Successful treatment of patients with newly diagnosed/untreated multiple myeloma and advanced renal failure using bortezomib in combination with bendamustine and prednisone

Purpose

Renal failure is a frequent complication of multiple myeloma (MM) and, if present at diagnosis, a considerable risk factor for outcome. Treatment with chemotherapy and/or new agents may result in recovery of renal function in up to 50?% of patients. The window of opportunity to reverse renal impairment is, however, rather small, making an immediate and highly active treatment strategy mandatory. Bortezomib as well as bendamustine has been demonstrated to be potent drugs in the treatment of MM.

Methods

A total of 18 patients with newly diagnosed/untreated MM and renal insufficiency (GFR?Results The majority of them (n?=?15; 83?%) responded after at least one cycle of chemotherapy with three sCR, five nCR, five VGPR, and two PR. With a median follow-up of 17?months, PFS at 18?months was 57?% and OS was 61?%. The myeloma protein decreased rapidly, reaching the best response after the first cycle in four and after the second cycle in additional seven patients. Thirteen patients (72?%) improved their renal function after treatment.

Conclusion

We conclude that the combination of bortezomib, bendamustine, and prednisone is effective and well tolerated in patients with a newly diagnosed MM and renal failure.     

Elderly alcoholics compared to middle-aged alcoholics in outpatient treatment – 6-month follow-up

Abstract

Purpose: This study examined 6-month drinking outcomes of elderly patients compared with middle-aged patients in a clinical sample after initiation of outpatient treatment for alcoholism.

Materials and methods: In a clinical prospective cohort study, 1398 consecutive patients from a municipality outpatient alcohol clinic were included. A total of 208 elderly patients aged from 60 to 82 years and 1190 middle-aged patients from 40 to 59 years participated in the study. The following psychosocial treatment interventions were offered: cognitive behavioral therapy, family therapy and supportive consultations. Using an ‘intention-to-treat’ method, primary outcomes included drinking outcomes (self-reported abstinence rates, drinking 3 drinks or less per day, and change in Addiction Severity Index [ASI] composite scores) during the 30 days prior to 6-month follow-up; secondary outcome was compliance to the recommended treatment.

Results: Compared to middle-aged, among elderly patients a higher proportion were females (33.5% vs. 42.8%) and had a lower family/social ASI-composite score (0.17 vs. 0.12) at baseline. Higher alcohol and family/social ASI-composite scores were inversely correlated with abstinence. Elderly patients had a higher chance for abstinence compared to middle-aged patients (Odds ratio 95% [confidence interval]) 1.40 (1.03–1.92). The proportion of elderly patients that drank 3 or less drinks per day was 17.8%, compared to 10.8% among middle-aged (p?<?.01). Finally, elderly patients obtained a higher compliance, which was similarly associated with abstinence (OR =2.46 (1.95–3.11)).

Discussion and conclusions: Elderly patients, who receive psychosocial outpatient treatment for alcoholism, have better 6-month outcomes within a range of drinking outcome measures compared to middle-aged patients.     

High heritability and genetic correlation of intravenous glucose- and tolbutamide-induced insulin secretion among non-diabetic family members of type 2 diabetic patients

Aims/hypothesis

The aim of this study was to estimate the heritability of quantitative measures of glucose regulation obtained from a tolbutamide-modified frequently sampled IVGTT (t-FSIGT) and to correlate the heritability of the glucose-stimulated beta cell response to the tolbutamide-induced beta cell response. In addition, single nucleotide polymorphisms (SNPs) having an exclusive effect on either glucose- or tolbutamide-stimulated insulin release were identified.

Methods

Two hundred and eighty-four non-diabetic family members of patients with type 2 diabetes underwent a t-FSIGT with intravenous injection of glucose at t?=?0 min and tolbutamide at t?=?20 min. Measurements of plasma glucose, serum insulin and serum C-peptide were taken at 33 time points from fasting to 180 min. Insulin secretion rate, acute insulin response (AIR), disposition index (D_I) after glucose and disposition index after tolbutamide (D_IT), insulin sensitivity (S_I), glucose effectiveness (S_G) and beta cell responsiveness to glucose were calculated. A polygenic variance component model was used to estimate heritability, genetic correlations and associations.

