Mecamylamine treatment for alcohol dependence: a randomized controlled trial

Background and aims

The nicotinic acetylcholine receptor antagonist, mecamylamine, is a potential novel pharmacotherapy for alcohol use disorder. The aims were to compare alcohol consumption between mecamylamine and placebo and test if smoking status modified treatment effects.

Design

Out‐patient, randomized, double‐blind clinical trial for 12 weeks of treatment with mecamylamine (10 mg) (n = 65) versus placebo (n = 63).

Setting

Connecticut, USA.

Participants

Individuals had current alcohol dependence (n = 128), had an average age of 48.5 [standard deviation (SD) = 9.4], 110 (85.9%) were men, and included 74 smokers (57.8%) and 54 non‐smokers (42.2%). Participants were randomized to mecamylamine 10 mg per day or placebo. All subjects also received medical management therapy administered by trained research personnel.

Measurements

Primary outcome was percentage of heavy drinking days during the last month of treatment; other outcomes included drinking days, drinks per drinking days, alcohol craving, smoking, symptoms of nicotine withdrawal and side effects.

Findings

There were no significant differences in the percentage of heavy drinking days at 3 months between the mecamylamine (mean = 18.4, SD = 29.0) and placebo treatment groups (mean = 20.4, SD = 29.2) [F_{1, 100} = 1.3, P = 0.25; effect size d = 0.07; mean difference = 2.06, 95% confidence interval (CI) = ?8.96 to 13.08]. There were no significant differences in percentage of drinking days or in drinks per drinking day at month 3 between the mecamylamine and placebo groups; there were no significant interactions.

Conclusions

Mecamylamine 10 mg per day did not reduce alcohol consumption significantly in treatment‐seeking smokers and non‐smokers with alcohol use disorder.     

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal

Background and Aims

Cannabidiol (CBD), a non‐intoxicating cannabinoid found in cannabis, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side effects and research showing that it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette‐related stimuli and increased craving and withdrawal; and (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette‐related stimuli, craving and withdrawal and not produce any side effects.

Design

Randomized, double‐blind cross‐over study with a fixed satiated session followed by two overnight abstinent sessions.

Setting

UK laboratory.

Participants

Thirty non‐treatment‐seeking, dependent cigarette smokers recruited from the community.

Intervention and comparator

800 mg oral CBD, or matched placebo (PBO) in a counterbalanced order

Measurements

AB to pictorial tobacco cues was recorded using a visual probe task and an explicit rating task. Withdrawal, craving, side effects, heart rate and blood pressure were assessed repeatedly.

Findings

When participants received PBO, tobacco abstinence increased AB (P = 0.001, d = 0.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (P = 0.007, d = 0.704) and no longer differed from satiety (P = 0.82). Compared with PBO, CBD also reduced explicit pleasantness of cigarette images (P = 0.011; d = 0.514). Craving (Bayes factor = 7.08) and withdrawal (Bayes factor = 6.95) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence.

Conclusions

A single 800‐mg oral dose of cannabidiol reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. Cannabidiol did not influence tobacco craving or withdrawal or any subjectively rated side effects.     

The prevalence and risk factors for acute respiratory infections in children aged 0‐59 months in rural Malawi: A cross‐sectional study

Background

Acute Respiratory Infections (ARI) are a leading cause of childhood mortality and morbidity. Malawi has high childhood mortality but limited data on the prevalence of disease in the community.

Methods

A cross‐sectional study of children aged 0‐59 months. Health passports were examined for ARI diagnoses in the preceding 12 months. Children were physically examined for malnutrition or current ARI.

Results

828 children participated. The annual prevalence of ARI was 32.6% (95% CI 29.3‐36.0%). Having a sibling with ARI (OR 1.44, P = .01), increasing household density (OR 2.17, P = .02) and acute malnutrition (OR 1.69, P = .01) were predictors of infection in the last year. The point prevalence of ARI was 8.3% (95% CI 6.8‐10.4%). Risk factors for current ARI were acute‐on‐chronic malnutrition (OR 3.06, P = .02), increasing household density (OR1.19, P = .05) and having a sibling with ARI (OR 2.30, P = .02).

