Predictors of treatment response to liraglutide in type 2 diabetes in a real-world setting.

AIMS: There is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment. METHODS: Data were taken from electronic medical records of participants of an observational, retrospective study in Italy. We used logistic regression models to assess the odds of achieving glycated haemoglobin (HbA1c) reduction ≥ 1.0% point after 12-month treatment with liraglutide (primary endpoint), according to various patient-related factors. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify distinct homogeneous patient subgroups with different odds of achieving the primary endpoint. RESULTS: Data from 1325 patients were included, of which 577 (43.5%) achieved HbA1c reduction ≥ 1.0% point (10.9 mmol/mol) after 12 months. Logistic regression showed that for each additional 1% HbA1c at baseline, the odds of reaching this endpoint were increased 3.5 times (95% CI: 2.90-4.32). By use of RECPAM analysis, five distinct responder subgroups were identified, with baseline HbA1c and diabetes duration as the two splitting variables. Patients in the most poorly controlled subgroup (RECPAM Class 1, mean baseline HbA1c > 9.1% [76 mmol/mol]) had a 28-fold higher odds of reaching the endpoint versus patients in the best-controlled group (mean baseline HbA1c ≤ 7.5% [58 mmol/mol]). Mean HbA1c reduction from baseline was as large as - 2.2% (24 mol/mol) in the former versus - 0.1% (1.1 mmol/mol) in the latter. Mean weight reduction ranged from 2.5 to 4.3 kg across RECPAM subgroups. CONCLUSIONS: Glycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.

Stratifying delays for assessment by type of substance to improve the probability of attendance in outpatient services.

AIMS: 1) To confirm the association between delay for assessment (DFA) and probability of first-time attendance in outpatient substance use disorder (SUD) treatment. 2) To evaluate whether this association varies by the type of primary substance for which the assessment was requested. 3) To assess the possibility of estimating differential DFAs to conform to equal probabilities of attendance across various types of primary substance. METHODS: A prospective observational cohort of consecutive patients (N=1015) who requested a first-time assessment appointment at a publicly funded outpatient SUD treatment center in France between January 2014 and December 2015 was conducted. Logistic regression analyses were performed to evaluate associations between DFA (after log-transformation) and attendance and to provide estimates of attendance probability over time by the type of primary substance. FINDINGS: After adjusting for gender, age and referral status, the attendance rate was observed to decrease significantly with longer DFA (OR=0.54; 95%CI: 0.44-0.66). The strength of this association differed across types of primary substance (p for heterogeneity <0.0001), with the strongest association being found for opioids (adjusted OR=0.21; 95%CI: 0.10-0.45). DFA was also associated with attendance for alcohol (OR=0.51; 95%CI: 0.37-0.71) and cannabis (OR=0.60; 95%CI: 0.37-0.96), but not for tobacco (OR=0.95; 95%CI: 0.60-1.50). Differential DFAs reflecting equal probabilities of attendance across types of substance could be estimated. CONCLUSION: Our study suggests that the approach of stratifying DFAs by the type of primary substance could be helpful to improve the probability of first-time attendance in outpatient SUD treatment services.

Screening for eating disorders in outpatient smoking cessation: Feasibility, pertinence, and acceptance of referral to specific treatment.

OBJECTIVE: To estimate (1) the feasibility and pertinence of implementing systematic screening for eating disorders (EDs) in outpatient smoking cessation (SC), and (2) the acceptance of a referral to ED-specific treatment. METHODS: Tobacco smokers (N = 203) who consecutively underwent the initial assessment of a SC program were screened for an ED. Screen-positive patients were administered the Mini International Neuropsychiatric Interview and received a referral to ED-specific treatment using brief advice when identified with a current ED. RESULTS: Among the total sample, the prevalence of a current ED at baseline was 8.9% (men: 1/109, 0.9%; women: 17/94, 18.1%). The acceptance rate of referral to ED-specific treatment was 17%, whereas having a current ED at baseline was significantly associated with a higher probability of dropping out of the SC program at 4 weeks (OR = 21.8, 95%CI: 3.0-161.2, P = 0.003). DISCUSSION: Screening for EDs in outpatient SC seems worthwhile and easily implementable, but patients who are identified with a current ED might not be prone to accept referral to specific treatment and tend to drop out early. This study underlines the need to explore this topic in larger clinical samples. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1018-1022).

