Pediatr Neurol. 2022 Sep 17;137:49-53. doi: 10.1016/j.pediatrneurol.2022.08.008. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the impact of COVID-19 on evaluations in the pediatric emergency department (ED) because of headache as main symptom.

METHODS: Number and clinical features of patients evaluated in the pediatric ED of a single site in Milan, Italy, were collected between January 2017 and January 2022. The impact of COVID-19 on evaluation rates was quantified by using the incidence rate ratio (IRR) and 95% confidence intervals (CI) between the pandemic (March 2020 to January 2022) and the prepandemic period (January 2017 to February 2020).

RESULTS: During the study period, 890 evaluations were registered: 689 over the prepandemic period and 201 over the pandemic period. Mean age at evaluation was 10 years (range: 1 to 17 years). Evaluation rates per month were 18.1 during the prepandemic period and 8.7 during COVID-19 pandemic, with peaks in autumn and winter months and considerable drops in the summer. The IRR was 0.49 (95% CI, 0.40-0.61). The reduction in evaluation rate was higher for secondary headache (IRR, 0.31; 95% CI, 0.23-0.42) when compared with primary headache (IRR, 0.56; 95% CI, 0.40-0.78).

CONCLUSIONS: We found a remarkable reduction in the number of evaluations in the pediatric ED for headache during the pandemic period.

PMID:36242889 | DOI:10.1016/j.pediatrneurol.2022.08.008

Obstet Gynecol Surv. 2022 Oct;77(10):606-610. doi: 10.1097/OGX.0000000000001062.

ABSTRACT

IMPORTANCE: Cystic fibrosis (CF) is one of the most common autosomal recessive disorders. Carrier screening for CF should be offered to all women considering becoming pregnant or who are pregnant. Understanding the available screening tests, their limitations, and the benefits of screening is of paramount importance to the obstetrician-gynecologist.

OBJECTIVES: The objective is to review the current guidelines for CF carrier screening including the options for carrier screening, the potential complexities associated with carrier screening for CF, and indications for referral to certified genetic counselors or maternal-fetal medicine specialists.

EVIDENCE ACQUISITION: A MEDLINE search of "cystic fibrosis," "cystic fibrosis carrier screening pregnancy," and "inheritance of cystic fibrosis" in the review was performed.

RESULTS: The evidence cited in this review includes 2 medical society committee opinions and 15 additional peer-reviewed journal articles that were original research or expert opinion summaries.

CONCLUSIONS AND RELEVANCE: The American College of Obstetricians and Gynecologists recommends that obstetricians offer CF carrier screening to all pregnant women or women considering becoming pregnant. Based on recent guidelines from ACMG, additional expanded carrier screening can be recommended to patients in the future, with additional CF variants and other autosomal or X-linked recessive conditions. It is important for the prenatal care provider to understand the guidelines for carrier screening as well as the potential complexities associated with carrier screening due to the multiple pathogenic variants in the CFTR gene that may be associated with varying phenotypes. With the options for CF carrier screening, screening performance in different populations, a basic understanding of the disease and interpretation of carrier screening results is of paramount importance to the prenatal care provider.

PMID:36242530 | DOI:10.1097/OGX.0000000000001062

J Obstet Gynaecol Can. 2022 Oct;44(10):1104-1112. doi: 10.1016/j.jogc.2022.08.012.

