Tag: statistics

JAMA Ophthalmol. 2022 Oct 27. doi: 10.1001/jamaophthalmol.2022.4394. Online ahead of print.

ABSTRACT

IMPORTANCE: Dry eye is a common clinical manifestation, a leading cause of eye clinic visits, and a significant societal and personal economic burden in the United States. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye.

OBJECTIVE: To conduct a systematic review and meta-analysis to obtain updated estimates of the prevalence and incidence of dry eye and MGD in the United States.

DATA SOURCES: Ovid MEDLINE and Embase.

STUDY SELECTION: A search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case-control studies, and interventional studies were excluded.

DATA EXTRACTION AND SYNTHESIS: The conduct of review followed a protocol registered on PROSPERO (CRD42021256934). PRISMA guidelines were followed for reporting. Joanna Briggs Institute and Newcastle Ottawa Scale tools were used to assess risk of bias. Data extraction was conducted by 1 reviewer and verified by another for accuracy. Prevalence of dry eye and MGD were combined in separate meta-analyses using random-effects models.

MAIN OUTCOMES AND MEASURES: Prevalence and incidence of dry eye and MGD in the United States. Summary estimates from meta-analysis of dry eye and MGD prevalence with 95% CI and 95% prediction intervals (95% PI).

RESULTS: Thirteen studies were included in the systematic review. Dry eye prevalence was reported by 10 studies, dry eye incidence by 2 studies, and MGD prevalence by 3 studies. Meta-analysis estimated a dry eye prevalence of 8.1% (95% CI, 4.9%-13.1%; 95% PI, 0%-98.9%; 3 studies; 9 808 758 participants) and MGD prevalence of 21.2% (95% CI, 7.2%-48.3%; 95% PI, 0%-100%; 3 studies; 19 648 participants). Dry eye incidence was 3.5% in a population 18 years and older and 7.8% in a population aged 68 years and older. No studies reported MGD incidence.

CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis demonstrated uncertainty about the prevalence and incidence of dry eye and MGD in the United States. Population-based epidemiological studies that use consistent and validated definitions of dry eye and MGD are needed for higher-certainty estimates of dry eye and MGD prevalence and incidence in the United States.

PMID:36301551 | DOI:10.1001/jamaophthalmol.2022.4394

JAMA Otolaryngol Head Neck Surg. 2022 Oct 27. doi: 10.1001/jamaoto.2022.3316. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite growing scientific knowledge and research, it is still unknown if office flexible laryngoscopy (FL) is aerosol generating and thereby potentially increases the risk of SARS-CoV-2 transmission. The limited literature that exists is conflicting, precluding formal conclusions.

OBJECTIVE: To determine whether FL is aerosol generating.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 134 patients seen in the otolaryngology clinic at a single tertiary care academic institution between February and May 2021. Two optical particle sizer instruments were used, quantifying particles ranging from 0.02 μm to 5 μm. Measurements were taken every 30 seconds, with sample periods of 15 seconds throughout the patient encounter. Instruments were located 12 inches from the patient’s nares. Timing of events was recorded, including the start and end of physical examination, topical spray administration, start and end of laryngoscopy, and other potential aerosol-generating events (eg, coughing, sneezing). Data analysis was performed from February to May 2021.

EXPOSURES: Office examination and office FL.

MAIN OUTCOMES AND MEASURES: Bayesian online change point detection (OCPD) algorithm was used to detect significant change points (CPs) in this time-series data. The primary outcome was significant CP after FL compared with baseline physiologic variations, such as breathing and phonation.

RESULTS: Data were collected from 134 patients between February and May 2021. Ninety-one encounters involved FL. Of this group, 51 patients (56%) wore no mask over their mouth during FL. There was no statistically significant CP in either visits involving FL or visits where FL was not performed. Use of nasal spray did not result in CP in aerosol levels. Overall, neither the number of people present in the examination room, masks over patients’ mouth, the duration of the visit, nor the duration of FL were associated with mean aerosol counts, regardless of the exposure. For larger aerosol sizes (≥1 μm), however, rooms with higher air exchange rates had significantly higher reductions in mean aerosol counts for visits involving FL.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study support that FL, including topical spray administration, is not a significant aerosol-generating procedure. The Bayesian OCPD model has a promising application for future aerosol studies in otolaryngology.

PMID:36301539 | DOI:10.1001/jamaoto.2022.3316

JAMA Oncol. 2022 Oct 27. doi: 10.1001/jamaoncol.2022.5041. Online ahead of print.