Conclusion

This study provides novel data on the high prevalence of ARI in Malawi. This baseline data can be used in the monitoring and planning of future interventions in this population.     

Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia

Background

Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo‐SCT).

Aims

The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized.

Materials and Methods

We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo‐SCT for AML in CR1 and separately 570 patients treated with IC alone.

Results

In the first 3 months after allo‐SCT, the factors associated with an increased risk of relapse included the presence of the FLT3‐ITD (P < 0.001), patient age (P = 0.012), time interval from CR1 to transplant (P < 0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse‐risk cytogenetics (P < 0.001), presence of FLT3‐ITD mutation (P < 0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft‐versus‐host disease (GVHD) and the use of in vivo T‐cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse‐risk cytogenetics (P < 0.001) and FLT3‐ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012).

Discussion and Conclusion

Taken together, these data provide novel insights into the biology of disease recurrence after both allo‐SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.     

Improved joint health in subjects with severe haemophilia A treated prophylactically with recombinant factor VIII Fc fusion protein

Introduction

Joint arthropathy is the long‐term consequence of joint bleeding in people with severe haemophilia.

Aim

This study assessed change in joint health over time in subjects receiving recombinant factor VIII Fc fusion protein (rFVIIIFc) prophylaxis.

Methods

ALONG is the phase 3 pivotal study in which the benefit of rFVIIIFc as a prophylactic treatment for bleeding control was shown in previously treated severe haemophilia patients ≥12 years of age (arm 1: 25‐65 IU/kg every 3‐5 days, arm 2: 65 IU/kg weekly and arm 3: episodic). After completing ALONG, subjects had the option to enrol into the extension study (ASPIRE). This interim, post hoc analysis assessed changes in joint health over ~2.8 years in these patients.

Results

Forty‐seven subjects had modified Haemophilia Joint Health Score (mHJHS) data at A‐LONG baseline, ASPIRE baseline and ASPIRE Year 1 and Year 2. Compared with A‐LONG baseline (23.4), mean improvement at ASPIRE Year 2 was ?4.1 (95% confidence interval [CI], ?6.5, ?1.8; P = .001). Regardless of prestudy treatment regimen, subjects showed continuous improvement in mHJHS from A‐LONG baseline through ASPIRE Year 2 (prestudy prophylaxis: ?2.4, P = .09; prestudy episodic treatment: ?7.2, P = .003). Benefits were seen in subjects with target joints (?5.6, P = .005) as well as those with severe arthropathy (?8.8, P = .02). The mHJHS components with the greatest improvement at ASPIRE Year 2 were swelling (?1.4, P = .008), range of motion (?1.1, P = .03) and strength (?0.8, P = .04).

Conclusions

Prophylaxis with rFVIIIFc may improve joint health over time regardless of prestudy prophylaxis or episodic treatment regimens.     

Left atrial dyssynchrony in veteran endurance athletes with and without paroxysmal atrial fibrillation

Background

Prolonged endurance exercise increase the risk of atrial fibrillation (AF) in men. Functional parameters may help separate physiological from pathological atrial remodeling in athletes. LA mechanical dispersion (LA MD) is associated with AF in the general population, but the associations between prolonged exercise, LA MD and AF are not known.

Purpose

To describe LA MD in veteran athletes with and without paroxysmal AF (pAF) and to investigate LA MD's ability to identify veteran athletes with pAF.

Methods

Two hundred and ninety-three men, skiers with (n = 57) and without (n = 87) pAF, and controls with (n = 61) and without pAF (n = 88) underwent an echocardiographic exam in sinus rhythm. LA reservoir strain (LASr) was measured, and LA MD defined as the standard deviation of time-to-peak strain (SD-TPS).

