The "vicious circle" of chronic cough: the patient experience - qualitative synthesis.

Aim: The aim of this study was to systematically search and synthesise findings from peer-reviewed qualitative studies describing the experiences of those living with chronic cough. Methods: A systematic search was conducted to identify all studies that used qualitative methodology to report on the experiences of adults living with chronic cough. A thematic synthesis of the first-hand narratives was undertaken. Key themes in relation to personal perspectives and experiences of living with chronic cough were identified and grouped into analytical themes. Results: Six studies met the inclusion criteria. The thematic synthesis generated three analytical themes: 1) "It's just a cough"; 2) "Constant cough and constant worry"; and 3) "No light at the end of the tunnel", highlighting the biopsychosocial nature of chronic cough. The synthesis highlights chronic cough as a heterogeneous experience that may appear idiosyncratic, completely consuming the lives of those living with it. Conclusion: This is to our knowledge the first qualitative synthesis reporting on the perceptions and experiences of adults living with chronic cough. Our review draws attention to the paucity of literature that utilises qualitative methodology to explore the experience of living with chronic cough. We highlight the missing voice of people living with chronic cough in the contemporary literature. There is now a requirement for research exploring the narratives of those living with chronic cough, to gain an understanding of the condition beyond simple quantification.

Subcutaneous octreotide as a therapeutic option for refractory chronic cough: subjective response pattern and adverse effects from a retrospective single-centre case series.

Therapeutic antitussive effect of octreotide on intractable cough https://bit.ly/3mVMEc6.

Arctic corridors and northern voices project: Methods for community-based participatory mapping for low impact shipping corridors in Arctic Canada.

Documenting Inuit and local knowledge is critical to its consideration within policy discussions around Arctic shipping; especially considering the rapid increase in ship traffic due to reductions in sea ice and climate change. We present our unique community-based research approach which incorporated youth training, participatory mapping, qualitative focus group discussions, and verification exercises to document Inuit communities' perspectives in Arctic Canada about Low Impact Shipping Corridors. These qualitative activities provided appropriate context and understanding around community-created maps, community-identified opportunities, concerns, and recommendations, and the policy relevance and feasibility of recommendations posed. Three activity phases were employed; 1) before engaging in in-community research, 2) during in-community research, and 3) after completing in-community research. Spatial and non-spatial data were analyzed using ArcGIS® and NVivo software, respectively. These methods and observations can inform future research initiatives, particularly transdisciplinary teams, including those involving southern-based (early career) researchers, working in Inuit Nunangat.•Methods presented here ensured that scientific processes and outputs were robust and rigorous and research was conducted in a respectful, reciprocal manner.•Only through the collaborative efforts of a transdisciplinary team could scientific rigour be attained and respect be afforded.•The approach can be easily applied to document community members' perspectives on local priorities.

Ancestry-specific hereditary cancer panel yields: Moving toward more personalized risk assessment.

Healthcare disparities in genomic medicine are well described. Despite some improvements, we continue to see fewer individuals of African American, Asian, and Hispanic ancestry undergo genetic counseling and testing compared to those of European ancestry. It is well established that variant of uncertain significance (VUS) rates are higher among non-European ancestral groups undergoing multi-gene hereditary cancer panel testing. However, pathogenic variant (PV) yields, and genomic data in general, are often reported in aggregate and derived from cohorts largely comprised of individuals of European ancestry. We performed a retrospective review of clinical and ancestral data for individuals undergoing multi-gene hereditary cancer panel testing to determine ancestry-specific PV and VUS rates. An ancestry other than European was reported in 29,042/104,851 (27.7%) of individuals. Compared to Europeans (9.4%), individuals of Middle Eastern ancestry were more likely to test positive for one or more pathogenic variants (12.1%, p = .0025), while African Americans were less likely (7.9%, p < .0001). Asian and Middle Eastern individuals were most likely (34.8% and 33.2%, respectively) to receive a report with an overall classification of VUS, while individuals of Ashkenazi Jewish and European ancestry were least likely (17.1% and 20.4%, respectively). These data suggest that in addition to higher VUS rates, there may be ancestry-specific PV yields. Providing aggregate data derived from cohorts saturated with European individuals does not adequately reflect genetic testing outcomes in minority groups, and interrogation of ancestry-specific data is a step toward a more personalized risk assessment.

