Major life events and risk of alcohol use disorders: a prospective cohort study

Aims

To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD).

Design

Prospective cohort study with baseline examination in 1991–93 and linkage to national registers to identify AUD at follow‐up.

Setting

Copenhagen, Denmark.

Participants

Individuals (aged 21–93 years) who participated in the Copenhagen City Heart Study in 1991–93 (n = 8758).

Measurements

The primary outcome was first registration with AUD during follow‐up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity.

Findings

Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD.

Conclusions

Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.     

Association Between Knee Pain,Impaired Function,and Development of Depressive Symptoms

Objectives

To examine the association between knee pain and function and depressive symptoms in older Japanese adults.

Design

Community‐based prospective cohort study.

Setting

Kurabuchi Town, Gumma Prefecture, Japan.

Participants

Individuals aged 65 and older (N = 573; n = 260 men, n = 313 women) without depressive symptoms participated in baseline examinations in 2005 and 2006; 95.6% participated in follow‐up interviews (2007–08).

Measurements

Degree of knee pain and functional impairment was assessed at baseline using a self‐administered questionnaire in Japanese based on an English version of the Western Ontario and McMaster Universities Osteoarthritis Index. The Geriatric Depression Scale was used to identify depressive symptoms in face‐to‐face home‐visit interviews conducted 2 years later, and the association between knee pain and functional impairment and depressive symptoms was assessed using logistic regression.

Results

During the 2‐year follow‐up, 11.9% of participants developed depressive symptoms, and pain and functional impairment were found to be associated with development of these symptoms. Pain at night while in bed (adjusted odds ratio (aOR) = 2.6, 95% confidence interval (CI) = 1.4–4.9) and difficulty putting on socks (aOR = 3.7, 95% CI: 1.8–7.5), getting into and out of a car (aOR = 3.4, 95% CI = 1.8–6.5), and taking off socks (aOR = 3.1, 95% CI = 1.5–6.5) were found to be most strongly associated with development of depressive symptoms.

Conclusion

Examining elderly people's responses to questions about pain at night and difficulties performing daily activities may be an efficient way of identifying those at high risk of developing depressive symptoms.     

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.     

Syncope,Hypotension, and Falls in the Treatment of Hypertension: Results from the Randomized Clinical Systolic Blood Pressure Intervention Trial

Objective

To determine predictors of serious adverse events (SAEs) involving syncope, hypotension, and falls, with particular attention to age, in the Systolic Blood Pressure Intervention Trial.

Design

Randomized clinical trial.

Setting

Academic and private practices across the United States (N = 102).

Participants

Adults aged 50 and older with a systolic blood pressure (SBP) of 130 to 180 mmHg at high risk of cardiovascular disease events, but without diabetes, history of stroke, symptomatic heart failure or ejection fraction less than 35%, dementia, or standing SBP less than 110 mmHg (N = 9,361).

Intervention

Treatment of SBP to a goal of less than 120 mmHg or 140 mmHg.

Measurements

Outcomes were SAEs involving syncope, hypotension, and falls. Predictors were treatment assignment, demographic characteristics, comorbidities, baseline measurements, and baseline use of cardiovascular medications.

Results

One hundred seventy‐two (1.8%) participants had SAEs involving syncope, 155 (1.6%) hypotension, and 203 (2.2%) falls. Randomization to intensive SBP control was associated with greater risk of an SAE involving hypotension (hazard ratio (HR) = 1.67, 95% confidence interval (CI) = 1.21–2.32, P = .002), and possibly syncope (HR = 1.32, 95% CI = 0.98–1.79, P = .07), but not falls (HR = 0.98, 95% CI = 0.75–1.29, P = .90). Risk of all three outcomes was higher for participants with chronic kidney disease or frailty. Older age was also associated with greater risk of syncope, hypotension, and falls, but there was no age‐by‐treatment interaction for any of the SAE outcomes.

Conclusions

Participants randomized to intensive SBP control had greater risk of hypotension and possibly syncope, but not falls. The greater risk of developing these events associated with intensive treatment did not vary according to age.     

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.     

Gender differences in individuals with obesity and binge eating disorder: A retrospective comparison of phenotypical features and treatment outcomes

Objective

Phenotypical comparisons between individuals with obesity without binge eating disorder (OB) and individuals with obesity and comorbid binge eating disorder (OB + BED) are subject to ongoing investigations. At the same time, gender-related differences have rarely been explored, raising the question whether men and women with OB and OB + BED may require differently tailored treatments.