Results

Skiers (mean age 70.7 ± 6.7 years) reported an average of 40–50 years of endurance exercise. LA volumes were associated with pAF and athletic status (p < .001). SD-TPS was associated with pAF (p < .001) but not athletic status (p = .173). We found no significant trend between years of exercise and SD-TPS in individuals without AF (p = .893). SD-TPS did not add incremental value in identifying athletes with pAF in addition to clinical markers, QRS width, LA volume, and LASr (p = .056).

Conclusion

LA MD was associated with pAF regardless of athletic status but not related to years of endurance exercise, suggesting LA MD could be a promising marker of pathological atrial remodeling in athletes. However, we found no incremental value of LA MD identifying athletes with pAF when LASr was included in the model.     

Micro‐ribonucleic acid‐binding site variants of type 2 diabetes candidate loci predispose to gestational diabetes mellitus in Chinese Han women

Aims/Introduction

Emerging evidence has suggested that the genetic background of gestational diabetes mellitus (GDM) was analogous to type 2 diabetes mellitus. In contrast to type 2 diabetes mellitus, the genetic studies for GDM were limited. Accordingly, the aim of the present study was to extensively explore the influence of micro‐ribonucleic acid‐binding single‐nucleotide polymorphisms (SNPs) in type 2 diabetes mellitus candidate loci on GDM susceptibility in Chinese.

Materials and Methods

A total of 839 GDM patients and 900 controls were enrolled. Six micro‐ribonucleic acid‐binding SNPs were selected from 30 type 2 diabetes mellitus susceptibility loci and genotyped using TaqMan allelic discrimination assays.

Results

The minor allele of three SNPs, PAX4 rs712699 (OR 1.366, 95% confidence interval 1.021–1.828, P = 0.036), KCNB1 rs1051295 (OR 1.579, 95% confidence interval 1.172–2.128, P = 0.003) and MFN2 rs1042842 (OR 1.398, 95% confidence interval 1.050–1.862, P = 0.022) were identified to significantly confer higher a risk of GDM in the additive model. The association between rs1051295 and increased fasting plasma glucose (b = 0.006, P = 0.008), 3‐h oral glucose tolerance test plasma glucose (b = 0.058, P = 0.025) and homeostatic model assessment of insulin resistance (b = 0.065, P = 0.017) was also shown. Rs1042842 was correlated with higher 3‐h oral glucose tolerance test plasma glucose (b = 0.056, P = 0.028). However, no significant correlation between the other included SNPs (LPIN1 rs1050800, VPS26A rs1802295 and NLRP3 rs10802502) and GDM susceptibility were observed.

Conclusions

The present findings showed that micro‐ribonucleic acid‐binding SNPs in type 2 diabetes mellitus candidate loci were also associated with GDM susceptibility, which further highlighted the similar genetic basis underlying GDM and type 2 diabetes mellitus.     

Education is the strongest socio‐economic predictor of smoking in pregnancy

Aims

To investigate socio‐economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions.

Design

Cross‐sectional analysis with linked survey and register data.

Setting

South‐western Finland.

Participants

A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study.

Measurements

The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire‐based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio‐economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated.

Findings

Mother's education was the strongest socio‐economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2–3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1–9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95% CI = 1.4–6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0–18.2; P < 0.001) for vocational secondary education and 14.4 (95% CI = 6.3–33.0; P < 0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1–3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4–2.8; P < 0.001), but did not attenuate its socio‐economic disparities.

Conclusions

In Finland, socio‐economic disparities in smoking in pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general).     

Comparing surgeon- and nephrologist-inserted Tenckhoff catheters: experience from a metropolitan centre in Sydney

Background

Peritoneal dialysis (PD) is an effective home-based form of dialysis. Although several factors limit its use, the timely and successful insertion of a PD catheter is essential for increased uptake.

Aims

This retrospective observational study was performed at a tertiary teaching hospital in Sydney with the aim of comparing outcomes of PD catheter insertion using a percutaneous, modified Seldinger technique utilised by a trained nephrologist to the traditional surgical insertion using a mini-laparotomy.