ABSTRACT

These documents have been archived because they contain outdated information. They should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines. The Use of Magnetic Resonance Imaging in the Obstetric Patient [J Obstet Gynaecol Can 36 (2014) 349-355] AUTHORS Yves Patenaude, MD, Sherbrooke, QC Denise Pugash, MD, Vancouver, BC Kenneth Lim, MD, Vancouver, BC Lucie Morin, MD, Montreal, QC The Role of Surgery in Endometrial Cancer [J Obstet Gynaecol Can 35 (2013) 370-371] AUTHORS Christopher Giede, MD, Saskatoon, SK Tien Le, MD, Ottawa, ON Patti Power, MD, St John's, NL Female Genital Cutting [J Obstet Gynaecol Can 35 (2013) 1028-1045] AUTHORS Liette Perron, MSW, Ottawa, ON Vyta Senikas, MD, Ottawa, ON Margaret Burnett, MD, Winnipeg, ON Victoria Davis, MD, Scarborough, ON Technical Update on Pessary Use [J Obstet Gynaecol Can 35 (2013) 664-674] AUTHORS Magali Robert, MD, Calgary, AB Jane A. Schulz, MD, Edmonton, AB Marie-Andrée Harvey, MD, Kingston, ON Cancer Chemotherapy and Pregnancy [J Obstet Gynaecol Can 35 (2013) 263-278] AUTHORS Gideon Koren, MD, Toronto, ON Nathalie Carey, BSc, Toronto, ON Robert Gagnon, MD, Montréal, QC Cynthia Maxwell, MD, Toronto, ON Irena Nulman, MD, Toronto, ON Vyta Senikas, MD, Ottawa, ON Current Status in Non-Invasive Prenatal Detection of Down Syndrome, Trisomy 18, and Trisomy 13 Using Cell-Free DNA in Maternal Plasma [J Obstet Gynaecol Can 35 (2013) 177-181] AUTHORS Sylvie Langlois, MD, Vancouver, BC Jo-Ann Brock, MD, Halifax, NS Mifepristone [J Obstet Gynaecol Can 25 (2003) 235] The Presence of a Third Party During Breast and Pelvic Examinations [J Obstet Gynaecol Can 25 (2003) 237] Midwifery [J Obstet Gynaecol Can 25 (2003) 239] Emergency Contraception [J Obstet Gynaecol Can 25 (2003) 673-678] Tension-Free Vaginal Tape (TVT) Procedure [J Obstet Gynaecol Can 25 (2003) 692-694] Uterine Fibroid Embolization (UFE) [J Obstet Gynaecol Can 26 (2004) 899-911] AUTHORS Guylaine G. Lefebvre, MD, Toronto, ON George Vilos, MD, Toronto, ON Murray Asch, MD, Oshawa, ON The Prevention of Early-Onset Neonatal Group B Streptococcal Disease [J Obstet Gynaecol Can 26 (2004) 826-832] AUTHORS Deborah M. Money, MD, FRCSC, Vancouver, BC Simon Dobson, MD, FRCPC, Vancouver, BC Cell-Free Fetal DNA in the Maternal Circulation and its Future Uses in Obstetrics [J Obstet Gynaecol Can 27 (2005) 54-57] AUTHOR R. Douglas Wilson, MD, Philadelphia, PA Cystic Fibrosis Carrier Testing in Pregnancy in Canada [J Obstet Gynaecol Can 24 (2002) 644-647] Amniocentesis and Women with Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus [J Obstet Gynaecol Can 25 (2003) 145-148] Fetal Health Surveillance in Labour [J Obstet Gynaecol Can 24 (2002) 250-262] Management of the Third Stage of Labour to Prevent Postpartum Hemorrhage [J Obstet Gynaecol Can 25 (2003) 952-953] Cervical Cancer Prevention in Low-Resource Settings [J Obstet Gynaecol Can 26 (2004) 205-206] Hirsutism: Evaluation and Treatment [J Obstet Gynaecol Can 24 (2002) 62-67] Breast Cancer, Pregnancy, and Breastfeeding [J Obstet Gynaecol Can 24 (2002) 164-171] Parvovirus B19 Infection in Pregnancy [J Obstet Gynaecol Can 24 (2002) 727-734] Diversity [J Obstet Gynaecol Can 25 (2003) 1042] Conflict of Interest [J Obstet Gynaecol Can 25 (2003) 1044] Canadian Contraception Consensus [J Obstet Gynaecol Can 26 (2004) 347-387] School-Based and School-Linked Sexual Health Education and Promotion in Canada [J Obstet Gynaecol Can 26 (2004) 596-600] Gestational Trophoblastic Disease [J Obstet Gynaecol Can 24 (2002) 434-439] FIGO Professional and Ethical Responsibilities Concerning Sexual and Reproductive Rights [J Obstet Gynaecol Can 26 (2004) 1097-1099] FIGO / ICM Global Initiative to Prevent Post-Partum Hemorrhage [J Obstet Gynaecol Can 26 (2004) 1102] Intimate Partner Violence Consensus Statement [J Obstet Gynaecol Can 27 (2005) 365-388] The Management of Nausea and Vomiting of Pregnancy [J Obstet Gynaecol Can 24 (2002) 817-823] Canadian Contraception Consensus [J Obstet Gynaecol Can 26 (2004) 143-156] Present Role of Stem Cells for Fetal Genetic Therapy [J Obstet Gynaecol Can 27 (2005) 1038-1042] Amended Canadian Guideline for Prenatal Diagnosis (2005) Change to 2005-Techniques for Prenatal Diagnosis [J Obstet Gynaecol Can 27 (2005) 1048-1054] Umbilical Cord Blood Banking: Implications for Perinatal Care Providers [J Obstet Gynaecol Can 27 (2005) 263-274] Breast Cancer and Abortion [J Obstet Gynaecol Can 27 (2005) 491] AUTHOR Robert H. Lea, MD, Halifax, NS Postural Health in Women: The Role of Physiotherapy [J Obstet Gynaecol Can 27 (2005) 493-500] AUTHORS S.J. Britnell, BScPT, Vancouver, BC J.V. Cole, BScPT, Vancouver, BC L. Isherwood, BScPT, Vancouver, BC M.M. Sran, PT, BScPT, Vancouver, BC N. Britnell, BScPT, Vancouver, BC S. Burgi, BScPT, Vancouver, BC G. Candido, BScPT, Vancouver, BC L. Watson, BScPT, Vancouver, BC The Management of Uterine Leiomyomas [J Obstet Gynaecol Can 25 (2003) 396-405] Guidelines for Vaginal Birth after Previous Caesarean Birth [J Obstet