Gastrointest Endosc Clin N Am. 2022 Jan;32(1):27-43. doi: 10.1016/j.giec.2021.08.006.

ABSTRACT

Hereditary pancreatitis (HP) is a rare inherited chronic pancreatitis (CP) with strong genetic associations, with estimated prevalence ranging from 0.3 to 0.57 per 100,000 across Europe, North America, and East Asia. Apart from the most well-described genetic variants are PRSS1, SPINK1, and CFTR, many other genes, such as CTRC, CPA1, and CLDN2 and CEL have been found to associate with HP, typically in one of the 3 main mechanisms such as altered trypsin activity, pancreatic ductal cell secretion, and calcium channel regulation. The current mainstay of management for patients with HP comprises genetic testing for eligible individuals and families, alcohol and tobacco cessation avoidance, pain control, and judicious screening for complications, including exocrine and endocrine insufficiency and pancreatic cancer.

PMID:34798985 | DOI:10.1016/j.giec.2021.08.006

Braz J Anesthesiol. 2021 Nov 17:S0104-0014(21)00390-0. doi: 10.1016/j.bjane.2021.07.041. Online ahead of print.

ABSTRACT

Lung transplantation is the last resort for end-stage lung disease treatment. Due to increased survival, lung recipients present an increased likelihood to be submitted to anesthesia and surgery. This case report describes a 23-year-old female patient with history of lung transplantation for cystic fibrosis, with multiple complications, and chronic kidney disease, and who underwent kidney transplantation under general anesthesia. Understanding the pathophysiology and changes related to immunosuppressive therapy is essential to anesthetic technique planning and safety, and for perioperative management. The success of both anesthesia and surgery requires a qualified multidisciplinary team due to the rarity of the clinical scenario and high incidence of associated morbidity and mortality.

PMID:34800496 | DOI:10.1016/j.bjane.2021.07.041

Sci Rep. 2021 Nov 19;11(1):22616. doi: 10.1038/s41598-021-02044-1.

ABSTRACT

Quantitation of CFTR function in vitro is commonly performed by acutely stimulating then inhibiting ion transport through CFTR and measuring the resulting changes in transepithelial voltage (Vte) and current (ISC). While this technique is suitable for measuring the maximum functional capacity of CFTR, it may not provide an accurate estimate of in vivo CFTR activity. To test if CFTR-mediated ion transport could be measured in the absence of acute CFTR stimulation, primary airway epithelia were analyzed in an Ussing chamber with treatment of amiloride followed by CFTR(inh)-172 without acute activation of CFTR. Non-CF epithelia demonstrated a decrease in Vte and ISC following exposure to CFTR(inh)-172 and in the absence of forskolin/IBMX (F/I); this decrease is interpreted as a measure of spontaneous CFTR activity present in these epithelia. In F508del/F508del CFTR epithelia, F/I-induced changes in Vte and ISC were ~ fourfold increased after treatment with VX-809/VX-770, while the magnitude of spontaneous CFTR activities were only ~ 1.6-fold increased after VX-809/VX-770 treatment. Method-dependent discrepancies in the responses of other CF epithelia to modulator treatments were observed. These results serve as a proof of concept for the analysis of CFTR modulator responses in vitro in the absence of acute CFTR activation. Future studies will determine the usefulness of this approach in the development of novel CFTR modulator therapies.

PMID:34799640 | DOI:10.1038/s41598-021-02044-1

J Cyst Fibros. 2021 Nov 16:S1569-1993(21)02106-8. doi: 10.1016/j.jcf.2021.10.004. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), which results in impaired airway mucociliary clearance, inflammation, infection, and respiratory insufficiency. The development of new therapeutics for CF are limited by the lack of reliable preclinical models that recapitulate the structural, immunological, and bioelectrical features of human CF lungs.

METHODS: We leveraged organ-on-a-chip technology to develop a microfluidic device lined by primary human CF bronchial epithelial cells grown under an air-liquid interface and interfaced with pulmonary microvascular endothelial cells (CF Airway Chip) exposed to fluid flow. The responses of CF and healthy Airway Chips were analyzed in the presence or absence of polymorphonuclear leukocytes (PMNs) and the bacterial pathogen, Pseudomonas aeruginosa.