Interventions for Increasing Subsequent Alcohol Treatment Utilisation Among Patients with Alcohol Use Disorders from Somatic Inpatient Settings: A Systematic Review.

AIMS: Alcohol Use Disorders (AUDs) are common in medical and surgical hospital wards. Brief Interventions (BIs) for reducing alcohol use and consequences are generally inefficacious in this population. Because there is evidence that receipt of formal treatment could be useful, we performed a systematic review to determine efficacious interventions for increasing subsequent alcohol treatment from these settings. METHODS: A systematic literature search of articles published prior to December 2013 to identify articles describing randomised controlled trials (RCTs) in three electronic databases: PubMed, PsycINFO and The Cochrane Library. Data were extracted independently by one reviewer and were checked by a second reviewer. Because of heterogeneity between study groups in treatment utilisation during the follow-up, a meta-analysis was considered inappropriate and a qualitative synthesis was conducted. RESULTS: From the 5030 identified records, only 5 RCTs, including 1113 patients with AUDs, met inclusion criteria. No evidence of efficacy in increasing subsequent treatment utilisation was reported for inpatient BIs alone, but interventions with post-discharge sessions might be beneficial. Increased treatment utilisation was generally associated with favourable drinking outcomes. CONCLUSIONS: Given the small number of included studies and the presence of several alternative methodological explanations for the present findings, no firm conclusions could be drawn on efficacious interventions for increasing subsequent treatment utilisation among somatic inpatients with AUDs. However the findings support efforts to explore this under-researched area.

Aliskiren: a new inhibitor of renin-angiotensin aldosterone system activity.

The importance of renin-angiotensin aldosterone system (RAAS) in cardiovascular and renal diseases has long ago been recognized. However despite the availability of many effective drugs, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, RAAS blockade is incomplete in several patients with consequent uncontrolled high blood pressure and not efficacy cardiovascular and renal protection. Aliskiren is a new renin inhibitor that block the RAAS at its origin. Recent studies suggest that Aliskiren reduces blood pressure, inhibits plasma renin activity and attenuates renal damage in diabetic patients with nephropathy. This review summarized the results of the more important studies performed in hypertensive and diabetic patients in which Aliskiren showed to be a safe and effective antihypertensive agent that can be used in monotherapy or in combination with other drugs to provide additional options to improve blood pressure control.

Renal effects of dual renin-angiotensin-aldosterone system blockade in patients with diabetic nephropathy.

Evidence from recent studies indicates that in patients with diabetic nephropathy combined therapy with ACE inhibitors (ACEI) and AT1-receptor antagonists (ARB) results in more complete blockade of the renin-angiotensin-aldosterone system (RAS) than monotherapy, and reduces proteinuria. Most of these trials, however, had short follow-up, included a small number of patients, and were heterogeneous, so the opportunity to start this treatment in these patients remains unclear. This review summarizes the results of these studies, describing the renal effects of dual RAS blockade in both type 1 and type 2 diabetic patients.

Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer.

Twenty-two advanced consecutive thyroid cancer patients with varying histologies were treated with the so called BAP regime which consisted of bleomycin (B) 30 mg a day for three days, adriamycin (A) 60 mg/m2 iv in day 5, and cisplatinum (P) 60 to mg/m2 iv in day 5. Patients with progressive, symptomatic recurrent or disseminated disease unresponsive to hormonal and/or isotopic treatment were eligible. Nine patients had an objective response: two long-lasting complete and seven partial responses were observed out of 21 evaluable patients. Stable disease was observed in four additional patients. The median duration of response was 12 months (range, 6-29). The total series experienced a median survival of 11 months (range, 1 to 57), with 2 patients actually disease free. Several histologic types of thyroid carcinoma responded, but the best responses were observed in medullary and anaplastic giant-cell carcinomas. Toxicity was reversible in all but one patient. Of the patients failing on BAP chemotherapy three responded to a four drug second line combination containing vincristine, fluorouracil, BCNU and methotrexate. BAP regime can achieve reasonable palliation, and probably increases survival, in poor-prognosis thyroid cancers.

Favorable long term results in patients with small differentiated thyroid cancer not treated with radioiodine.