Gynaecol Can 26 (2004) 660-670] Fetal Health Surveillance in Labour [J Obstet Gynaecol Can 24 (2002) 342-348] Number of Births to Maintain Competence [J Obstet Gynaecol Can 24 (2002) 359] Sexual Abuse by Physicians [J Obstet Gynaecol Can 25 (2003) 862] The Use of First Trimester Ultrasound [J Obstet Gynaecol Can 25 (2003) 864-869] Use of Hormonal Replacement Therapy After Treatment of Breast Cancer [J Obstet Gynaecol Can 26 (2004) 49-54] Obstetric Ultrasound Biological Effects and Safety [J Obstet Gynaecol Can 27 (2005) 572-575] Fetal Soft Markers in Obstetric Ultrasound [J Obstet Gynaecol Can 27 (2005) 592-612] Maternal Transport Policy [J Obstet Gynaecol Can 27 (2005) 956-959] Choice of Surgery for Stress Incontinence [J Obstet Gynaecol Can 27 (2005) 964-971] The Use of Fetal Doppler in Obstetrics [J Obstet Gynaecol Can 25 (2003) 601-607] Screening for Gestational Diabetes Mellitus [J Obstet Gynaecol Can 24 (2002) 894-903] Hormone Replacement Therapy and Cardiovascular Disease [J Obstet Gynaecol Can 24 (2002) 577-579] Providing Opinion for Medico-Legal Cases [J Obstet Gynaecol Can 24 (2002) 590-592] Antenatal Corticosteroid Therapy for Fetal Maturation [J Obstet Gynaecol Can 25 (2003) 45-48] Mastalgia [J Obstet Gynaecol Can 28 (2006) 49-57] AUTHORS Vera Rosolowich, RN, SCM, IBCLC, Winnipeg, MB Elizabeth Saettler, MD, Winnipeg, MB Beth Szuck, BA, HEc, CACE, RD, Winnipeg, MB Pregnancy Outcomes After Assisted Reproductive Technology [J Obstet Gynaecol Can 28 (2006) 220-233] AUTHORS Victoria M. Allen, MD, MSc, Halifax, NS R. Douglas Wilson, MD, MSc, Philadelphia, PA Canadian Contraception Consensus-Update on Depot Medroxyprogesterone Acetate (DMPA) [J Obstet Gynaecol Can 28 (2006) 305-308] AUTHOR Amanda Black, MD, Ottawa, ON Guidelines for Training Requirements in Colposcopy and its Related Treatment Modalities [J Obstet Gynaecol Can 28 (2006) 314-316] AUTHOR Susan M. McFaul, MD, Ottawa, ON Pelvic Examinations by Medical Trainees [J Obstet Gynaecol Can 28 (2006) 320-321] AUTHORS Kimberly E. Liu, MD, Edmonton, AB Deborah Robertson, MD, Montréal, QC Glenn Posner, MDCM, Ottawa, ON Sukhbir S. Singh, MD, London, ON Lawrence Oppenheimer, MD, Ottawa, ON Stillbirth and Bereavement: Guidelines for Stillbirth Investigation [J Obstet Gynaecol Can 28 (2006) 540-545] AUTHOR Line Leduc, MD, Montréal, QC Progesterone-Only and Non-Hormonal Contraception in the Breast Cancer Survivor: Joint Review and Committee Opinion of the Society of Obstetricians and Gynaecologists of Canada and the Society of Gynecologic Oncologists of Canada [J Obstet Gynaecol Can 28 (2006) 616-626] AUTHORS Jenna McNaught, MD, Winnipeg, MB Robert L. Reid, MD, Kingston, ON Breast Self-Examination [J Obstet Gynaecol Can 28 (2006) 728-730] AUTHOR Vera Rosolowich, RN, SCM, IBCLC, Winnipeg, MB The Physician Expert in Legal Proceedings [J Obstet Gynaecol Can 28 (2006) 913-915] AUTHORS Titus Owolabi, MD, Toronto, ON George Vilos, MD, Toronto, ON Induced Abortion Guidelines [J Obstet Gynaecol Can 28 (2006) 1014-1027] AUTHOR Victoria Jane Davis, MD Health Professionals Working With First Nations, Inuit, and Métis Consensus Guideline [J Obstet Gynaecol Can 35 (2013) S1-S4] AUTHORS Don Wilson, MD, FRCSC (Co-chair), Hellisuk Nation, Comox, BC Sandra de la Ronde, MD, FRCSC (Co-chair), Ottawa, ON Simon Brascoupé, Kitigan Zibi Anishinabeg, Ottawa, ON Alisha Nicole Apale, MSc, Ottawa, ON Lucy Barney, RN, MSN, Lillooet Nation, Vancouver, BC Bing Guthrie, MD, FRCSC, Yellowknife, NT Elizabeth Harrold, RN, Vancouver, BC Ojistoh Horn, MD, CCFP, Mohawk, Kahnawake, QC Robin Johnson, MD, FRCSC, Esdilagh, First Nation, Williams Lake, BC Darrien Rattray, MD, Tahltan, Halifax, NS Nicole Robinson, MA, Ottawa, ON Introduction [J Obstet Gynaecol Can 35 (2013) S5-S6] Chapter 1 Definitions [J Obstet Gynaecol Can 35 (2013) S7-S8] Chapter 2 Demographics [J Obstet Gynaecol Can 35 (2013) S9-S12] Chapter 3 Social Determinants of Health Among First Nations, Inuit, and Métis [J Obstet Gynaecol Can 35 (2013) S13-S23] Chapter 4 Health Systems, Policies, and Services for First Nations, Inuit, and Métis [J Obstet Gynaecol Can 35 (2013) S24-S27] Chapter 5 First Nations, Inuit, and Métis Women's Sexual and Reproductive Health [J Obstet Gynaecol Can 35 (2013) S28-S32] Chapter 6 First Nations, Inuit, and Métis Maternal Health [J Obstet Gynaecol Can 35 (2013) S33-S36] Chapter 7 Mature Women's Health [J Obstet Gynaecol Can 35 (2013) S37] Chapter 8 Changing Outcomes Through Culturally Competent Care [J Obstet Gynaecol Can 35 (2013) S38-S41] Chapter 9 Conclusion [J Obstet Gynaecol Can 35 (2013) S42-S43] Chapter 10 Case Studies [J Obstet Gynaecol Can 35 (2013) S44-S47] Appendix 1. Apology for the Forced Relocation of Inukjuak and Pond Inlet Families [J Obstet Gynaecol Can 35 (2013) S48] Appendix 2. Apology for the Residential School System [J Obstet Gynaecol Can 35 (2013) S49] Appendix 3. Avoiding Re-Traumatization of Sexual Abuse/Assault Victims During the Birthing Process [J Obstet Gynaecol Can 35 (2013) S50].