RESULTS: The CF Airway Chip faithfully recapitulated many features of the human CF airways, including enhanced mucus accumulation, increased cilia density, and a higher ciliary beating frequency compared to chips lined by healthy bronchial epithelial cells. The CF chips also secreted higher levels of IL-8, which was accompanied by enhanced PMN adhesion to the endothelium and transmigration into the airway compartment. In addition, CF Airway Chips provided a more favorable environment for Pseudomonas aeruginosa growth, which resulted in enhanced secretion of inflammatory cytokines and recruitment of PMNs to the airway.

CONCLUSIONS: The human CF Airway Chip may provide a valuable preclinical tool for pathophysiology studies as well as for drug testing and personalized medicine.

PMID:34799298 | DOI:10.1016/j.jcf.2021.10.004

J Cyst Fibros. 2021 Nov 16:S1569-1993(21)02132-9. doi: 10.1016/j.jcf.2021.11.004. Online ahead of print.

ABSTRACT

Macrophages represent prominent immune orchestrators of cystic fibrosis (CF) inflammation and, as such, are an ever-increasing focus of CF research with several reports of intrinsic immune dysfunction related to loss of CFTR activity in macrophages themselves. Animal models of CF have contributed, in no small part, to a deepening of our understanding of the pathophysiology of the disease and towards therapeutic development. A commonly-used animal model in CF research is the Cftrtm1Unc Tg(FABP-hCFTR) mouse, which displays gut-specific expression of a human CFTR transgene in order to rescue the high rate of early mortality in Cftr-null mice associated with severe intestinal obstruction. We find significant variation in the response to inflammatory challenge of patient macrophages and cells derived from the Cftrtm1Unc Tg(FABP-hCFTR) mouse and show that macrophages derived from this mouse exhibit aberrant expression of human CFTR. This may contribute to the absence of inflammatory changes in this model.

PMID:34799297 | DOI:10.1016/j.jcf.2021.11.004

J Otolaryngol Head Neck Surg. 2021 Nov 19;50(1):66. doi: 10.1186/s40463-021-00541-x.

ABSTRACT

BACKGROUND: The advent of 3D navigation imaging has opened new borders to the endoscopic surgical approaches of naso-sinusal inflammatory and neoplastic disease. This technology has gained in popularity among otolaryngologists for endoscopic sinus and skull base surgeries in both adults and children. However, the increased tissue radiation required for data acquisition associated with 3D navigation protocols CT scans is a source of concern because of its potential health hazards. We aimed to compare the effective doses of radiation between 3D navigation protocols and standard protocols for sinus computed tomography (CT) scans for both the adult and pediatric population.

METHODS: We performed a retrospective cohort study through electronic chart review of patients undergoing sinus CT scans (standard and 3D navigation protocols) from May 2019 to December 2019 using a Siemens Drive (VA62A) CT scanner. The effective dose of radiation was calculated in mSv for all exams. Average irradiation doses were compared using a Student's T-Test or a Kruskall-Wallis test when appropriate.

RESULTS: A total of 115 CT scans were selected for analysis, of which 47 were standard protocols and 68 were 3D navigation protocols CT scans. Among these, 31 exams were performed on children and 84 exams on adults. For the total population, mean effective dose in the non-navigation CT scans was 0.37 mSv (SD: 0.16, N = 47) and mean effective dose in the 3D navigation sinus CT group was 2.33 mSv (SD: 0.45, N = 68). The mean difference between the two groups was statistically significant 1.97 mSv (CI 95% - 2.1 to - 1.83; P < 0.0001). There was a sixfold increase in radiation with utilization of 3D navigation protocols. The ratio was identical when the pediatric as well as the adult subset of patients were analyzed.

CONCLUSION: In our center, utilization of 3D navigation sinus CT protocols significantly increases radiation exposure. Otolaryngologists should be aware of this significant increase and should attempt to decrease the radiation exposure of their patients by limiting unnecessary scan orders and by evaluating 3D acquisition protocols locally with radiation physicists.

LEVEL OF EVIDENCE: Level IV.

PMID:34798901 | DOI:10.1186/s40463-021-00541-x

Clin Transl Gastroenterol. 2021 Nov 18;12(11):e00427. doi: 10.14309/ctg.0000000000000427.

