Incidence and mortality of interstitial lung disease in rheumatoid arthritis: A population‐based study

Objective

Interstitial lung disease (ILD) has been recognized as an important comorbidity in rheumatoid arthritis (RA). We undertook the current study to assess incidence, predictors, and mortality of RA‐associated ILD.

Methods

We examined a population‐based incidence cohort of patients with RA and a matched cohort of individuals without RA. All subjects were followed up longitudinally. The lifetime risk of ILD was estimated. Cox proportional hazards models were used to compare the incidence of ILD between cohorts, to investigate predictors, and to explore the impact of ILD on survival.

Results

Patients with RA (n = 582) and subjects without RA (n = 603) were followed up for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for non‐RA subjects. This difference translated into a hazard ratio (HR) of 8.96 (95% confidence interval [95% CI] 4.02–19.94). The risk of developing ILD was higher in RA patients who were older at the time of disease onset, in male patients, and in individuals with more severe RA. The risk of death for RA patients with ILD was 3 times higher than in RA patients without ILD (HR 2.86 [95% CI 1.98–4.12]). Median survival after ILD diagnosis was only 2.6 years. ILD contributed ∼13% to the excess mortality of RA patients when compared with the general population.

Conclusion

Our results emphasize the increased risk of ILD in patients with RA. The devastating impact of ILD on survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality among individuals with RA.

     

Pelvic floor muscle function in women presenting with pelvic floor disorders

Introduction and hypothesis  This observational study was undertaken to determine knowledge, prior instruction, frequency of performance, and ability to perform pelvic floor muscle exercises in a group of women presenting for evaluation of pelvic floor disorders. Methods  Three hundred twenty-five women presenting for evaluation of pelvic floor disorders were questioned concerning knowledge and performance of pelvic floor muscle exercises (PMEs) and then examined to determine pelvic floor muscle contraction strength. Results  The majority of women (73%) had heard of PMEs, but only 42% had been instructed to perform them and 62.5% stated they received verbal instruction only. Only 23.4% of patients could perform pelvic muscle contractions with Oxford Scale 3, 4, or 5 strengths. Increased age, parity, and stage of prolapse were associated with lower Oxford scores. Conclusions  Although most women with pelvic floor disorders are familiar with PMEs, less than one fourth could perform adequate contractions at the time of initial evaluation.     

Comparison of the in vitro properties of apheresis platelets during 7-day storage after interrupting agitation for one or three periods

BACKGROUND: Many platelet (PLT) components undergo multiple periods of shipment before transfusion. We have previously conducted studies investigating maintenance of apheresis PLT in vitro quality measures during a single 24‐ or 30‐hour interruption of agitation, but data are not available for multiple periods without agitation. STUDY DESIGN AND METHODS: Apheresis PLTs were collected with both the Amicus (Fenwal, Inc.) and the Trima (Gambro BCT) cell separators to provide two identical PLT products, each with approximately 4 × 10¹¹ to 5 × 10¹¹ PLTs. One product was subjected to a single contiguous 24‐ or 30‐hour period of interrupted agitation between Days 2 and 3 of storage by placement in a standard shipping box at room temperature. The matched product was not agitated on each of 3 days (Days 0, 1, and 3) for specified intervals totaling an identical period of time. RESULTS: Interrupting agitation for three periods resulted in greater maintenance of pH during storage than that observed using one contiguous period. These differences were significant for units held without agitation for 24 hours (Day 5, 0.08 pH units, p < 0.0001; Day 7, 0.10 pH units, p = 0.0059) and were also significant for units held without agitation for 30 hours (Day 5, 0.15, p < 0.0001; Day 7, 0.20, p < 0.0001). The two different interruption of agitation scenarios did not result in significant differences in the extent of shape change and hypotonic shock response variables after 5 or 7 days of storage. CONCLUSION: Apheresis PLTs subjected to three periods without agitation maintained overall pH levels slightly greater than those of matched units subjected to one contiguous period without agitation. Other measures showed comparability of PLT in vitro variables with the two scenarios for interruption of agitation.     

Excitatory synaptic transmission is depressed in cultured hippocampal neurons of APP/PS1 mice

One of the strongest anatomical correlates of the degree of clinical impairment in Alzheimer's disease is a decrease in synaptic density. A detailed understanding of the pathophysiological mechanism operating at a synaptic level remains incomplete, in particular whether the pre- or the post-synaptic compartment is initially involved. Here, we studied synaptic transmission in autaptic hippocampal cultures from a double-transgenic mouse model (APPPS1, APP(swe) and PS1(L166P)) and a single-mutant APP transgenic model (APP23, APPswe). APPPS1 neurons revealed significantly reduced amplitudes of evoked AMPA- and NMDA-receptor-mediated excitatory post-synaptic currents, whereas the amplitudes of spontaneous miniature synaptic responses were not altered. The size of the readily releasable synaptic vesicle pool was also decreased, whereas the release probability was not affected. Morphometric immunohistochemical analysis showed a reduction in synaptophysin-positive puncta. In contrast, we did not identify any alterations in synaptic transmission in neurons derived from single APP(swe) transgenic mice. Taken together, our findings suggest that cultured neurons of APPPS1 double-transgenic mice have a significantly reduced number of functional excitatory synapses.     

Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of serum- and glucocorticoid-regulated kinase type 1

Persistent β-adrenergic receptor stimulation with isoproterenol is associated with cardiac hypertrophy as well as cardiac synthesis of angiotensin II. Serum- and glucocorticoid-regulated kinase type 1 (SGK-1) is a key mediator in structural, functional and molecular cardiac effects of aldosterone in rats. This study was designed to investigate the cardiac effects of the mineralocorticoid receptor antagonist spironolactone on the response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in the heart. Male Wistar rats received isoproterenol (3 mg kg(-1) day(-1)) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg(-1) day(-1)). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end-diastolic pressure observed in isoproterenol-treated rats. Isoproterenol treatment induced cardiac hypertrophy and increased collagen content, both of which were normalized by spironolactone treatment. The mRNA levels of transforming growth factor β, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor α, interleukin 1β, p22phox and xanthine dehydrogenase were increased (P < 0.05) in isoproterenol-treated rats, and this effect was prevented by spironolactone (P < 0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK-1, by spironolactone in hearts from isoproterenol-treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats.     

Comparative evaluation of gustatory function between postmenopausal women and age‐matched men

Oral Diseases (2010) 16 , 469–475 Objective: The aim of the study was to compare the gustatory function between postmenopausal women and age‐matched men. Subjects and methods: During a period of 4 months, 30 postmenopausal women and 30 age‐matched men were prospectively evaluated for gustatory function. Each subject was given a symptoms questionnaire for self‐assessment of taste function. Then, whole mouth taste test was performed in which the quality identification and intensity ratings of taste solutions were measured. Results: Regarding correct quality identification, the results were statistically non‐significant (P > 0.05). As far as the intensity judgments are concerned, significant difference exists between postmenopausal women and age‐matched men. Intensity of taste perception for sucrose was significantly lower in postmenopausal women than intensity of taste perception for other tastes (P < 0.05). One of the noticeable findings is that 15 (50%) postmenopausal women reported a change in dietary habits; all expressed liking for sweeter food. Conclusion: Postmenopausal women appeared to have a reduced perception of sucrose, which can alter eating habits, such as intake of more sweet foods, whereas no significant difference is observed in taste perception of NaCl, citric acid and quinine hydrochloride between postmenopausal women and age‐matched men. Fifteen (50%) postmenopausal women stated fondness for sweet taste.     

Influence of Renal Sympathetic Denervation on Quality of Life

Background

Therapy‐resistant arterial hypertension causing psychosocial stress and is associated with cardiovascular morbidity and mortality. The aim of the study was to evaluate the effect on quality of life (QoL) in patients with resistant hypertension undergoing renal sympathetic denervation (RSD).

Methods and Results

We analyzed responses to the SF‐36 Quality of Life Questionnaire provided by patients with resistant arterial hypertension after RSD. Thirty consecutive patients from 2 centers were included in this study, from October 2011 until February 2012. The phone interview was performed after the 3‐month follow‐up. A significant reduction (26 ± 13.5 mmHg) in systolic blood pressure (BP) was detected at the 3‐month follow‐up (142.0 ± 15.1 mmHg vs 168.0 ± 13.7 mmHg; P < 0.001). Seventy‐five percent of the patients indicated that their health situation was a lot better (better, 21%; equal to, 4%) 3 months after RSD compared to the time before the therapeutic procedure. Furthermore, the majority of patients felt full of pep (always, 29%; mostly, 58%; quite often, 8%; sometimes, 4%), and full of energy (always, 25%; mostly, 54%; quite often, 16.7%; sometimes, 4.2%) after the procedure. Recipients of RSD indicated that they felt more light and healthy, and nearly all recipients (93%) described a loss of anxiety and indisposition.

Conclusions

This investigation revealed that sufficient BP reduction by RSD and time following therapeutic success lead to significant improvements in patient QoL. (J Interven Cardiol 2013;26:536‐541)

     

A critical comparison of platelet preparation methods

PURPOSE OF REVIEW: Platelet concentrates may be prepared from whole blood or by plateletpheresis. Currently, the non-evidence-based preponderance of apheresis units in the United States and the 50: 50 ratio in Europe may not optimize the gifts of whole-blood donors or minimize healthcare costs. Post-storage pooled, whole-blood-derived platelets, on the other hand, do not provide the convenience of or an equivalent level of safety as apheresis platelets. RECENT FINDINGS: Some data suggest that different methods of manufacture of whole-blood-derived platelets (platelet-rich plasma or buffy coat intermediate steps) result in differing degrees of platelet activation, which may impact on the quality of stored concentrates. Recent studies have observed superior radiolabel recovery and post-transfusion increments for platelets derived from apheresis compared with platelet-rich plasma whole-blood-derived platelets. A pre-storage pooling system for whole-blood-derived platelets has just been licensed in the USA, and may eventually combine the benefits of apheresis-derived and whole-blood-derived platelets. The advantages of the European method of manufacture of buffy coat whole-blood-derived platelet concentrate have convinced the Canadian Blood Services to abandon platelet-rich-plasma-derived concentrates. SUMMARY: We present a literature-based review of the relative merits of apheresis-derived and whole-blood-derived platelets. Additional studies are needed in order to define the optimal proportion of the platelet supply from apheresis collections and the choice of whole-blood-derived production method for US blood providers.