PMID:36241341 | DOI:10.1016/j.jogc.2022.08.012

Eur J Pharm Biopharm. 2022 Oct 11:S0939-6411(22)00230-2. doi: 10.1016/j.ejpb.2022.10.005. Online ahead of print.

ABSTRACT

Co-amorphization of a single drug with amino acid is a technique to improve aerosolization of inhalable spray-dried formulation for inhalation therapy. However, the incorporation of a second drug molecule into drug-amino acid co-amorphous particles to prepare combination formulations has not been explored. Here, we prepared combination powders using two model drugs, ceftazidime and roflumilast, which when concurrently used can potentially improve therapeutic outcome in non-cystic fibrosis bronchiectasis by counteracting both infection and inflammation. The study was performed using a two-step approach. The first step involved the identification of an amino acid and its concentration (% w/w) for the best aerosolization enhancement of ceftazidime by varying the ratios of leucine and tryptophan in combination (0-25% w/w). In the second step, roflumilast (5-20% w/w) was incorporated into the formulation containing the selected concentration of the amino acid to understand the impact of introducing a second drug into ceftazidime-amino acid(s) co-amorphous particles. In total, 10 formulations were prepared and characterized in terms of solid-state and aerosol performance. Leucine introduced surface asperity which correlated well with improved aerosolization of the particles. The best fine particle fraction (FPF) (75%) was achieved with 25% leucine; hence, leucine was selected as the ideal amino acid at the given concentration to understand the impact of roflumilast inclusion on ceftazidime-leucine system. The ceftazidime-roflumilast powder retained their antibacterial and anti-inflammatory properties following formulation. However, inclusion of roflumilast at 5% dramatically decreased the FPF to 55% and higher roflumilast concentration did not have much effect on FPF. The decrease in FPF ascribed to the change in particle surface as roflumilast was found to decrease surface asperity. In addition, leucine crystallized with inclusion of roflumilast. This study indicates that inclusion of a second drug into drug-amino acid amorphous matrix particles can affect its solid-state dynamics and aerosol performance; hence, such parameters should be cautiously considered while undertaking similar endeavors of preparing combination formulations.

PMID:36241076 | DOI:10.1016/j.ejpb.2022.10.005

Transplantation. 2022 Oct 13. doi: 10.1097/TP.0000000000004400. Online ahead of print.

NO ABSTRACT

PMID:36240442 | DOI:10.1097/TP.0000000000004400

Curr Med Chem. 2022 Oct 14. doi: 10.2174/0929867330666221014110730. Online ahead of print.