ABSTRACT

INTRODUCTION: Gain-of-function mutations in guanylyl cyclase C (GCC) result in persistent diarrhea with perinatal onset. We investigated a specific GCC inhibitor, SSP2518, for its potential to treat this disorder.

METHODS: We investigated the effect of SSP2518 on GCC-mediated intracellular cyclic guanosine monophosphate (cGMP) levels and on GCC-mediated chloride secretion in intestinal organoids from 3 patients with distinct activating GCC mutations and from controls, with and without stimulation of GCC with heat-stable enterotoxin.

RESULTS: Patient-derived organoids had significantly higher basal cGMP levels than control organoids, which were lowered by SSP2518 to levels found in control organoids. In addition, SSP2518 significantly reduced cGMP levels and chloride secretion in patient-derived and control organoids (P < 0.05 for all comparisons) after heat-stable enterotoxin stimulation.

DISCUSSION: We reported in this study that the GCC inhibitor SSP2518 normalizes cGMP levels in intestinal organoids derived from patients with GCC gain-of-function mutations and markedly reduces cystic fibrosis transmembrane conductance regulator-dependent chloride secretion, the driver of persistent diarrhea.

PMID:34797252 | DOI:10.14309/ctg.0000000000000427

J Thorac Dis. 2021 Oct;13(10):5843-5850. doi: 10.21037/jtd-21-879.

ABSTRACT

BACKGROUND: Bronchiectasis is a mostly irreversible bronchial dilatation induced by the destruction of elastic and muscular fibers of the bronchial wall. Surgical treatment is usually reserved for focal disease, and whenever complications, like hemoptysis or secondary aspergilloma, arise. In this study, we report our experience and outcomes in surgical bronchiectasis management between 2016 and 2020.

METHODS: We retrospectively searched our database for patients admitted for surgical treatment of bronchiectasis between 2016 and 2020. All records were screened for pre-surgical management. Age, gender, distribution of bronchiectatic lesions, type of surgery, perioperative complications, chest tube duration, length of hospital stay as well as 30-day-mortality were recorded, and a brief follow-up was made.

RESULTS: A total of n=34 patients underwent pulmonary resection with bronchiectasis. Mean age on admission was 56.2±15.1 years and n=21 patients (62%) were female. In n=23 cases the right lung was affected, in n=9 cases the left side and in two cases both lungs. Indications for surgery included persistent major alterations after conservative therapy (n=9), massive hemoptysis (n=4), and full-blown "destroyed lobe" (n=7). All patients received anatomical lung resection (n=21 lobectomies, n=2 bilobectomies and n=11 segmentectomies), either by uniportal video assisted thoracoscopic surgery (n=28) or by lateral thoracotomy (n=6). Average length of hospital stay was 7.9±6.3 days; one patient died on POD 7 due to myocardial infarction.

CONCLUSIONS: In spite of a decreasing number of patients with bronchiectasis referred to surgery due to improvements in preventing and managing the disease, pulmonary resection still plays a significant role in treating this pathology in Central Europe. Surgery remains a viable approach for localized forms of bronchiectasis, and the only option in treating acute deterioration and complications like massive hemoptysis.

PMID:34795933 | PMC:PMC8575831 | DOI:10.21037/jtd-21-879

Eur Respir J. 2021 Nov 18:2101344. doi: 10.1183/13993003.01344-2021. Online ahead of print.

ABSTRACT

OBJECTIVES: Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). This study aimed to assess lung structural changes after one year of lumacaftor-ivacaftor treatment, and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor.

METHODS: Adolescents and adults with CF from the French multicenter real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pretherapeutic and follow-up chest computed tomography (CT)-scans available. CT scans were visually scored using a modified Bhalla score. A k-mean clustering method was performed based on 120 radiomics features extracted from unenhanced pretherapeutic chest CT scans.

RESULTS: A total of 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (-1.40±1.53 points compared with pretherapeutic CT; p<0.001). This finding was related to a significant decrease in mucus plugging (-0.35±0.62 points; p<0.001), bronchial wall thickening (-0.24±0.52 points; p<0.001) and parenchymal consolidations (-0.23±0.51 points; p<0.001). Cluster analysis identified 3 morphological clusters. Patients from cluster C were more likely to experience an increase in percent predicted forced expiratory volume in 1 sec (ppFEV1) ≥5 under lumacaftor-ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.01).