A Wireless Implantable Strain Sensing Scheme Using Ultrasound Imaging of Highly Stretchable Zinc Oxide/Poly Dimethylacrylamide Nanocomposite Hydrogel.

We are introducing a wireless and passive strain sensing scheme that utilizes ultrasound imaging of a highly stretchable hydrogel embedded with zinc oxide (ZnO) nanoparticles, named "ZnO-gel". The incorporation of ZnO nanoparticles into a polymer network of the hydrogel improves both its elasticity and strength. It also serves as an ideal biocompatible ultrasound contrast agent that allows remote interrogation of the changes in volume or dimensions of the hydrogel in response to mechanical strains through simple ultrasound imaging. A systematic study of various ratios of ZnO nanoparticle fillers (ranging from 0 to 40% w/w), cross-linked within the poly (DMA-co-MAA) hydrogel, was performed to identify the appropriate ZnO-to-gel ratio that provided the optimal mechanical and ultrasound imaging properties. The results of these investigations showed that 10% w/w of ZnO nanoparticles provided the highest stretchability of 260% with the effective amount of contrast agents to achieve clear visibility of the hydrogel dimension during ultrasound imaging. In general, the applied strain deforms the ZnO-gel specimens by reducing the cross-sectional area at a linear rate of 0.24% area change per % of applied strain for strain levels of up to 250%. Biocompatibility tests with stromal cells (fibroblasts) did not show any acute toxicity of the hydrogel and the ZnO nanoparticles used in this technology. It is anticipated that this technology can be applied to a broad range of wireless and passive monitoring of physiological functions for which microenvironmental strain matters throughout the body, simply by tuning both the mechanical properties of the hydrogel and ZnO nanoparticle concentration.

Age-adjusted association of homologous recombination genes with ovarian cancer using clinical exomes as controls.

BACKGROUND: Genes in the homologous recombination pathway have shown varying results in the literature regarding ovarian cancer (OC) association. Recent case-control studies have used allele counts alone to quantify genetic associations with cancer. METHODS: A retrospective case-control study was performed on 6,182 women with OC referred for hereditary cancer multi-gene panel testing (cases) and 4,690 mothers from trios who were referred for whole-exome sequencing (controls). We present age-adjusted odds ratios (ORAdj) to determine association of OC with pathogenic variants (PVs) in homologous recombination genes. RESULTS: Significant associations with OC were observed in BRCA1, BRCA2, RAD51C and RAD51D. Other homologous recombination genes, BARD1, NBN, and PALB2, were not significantly associated with OC. ATM and CHEK2 were only significantly associated with OC by crude odds ratio (ORCrude) or by ORAdj, respectively. However, there was no significant difference between ORCrude and ORAdj for these two genes. The significant association of PVs in BRIP1 by ORCrude (2.05, CI = 1.11 to 3.94, P = 0.03) was not observed by ORAdj (0.87, CI = 0.41 to 1.93, P = 0.73). Interestingly, the confidence intervals of the two effect sizes were significantly different (P = 0.04). CONCLUSION: The lack of association of PVs in BRIP1 with OC by ORAdj is inconsistent with some previous literature and current management recommendations, highlighted by the significantly older age of OC onset for BRIP1 PV carriers compared to non-carriers. By reporting ORAdj, this study presents associations that reflect more informed genetic contributions to OC when compared to traditional count-based methods.

Clinical validity assessment of genes frequently tested on hereditary breast and ovarian cancer susceptibility sequencing panels.

