koizumi method should be redefined as a model of ischemia with chronic hypoperfusion rather than of ischemia and reperfusion.