NO ABSTRACT

PMID:36239719 | DOI:10.2174/0929867330666221014110730

Lab Chip. 2022 Oct 14. doi: 10.1039/d2lc00728b. Online ahead of print.

ABSTRACT

Microbes are typically found in multi-species (polymicrobial) communities. Cooperative and competitive interactions between species, mediated by diffusible factors and physical contact, leads to highly dynamic communities that undergo changes in composition diversity and size. Infections can be more severe or more difficult to treat when caused by multiple species. Interactions between species can improve the ability of one or more species to tolerate anti-microbial treatments and host defenses. Pseudomonas aeruginosa (Pa), a ubiquitous bacterium, and the opportunistic pathogenic yeast, Candida albicans (Ca), are frequently found together in cystic fibrosis lung infections and wound infections. While significant progress has been made in determining interactions between Pa and Ca, there are still important questions that remain unanswered. Here, we probe the mutual interactions between Pa and Ca in a custom-made microfluidic device using biopolymer chitosan membranes that support cross-species communication. By assembling microbes in physically separated, chemically communicating populations or bringing into direct interactions in a mixed culture, in situ polymicrobial growth and biofilm morphology were qualitatively characterized and quantified. Our work reveals new dynamic details of their mutual interactions including cooperation, competition, invasion, and biofilm formation. The membrane-based microfluidic platform can be further developed to understand the polymicrobial interactions within a controlled interactive microenvironment to improve microbial infection prevention and treatment.

PMID:36239125 | DOI:10.1039/d2lc00728b

J Inflamm Res. 2022 Oct 10;15:5677-5685. doi: 10.2147/JIR.S365772. eCollection 2022.

ABSTRACT

OBJECTIVE AND DESIGN: Cystic fibrosis-related diabetes (CFRD) is a severe complication associated with increased morbidity and mortality in cystic fibrosis (CF) patients. Extensive inflammatory state in CF leads to pancreas damage and insulin resistance with consequent altered glucose tolerance and CFRD development. The aim of the present study was to identify circulating levels of inflammatory markers specifically associated with impaired glucose tolerance (IGT) and overt CFRD in a sample of young adults with CF.

MATERIALS AND METHODS: Sixty-four CF outpatients, without evident active pulmonary exacerbation, infectious and autoimmune diseases, were enrolled in the study and the levels of 45 inflammatory serum mediators were measured through x magnetic bead panel multiplex technology.

RESULTS: Serum levels of PDGF-AA, CCL20/MIP3α, IFNα, CCL11/eotaxin, CXCL1/GROα, GMCSF, B7H1/PDL1, IL13, IL7, VEGF, and TGFα were all significantly (p<0.05) elevated in patients according to glycemic status and directly correlated with glycated hemoglobin and C-reactive protein levels.

CONCLUSION: Our findings suggest that increased levels of specific circulating inflammatory mediators are directly associated with impaired glucose tolerance in CF patients, thus, potentially implicating them in CFRD pathogenesis and warranting larger longitudinal studies to validate their monitoring as predictor of CFRD onset.

PMID:36238762 | PMC:PMC9553277 | DOI:10.2147/JIR.S365772

Respir Med Case Rep. 2022 Oct 5;40:101750. doi: 10.1016/j.rmcr.2022.101750. eCollection 2022.

ABSTRACT

Here, we describe a cystic fibrosis (CF) family with affected siblings, two of whom have a combination of I1234V and 1677delTA variants with classic CF features, the third child with a combination of I1234V and L997F variants with atypical CF, and the apparently healthy mother with a combination of 1677delTA and L997F alleles. Interestingly, the sibling with I1234V and L997F variants had normal sweat test results and had a much milder phenotype than the other two siblings with I1234V and 1677delTA variants, suggesting that this combination is causative for atypical CF. The fact that their mother with the combination of 1677delTA and L997F appears to be healthy suggests that the L997F variant causes different phenotypes in different allele combinations. The current cases show that there is a genotype-phenotype correlation in this disease and underline the importance of genotyping individuals with suspected CF to allow prediction of disease severity and effective treatment.

PMID:36238659 | PMC:PMC9550642 | DOI:10.1016/j.rmcr.2022.101750

Front Endocrinol (Lausanne). 2022 Sep 27;13:953879. doi: 10.3389/fendo.2022.953879. eCollection 2022.

ABSTRACT

OBJECTIVE: Studies investigating strategies to limit the risk of nocturnal hypoglycemia associated with physical activity (PA) are scarce and have been conducted in standardized, controlled conditions in people with type 1 diabetes (T1D). This study sought to investigate the effect of daily PA level on nocturnal glucose management in free-living conditions while taking into consideration reported mitigation strategies to limit the risk of nocturnal hyoglycemia in people with T1D.