PURPOSE: Several genes on hereditary breast and ovarian cancer susceptibility test panels have not been systematically examined for strength of association with disease. We employed the Clinical Genome Resource (ClinGen) clinical validity framework to assess the strength of evidence between selected genes and breast or ovarian cancer. METHODS: Thirty-one genes offered on cancer panel testing were selected for evaluation. The strength of gene-disease relationship was systematically evaluated and a clinical validity classification of either Definitive, Strong, Moderate, Limited, Refuted, Disputed, or No Reported Evidence was assigned. RESULTS: Definitive clinical validity classifications were made for 10/31 and 10/32 gene-disease pairs for breast and ovarian cancer respectively. Two genes had a Moderate classification whereas, 6/31 and 6/32 genes had Limited classifications for breast and ovarian cancer respectively. Contradictory evidence resulted in Disputed or Refuted assertions for 9/31 genes for breast and 4/32 genes for ovarian cancer. No Reported Evidence of disease association was asserted for 5/31 genes for breast and 11/32 for ovarian cancer. CONCLUSION: Evaluation of gene-disease association using the ClinGen clinical validity framework revealed a wide range of classifications. This information should aid laboratories in tailoring appropriate gene panels and assist health-care providers in interpreting results from panel testing.

Germline pathogenic variants identified in women with ovarian tumors.

OBJECTIVE: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel. METHODS: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants. Statistical comparisons were made using t-tests and Fisher's exact tests. RESULTS: The positive yield was 13.2%. While BRCA1/2 pathogenic variants were most frequent, one third (33.7%) of positive findings were in other homologous recombination genes, and accounted for over 40.0% of findings in endometrioid and clear cell cases. Women with a personal history of breast cancer (22.1%), who reported a family history of ovarian cancer (17.7%), and/or serous histology (14.7%) were most likely to harbor a pathogenic variant. Those with very early onset (<30 years) and late onset (≥70 years) ovarian cancer had low positive yields. CONCLUSIONS: Our study highlights the genetic heterogeneity of ovarian cancer, showing that a large proportion of cases are not due to BRCA1/2 and the Lynch syndrome genes, but still have an identifiable hereditary basis. These findings substantiate the utility of multi-gene panel testing in ovarian cancer care regardless of age at diagnosis, family history, or histologic subtype, providing evidence for testing beyond BRCA1/2 and the Lynch syndrome genes.

Synchronous Bilateral Tubal Serous Carcinomas in a Patient With Exon 13 Duplication and Loss of Function of BRCA1.

We report the first case of distinct, synchronous serous carcinomas of the adnexa arising in a patient with a family history of breast and ovarian cancer and a germline loss of function mutation in BRCA1. Illustrating an exceedingly rare phenomenon of synchronous high-grade carcinomas with distinct histomorphologic, immunohistochemical and cytogenetic features, the case serves as a point of departure for the discussion of phenotypic patterns of carcinomas arising in BRCA1 mutation carriers. We also review patient management, including the importance of risk-reducing salpingo-oophorectomy in women with deleterious BRCA1 mutations, as well as the potential need for an intraoperative pathologic assessment to find occult, high-grade carcinomas in this setting.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.

BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Nutrient requirements and low-cost balanced diets, based on seasonally available local feedstuffs, for local pigs on smallholder farms in Western Kenya.

Growth performance of pigs on smallholder farms in the tropics is low. Lack of feedstuffs, seasonal feed shortages, and feeding nutritionally unbalanced diets contribute to slow growth. Low-cost balanced diets are needed to improve pig performance. In this study, we estimated the nutrient requirements of local pigs on smallholder farms in Kenya and developed balanced low-cost diets using seasonally available local feedstuffs. Diets were formulated to provide pigs with 80 % of the nutrient density in corn and soybean meal-based (reference) diets to minimize the cost per unit of energy and other nutrients. Estimated requirements for starting and growing pigs (8 to 35 kg body weight) were as follows: digestible energy (DE) 2960 kcal/kg of dry matter (DM), standardized ileal digestibility (SID) lysine 5.8 g/kg of DM, calcium 2.8 g/kg of DM, standardized total tract digestible (STTD) phosphorous 1.4 g/kg of DM, and crude protein 85 g/kg of DM. Nutrient requirements of local pigs on smallholder farms in Kenya were lower than those of exotic breed pigs raised in commercial settings. Seasonally available local feedstuffs were used to develop low-cost balanced diets. Twenty-two diets are presented based on season, cost, and feedstuff availability. This study has broad applicability as a case study of an approach that could be applied in other tropical regions in which smallholder pig keeping is practiced and where local feedstuffs for pigs are available seasonally.

Regulatory B cells are induced by gut microbiota-driven interleukin-1ß and interleukin-6 production.