Method

We retrospectively compared pre- versus post-treatment data in a matched sample of n = 180 men and n = 180 women with OB or OB + BED who received inpatient treatment.

Results

We found that men displayed higher weight loss than women independent of diagnostic group. In addition, men with OB + BED showed higher weight loss than men with OB after 7 weeks of treatment.

Conclusions

The present findings add to an emerging yet overall still sparse body of studies comparing phenotypical features and treatment outcomes in men and women with OB and OB + BED; implications for further research are discussed.

Clinical Trial Registration

The study was prospectively registered with the German Clinical Trial Register as part of application DRKS00028441.     

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.     

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.     

Effects of comorbid substance use disorders on outcomes in a Housing First intervention for homeless people with mental illness

Background and Aims

Evidence supports the effectiveness of Housing First (HF) programmes for people who are experiencing homelessness and mental illness; however, questions remain about its use in people with comorbid substance use disorders (SUD). The aim of this project was to test whether SUD modifies the effectiveness of an HF intervention.

Design

Secondary analysis of data from a randomized controlled trial of HF versus treatment‐as‐usual (TAU) with 24‐month follow‐up, comparing those with and without SUD at trial entry.

Setting

Vancouver, Toronto, Winnipeg, Moncton and Montreal, Canada.

Participants

A total of 2154 participants recruited from 2009 to 2013 and randomized to HF versus TAU (67% male, mean age 40.8 ± 11.2, 25% ethno‐cultural minority). All were homeless and had a mental disorder at baseline; 35% reported symptoms consistent with SUD.

Intervention

Housing paired with Intensive Case Management or Assertive Community Treatment.

Measurements

Primary outcomes were days housed and community functioning. Secondary outcomes were general and health‐related quality of life and mental health symptoms. Predictors were SUD status crossed with intervention group (HF versus TAU).

Findings

People with SUD in both the HF and TAU groups spent less time in stable housing, but the effect of HF did not vary by SUD status [odds ratio (OR) = 1.17, 95% confidence interval (CI) = ?0.77, 1.76]. Similarly, there was no difference between those with and without SUD in the effect of HF (over TAU) on community functioning (b = 0.75, 95% CI = ?0.36, 1.87), quality of life (b = ?1.27, 95% CI = ?4.17, 1.63), health‐related quality of life (b = ?0.01, 95% CI = ?0.03, 0.02) or mental health symptoms (b = 0.43, 95% CI = ?0.99, 1.86).

Conclusions

Housing First programs in Canada are equally effective in people with and without comorbid substance use disorder (SUD). Overall, the intervention appears to be able to engage people with SUD and is reasonably successful at housing them, without housing being contingent upon abstinence or treatment.     

New Institutionalization in Long‐Term Care After Hospital Discharge to Skilled Nursing Facility

Background/Objectives

Approximately half of individuals newly admitted to long‐term care (LTC) nursing homes (NHs) experienced a prior hospitalization followed by discharge to a skilled nursing facility (SNF). The objective was to examine characteristics associated with new institutionalizations of older adults on this care trajectory.

Design

Retrospective cohort study.

Setting

SNFs and LTC NHs.

Patients

Medicare fee‐for‐service beneficiaries admitted to 7,442 SNFs in 2013 (N = 597,986).

Measurements

We used demographic and clinical characteristics from Medicare data and the Minimum Data Set. We defined “new institutionalization” as LTC NH residence for longer than 90 non‐SNF days, starting within 6 months of hospital discharge.

Results

For individuals who survived 6 months after hospital discharge, the overall rate of new LTC institutionalizations was 10.0% (N = 59,736). Older age, white race, being unmarried, Medicaid eligibility, higher income, more comorbidities, cognitive impairment, depression, functional limitations, hallucinations and delusions, aggressive behavior, incontinence, and pressure ulcers were associated with higher adjusted odds of new LTC institutionalization. In analyses stratified according to race and ethnicity, higher income was associated with lower odds of LTC institutionalization for whites (odds ratio (OR) = 0.92, 95% confidence interval (CI) = 0.89–0.96) and greater odds for blacks (OR = 1.40, 95% CI = 1.27–1.55) and Hispanics (OR = 1.44, 95% CI = 1.25–1.66). Moderate or severe depression, functional limitations, hallucinations and delusions, aggressive behavior, and being unmarried were stronger risk factors for LTC for cognitively intact individuals than for those with moderate to severe cognitive impairment. Being unmarried and having more comorbidities were stronger predictors in those aged 66 to 70 than in those aged 81 to 85 and 91 and older.