Results

We found high heritabilities for acute insulin secretion subsequent to glucose stimulation (AIR_glucose h ²?±?SE: 0.88?±?0.14), but these were slightly lower after tolbutamide (AIR_tolbutamide h ²?±?SE: 0.69?±?0.14). We also estimated the heritabilities for S_I (h ²?±?SE: 0.26?±?0.12), S_G (h ²?±?SE: 0.47?±?0.13), D_I (h ²?±?SE: 0.56?±?0.14), D_IT (h ²?±?SE: 0.49?±?0.14) and beta cell responsiveness to glucose (h ²?±?SE: 0.66?±?0.12). Additionally, strong genetic correlations were found between measures of beta cell response after glucose and tolbutamide stimulation, with correlation coefficients ranging from 0.77 to 0.88. Furthermore, we identified five SNPs with an exclusive effect on either glucose-stimulated (rs5215, rs1111875, rs11920090) or tolbutamide-stimulated (rs10946398, rs864745) insulin secretion.

Conclusions/interpretation

Our data demonstrate that both glucose- and tolbutamide-induced insulin secretions are highly heritable traits, which are largely under the control of the same genes.     

Is breastfeeding related to bone properties? A longitudinal analysis of associations between breastfeeding duration and pQCT parameters in children and adolescents

Nutritive and bioactive components of human milk could be involved in programming metabolic systems that affect bone growth throughout the life course. Bone properties in childhood and adolescence might differ, depending on breastfeeding duration. Thus, breastfeeding could be a relevant factor in the context of primary osteoporosis prevention. The prospective association between breastfeeding duration and bone properties was investigated using the data of 284 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Breastfeeding duration was assessed during infancy. Bone properties were measured by peripheral quantitative computed tomography (pQCT) at ages 5–23 years. Cortical volumetric bone mineral density, cortical bone mineral content, strength strain index, total cross‐sectional area of the bone and cross‐sectional area of the cortical bone were determined at the 65% site of the radius. Linear regression analyses were performed to check for differences in pQCT parameters of subjects who had not or shortly been breastfed (0–16 weeks) and subjects who had been breastfed for a long duration (≥17 weeks). Multivariable models adjusted for age, gender, forearm length, muscle cross‐sectional area, body mass index standard deviation score (SDS), height SDS and socio‐economic status did not yield associations between breastfeeding duration and pQCT parameters. These findings suggest neither protective nor adverse effects of prolonged breastfeeding on bone health in childhood and adolescence. Influences of early nutrition on bone growth might be overridden by current effects of mechanical loads on bone physiology.     

Use of the mobile phone multimedia messaging service for teledermatology

We examined the feasibility of using mobile phone Multimedia Messaging Service (MMS) to send teledermatology referrals from a general practitioner to a dermatologist. Digital photographs of skin conditions in 40 consecutive patients were sent together with relevant clinical information to dermatologists at a university hospital. Two dermatologists separately assessed the MMS referrals. The suspected diagnosis, triage and management decisions were compared to those given after separate face-to-face (FTF) visits, and again after agreeing on a final clinical and/or histopathological diagnosis. Thirty-two patients (80%) were diagnosed with skin tumours and 8 patients (20%) with other skin conditions. Both dermatologists were able to make a correct diagnosis in 31 patients (78%) based solely on the MMS referral. They also provided adequate management recommendations for 98% of the patients. Adequate triage decisions after assessment of the MMS referrals were made for 34 (85%) and 38 (95%) patients by the two dermatologists. There was an inter-observer concordance of 68% for the teledermatology diagnosis, compared to 88% concordance after the separate FTF visits. The diagnostic accuracy and adequacy of the triage and management decisions achieved using MMS referrals were similar to those obtained with other store-and-forward teledermatology methods.     

The confidence in health care and social services in northern Sweden - a comparison between reindeer-herding Sami and the non-Sami majority population

Aims: To investigate the confidence in primary health care, psychiatry and social services among the reindeer-herding Sami and the non-Sami population of northern Sweden. Methods: A semi-randomized, cross-sectional study design comprising 325 reindeer-herding Sami (171 men, 154 women) and a control population of 1,437 non-Sami (684 men, 753 women). A questionnaire on the confidence in primary health care, psychiatry, social services, and work colleagues was distributed to members of reindeer-herding families through the Sami communities and to the control population through the post. The relative risk for poor confidence was analyzed by calculating odds ratios with 95% confidence intervals adjusted for age and level of education. Results: The confidence in primary health care and psychiatry was significantly lower among the reindeer-herding Sami compared with the control group. No differences were found between men and women in the reindeer-herding Sami population. In both the reindeer-herding Sami and the control population, younger people (≤48 years) reported significantly lower confidence in primary health care than older individuals (>48 years). Conclusions: A conceivable reason for the poor confidence in health care organizations reported by the reindeer-herding Sami is that they experience health care staff as poorly informed about reindeer husbandry and Sami culture, resulting in unsuitable or unrealistic treatment suggestions. The findings suggest that the poor confidence constitutes a significant obstacle of the reindeer-herding Sami to fully benefit from public health care services.