Regulatory B cells (Breg cells) differentiate in response to inflammation and subsequently restrain excessive immune responses via the release of interleukin-10 (IL-10). However, the precise inflammatory signals governing their differentiation remain to be elucidated. Here we show that the gut microbiota promotes the differentiation of Breg cells in the spleen as well as in the mesenteric lymph nodes. Perturbation of the gut microbiome imposed either by antibiotic treatment or by changes in the sterility of housing conditions reduces the number and function of Breg cells. Following the induction of arthritis, IL-1ß and IL-6 are produced only in conventionally housed mice and both cytokines directly promote Breg cell differentiation and IL-10 production. Mice lacking IL-6 receptor (IL-6R) or IL-1 receptor 1 (IL-1R1) specifically on B cells have a reduced number of IL-10-producing B cells and develop exacerbated arthritis compared to control animals. Thus, in response to inflammatory signals induced by both the gut flora and arthritis, Breg cells increase in number and restrain excessive inflammation.

RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction.

AIMS: Programmed necrosis (necroptosis) represents a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Like apoptosis, necroptosis is tightly regulated by distinct signalling pathways. A key regulatory role in programmed necrosis has been attributed to interactions of the receptor-interacting protein kinases, RIP1 and RIP3. However, the specific functional role of RIP3-dependent signalling and necroptosis in the heart is unknown. The aims of this study were thus to assess the significance of necroptosis and RIP3 in the context of myocardial ischaemia. METHODS AND RESULTS: Immunoblots revealed strong expression of RIP3 in murine hearts, indicating potential functional significance of this protein in the myocardium. Consistent with a role in promoting necroptosis, adenoviral overexpression of RIP3 in neonatal rat cardiomyocytes and stimulation with TNF-α induced the formation of a complex of RIP1 and RIP3. Moreover, RIP3 overexpression was sufficient to induce necroptosis of cardiomyocytes. In vivo, cardiac expression of RIP3 was up-regulated upon myocardial infarction (MI). Conversely, mice deficient for RIP3 (RIP3(-/-)) showed a significantly better ejection fraction (45 ± 3.6 vs. 32 ± 4.4%, P < 0.05) and less hypertrophy in magnetic resonance imaging studies 30 days after experimental infarction due to left anterior descending coronary artery ligation. This was accompanied by a diminished inflammatory response of infarcted hearts and decreased generation of reactive oxygen species. CONCLUSION: Here, we show that RIP3-dependent necroptosis modulates post-ischaemic adverse remodelling in a mouse model of MI. This novel signalling pathway may thus be an attractive target for future therapies that aim to limit the adverse consequences of myocardial ischaemia.

Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells.

Patients deficient in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) are predisposed to varied autoimmunity, suggesting it has an important controlling role in participating cells. IL-10-producing regulatory B (Breg) cells are emerging as important mediators of immunosuppressive activity. In experimental, antigen-induced arthritis WASp-deficient (WASp knockout [WAS KO]) mice developed exacerbated disease associated with decreased Breg cells and regulatory T (Treg) cells, but increased Th17 cells in knee-draining LNs. Arthritic WAS KO mice showed increased serum levels of B-cell-activating factor, while their B cells were unresponsive in terms of B-cell-activating factor induced survival and IL-10 production. Adoptive transfer of WT Breg cells ameliorated arthritis in WAS KO recipients and restored a normal balance of Treg and Th17 cells. Mice with B-cell-restricted WASp deficiency, however, did not develop exacerbated arthritis, despite exhibiting reduced Breg- and Treg-cell numbers during active disease, and Th17 cells were not increased over equivalent WT levels. These findings support a contributory role for defective Breg cells in the development of WAS-related autoimmunity, but demonstrate that functional competence in other regulatory populations can be compensatory. A properly regulated cytoskeleton is therefore important for normal Breg-cell activity and complementation of defects in this lineage is likely to have important therapeutic benefits.

Degarelix: a review of its use in patients with prostate cancer.