CONCLUSION: One year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pretherapeutic CT scan may help in predicting lung function response under lumacaftor-ivacaftor.

PMID:34795038 | DOI:10.1183/13993003.01344-2021

Pulm Pharmacol Ther. 2021 Nov 15:102098. doi: 10.1016/j.pupt.2021.102098. Online ahead of print.

ABSTRACT

The cystic fibrosis (CF) lung disease is due to the lack/dysfunction of the CF Transmembrane Conductance Regulator (CFTR), a chloride channel expressed by epithelial cells as the main regulator of ion and fluid homeostasis. More than 2000 genetic variation in the CFTR gene are known, among which those with identified pathomechanism have been divided into six VI mutation classes. A major advancement in the pharmacotherapy of CF has been the development of small-molecule drugs hitting the root of the disease, i.e. the altered ion and fluid transport through the airway epithelium. These drugs, called CFTR modulators, have been advanced to the clinics to treat nearly 90% of CF patients, including the CFTR potentiator ivacaftor, approved for residual function mutations (Classes III and IV), and combinations of correctors (lumacaftor, tezacaftor, elexacaftor) and ivacaftor for patients bearing at least one the F508del mutation, the most frequent mutation belonging to class II. To cover the 10% of CF patients without etiological therapies, other novel small-molecule CFTR modulators are in evaluation of their effectiveness in all the CFTR mutation classes: read-through agents for Class I, correctors, potentiators and amplifiers from different companies for Class II-V, stabilizers for Class VI. In alternative, other solute carriers, such as SLC26A9 and SLC6A14, are the focus of intensive investigation. Finally, other molecular targets are being evaluated for patients with no approved CFTR modulator therapy or as means of enhancing CFTR modulatory therapy, including small molecules forming ion channels, inhibitors of the ENaC sodium channel and potentiators of the calcium-activated chloride channel TMEM16A. This paper aims to give an up-to-date overview of old and novel CFTR modulators as well as of novel strategies based on small-molecule drugs. Further investigations in in-vivo and cell-based models as well as carrying out large prospective studies will be required to determine if novel CFTR modulators, stabilizers, amplifiers, and the ENaC inhibitors or TMEM16A potentiators will further improve the clinical outcomes in CF management.

PMID:34793977 | DOI:10.1016/j.pupt.2021.102098

PLoS Negl Trop Dis. 2021 Nov 18;15(11):e0009969. doi: 10.1371/journal.pntd.0009969. Online ahead of print.

ABSTRACT

Cholera remains a major cause of infectious diarrhea globally. Despite the increased availability of cholera vaccines, there is still an urgent need for other effective interventions to reduce morbidity and mortality. Furthermore, increased prevalence of antibiotic-resistant Vibrio cholerae threatens the use of many drugs commonly used to treat cholera. We developed iOWH032, a synthetic small molecule inhibitor of the cystic fibrosis transmembrane conductance regulator chloride channel, as an antisecretory, host-directed therapeutic for cholera. In the study reported here, we tested iOWH032 in a Phase 2a cholera controlled human infection model. Forty-seven subjects were experimentally infected with V. cholerae El Tor Inaba strain N16961 in an inpatient setting and randomized to receive 500 mg iOWH032 or placebo by mouth every 8 hours for 3 days to determine the safety and efficacy of the compound as a potential treatment for cholera. We found that iOWH032 was generally safe and achieved a mean (± standard deviation) plasma level of 4,270 ng/mL (±2,170) after 3 days of oral dosing. However, the median (95% confidence interval) diarrheal stool output rate for the iOWH032 group was 25.4 mL/hour (8.9, 58.3), compared to 32.6 mL/hour (15.8, 48.2) for the placebo group, a reduction of 23%, which was not statistically significant. There was also no significant decrease in diarrhea severity and number or frequency of stools associated with iOWH032 treatment. We conclude that iOWH032 does not merit future development for treatment of cholera and offer lessons learned for others developing antisecretory therapeutic candidates that seek to demonstrate proof of principle in a cholera controlled human infection model study. Trial registration: This study is registered with ClinicalTrials.gov as NCT04150250.

PMID:34793441 | DOI:10.1371/journal.pntd.0009969

J Clin Endocrinol Metab. 2021 Nov 18:dgab807. doi: 10.1210/clinem/dgab807. Online ahead of print.