Data on a group of 110 patients with differentiated thyroid cancer not treated by radioiodine are reported. Most of them had intrathyroid (stage I) papillary or capsuled follicular cancer of less than 3 cm diameters. They all received thyroxine at TSH suppressive doses. The follow-up ranged between 4 and 25 years, mean 8.7. No patient died of tumor. Two very old patients died free of disease. Four recurrences occurred, within 8 years, all in patients over 45 years, all local or nodal, all papillary, 3 out of 4 after total thyroidectomy. This study shows that radioiodine therapy may be avoided and that lobectomy may be sufficient in patients under 45 years with small papillary or capsuled follicular cancer.

Acute and chronic effects of dextro-thyroxine on pituitary thyroid axis and on reverse triiodothyronine production in euthyroid subjects.

Serum levels of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and TSH were measured in euthyroid subjects after a single dose of 4 mg D-thyroxine (DT4) or of 0.25 mg L-thyroxine (LT4). The same parameters and TSH response to TRH were also evaluated in 7 dyslipidemic patients before and after one month of treatment with 6 mg DT4. T4 levels increased about 165% at h 4 after DT4 and only 47% after LT4; T3 levels remained unchanged until h 10 both after DT4 and after LT4; rT3 levels increased almost 179% after DT4 and only 32% after LT4. TSH levels decreased about 30% after both DT4 and LT4. In the long term study similar variations of the same parameters were observed: basal TSH levels decreased and TSH response to TRH was inhibited in all patients but one; T4 levels increased 62%, T3 levels increased 35%, while rT3 levels increased 545%. Our results show that: both acute and long-term treatment with DT4 suppress TSH secretion; DT4 both in acute and in long-term administration, is preferentially dealogenated in the alaninic ring with production of rDT3, instead of in the phenolic ring with production of DT3. This may contribute to explain its lower metabolic activity.

Effects of dextro-thyroxine, a preparation almost free of levo-thyroxine, on thyroid function, serum lipids and apolipoprotein A-I in "double pre-beta lipoproteinemia".

Eight subjects, belonging to a large family kindred repeatedly showing the electrophoretic pattern of the "double pre-beta lipoproteinemia", were studied. In seven of them thyroid function, serum lipids and apolipoprotein A-I were determined before and after treatment with dextro-thyroxine, preparation almost free of levo-thyroxine. In most of the patients, total-T4 levels and free-T4 Index were in the lower normal range, but basal TSH levels and the TSH response to TRH were normal. Dextro-thyroxine was effective in reducing both serum total cholesterol and triglycerides, but the percentage decrease in serum triglycerides was definitely greater than that of serum total cholesterol. This marked, unexpected hypotriglyceridemic effect is similar to that observed in a group of obese, hypertriglyceridemic hypothyroid patients treated with levo-thyroxine. Besides serum total cholesterol and triglycerides, the VLDL cholesterol/triglycerides ratio and the electrophoretic "slow moving" pre-beta component were also significantly reduced after treatment, suggesting that dextro-thyroxine can remove efficiently "remnant" VLDL particles from the plasma. Following dextro-thyroxine therapy, the relatively low pretreatment values of apolipoprotein A-I were significantly increased, being restored to normal.

Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma.

Serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) were evaluated in a group of 41 patients with histologically proven medullary thyroid carcinoma (MCT) before and sequentially after treatment for a period up to 7 years. Before thyroidectomy, CT levels were high in all patients, and significantly more elevated when metastases were present. On the other hand, CEA levels were high in most but not all the patients, and they also were found more frequently to be elevated in patients with metastases. After treatment, most of the patients without metastases showed persistently normal basal and pentagastrin stimulated CT and CEA levels. In some patients either without or with local metastases, postoperative CT levels, although considerably reduced, remained persistently above normal limits, whereas CEA levels became completely normal. This pattern may be due to the persistence of minute occult foci of the tumor, not sufficient to produce measurable amounts of CEA, which is not synthesized by all tumor cells. Most of the patients with metastases at diagnosis, showed still elevated CT and CEA levels after treatment. In the nonprogressive cases both markers decreased after adjunctive treatment or remained unchanged. In patients with progressive disease, an increase of CEA levels in the absence of a parallel increase of CT levels, which even decreased, was often observed. In one patient with progressive disease high CEA levels were seen for the first time when liver metastases had occurred. These data seem to suggest that, even though CEA production is not recognizable in all patients with MCT, in the CEA positive cases CEA levels may follow a nonparallel pattern and may have a distinct diagnostic meaning with respect to CT levels. In some cases, particularly in advanced disease, CEA may be a more useful marker of poor prognosis.