Conclusion

Associations between risk factors and new LTC institutionalizations varied according to race and ethnicity, age, and level of cognitive function. Programs that target older adults at greater risk may be an effective strategy for reducing new institutionalizations and fostering aging in place.     

A French observational study describing the use of human polyvalent immunoglobulins in hematological malignancy‐associated secondary immunodeficiency

Objective

To describe the characteristics of patients suffering from secondary immunodeficiencies (SID) associated with hematological malignancies (HM), who started immunoglobulin replacement therapy (IgRT), physicians’ expectations regarding IgRT, and IgRT modalities.

Methods

Non‐interventional, prospective French cross‐sectional study.

Results

The analysis included 231 patients (66 ± 12 years old) suffering from multiple myeloma (MM) (N = 64), chronic lymphoid leukemia (CLL) (N = 84), aggressive non‐Hodgkin B‐cell lymphoma (aNHL) (N = 32), indolent NHL (N = 39), acute leukemia (N = 6), and Hodgkin disease (N = 6). Of the HM, 47% were currently treated, 42% were relapsing or refractory, 23% of patients had received an autologous hematopoietic stem‐cell transplant, and 1% had received an allograft. Serum immunoglobulin trough levels in 195 individuals were less than 5 g/L in 68.7% of cases. Most patients had a history of recurrent infections. Immunoglobulin dose was about 400 mg/kg/mo. Half of patients started with subcutaneous infusion. When starting IgRT, physicians mainly expected to prevent severe and moderate infections. They also anticipated improvement in quality of life and survival which is beyond evidence‐based medicine.

Conclusion

NHL is a frequent condition motivating IgRT besides well‐recognized indications. Physicians mainly based the decision of starting IgRT on hypogammaglobulinemia and recurrence of infections but, irrespective of current recommendations, were also prepared to start IgRT prophylactically even in the absence of a history of infections.     

Excess overdose mortality immediately following transfer of patients and their care as well as after cessation of opioid substitution therapy

Aims

To investigate clustering of all‐cause and overdose deaths after a transfer of patients and their care to alternative treatment provider and after the end of opioid substitution therapy (OST) in opioid‐dependent individuals in specialist addiction treatment.

Design, Setting and Participants

Mortality data were identified within a sample of 5335 patients with opioid use disorder who had received OST treatment between 1 April 2008 and 31 December 2013 from a large mental health‐care provider in the United Kingdom. We investigated the circumstances and distribution of the 332 deaths identified within the observation window with a specific focus on overdose deaths (n = 103) after a planned discharge, dropout and transfer between services.

Measurements

Crude mortality rates for overdose mortality 14 days, 28 days and more than 1 month after the end of treatment/transfer for overdose mortality.

Findings

Of 47 individuals who died from overdose after having been transferred between services, nine died during the first 2 weeks [crude mortality rate (CMR) = 136.4, 95% confidence interval (CI) = 64.3–243.1] and a further five died during the first month post‐transfer (CMR= 79.5, 95% CI = 44.2–129.7). Of the 32 individuals who died from overdose after planned OST cessation, five died during the first 2 weeks (CMR = 151.5, 95% CI = 51.1–319.0) and a further four died during the first month post‐discharge (CMR = 82.6, 95% CI = 38.4–151.0).

Conclusions

In the United Kingdom, opioid‐dependent people who are transferred to an alternative treatment provider for continuation of their opioid substitution therapy experience high overdose mortality rates, with substantially higher rates during the first month (especially during the first 14 days) following transfer.     

The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom

Aims

To estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all‐cause mortality (ACM) and opioid drug‐related poisoning (DRP) mortality.

Design

Cohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register.

Setting

UK primary care.

Participants

A total of 11 033 opioid‐dependent patients who received OST from 1998 to 2014, followed‐up for 30 410 person‐years.

Measurements

Exposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed‐up for 16 363 person‐years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone and buprenorphine. Inverse probability weights were included to adjust for confounding and balance characteristics of patients prescribed methadone or buprenorphine.