NO ABSTRACT

PMID:34792139 | DOI:10.1210/clinem/dgab807

Stat Biopharm Res. 2021;13(3):270-279. doi: 10.1080/19466315.2020.1870546. Epub 2021 Feb 4.

ABSTRACT

Longitudinal studies of rapid disease progression often rely on noisy biomarkers; the underlying longitudinal process naturally varies between subjects and within an individual subject over time; the process can have substantial memory in the form of within-subject correlation. Cystic fibrosis lung disease progression is measured by changes in a lung function marker (FEV1), such as a prolonged drop in lung function, clinically termed rapid decline. Choosing a longitudinal model that estimates rapid decline can be challenging, requiring covariate specifications to assess drug effect while balancing choices of covariance functions. Two classes of longitudinal models have recently been proposed: segmented and stochastic linear mixed effects (LMEs) models. With segmented LMEs, random changepoints are used to estimate the timing and degree of rapid decline, treating these points as structural breaks in the underlying longitudinal process. In contrast, stochastic LMEs, such as random walks, are locally linear but utilize continuously changing slopes, viewing bouts of rapid decline as localized, sharp changes. We compare commonly utilized variants of these approaches through an application using the Cystic Fibrosis Foundation Patient Registry. Changepoint modeling had the worst fit and predictive accuracy but certain covariance forms in stochastic LMEs produced problematic variance estimates.

PMID:34790289 | PMC:PMC8594909 | DOI:10.1080/19466315.2020.1870546

J Pediatr Pharmacol Ther. 2021;26(8):828-833. doi: 10.5863/1551-6776-26.8.828. Epub 2021 Nov 10.

ABSTRACT

OBJECTIVE: This study describes the creation of a combination antibiogram directed toward Pseudomonas aeruginosa to determine the most appropriate empiric antimicrobial regimen(s).

METHODS: P aeruginosa isolates were collected from all sites between January 2013 and December 2017 for patients admitted to the PICU. Patients with cystic fibrosis and isolates from the same site and susceptibility pattern obtained within 30 days were excluded. β-Lactam susceptibilities were determined and compared with the addition of an aminoglycoside or fluroquinolone and summarized in a combination antibiogram.

RESULTS: One hundred ninety-nine P aeruginosa isolates were included for analysis. The addition of a second agent to piperacillin-tazobactam was shown to have the most significant improvement among the β-lactams, with 70% susceptibility as monotherapy and increases to above 90% with the addition of an aminoglycoside or fluroquinolone. The addition of an aminoglycoside or fluroquinolone to cefepime and meropenem increased coverage to above 95%. The addition of a second agent was likely to increase susceptibility of a monotherapy backbone; however, as the susceptibility of the first-line agent decreased, the susceptibility of the second agent needed to be higher to achieve a 95% coverage threshold.

CONCLUSIONS: Our results support use of a second agent to significantly improve the likelihood of appropriate empiric coverage of P aeruginosa. Use of a combination antibiogram may be more beneficial than a simple antibiogram for units with increasing resistance rates, or for coverage of specific resistant organisms.

PMID:34790073 | PMC:PMC8592000 | DOI:10.5863/1551-6776-26.8.828

J Pediatr Gastroenterol Nutr. 2021 Nov 16. doi: 10.1097/MPG.0000000000003357. Online ahead of print.

ABSTRACT

OBJECTIVES: This prospective study evaluated the relationship between fecal markers of intestinal inflammation and cystic fibrosis (CF)-associated abdominal symptoms. These were assessed using the CFAbd-Score, a CF-specific patient-related outcome measure developed and validated, following FDA guidelines.

METHODS: In feces from patients with CF (n = 41) and healthy volunteers (n = 27), concentrations of fecal calprotectin (FC), M2-pyruvate kinase (M2-PK), interleukins IL-1β, IL-6, IL-8, and neutrophilic elastase (NE) were measured. Abdominal symptoms during the 2 preceding weeks were recorded using the CFAbd-Score. This patient-reported outcome measure (PROM) for assessment of the multi-organic abdominal involvement in CF includes 28 items in 5 domains.