Degarelix (Firmagon(®); Gonax(®)) is a gonadotropin-releasing hormone receptor antagonist that is approved for the treatment of advanced (hormone-dependent) prostate cancer in the US and EU and the treatment of prostate cancer in Japan. In a pivotal randomized, controlled, 12-month phase III study, degarelix (initial subcutaneous dose of 240 mg followed by monthly dosages of 80 mg) was noninferior to leuprolide (monthly intramuscular dosages of 7.5 mg) in patients with prostate cancer of any stage for which endocrine treatment was indicated (except neoadjuvant hormonal therapy) with regard to suppression of testosterone to castration levels (i.e. ≤0.5 ng/mL). Suppression of testosterone and prostate-specific antigen (PSA) levels was faster with degarelix than with leuprolide, and no testosterone surges or microsurges were seen in degarelix recipients. Suppression of testosterone and PSA levels was maintained for the 12-month study duration and continued for up to 5 years in an extension to the main trial (including in patients switching from leuprolide to degarelix in the extension). The drug was generally well tolerated, with most adverse events being mild to moderate in severity. Injection-site reactions and events reflecting the expected effects of testosterone suppression (e.g. hot flushes, weight increase) were the most common treatment-emergent adverse events. Thus, degarelix is a useful option for the treatment of prostate cancer in patients for whom endocrine treatment is indicated.

Evaluating critical factors to the economic feasibility of semi-intensive pig rearing in western Kenya.

The purpose of this research is to assess how season, ADG, opportunity costs of farm-grown feeds, pig weight, and butcher price variation impact the economic potential of semi-intensive pig rearing. We developed a unique algorithm that emulates least-cost pig feeding and used it to assess the impact of the aforementioned factors on farmers' maximum revenue and profit potential when pigs are sold to local butchers in western Kenya. When considered as independent factors influencing feed costs to grow a pig to a market weight of 30 kg, variation in ADG, opportunity cost of feed, and weaning season resulted in feed cost differences of up to 982, 947, and 379 Kenyan shillings (KES), respectively. The variation in revenues attributable to butcher or butcher negotiation and seasonal variance of butcher prices for a 30 kg pig was 744 and 225 KES, respectively. Feed items most commonly chosen for least-cost feed rations were small dried fish, cooked ground maize, whole maize, millet, cassava foliage, sweet potato vines, bone meal, avocado, and mango. Smallholder farmers who can feed pigs to reach higher ADG, have lower opportunity costs of feeds and/or who effectively bargain with butchers can benefit from semi-intensive pig rearing. Farmers without access to at least some zero-cost feeds and farmers with opportunity costs of feeds exceeding 50 % of the market price will not earn positive returns from semi-intensive pig rearing.

Regorafenib: a review of its use in previously treated patients with progressive metastatic colorectal cancer.

Regorafenib (Stivarga) is an inhibitor of multiple protein kinases, including those involved in oncogenesis, tumour angiogenesis and maintenance of the tumour microenvironment. The drug is approved as monotherapy for the treatment of metastatic colorectal cancer (mCRC) in patients who have previously received all standard systemic anticancer treatments (US, EU and Canada) or in patients with unresectable, advanced or recurrent colorectal cancer (Japan). In the randomized, controlled COloRectal cancer treated with REgorafenib or plaCebo after failure of standard Therapy (CORRECT) trial, regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle plus best supportive care (BSC) was associated with a significantly longer median overall survival than placebo plus BSC in patients with previously treated, progressive mCRC. The drug was also associated with significantly longer progression-free survival and better disease control rates than placebo, although objective response rates were similar in both treatment groups. Regorafenib did not appear to compromise health-related quality of life over the study duration and had a generally acceptable tolerability profile. The introduction of regorafenib expands the currently limited range of effective treatment options in patients with previously treated, progressive mCRC.

The association between obsessive compulsive disorder and obsessive compulsive personality disorder: prevalence and clinical presentation.