Findings

ACM and DRP rates were 1.93 and 0.53 per 100 person‐years, respectively. DRP was elevated during the first 4 weeks of OST [incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97–3.82], the first 4 weeks off OST (IRR = 8.15, 95% CI = 5.45–12.19) and the rest of time out of OST (IRR = 2.13, 95% CI = 1.47–3.09) compared with mortality risk from 4 weeks to end of treatment. Patients on buprenorphine compared with methadone had lower ACM rates in each treatment period. After adjustment, there was evidence of a lower DRP risk for patients on buprenorphine compared with methadone at treatment initiation (IRR = 0.08, 95% CI = 0.01–0.48) and rest of time on treatment (IRR = 0.37, 95% CI = 0.17–0.79). Treatment duration (mean and median) was shorter on buprenorphine than methadone (173 and 40 versus 363 and 111, respectively). Model estimates suggest that there was a low probability that methadone or buprenorphine reduced the number of DRP in the population: 28 and 21%, respectively.

Conclusions

In UK general medical practice, opioid substitution treatment with buprenorphine is associated with a lower risk of all‐cause and drug‐related poisoning mortality than methadone. In the population, buprenorphine is unlikely to give greater overall protection because of the relatively shorter duration of treatment.     

Clinical significance of serum interleukin‐8 and soluble tumor necrosis factor‐like weak inducer of apoptosis levels in patients with diabetic nephropathy

Aims/Introduction

Recent studies suggest that chronic inflammatory responses are important in the development of diabetic nephropathy (DN). Various inflammatory and angiogenesis molecules affect the pathogenesis and progression of DN. Inflammation damages the microcirculation and causes kidney damage. In the present study, we studied changes in interleukin‐8 (IL‐8) and soluble tumor necrosis factor‐like weak inducer of apoptosis (sTWEAK) levels in patients with DN, and investigated the clinical significance of these two inflammatory factors.

Materials and Methods

Participants were categorized into healthy controls (n = 30) and patients with type 2 diabetes mellitus (n = 124). The type 2 diabetes mellitus group was further subdivided into the normoalbuminuria (n = 34), microalbuminuria (MAU; n = 46,) and proteinuria (MaAU; n = 44,) groups. Patients with DN were included in the MAU and MaAU groups. Total cholesterol, triglyceride, low‐density lipoprotein cholesterol, glycosylated hemoglobin, fasting blood glucose, 2‐h postprandial blood glucose, blood urea nitrogen, serum creatinine, 24‐h urine microalbumin, IL‐8 and sTWEAK levels were measured. Logistic regression was used to analyze the factors associated with proteinuria.

Results

In the healthy controls, normoalbuminuria, MAU and MaAU groups, we found that IL‐8 levels increased, whereas sTWEAK levels decreased (P < 0.05). IL‐8 might be an independent risk factor and serum sTWEAK a protective factor for MAU and MaAU. Serum levels of sTWEAK, IL‐8 and microalbumin were significantly correlated in the MAU and MaAU groups.

Conclusions

Serum IL‐8 and sTWEAK levels might be markers that can be used for an early diagnosis of DN.     

Ovarian morphology and prevalence of polycystic ovary syndrome in Japanese women with type 1 diabetes mellitus

Aims/Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder including polycystic ovary morphology (PCOM), ovulatory dysfunction and hyperandrogenism. PCOS is frequently associated with type 2 diabetes mellitus; however, it is unknown whether PCOM and PCOS are prevalent in Japanese patients with type 1 diabetes mellitus. The purpose of our study was to determine the frequency of PCOM and PCOS in women with type 1 diabetes mellitus.

Materials and Methods

We evaluated clinical, hormonal and ovarian ultrasound data from 21 type 1 diabetes mellitus patients whose average glycated hemoglobin levels were 7.9 ± 1.5%.

Results

Ultrasound identified PCOM in 11 patients (52.4%) and these patients also had higher levels of the androgen dehydroepiandrosterone sulfate (DHEA‐S) than those without PCOM (P < 0.05). Of the patients with PCOM, five presented menstrual irregularities (45.5%) and three met the Japanese criteria for PCOS (27.2%); whereas all patients without PCOM had a normal menstrual cycle (P < 0.05).

Conclusions

Japanese premenopausal women with type 1 diabetes mellitus had a high frequency of PCOM as well as PCOS. This is the first research of this area carried out in an Asian population.     

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.