Obesity Predicts Treatment Response to Proton Pump Inhibitor Therapy in Patients with Chronic Cough

Background

Chronic cough management is challenging as this condition is often associated with multiple comorbidities, requiring a multidisciplinary diagnostic approach. Little is known about the characteristics of obese patients with chronic cough. This study aims to describe treatable traits of chronic cough and the response to pump proton inhibitor (PPI) therapy in this sub-group of patients.

Methods

A retrospective, observational study was performed in patients with chronic cough in a French University Hospital. Characteristics of chronic cough were analyzed for obese (N = 112) and non-obese (N = 355) patients. Refractory cough was estimated at 6 and 12 months.

Results

The 3 main treatable traits associated with chronic cough in obese patients and non-obese patients were gastroesophageal reflux disease (GERD), asthma, and upper airway cough syndrome (UACS). A noticeable difference was the higher frequency of GERD (47.3% vs 34.6%, p = 0.0188) and obstructive sleep apnea (OSA) (9.8% vs 3.1%, p = 0.0080) in obese patients compared to non-obese patients. Pump proton inhibitor (PPI) treatment had a significantly higher success rate in obese patients (32.5% vs 17.0%, p < 0.05) and refractory cough at 12 months was less frequently reported in obese patients (22.3% vs 34.1%, p < 0.05).

Conclusion

In a context of chronic cough, a higher prevalence of GERD was noted in obese patients compared to non-obese patients and obese patients were more responsive to PPI treatment. Moreover, OSA was reported more frequently as a treatable trait in obese patients and should be considered early in the diagnostic evaluation. Prospective clinical studies that evaluate the contribution of obesity to chronic cough are further needed.

     

Epidemiology,clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.     

Medial prefrontal theta phase coupling during spatial memory retrieval

Memory retrieval is believed to involve a disparate network of areas, including medial prefrontal and medial temporal cortices, but the mechanisms underlying their coordination remain elusive. One suggestion is that oscillatory coherence mediates inter‐regional communication, implicating theta phase and theta‐gamma phase‐amplitude coupling in mnemonic function across species. To examine this hypothesis, we used non‐invasive whole‐head magnetoencephalography (MEG) as participants retrieved the location of objects encountered within a virtual environment. We demonstrate that, when participants are cued with the image of an object whose location they must subsequently navigate to, there is a significant increase in 4–8 Hz theta power in medial prefrontal cortex (mPFC), and the phase of this oscillation is coupled both with ongoing theta phase in the medial temporal lobe (MTL) and perceptually induced 65–85 Hz gamma amplitude in medial parietal cortex. These results suggest that theta phase coupling between mPFC and MTL and theta‐gamma phase‐amplitude coupling between mPFC and neocortical regions may play a role in human spatial memory retrieval. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Daily life functioning of community‐dwelling elderly couples: an investigation of the feasibility and validity of Ecological Momentary Assessment

Although ambulatory data collection techniques have been used in elderly populations, their feasibility and validity amongst elderly individuals with cognitive impairment and amongst couples remains unexplored. The main objective of this study is to examine the validity of Ecological Momentary Assessment (EMA) in elderly persons with or without cognitive impairment and their spouses. The sample included 58 retired farmers (mean 77.3 years, standard deviation [SD] 5.5) with or without cognitive impairment, recruited within a French cohort and 60 spouses (mean 73.4 years, SD 6.9). The presence of cognitive impairment determining by a panel of specialized neurologists permitted to define two groups: “The Cognitive Impairment Group” and “The Control Group”. EMA procedures consisted of repeated telephone interviews five times per day during four days for each spouse. Our results demonstrate the validity of EMA procedures through a 92.1% level of compliance, the absence of fatigue effects, and the lack of evidence for major reactivity to the methods. However, the specificity of our sample may explain the acceptance (42%) and response (75%) rates and may reduce the generalizability of the results to the general population of elderly individuals. Finally, the validation of such techniques may contribute to future research examining community‐dwelling elderly individuals and their spouses. Copyright © 2013 John Wiley & Sons, Ltd.     