Results

Over an 8-year period, 194 PD catheters were inserted. Aside from lower body mass indexes in the nephrologist-led interventions (P = 0.02), patient demographics were well matched. Time-to-insertion was significantly shorter with the percutaneous technique (P < 0.001). Univariant logistic regression noted no difference in the complication rate between the nephrologist-inserted and surgically inserted groups (likelihood ratio, 1.59; P = 0.08). There were differences in the type of adverse outcomes with each technique. Surgical procedures were more likely to have exit site leaks (P = 0.009) and peritonitis (P = 0.004), whereas procedure abandonment (P = 0.009) was more common in nephrologist-led procedures.

Conclusions

The current study highlights that with careful patient selection, trained nephrologists in metropolitan areas can successfully insert PD catheters. Our experience noted fewer delays to catheter insertion, with similar total complication rates.     

Imaging sublingual microcirculatory perfusion in pediatric patients receiving procedural sedation with propofol: A pilot study

Objective

Procedural sedation with propofol is widely used in the pediatric population. A well‐known side effect of propofol is a decrease in peripheral vascular resistance resulting in hypotension, but little is known about the effects on microcirculation in humans. We aimed to evaluate the effects of propofol on the sublingual microcirculatory perfusion by continuous video imaging in pediatric patients undergoing procedural sedation.

Methods

Patients admitted to the Pediatric Intensive Care Unit for procedural sedation were recruited. Oral microcirculation was measured employing a continuous monitoring strategy with incident dark‐field illumination imaging. Measurements were obtained before and 3 minutes after propofol induction. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, blood vessel diameter (Ø_bv), and systemic hemodynamics were analyzed.

Results

Continuous measurements were achieved in seven patients. Three minutes after propofol induction mean arterial pressure decreased (P = 0.028) and total and perfused vessel densities increased by 12% (P = 0.018) and 16% (P = 0.018), respectively. MFI was unaltered and mean Ø_bv increased but not significantly.

Conclusions

Propofol induction induces a reduction in mean arterial pressure and a rise in sublingual microvascular perfusion. The observed effects of propofol on the sublingual microcirculation may be due to a decrease in microvascular resistance.     

Cultures of aged care delivery: Qualitative content analysis of Australia's Royal Commission into Aged Care Quality and Safety

Objectives

Organisational culture is increasingly recognised as influencing the quality of care provided to patients and residents of aged care, both in research and in policy. For example, investigations into quality and safety issues in health care frequently highlight cultural problems, but often without adequate theorisation of culture. This study aimed at identifying how cultures of care delivery are considered in the final report of the Royal Commission into Aged Care Quality and Safety, and its subsequent implications.

Methods

A documentary analysis was performed on the five volumes of the final report using qualitative content analysis.

Results

Of 211 references to culture, the majority focussed on organisational culture (n = 155), followed by the sector's culture (n = 26), the culture of the agencies involved in managing aged care (n = 21) and the national culture relating to the treatment of older people (n = 8). These cultures were discussed in five ways: (1) highlighting poor culture as a problem (n = 56); (2) showcasing the style of culture that should be aspired to (n = 45); (3) reinforcing the importance of culture (n = 38); (4) making attributions about factors contributing to culture (n = 33); and (5) discussing the need for culture change (n = 30).

Conclusions

The Royal Commission's findings emphasise the importance of care culture and the need for change but provided limited guidance on how this should be achieved, or culture conceptualised.     

Insulin deficiency with and without glucagon: A comparative study between total pancreatectomy and type 1 diabetes

Aims/Introduction

Patients with a total pancreatectomy and type 1 diabetes are similar in regard to absolute insulin deficiency, but different in regard to glucagon, providing a unique opportunity to study the contribution of glucagon to glucose metabolism in an insulin‐dependent state. The aim of the present study was to investigate the contribution of glucagon to glucose homeostasis in complete insulin deficiency in vivo.