RESULTS: Inflammatory parameters FC, IL-1β, M2-PK, and NE in feces, as well as CFAbd-Scores resulted significantly higher in CF patients than in healthy controls (all p < 0.01). Furthermore, significant differences between both groups were found for pain-symptoms, disorders of bowel movement, impaired quality of life, as well as disorders of eating and appetite. With 83% sensitivity and 74% specificity, FC was the most reliable measure for CF-related intestinal inflammation, which, in the CFAbd-Score, was associated to significantly higher rates of abdominal pain, as well as to general quality of life items such as GI-related impaired sleep and frustration.

CONCLUSION: Using the CFAbd-Score as a CF-specific PROM for identification and quantification of abdominal symptoms revealed that abdominal pain and impaired quality of life are associated with intestinal inflammation in CF.

PMID:34789668 | DOI:10.1097/MPG.0000000000003357

Eur Respir Rev. 2021 Nov 17;30(162):210103. doi: 10.1183/16000617.0103-2021. Print 2021 Dec 31.

ABSTRACT

In people with cystic fibrosis (PwCF), viscous sputum and dysfunction of the mucociliary escalator leads to early and chronic infections. The prevalence of Aspergillus fumigatus in sputum is high in PwCF and the contribution of A. fumigatus to the progression of structural lung disease has been reported. However, overall, relatively little is known about the contribution of A. fumigatus to CF lung disease. More knowledge is needed to aid clinical decisions on whether to start antifungal treatment. In this review, we give an overview of A. fumigatus colonisation and infection in PwCF and the different types of pulmonary disease caused by it. Furthermore, we discuss the current evidence for structural lung damage associated with A. fumigatus in PwCF on chest computed tomography and magnetic resonance imaging. We conclude that radiological outcomes to identify disease caused by A. fumigatus can be important for clinical studies and management.

PMID:34789463 | DOI:10.1183/16000617.0103-2021

Intensive Crit Care Nurs. 2021 Oct 28:103160. doi: 10.1016/j.iccn.2021.103160. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the muscle strength and functional level of patients discharged from intensive care unit (ICU) in relation to the swimmer position as a nurse intervention during pronation.

METHODS: Prospective study conducted in the hub COVID-19 center in Milan (Italy), between March and June 2020. All patients with COVID-19 discharged alive from ICU who received invasive mechanical ventilation were included. Forward continuation ratio model was fitted to explore the statistical association between muscle strength grades and body positioning during ICU stay.

RESULTS: Over the 128 patients admitted to ICU, 87 patients were discharged alive from ICU, with available follow-up measures at hospital discharge. Thirty-four patients (39.1%) were treated with prone positioning as rescue therapy, for a total of 106 pronation cycles with a median duration of 72 (IQR 60-83) hours. Prone positioning did not influence the odds of showing particular level of muscle strength, in any of the evaluated districts, namely shoulder (OR 1.34, 95%CI:0.61-2.97), elbow (OR 1.10, 95%CI:0.45-2.68) and wrist (OR 0.97, 95%CI:0.58-1.63). Only in the shoulder district, age showed evidence of association with strength (OR 1.06, 95%CI:1.02-1.10), affecting people as they get older. No significant sequalae related to swimmer position were reported by physiotherapists or nurses.

CONCLUSION: Swimmer position adopted during prone ventilation is not associated with worse upper limb strength or poor mobility level in COVID-19 survivors after hospital discharge.

PMID:34789437 | DOI:10.1016/j.iccn.2021.103160

BMC Infect Dis. 2021 Nov 17;21(1):1165. doi: 10.1186/s12879-021-06825-x.

ABSTRACT

BACKGROUND: The objective of the study was to describe the epidemiology, management and cost of non-tuberculous mycobacteria pulmonary disease (NTM-PD) in France.

METHODS: A retrospective analysis was performed using the SNDS ("Système national des données de santé") database over 2010-2017. Patients with NTM-PD were identified based on the ICD10 codes during hospitalizations and/or specific antibiotics treatment regimens. The study population was matched (age, sex and region) to a control group (1:3) without NTM-PD.