How do we process event‐based and time‐based intentions in the brain? an fMRI study of prospective memory in healthy individuals

Prospective memory (PM) refers to the ability to remember to do something in the future, either in response to an event (event‐based) or after a certain amount of time has elapsed (time‐based). While the distinction between event‐ and time‐based PM is widely acknowledged in the literature, little is known about the processes they share and those they do not. This is particularly true concerning their brain substrates, as almost all neuroimaging studies so far have focused on event‐based PM. We proposed a functional magnetic resonance imaging paradigm assessing both event‐based and time‐based PM to 20 healthy young individuals. Analyses revealed that event‐ and time‐based PM both induced activation in the posterior frontal and parietal cortices, and deactivation in the medial rostral prefrontal cortex. In addition, activation more specific to each condition, which may underlie differences in strategic monitoring, was highlighted. Thus, occipital areas were more activated during event‐based PM, probably reflecting target‐checking, while a network comprising the dorsolateral prefrontal cortex, the cuneus/precuneus and, to a lesser extent, the inferior parietal lobule, superior temporal gyrus, and the cerebellum, was more activated in time‐based PM, which may reflect the involvement of time‐estimation processes. These results confirm the allocation of attentional resources to the maintenance of intention for event‐based and time‐based PM, as well as the engagement of distinct mechanisms reflecting the monitoring strategies specific to each condition. Hum Brain Mapp 35:3066–3082, 2014. © 2013 Wiley Periodicals, Inc.     

Intraoperative blood loss during decompressive craniectomy for intractable intracranial hypertension after severe traumatic brain injury in children

Purpose

There are no data available on the risk of intraoperative bleeding during decompressive craniectomy (DC) after traumatic brain injury (TBI) in children. The objectives of this study were to assess the risk of intraoperative bleeding during DC for intractable intracranial hypertension after TBI, to identify potential factors associated with the risk of bleeding during DC, and to assess the impact of DC on systemic and cerebral hemodynamics and on coagulation.

Methods

Twelve children were identified as having undergone DC after TBI from April 2009 to June 2013 in our center. Subjects were allocated into two groups according to the percentage of blood loss (IBL) during the intraoperative period (<or ≥50 % of the estimated blood volume (EBV)).

Results

The median IBL during DC was 49 [17–349] % of the EBV. Children with an IBL?≥?50 % of EBV had higher preoperative intracranial pressure (ICP) (p?=?0.03) and international normalized ratio (INR) (p?=?0.02) than those with an IBL?<?50 % of EBV. DC induced significant decreases in ICP (p?=?0.0005), mean arterial pressure (p?=?0.01), and a significant increase in norepinephrine flow rate (p?=?0.04) between the immediate pre- and postoperative periods.

Conclusions

DC allows a significant decrease in ICP after severe pediatric TBI but is a surgical procedure at a high risk of bleeding. High ICP and INR during the immediate preoperative period are the main factors associated with increased IBL during DC. Further studies are needed to confirm our results and to assess the impact of the amount of IBL on the postoperative survival and functional outcome.     

Prospective associations between serum biomarkers of lipid metabolism and overall,breast and prostate cancer risk

Experimental studies provided evidence about mechanisms by which cholesterol, especially high density lipoprotein cholesterol (HDL-C), could influence carcinogenesis, notably through antioxidant and anti-inflammatory properties. However, prospective studies that investigated the associations between specific lipid metabolism biomarkers and cancer risk provided inconsistent results. The objective was to investigate the prospective associations between total cholesterol (T-C), HDL-C, low density lipoprotein cholesterol, apolipoproteins A1 (apoA1) and B, and triglycerides and overall, breast and prostate cancer risk. Analyses were performed on 7,557 subjects of the Supplémentation en Vitamines et Minéraux Antioxydants Study, a nationwide French cohort study. Biomarkers of lipid metabolism were measured at baseline and analyzed regarding the risk of first primary incident cancer (N = 514 cases diagnosed during follow-up, 1994–2007), using Cox proportional hazards models. T-C was inversely associated with overall (HR_{1mmol/L increment} = 0.91, 95 % CI 0.82–1.00; P = 0.04) and breast (HR_{1mmol/L increment} = 0.83, 95 % CI 0.69–0.99; P = 0.04) cancer risk. HDL-C was also inversely associated with overall (HR_{1mmol/L increment} = 0.61, 95 % CI 0.46–0.82; P = 0.0008) and breast (HR_{1mmol/L increment} = 0.48, 95 % CI 0.28–0.83; P = 0.009) cancer risk. Consistently, apoA1 was inversely associated with overall (HR_{1g/L increment} = 0.56, 95 % CI 0.39–0.82; P = 0.003) and breast (HR_{1g/L increment} = 0.36, 95 % CI 0.18–0.73; P = 0.004) cancer risk. This prospective study suggests that pre-diagnostic serum levels of T-C, HDL-C and ApoA1 are associated with decreased overall and breast cancer risk. The confirmation of a role of cholesterol components in cancer development, by further large prospective and experimental studies, may have important implications in terms of public health, since cholesterol is already crucial in cardiovascular prevention.     