Methods

A total of 38 individuals with a complete lack of endogenous insulin (fasting C‐peptide <0.0066 nmol/L) and whose glycemic control was optimized with an insulin pump during hospitalization were retrospectively studied. The basal insulin requirement, time‐to‐time adjustment of the basal insulin infusion rate, prandial insulin requirement and fasting plasma glucagon were compared between patients with a total pancreatectomy (n = 10) and those with type 1 diabetes (n = 28) after achievement of optimal glycemic control.

Results

Total daily insulin (P = 0.03) and basal insulin (P = 0.000006), but not prandial insulin requirements, were significantly lower in total pancreatectomy patients than in type 1 diabetes patients. The basal percentage (basal insulin/total daily insulin) was also significantly lower in total pancreatectomy patients than in type 1 diabetes patients (15.8 ± 7.8 vs 32.9 ± 10.1%, P = 0.00003). An increase in the insulin infusion rate early in the morning was not necessary in most patients with a pancreatectomy. The fasting plasma glucagon concentration was significantly lower in total pancreatectomy patients than in type 1 diabetes patients (P = 0.00007), and was positively correlated with the basal insulin requirement (P = 0.038).

Conclusions

The difference in insulin requirements between total pancreatectomy and type 1 diabetes patients suggests a contribution of glucagon to the basal insulin requirement and dawn phenomenon.     

Impact of timing of prophylaxis commencement,F8 genotype and age on factor consumption and health-related quality of life in patients with severe haemophilia A

Introduction

The timing of prophylaxis and F8 genotype can impact treatment outcomes in adults with severe haemophilia A (HA).

Aim

To investigate how F8 genotype, timing, and type of prophylaxis influence arthropathy, bleeding rates, factor consumption and health-related quality of life (HRQoL).

Methods

Thirty-eight patients with severe HA were enrolled. Bleeding events were recorded retrospectively during median 12.5 months. F8 gene variants were classified as null or non-null. Joint health and HRQoL were assessed with HJHS and EQ-5D-5L, respectively.

Results

The median age at prophylaxis start was 1.25 years in the primary prophylaxis group (N = 15, median age 26 years) and 31.5 years in the secondary group (N = 22, 45 years), respectively. There were significant differences in the medians of HJHS (4 vs. 20, p < .001), EQ-5D-5L index (0.9647 vs. 0.904, p = .022), EQ VAS (87 vs. 75, p = .01) and FVIII consumption (3883 vs. 2737 IU/kg/year, p = .02), between the primary and secondary groups, respectively. Median annualized bleeding rate (ABR) was 0 for both groups. Twenty-five null and thirteen non-null F8 gene variants were identified. In the secondary prophylaxis group, lower median FVIII consumption (1926 vs. 3370 IU/kg/year) was shown for non-null compared to null variants, respectively, with similar ABR and HJHS.

Conclusion

Delayed prophylaxis start with intermediate dose intensity prevents bleeds but at a cost of more arthropathy and reduced HRQoL, compared to higher intensity primary prophylaxis. Non-null F8 genotype may allow lower factor consumption with similar HJHS and bleeding rates, compared to null genotype.     

Medications That Cause Dry Mouth As an Adverse Effect in Older People: A Systematic Review and Metaanalysis

Objectives

To assess and quantify the risk of drug‐induced dry mouth as a side effect in older people.

Design

Systematic review and metaanalysis.

Setting

A search of the literature was undertaken using Medline, Embase, Cochrane, Web of Science, and PubMed from 1990 to 2016.

Participants

Older people (aged ≥60) who participated in intervention or observational studies investigating drug use as an exposure and xerostomia or salivary gland hypofunction as adverse drug outcomes.

Measurements

Two pairs of authors screened titles and abstracts of studies for relevance. Two authors independently extracted data, including study characteristics, definitions of exposure and outcome, and methodological quality. For the metaanalyses, random‐effects models were used for pooling the data and I² statistics for exploring heterogeneity.

