Patient satisfaction with alosetron for the treatment of women with diarrhea-predominant irritable bowel syndrome

OBJECTIVE: The efficacy and tolerability of alosetron in women with diarrhea-predominant irritable bowel syndrome (IBS) have been established in double-blind, placebo-controlled trials. However, the degree to which alosetron fulfills the needs of those suffering from IBS has not been thoroughly examined from the patient's perspective. This randomized, double-blind, placebo-controlled study conducted in women with diarrhea-predominant IBS evaluated patients' overall satisfaction with treatment as well as their satisfaction with respect to several specific medication attributes. METHODS: Patients randomized to receive either alosetron 1 mg b.id. (n = 532) or placebo (n = 269) were administered a questionnaire on which they rated on 7-point Likert scales their prestudy IBS treatment (at the screening visit) or study medication (on wk 12 or final study visit) with respect to overall satisfaction and 11 specific medication attributes. RESULTS: Whereas approximately 10% of patients were satisfied or very satisfied overall with prestudy IBS medication, 69% of patients were satisfied or very satisfied overall with alosetron and 46% with placebo (p < 0.001) at the end of 12 wk of therapy. The majority of alosetron-treated patients (61-87%) were satisfied or very satisfied with each of 11 specific medication attributes (p < 0.001 vs placebo for each attribute). Favorable satisfaction ratings for alosetron were assigned to the five medication attributes that patients considered to be most important, including relief of urgency (68% alosetron vs 41% placebo), speed of relief (71% vs 40%), time to return to normal activities (75% vs 49%), relief of abdominal pain (62% vs 44%), and prevention of return of urgency (68% vs 42%). CONCLUSIONS: Women with diarrhea-predominant IBS are satisfied with alosetron 1 mg b.i.d. treatment overall and also with respect to specific attributes of IBS medication they consider most important.     

Outcomes of young adults (aged ≤ 40 years) with newly diagnosed multiple myeloma after up-front autologous stem cell transplant

Multiple myeloma (MM) primarily affects older patients. There are scarce data on the outcomes of young adults undergoing autologous transplantation (auto-HCT). In this single-centre analysis, we included 117 younger patients, with a median age of 37 years (range 22–40) at transplant. Seventeen (15%) patients had high-risk cytogenetics. Before transplant, 10% of patients achieved ≥CR and 44% achieved ≥VGPR. At best post-transplant response, 56% and 77% of patients achieved ≥CR and ≥VGPR respectively. With a median follow-up for survivors of 72.6 months (range 0.9–238.0), median PFS and OS were 43.1 months (95% CI 31.2–65.0) and 146.6 months (95% CI 100.0–208.1) respectively. Patients who underwent auto-HCT after 2010 had better median PFS (84.9 months vs. 28.2 months, p < 0.001) and OS (NR vs. 91.8 months, p < 0.001) compared with those transplanted earlier. In multi-variate analysis, achieving ≥CR as best post-transplant response was associated with improved PFS (HR [95% CI] 0.55 [0.32–0.95], p = 0.032), while achieving ≥VGPR was predictive of superior OS (0.32 [0.16–0.62], p < 0.001). Three patients (3%) developed a second primary malignancy. Younger MM patients had durable survival after auto-HCT, which further improved after the availability of novel anti-myeloma drugs in recent years. Depth of response following transplant remains a key predictor of survival.     

Linear Friction Welding of an AZ91 Magnesium Alloy and the Effect of Ca Additions on the Weld Characteristics

Solid-state welding offers distinct advantages for joining reactive materials, such as magnesium (Mg) and its alloys. This study investigates the effect of linear friction welding (LFW) on the microstructure and mechanical properties of cast AZ91 (Mg–9Al–1Zn) and AZ91–2Ca alloys, which (to the best knowledge of the authors) has not been reported in the literature. Using the same set of LFW process parameters, similar alloy joints—namely, AZ91/AZ91 and AZ91–2Ca/AZ91–2Ca—were manufactured and found to exhibit integral bonding at the interface without defects, such as porosity, inclusions, and/or cracking. Microstructural examination of the AZ91/AZ91 joint revealed dissolution of the Al-rich second phase in the weld zone, while the Mn containing phases remained and were refined. In the AZ91–2Ca/AZ91–2Ca joint, the weld zone retained Ca- and Mn-rich phases, which were also refined due to the LFW process. In both joint types, extensive recrystallization occurred during LFW, as evidenced by the refinement of the grains from ~1000 µm in the base materials to roughly 2–6 µm in the weld zone. These microstructural changes in the AZ91/AZ91 and AZ91–2Ca/AZ91–2Ca joints increased the hardness in the weld zone by 32%. The use of digital image correlation for strain mapping along the sample gage length during tensile testing revealed that the local strains were about 50% lower in the weld zone relative to the AZ91 and AZ91–2Ca base materials. This points to the higher strength of the weld zone in the AZ91/AZ91 and AZ91–2Ca/AZ91–2Ca joints due to the fine grain size, second phase refinement, and strong basal texture. Final fracture during tensile loading of both joints occurred in the base materials.     