RESULTS: 5628 patients with NTM-PD (men: 52.9%, mean age = 60.9 years) were identified over the study period and 1433 (25.5%) were treated with antibiotics. The proportion of patients still receiving treatment at 6 and 12 months was 40% and 22%, respectively. The prevalence of NTM-PD was estimated at 5.92 per 100,000 inhabitants and the incidence rate of NTM-PD remained stable over time between 1.025/100,000 in 2010 and 1.096/100,000 in 2017. Patients with NTM-PD had more co-morbidities compared to controls: corticoids (57.3% vs. 33.8%), chronic lower respiratory disease (34.4% vs. 2.7%), other infectious pneumonia (24.4% vs. 1.4%), malnutrition (based on hospitalization with the ICD-10 code reported during a hospital stay as a main or secondary diagnosis) (22.0% vs. 2.0%), history of tuberculosis (14.1% vs. 0.1%), HIV (8.7% vs. 0.2%), lung cancer and lung graft (5.7% vs. 0.4%), cystic fibrosis (3.2% vs. 0.0%), gastro-esophageal reflux disease (2.9% vs. 0.9%) and bone marrow transplant (1.3% vs. 0.0%) (p < 0.0001). The mean Charlson comorbidity index score was 1.6 (vs. 0.2 for controls; p < 0.0001). NTM-PD was independently associated with an increased mortality rate with a hazard ratio of 2.8 (95% CI: 2.53; 3.11). Mortality was lower for patients treated with antibiotics compared to untreated patients (HR = 0.772 (95% CI [0.628; 0.949]). Annual total expenses the year following the infection in a societal perspective were € 24,083 (SD: 29,358) in NTM-PD subjects vs. € 3402 (SD: 8575) in controls (p < 0.0001). Main driver of the total expense for NTM-PD patients was hospital expense (> 50% of the total expense).

CONCLUSION: Patients with NTM-PD in France were shown to have many comorbidities, their mortality risk is high and mainly driven by NTM-PD, and their management costly. Only a minority of patients got treated with antibiotics and of those patients treated, many stopped their therapy prematurely. These results underline the high burden associated with NTM-PD and the need for improvement of NTM-PD management in France.

PMID:34789152 | DOI:10.1186/s12879-021-06825-x

J Insur Med. 2021 Nov 1;49(s1):1-31. doi: 10.17849/insm-49-s1-1-31.1.

ABSTRACT

OBJECTIVE.—: To propose an insurance product called special needs insurance. The insurance will pay parents a lump sum up to $100,000 if they have a child that is born with or develops a special needs condition such as Down syndrome, cerebral palsy or autism.

BACKGROUND.—: Raising a child is expensive; raising a child with a special need can be hundreds of thousands of dollars more expensive. These additional costs include direct costs that are not covered by health insurance and indirect costs such as the loss of earnings when a working parent must tend to a special needs child.

METHOD.—: We analyze a gamut of birth and early childhood disabilities, both physical and cognitive, from the medico-actuarial perspective. We describe each condition using relevant medical literature and calculate prevalence rates from epidemiological studies (appendix A1-A15). After accounting for multiple births, we develop a final premium.

RESULTS.—: We find that physical impairments are sufficiently well understood to guarantee a fixed payout, whereas cognitive impairments such as autism are less understood, and so for these we propose a cognitive fund that does not guarantee a fixed payout. We find that an average single premium of $4,600 allows the insurer to profitably pay out the proposed benefits.

CONCLUSIONS.—: Raising a special needs child can put a significant strain on the affected family's budget. We propose an insurance product that provides relief through a large lump sum payout. Although no new insurance product can be guaranteed success, our analysis of this product gives an interested insurer reasonable justification to take on this new risk.

PMID:34788842 | DOI:10.17849/insm-49-s1-1-31.1

Respir Med. 2021 Nov 1;190:106674. doi: 10.1016/j.rmed.2021.106674. Online ahead of print.

ABSTRACT

Influenza and pneumococcal disease represent a well-known burden on healthcare systems worldwide, as well as they still have an attributed morbidity and mortality, especially in elderly individuals and vulnerable populations. In the context of the ongoing pandemic of COVID-19, a series of considerations in favor of extensive influenza and pneumococcal vaccination campaign are emerging, including a possible reduction of hospital extra burden and saving of sanitary resources. In addition, recent studies have suggested that prior vaccinations towards non SARS-CoV-2 pathogens might confer some protection against COVID-19. In this paper the authors consider all factors in support of these hypotheses and provide a consensus statement to encourage influenza and pneumococcal vaccinations in targeted populations.

PMID:34788734 | DOI:10.1016/j.rmed.2021.106674