Results

Of 1,544 potentially relevant studies, 52 were deemed eligible for inclusion in the final review and 26 in metaanalyses. The majority of studies were of moderate methodological quality. In the intervention studies, urological medications (odds ratio (OR) = 5.91, 95% confidence interval (CI) = 4.04–8.63; I² = 62%), antidepressants (OR = 4.74, 95% CI = 2.69–8.32, I² = 21%), and psycholeptics (OR = 2.59, 95% CI = 1.79–3.95, I² = 0%) were significantly associated with dry mouth. In the observational studies, numbers of medications and several medication classes were significantly associated with xerostomia and salivary gland hypofunction.

Conclusion

Medication use was significantly associated with xerostomia and salivary gland hypofunction in older adults. The risk of dry mouth was greatest for drugs used for urinary incontinence. Future research should develop a risk score for medication‐induced dry mouth to assist with prescribing and medication management.     

The İmportance of tumor markers in patients undergoing resection for lung metastasis of colorectal carcinoma

Objectives

In patients with suitable conditions, complete resection is a potential curative treatment for lung metastases of colorectal cancers (CRC). Various prognostic factors affecting survival have been reported in these patients. In our study, the prognostic significance of CEA and CA19-9 tumor markers in patients who underwent lung resection for CRC metastasis was researched.

Methods

Fifty-three patients who underwent lung resection for CRC metastasis between January 2015 and July 2021 were included in the study. The relationship between preoperative and postoperative CEA and CA19-9 values, survival times, tumor size, and preoperative CEA and CA19-9 levels were investigated.

Results

Patients with high preoperative and postoperative CEA had shorter survival (OS) compared with patients with lower values (p ≤ 0.001 and p = 0.009, respectively). Disease-free survival (DFS) was also shorter in patients with higher preoperative CEA values (p = 0.008). For patients with higher preoperative and postoperative CA 19–9 values, OS and DFS were shorter (p = 0.013 and p ≤ 0.001) and (p = 0.042 and p ≤ 0.001), respectively. There was a weak positive correlation between preoperative CEA value and tumor size (p = 0.008, Pearson correlation coefficient = 0.360). However, a strong positive correlation between preoperative CA19-9 value and tumor size was discovered (p ≤ 0.001, Pearson correlation coefficient = 0.603).

Conclusion

In our study, it was shown that preoperative-postoperative CEA and CA19-9 levels in patients with metastatic colon carcinoma are associated with overall survival.     

IN.PACT AV access randomized trial: Japan cohort outcomes through 12 months

Purpose

There is a lack of adjudicated and prospectively randomized published outcomes on the use of drug-coated balloons (DCB) to treat dysfunctional arteriovenous fistula in Asian patients. This post hoc subgroup analysis of 112 Japanese participants from the global IN.PACT AV Access trial reports outcomes through 12 months.

Materials and Methods

Participants were treated with DCB (n = 58) or standard non-coated percutaneous transluminal angioplasty (PTA) balloons (n = 54). Outcomes included target lesion primary patency (TLPP), access circuit primary patency, and safety.

Results

Through 6 months, TLPP was 86.0% (49/57) in the DCB group and 49.1% (26/53) in the PTA group (p < 0.001). Through 12 months, TLPP was 67.3% (37/55) in the DCB group and 43.4% (23/53) in the PTA group (p = 0.013).

Conclusion

In this post hoc analysis of Japanese participants from the IN.PACT AV Access trial, participants treated with DCB had higher TLPP through 6 and 12 months compared with PTA.     

Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin

Background & Aims

Some individuals with hepatitis C virus infection treated with direct‐acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus‐infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

Methods

We performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia.

Results

Of 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post‐treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001).

Conclusions

Ribavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post‐treatment. Patients with low baseline haemoglobin should be monitored for on‐treatment anaemia.     

Research on the relationships between pancreatic cancer and hyperglycemia in Chinese populations

Aims/Introduction

Pancreatic cancer (PC) is related to diabetes. Long‐standing diabetes should be a prerequisite, whereas new‐onset hyperglycemia might be a result of PC. However, the association between diabetes and PC is still in dispute.