Optimizing Peritoneal Dialysis–Associated Peritonitis Prevention in the United States: From Standardized Peritoneal Dialysis–Associated Peritonitis Reporting and Beyond

Peritoneal dialysis (PD)–associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.     

Successful colonoscopic fecal microbiota transplantation for active ulcerative colitis: First report from India

Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative. Following informed consent and approval from IEC, three sessions of fecal microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was a 34-year-old relative with no history of gastrointestinal illness, no use of antibiotics over 3 months, and free from transmissible disease as per standard protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into seven syringes of 50 cm³, was instilled from terminal ileum to sigmoid. Follow up sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was symptomatic, colonoscopic, and histopathological improvement with the Mayo scores of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were tapered sequentially between months 4 and 6 of FMT. He remains in clinical and endoscopic remission 8 months after FMT and 2 months after withdrawal of all medication. Colonoscopic FMT may be effective in inducing drug-free remission in patients with active UC.     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.

A comparison of modality-specific somatosensory changes during menstruation in dysmenorrheic and nondysmenorrheic women

OBJECTIVE: The objective was to evaluate somatosensory thresholds to a multimodality stimulation regimen applied both within and outside areas of referred menstrual pain in dysmenorrheic women, over four phases of confirmed ovulatory cycles, and to compare them with thresholds in nondysmenorrheic women during menstruation. DESIGN: Twenty dysmenorrheic women with menstrual pain scoring 5.45 +/- 0.39 cm (mean +/- standard error of mean) on a visual analog scale (10 cm) participated. Fifteen nondysmenorrheic women with a menstrual pain score of 0.4 +/- 0.2 cm participated as controls. Ovulation was confirmed by an enzyme-multiplied immunoassay technique. Menstrual pain was described with the McGill Pain Questionnaire. Areas within menstrual pain referral were two abdominal sites and the midline of the low back, and the arm and thigh were the control areas. The pressure pain threshold (PPT) and pinch pain threshold were determined by a hand-held electronic pressure algometer, the heat pain threshold (HPT) by a contact thermode, and the tactile threshold with von Frey hairs. RESULTS: In dysmenorrheic women the McGill Pain Questionnaire showed a larger sensory and affective component of pain than the evaluative and miscellaneous groups. The HPT and PPT were lower in the menstrual phase than in the ovulatory, luteal, and premenstrual phases, both within and outside areas of referred menstrual pain (p <0.01), with a more pronounced decrease at the referral pain areas. The pinch pain threshold was lower in the menstrual phase than in the ovulatory phase (p <0.02), and the tactile threshold did not differ significantly across the menstrual phases or within any site. Dysmenorrheic women had a lower HPT at the control sites and a lower PPT at the abdomen, back, and control sites, than in those of nondysmenorrheic women in the menstrual phase. CONCLUSIONS: The results show reduced somatosensory pain thresholds during menstruation to heat and pressure stimulation, both within and outside areas of referred menstrual pain in dysmenorrheic women. Dysmenorrheic women showed a lower HPT at the control sites and a lower PPT at all the sites than those for nondysmenorrheic women in the menstrual phase. The altered somatosensory thresholds may be dependent on a spinal mechanism of central hyperexcitability, induced by recurrent moderate to severe menstrual pain.     

Motor "dexterity"?: Evidence that left hemisphere lateralization of motor circuit connectivity is associated with better motor performance in children

Motor control relies on well-established motor circuits, which are critical for typical child development. Although many imaging studies have examined task activation during motor performance, none have examined the relationship between functional intrinsic connectivity and motor ability. The current study investigated the relationship between resting state functional connectivity within the motor network and motor performance assessment outside of the scanner in 40 typically developing right-handed children. Better motor performance correlated with greater left-lateralized (mean left hemisphere-mean right hemisphere) motor circuit connectivity. Speed, rhythmicity, and control of movements were associated with connectivity within different individual region pairs: faster speed was associated with more left-lateralized putamen-thalamus connectivity, less overflow with more left-lateralized supplementary motor-primary motor connectivity, and less dysrhythmia with more left-lateralized supplementary motor-anterior cerebellar connectivity. These findings suggest that for right-handed children, superior motor development depends on the establishment of left-hemisphere dominance in intrinsic motor network connectivity.