METHODS: Data from 25 adults (10 males, 15 females, HbA1c: 7.6 ± 0.8%), 20-60 years old, living with T1D, were collected. One week of continuous glucose monitoring and PA (assessed using an accelerometer) were collected in free-living conditions. Nocturnal glucose values (midnight-6:00 am) following an active day "ACT" and a less active day "L-ACT" were analyzed to assess the time spent within the different glycemic target zones (<3.9 mmol/L; 3.9 - 10.0 mmol/L and >10.0 mmol/L) between conditions. Self-reported data about mitigation strategies applied to reduce the risk of nocturnal hypoglycemia was also analyzed.

RESULTS: Only 44% of participants reported applying a carbohydrate- or insulin-based strategy to limit the risk of nocturnal hypoglycemia on ACT day. Nocturnal hypoglycemia occurrences were comparable on ACT night versus on L-ACT night. Additional post-meal carbohydrate intake was higher on evenings following ACT (27.7 ± 15.6 g, ACT vs. 19.5 ± 11.0 g, L-ACT; P=0.045), but was frequently associated with an insulin bolus (70% of participants). Nocturnal hypoglycemia the night following ACT occurred mostly in people who administrated an additional insulin bolus before midnight (3 out of 5 participants with nocturnal hypoglycemia).

CONCLUSIONS: Although people with T1D seem to be aware of the increased risk of nocturnal hypoglycemia associated with PA, the risk associated with additional insulin boluses may not be as clear. Most participants did not report using compensation strategies to reduce the risk of PA related late-onset hypoglycemia which may be because they did not consider habitual PA as something requiring treatment adjustments.

PMID:36237197 | PMC:PMC9551602 | DOI:10.3389/fendo.2022.953879

Pediatr Pulmonol. 2022 Oct 13. doi: 10.1002/ppul.26209. Online ahead of print.

ABSTRACT

BACKGROUND: Newborn screening (NBS) algorithms for cystic fibrosis (CF) vary in the USA and include different CFTR variants. CFTR variant distribution varies among racial and ethnic groups.

OBJECTIVE: Our objectives were to identify differences in detection rate by race and ethnicity for CFTR variant panels, identify each U.S. state detection rate for CFTR variant panels, and describe the rate of false-negative NBS and delayed diagnoses by race and ethnicity.

METHODS: This is a cross-sectional analysis of the detection rate of at least 1 CFTR variant for 7 panels by race and ethnicity in genotyped people with CF (PwCF) or CRMS/CFTR-related disorders in CF Foundation Patient Registry (CFFPR) in 2020. We estimated the case detection rate of CFTR variant panels by applying the detection rate to Census data. Using data from CFFPR, we compared the rate of delayed diagnosis or false-negative NBS by race and ethnicity.

RESULTS: For all panels, detection of at least 1 CFTR variant was highest in non-Hispanic White PwCF (87.5-97.0%), and lowest in Black, Asian, and Hispanic PwCF (41.9-93.1%). Detection of at least 1 CFTR variant was lowest in Black and Asian people with CRMS/CFTR-related disorders (48.4-64.8%). States with increased racial and ethnic diversity have lower detection rates for all panels. Overall, 3.8% PwCF had a false-negative NBS and 11.8% had a delayed diagnosis; Black, Hispanic, and mixed-race PwCF were over-represented.

CONCLUSION: CFTR variant panels have lower detection rates in minoritized racial and ethnic groups leading to false-negative NBS, delayed diagnosis, and likely health disparities. This article is protected by copyright. All rights reserved.

PMID:36237137 | DOI:10.1002/ppul.26209

Int J Mol Sci. 2022 Sep 29;23(19):11528. doi: 10.3390/ijms231911528.

ABSTRACT

A small library of new angelicin derivatives was designed and synthesized with the aim of bypassing the side effects of trimethylangelicin (TMA), a promising agent for the treatment of cystic fibrosis. To prevent photoreactions with DNA, hindered substituents were inserted at the 4 and/or 6 positions. Unlike the parent TMA, none of the new derivatives exhibited significant cytotoxicity or mutagenic effects. Among the synthesized compounds, the 4-phenylderivative 12 and the 6-phenylderivative 25 exerted a promising F508del CFTR rescue ability. On these compounds, preliminary in vivo pharmacokinetic (PK) studies were carried out, evidencing a favorable PK profile per se or after incorporation into lipid formulations. Therefore, the selected compounds are good candidates for future extensive investigation to evaluate and develop novel CFTR correctors based on the angelicin structure.