Materials and Methods

We investigated the relationship between glucose metabolism and other factors by retrospectively analyzing the clinical data of 331 PC patients. Any histopathological type was eligible. The patients were divided into three groups: group A, normal glucose metabolism; group B, hyperglycemia duration≤6 months; and group C, diabetes duration >24 months.

Results

The prevalence of hyperglycemia was 59.5%. Most patients were diagnosed with diabetes mellitus either concomitantly with cancer (39.0%) or within 6 months before cancer diagnosis (6.9%). There were more females in group C than group A (P = 0.005) and B (P = 0.018). Patients in group A were younger (A vs B, P < 0.001; A vs C, P = 0.032) and thinner (A vs B, P = 0.013; A vs C, P = 0.027). In group C, more individuals shared a family history of diabetes (A vs C, P = 0.004; B vs C, P = 0.023), but fewer smoked (A vs C, P = 0.027; B vs C, P = 0.020). Patients in group C had a larger proportion of poorly differentiated cancer (A vs C, P = 0.002; B vs C, P = 0.012). No differences in glucose metabolism were found among the different histological types.

Conclusions

We further support the notion that diabetes duration >24 months might not be cancer related. Older and fatter PC patients were more likely to develop hyperglycemia. More patients with long‐standing diabetes had poor tumor differentiation. We speculate that smoking and alcohol intake might advance PC onset.     

Comparison of clinicopathological characteristics between patients with occupational and non‐occupational intrahepatic cholangiocarcinoma

Background

An outbreak of cholangiocarcinoma has been reported among workers of an offset color proof‐printing department at a printing company in Japan. In this study, we compared the clinicopathological findings of this type of intrahepatic cholangiocarcinoma (occupational ICC) and non‐occupational ICC.

Methods

The clinical records of 51 patients with perihilar‐type ICC who underwent liver resection, including five patients with occupational ICC were retrospectively reviewed. The clinicopathological features were compared.

Results

In the occupational group, the patients were significantly younger (P < 0.01), while serum γ‐glutamyl transpeptidase activity and the proportions of patients with regional dilatation of the bile ducts without tumor‐induced obstruction were significantly higher (P = 0.041 and P < 0.01, respectively); the indocyanine green retention rate at 15 min was significantly lower (P = 0.020). On pathological examinations, precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct, were observed at various sites of the bile ducts in all occupational ICC patients; such lesions were observed in only six patients in the control group (P < 0.01).

Conclusions

The clinicopathological findings including age, liver function test results, diagnostic imaging findings, and pathological findings differed between the occupational and control groups.     

‘Mindful eating’ for reducing emotional eating in patients with overweight or obesity in primary care settings: A randomized controlled trial

Objective

The primary aim of this study was to analyse the efficacy of a ‘mindful eating’ programme for reducing emotional eating in patients with overweight or obesity.

Method

A cluster randomized controlled trial (reg. NCT03927534) was conducted with 76 participants with overweight/obesity who were assigned to ‘mindful eating’ (7 weeks) + treatment as usual (TAU), or to TAU alone. They were assessed at baseline, posttreatment and 12-month follow-up. The main outcome was ‘emotional eating’ (Dutch Eating Behaviour Questionnaire, DEBQ); other eating behaviours were also assessed along with psychological and physiological variables.

Results

‘Mindful eating’ + TAU reduced emotional eating both at posttreatment (B = −0.27; p = 0.006; d = 0.35) and follow-up (B = −0.53; p < 0.001; d = 0.69) compared to the control group (TAU alone). ‘External eating’ (DEBQ) was also significantly improved by the intervention at both timepoints. Significant effects at follow-up were observed for some secondary outcomes related to bulimic behaviours, mindful eating, mindfulness, and self-compassion. Weight and other physiological parameters were not significantly affected by ‘mindful eating’ + TAU.

Conclusions

These findings support the efficacy of the ‘mindful eating’ + TAU programme for reducing emotional and external eating, along with some other secondary measures, but no significant changes in weight reduction were observed.