Effects of water soaking and/or sodium polystyrene sulfonate addition on potassium content of foods

In this study, we determined, by atomic absorption spectrophotometry, the potassium amount leached by soaking or boiling foods identified by children suffering from chronic renal failure as “pleasure food” and that they cannot eat because of their low-potassium diet, and evaluated whether addition of sodium polystyrene sulfonate resin (i.e. Kayexalate®) during soaking or boiling modulated potassium loss. A significant amount of potassium content was removed by soaking (16% for chocolate and potato, 26% for apple, 37% for tomato and 41% for banana) or boiling in a large amount of water (73% for potato). Although Kayexalate® efficiently dose-dependently removed potassium from drinks (by 48% to 73%), resin addition during soaking or boiling did not eliminate more potassium from solid foods. Our results therefore provide useful information for dietitians who elaborate menus for people on potassium-restricted diets and would give an interesting alternative to the systematic elimination of all potassium-rich foods from their diet.     

Quantitative dynamic nuclear polarization‐NMR on blood plasma for assays of drug metabolism

Analytical platforms for the fast detection, identification and quantification of circulating drugs with a narrow therapeutic range are vital in clinical pharmacology. As a result of low drug concentrations, analytical tools need to provide high sensitivity and specificity. Dynamic nuclear polarization‐NMR (DNP‐NMR) in the form of the hyperpolarization–dissolution method should afford the sensitivity and spectral resolution for the direct detection and quantification of numerous isotopically labeled circulating drugs and their metabolites in single liquid‐state NMR transients. This study explores the capability of quantitative in vitro DNP‐NMR to assay drug metabolites in blood plasma. The lower limit of detection for the anti‐epileptic drug ¹³C‐carbamazepine and its pharmacologically active metabolite ¹³C‐carbamazepine‐10,11‐epoxide is 0.08 µg/mL in rabbit blood plasma analyzed by single‐scan ¹³C DNP‐NMR. An internal standard is used for the accurate quantification of drug and metabolite. Comparison of quantitative DNP‐NMR data with an established analytical method (liquid chromatography‐mass spectrometry) yields a Pearson correlation coefficient r of 0.99. Notably, all DNP‐NMR determinations were performed without analyte derivatization or sample purification other than plasma protein precipitation. Quantitative DNP‐NMR is an emerging methodology which requires little sample preparation and yields quantitative data with high sensitivity for therapeutic drug monitoring. Copyright © 2010 John Wiley & Sons, Ltd.     

Candida and dysbacteriosis: A cytologic,population‐based study of 100,605 asymptomatic women concerning cervical carcinogenesis

BACKGROUND.

The objective of this study was to investigate whether the presence of vaginal Candida or dysbacteriosis predisposes women to an increased susceptibility for (pre)neoplasia over time.

METHODS.

A retrospective, longitudinal, cohort study was performed and was conducted in a population of 100,605 women, each of whom had 2 smears taken over a period of 12 years as part of the Dutch Cervical Screening Program. From these women, a cohort of 1439 women with Candida and a cohort of 5302 women with dysbacteriosis were selected as 2 separate study groups. The control cohort consisted of women who had completely normal cervical smears (n = 87,903 women). These groups were followed retrospectively over time. The odds ratios (OR) for squamous abnormalities in the follow‐up smear for the women in these 3 cohorts were established.

RESULTS.

The dysbacteriotic cohort was significantly more likely to have low‐grade squamous intraepithelial lesions (LSIL) and high‐grade squamous intraepithelial lesions (HSIL+) in their follow‐up smear (OR, 1.85; 95% confidence interval [95% CI], 1.28–2.67 and OR, 2.00; 95% CI, 1.31–3.05, respectively) compared with women in the control group. In contrast, the Candida cohort had no significantly increased or decreased risk of developing SIL. The equivocal diagnosis ‘atypical squamous cells of undetermined significance’ was rendered significantly more often in the follow‐up smear of both study cohorts (Candida cohort: OR, 1.42; 95% CI, 1.03–1.95; dysbacteriotic cohort: OR, 1.44; 95% CI, 1.22–1.71).

CONCLUSIONS.

The results from this study indicated that the presence of Candida vaginalis was not associated with an increased risk for SIL over time. In contrast, women with dysbacteriosis had a significantly increased risk of developing (pre)neoplastic changes. These findings should be taken into account in further research concerning predisposing factors for cervical carcinogenesis. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.