PMID:36232826 | DOI:10.3390/ijms231911528

Int J Mol Sci. 2022 Sep 28;23(19):11443. doi: 10.3390/ijms231911443.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and ultimately fatal diffuse parenchymal lung disease. The molecular mechanisms of fibrosis in IPF patients are not fully understood and there is a lack of effective treatments. For decades, different types of drugs such as immunosuppressants and antioxidants have been tested, usually with unsuccessful results. Although two antifibrotic drugs (Nintedanib and Pirfenidone) are approved and used for the treatment of IPF, side effects are common, and they only slow down disease progression without improving patients' survival. Macrophages are central to lung homeostasis, wound healing, and injury. Depending on the stimulus in the microenvironment, macrophages may contribute to fibrosis, but also, they may play a role in the amelioration of fibrosis. In this review, we explore the role of macrophages in IPF in relation to the fibrotic processes, epithelial-mesenchymal transition (EMT), and their crosstalk with resident and recruited cells and we emphasized the importance of macrophages in finding new treatments.

PMID:36232756 | DOI:10.3390/ijms231911443

Int J Mol Sci. 2022 Sep 27;23(19):11396. doi: 10.3390/ijms231911396.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a plasma membrane protein expressed on the apical surface of secretory epithelia of the airways. In the airways, defective or absent function of the CFTR protein determines abnormalities of chloride and bicarbonate secretion and, in general, of the transepithelial homeostasis that lead to alterations of airway surface liquid (ASL) composition and properties. The reduction of ASL volume impairs ciliary beating with the consequent accumulation of a sticky mucus. This situation prevents normal mucociliary clearance, favoring the survival and proliferation of bacteria and contributing to the genesis of the CF pulmonary disease. We explored the potential of some CFTR modulators, namely ivacaftor, tezacaftor, elexacaftor and their combination KaftrioTM, capable of partially recovering the basic defects of the CFTR protein, to ameliorate the transepithelial fluid transport and the viscoelastic properties of the mucus when used singly or in combination. Primary human bronchial epithelial cells obtained from CF and non-CF patients were differentiated into a mucociliated epithelia in order to assess the effects of correctors tezacaftor, elexacaftor and their combination with potentiator ivacaftor on the key properties of ASL, such as fluid reabsorption, viscosity, protein content and pH. The treatment of airway epithelia bearing the deletion of a phenylalanine at position 508 (F508del) in the CFTR gene with tezacaftor and elexacaftor significantly improved the pericilial fluid composition, reducing the fluid reabsorption, correcting the ASL pH and reducing the viscosity of the mucus. KaftrioTM was more effective than single modulators in improving all the evaluated parameters, demonstrating once more that this combination recently approved for patients 6 years and older with cystic fibrosis who have at least one F508del mutation in the CFTR gene represents a valuable tool to defeat CF.

PMID:36232697 | DOI:10.3390/ijms231911396

Eur Respir J. 2022 Oct 13:2200611. doi: 10.1183/13993003.00611-2022. Online ahead of print.

ABSTRACT

INTRODUCTION: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India.

METHODS: The EMBARC-India registry is a prospective observational study of adults with CT confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: Mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and FEV1 decline.

RESULTS: 1018 patients with at least 12 months follow-up data were enrolled in the follow-up study. Frequent exacerbations (3 or more per year) at baseline were associated with an increased risk of mortality (hazard ratio(HR) 3.23 95%CI 1.39-7.50), severe exacerbations (HR 2.71 95%CI 1.92-3.83), future exacerbations (rate ratio(RR) 3.08 95%CI 2.36-4.01) and lung function decline. Co-existing COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all endpoints studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular co-morbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13 95%CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41 95%CI 1.01-1.97) and overall exacerbation rate (RR 1.47 95%CI 1.13-1.91).

CONCLUSION: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and Asthma and Lung UK.

PMID:36229049 | DOI:10.1183/13993003.00611-2022

Eur Respir J. 2022 Oct 13:2200606. doi: 10.1183/13993003.00606-2022. Online ahead of print.

ABSTRACT

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.

METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.

RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).

CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

PMID:36229046 | DOI:10.1183/13993003.00606-2022

Adv Drug Deliv Rev. 2022 Oct 10:114540. doi: 10.1016/j.addr.2022.114540. Online ahead of print.

ABSTRACT

Mucin glycoproteins are the major component of mucus and coat epithelial cell surfaces forming the glycocalyx. The glycocalyx and mucus are involved in the transport of nutrients, drugs, gases, and pathogens toward the cell surface. Mucins are also involved in diverse diseases such as cystic fibrosis and cancer. Due to inherent heterogeneity in native mucin structure, many synthetic materials have been designed to probe mucin chemistry, biology, and physics. Such materials include various glycopolymers, low molecular weight glycopeptides, glycopolypeptides, polysaccharides, and polysaccharide-protein conjugates. This review highlights advances in the area of design and synthesis of mucin mimic materials, and their biomedical applications in glycan binding, epithelial models of infection, therapeutic delivery, vaccine formulation, and beyond.