OBJECTIVES: The relationship between Obsessive Compulsive Disorder (OCD) and Obsessive Compulsive Personality Disorder (OCPD) has been the subject of interest for some time due to the historical assumption that OCPD causes OCD. This study systematically examined the association between OCD and OCPD in terms of prevalence and clinical presentation. The specificity of the association between OCD and OCPD was investigated relative to another axis I anxiety disorder (Panic disorder). DESIGN AND METHOD: Data for this study were drawn from measures taken at initial assessment at a specialist treatment centre for anxiety disorders. Of the 359 participants included in this study, 189 had a principal diagnosis of OCD, while 170 had a principal diagnosis of Panic disorder. Measures included SCID I and II interview modules and self-report measures of anxiety, depression, and OCD syptomatology. RESULTS: Significantly elevated rates of OCPD were found in OCD relative to Panic disorder. Regardless of axis I disorder, individuals with comorbid OCPD reported more severe depression relative to those without. Participants with both OCD and OCPD had greater self-reported OCD symptom severity, doubting, ordering, and hoarding symptoms at assessment relative to those without OCPD. Participants with OCD and comorbid OCPD also reported significantly higher levels of alcohol consumption. CONCLUSIONS: There appears to be a significant and specific association between OCD and OCPD. Co-occurring OCD and OCPD is associated with greater severity of impairment in terms of certain OCD symptoms. CLINICAL IMPLICATIONS: The significant and specific association between OCD and OCPD suggests that OCPD occurs more frequently with OCD than previously suggested. A comorbid OCPD diagnosis is associated with a greater degree of depression, regardless of axis I disorder, either OCD or Panic disorder. This is an important consideration, as depression can interfere with therapeutic progress (Foa, 1979). Participants with OCD and OCPD had greater self-reported OCD severity, along with doubting, ordering, and hoarding symptoms, relative to those without OCPD. In clinical practice, where OCD symptoms are severe, and the primary OCD symptoms include doubting, ordering, and hoarding, this may indicate a need to assess for comorbid OCPD. This may be useful in terms of including relevant information in formulation with the patient, and in addressing these issues in treatment. LIMITATIONS OF THE STUDY: There may have been a sampling issue, as the study compared patients from a specialist clinic for the treatment of OCD and Panic disorder. Furthermore, OCD referrals were primary, secondary, or tertiary, whereas Panic disorder referrals were primary or secondary from the immediate catchment area only. This suggests the possibility of greater severity of the OCD sample relative to Panic disorder patients. All participants who met criteria for OCD were assessed for OCPD regardless of whether or not this was indicated by the SCID II screener self-report measure, while participants with Panic disorder were interviewed for OCPD only if indicated by the SCID-II screener. Had participants with Panic disorder been assessed for OCPD regardless of whether or not this was indicated by the SCID-II screener, there is a possibility that a higher rate of OCPD in the Panic disorder sample may have been found.

Inhaled glycopyrronium bromide: a review of its use in patients with moderate to severe chronic obstructive pulmonary disease.

Inhaled glycopyrronium bromide (Seebri(®) Breezhaler(®) capsules; NVA237) is a once-daily, long-acting muscarinic receptor antagonist (LAMA) that is approved in several countries, including the EU, as a maintenance bronchodilator for the symptomatic treatment of adult patients with chronic obstructive pulmonary disease (COPD). In the randomized, controlled, phase III GLOW (GLycopyrronium bromide in chronic Obstructive pulmonary disease airWays clinical study)-1 and -2 trials, treatment with inhaled glycopyrronium bromide 50 µg once daily was associated with significantly better lung function than placebo in patients with moderate to severe COPD in terms of the trough forced expiratory volume in one second (FEV1) at 12 weeks (primary endpoint). Significant between-group differences in trough FEV1 in favour of inhaled glycopyrronium bromide were maintained for up to 52 weeks. Dyspnoea scores, health status and exacerbation rates were also improved to a greater extent in the inhaled glycopyrronium bromide than placebo groups in these trials. In the randomized, controlled, phase III GLOW3 trial, inhaled glycopyrronium bromide was associated with a significantly longer exercise endurance time than placebo after 3 weeks' treatment in patients with moderate to severe COPD. The drug was generally well tolerated over the 26-week (GLOW1) or 52-week (GLOW2) study duration, and had a tolerability profile that was generally similar to that of tiotropium bromide. Serious adverse events were consistent with those expected in patients with moderate to severe COPD. In conclusion, inhaled glycopyrronium bromide is a once-daily LAMA that is an effective bronchodilator for use in the treatment of patients with moderate to severe COPD.