PMID:36228896 | DOI:10.1016/j.addr.2022.114540

JMIR Res Protoc. 2022 Jun 16. doi: 10.2196/39080. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic is negatively impacting the mental health of both COVID-19 patients and the general population. As current guidelines are limiting in-person contacts to reduce the spread of the virus, the development of a digital approach to implement in psychiatric and psychological consultation is needed. In this paper we present the DigiCOVID protocol, a digital approach to offer remote, personalized psychological and psychiatric support to former or current COVID-19 patients and/or their relatives.

OBJECTIVE: The main goal of this project is to evaluate the feasibility, acceptability and usability of the DigiCOVID protocol. Furthermore, we also aim to assess the impact of the abovementioned protocol by means of pre-post changes in psychological clinical variables.

METHODS: Participants undergo an initial telephonic screening to ensure inclusion criteria are met. Secondly, participants complete a video-assisted neuropsychological IQ test, and complete online self-reports of health and general wellbeing. Participants are then assigned to a psychotherapist who offers 8 tele-therapy sessions. At the end of the therapy cycle, the online questionnaires are administered for a post-treatment evaluation.

RESULTS: As of April 2022, we enrolled a total of 122 subjects, of which 94 have completed neuropsychological tests and online questionnaires.

CONCLUSIONS: Our study aims at testing the feasibility and preliminary efficacy of DigiCOVID, a remote tele-medicine protocol for the improvement of psychological and psychiatric health in COVID-19 patients and their relatives. To date, the approach used seems to be feasible and highly customizable to patients' needs, and thus the DigiCOVID protocol might pave the way for future tele-psychiatry-based interventions.

CLINICALTRIAL: This study was approved by our local Ethics Committee (IRCCS Ca' Granda Ospedale Maggiore Policlinico) on 28.10.2020. The trial is registered on clinicaltrials.gov with the following ID: NCT05231018.

INTERNATIONAL REGISTERED REPORT: DERR1-10.2196/39080.

PMID:36228130 | DOI:10.2196/39080

J Antimicrob Chemother. 2022 Oct 13:dkac320. doi: 10.1093/jac/dkac320. Online ahead of print.

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa infection is the leading cause of death among patients with cystic fibrosis (CF) and a common cause of difficult-to-treat hospital-acquired infections. P. aeruginosa uses several mechanisms to resist different antibiotic classes and an individual CF patient can harbour multiple resistance phenotypes.

OBJECTIVES: To determine the rates and distribution of polyclonal heteroresistance (PHR) in P. aeruginosa by random, prospective evaluation of respiratory cultures from CF patients at a large referral centre over a 1 year period.

METHODS: We obtained 28 unique sputum samples from 19 CF patients and took multiple isolates from each, even when morphologically similar, yielding 280 unique isolates. We performed antimicrobial susceptibility testing (AST) on all isolates and calculated PHR on the basis of variability in AST in a given sample. We then performed whole-genome sequencing on 134 isolates and used a machine-learning association model to interrogate phenotypic PHR from genomic data.

RESULTS: PHR was identified in most sampled patients (n = 15/19; 79%). Importantly, resistant phenotypes were not detected by routine AST in 26% of patients (n = 5/19). The machine-learning model, using the extended sampling, identified at least one genetic variant associated with phenotypic resistance in 94.3% of isolates (n = 1392/1476).

CONCLUSION: PHR is common among P. aeruginosa in the CF lung. While traditional microbiological methods often fail to detect resistant subpopulations, extended sampling of isolates and conventional AST identified PHR in most patients. A machine-learning tool successfully identified at least one resistance variant in almost all resistant isolates by leveraging this extended sampling and conventional AST.

PMID:36227655 | DOI:10.1093/jac/dkac320

Lab Med. 2022 Oct 11:lmac101. doi: 10.1093/labmed/lmac101. Online ahead of print.

ABSTRACT

A burdensome, atypical phenotype of Staphylococcus aureus (SA) called S aureus small colony variant (SA-SCV) has been identified, which is induced as a result of a combination of environmental stressors, including polymicrobial interactions. The SA-SCVs exhibit altered phenotypes as a result of metabolic dormancy caused by electron transport deficiency, leading to increased biofilm production and alterations to antimicrobial susceptibility. The SA-SCVs typically exhibit altered colony morphology and biochemical reactions compared with wild-type SA, making them difficult to detect via routine diagnostics. The SA-SCVs have been found to contribute to chronic or recurrent infections, including skin and soft-tissue infections, foreign-body associated infection, cystic fibrosis, and sepsis. There is evidence that SA-SCVs contribute to patient morbidity and mortality as a result of diagnostic difficulties and limited treatment options. New detection methods may need to be developed that can be incorporated into routine diagnostics, which would allow for better assessment of specimens and introduce new considerations for treatment.

PMID:36226897 | DOI:10.1093/labmed/lmac101