ABSTRACT

IMPORTANCE: Management of checkpoint inhibitor-induced immune-related adverse events (irAEs) is primarily based on expert opinion. Recent studies have suggested detrimental effects of anti-tumor necrosis factor on checkpoint-inhibitor efficacy.

OBJECTIVE: To determine the association of toxic effect management with progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS) in patients with advanced melanoma treated with first-line ipilimumab-nivolumab combination therapy.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, multicenter cohort study included patients with advanced melanoma experiencing grade 3 and higher irAEs after treatment with first-line ipilimumab and nivolumab between 2015 and 2021. Data were collected from the Dutch Melanoma Treatment Registry. Median follow-up was 23.6 months.

MAIN OUTCOMES AND MEASURES: The PFS, OS, and MSS were analyzed according to toxic effect management regimen. Cox proportional hazard regression was used to assess factors associated with PFS and OS.

RESULTS: Of 771 patients treated with ipilimumab and nivolumab, 350 patients (median [IQR] age, 60.0 [51.0-68.0] years; 206 [58.9%] male) were treated with immunosuppression for severe irAEs. Of these patients, 235 received steroids alone, and 115 received steroids with second-line immunosuppressants. Colitis and hepatitis were the most frequently reported types of toxic effects. Except for type of toxic effect, no statistically significant differences existed at baseline. Median PFS was statistically significantly longer for patients treated with steroids alone compared with patients treated with steroids plus second-line immunosuppressants (11.3 [95% CI, 9.6-19.6] months vs 5.4 [95% CI, 4.5-12.4] months; P = .01). Median OS was also statistically significantly longer for the group receiving steroids alone compared with those receiving steroids plus second-line immunosuppressants (46.1 months [95% CI, 39.0 months-not reached (NR)] vs 22.5 months [95% CI, 36.5 months-NR]; P = .04). Median MSS was also better in the group receiving steroids alone compared with the group receiving steroids plus second-line immunosuppressants (NR [95% CI, 46.1 months-NR] vs 28.8 months [95% CI, 20.5 months-NR]; P = .006). After adjustment for potential confounders, patients treated with steroids plus second-line immunosuppressants showed a trend toward a higher risk of progression (adjusted hazard ratio, 1.40 [95% CI, 1.00-1.97]; P = .05) and had a higher risk of death (adjusted hazard ratio, 1.54 [95% CI, 1.03-2.30]; P = .04) compared with those receiving steroids alone.

CONCLUSIONS AND RELEVANCE: In this cohort study, second-line immunosuppression for irAEs was associated with impaired PFS, OS, and MSS in patients with advanced melanoma treated with first-line ipilimumab and nivolumab. These findings stress the importance of assessing the effects of differential irAE management strategies, not only in patients with melanoma but also tumor types.

PMID:36301521 | DOI:10.1001/jamaoncol.2022.5041

J Cardiovasc Transl Res. 2022 Oct 27. doi: 10.1007/s12265-022-10335-9. Online ahead of print.

ABSTRACT

Neonatal coarctation of the aorta (CoA) is a common congenital heart defect. Its antenatal diagnosis remains challenging, and its pathophysiology is poorly understood. We present a novel statistical shape modeling (SSM) pipeline to study the role and predictive value of arch shape in CoA in utero. Cardiac magnetic resonance imaging (CMR) data of 112 fetuses with suspected CoA was acquired and motion-corrected to three-dimensional volumes. Centerlines from fetal arches were extracted and used to build a statistical shape model capturing relevant anatomical variations. A linear discriminant analysis was used to find the optimal axis between CoA and false positive cases. The CoA shape risk score classified cases with an area under the curve of 0.907. We demonstrate the feasibility of applying a SSM pipeline to three-dimensional fetal CMR data while providing novel insights into the anatomical determinants of CoA and the relevance of in utero arch anatomy for antenatal diagnosis of CoA.

PMID:36301513 | DOI:10.1007/s12265-022-10335-9

Methods Mol Biol. 2023;2575:305-321. doi: 10.1007/978-1-0716-2716-7_16.

ABSTRACT

Infectious agents often challenge therapeutics, from antibiotics resistance to antigenic variability affecting inoculation measures. Over the last decades, genome sequencing arose as an important ally to address such challenges. In bacterial infection, whole-genome-sequencing (WGS) supports tracking pathogenic alterations affecting the human microbiome. In viral infection, the analysis of the relevant sequence of nucleotides helps with determining historical variants of a virus and elucidates details about infection clusters and their distribution. Additionally, genome sequencing is now an important step in inoculation protocols, isolating target genes to design more robust immunisation assays. Ultimately, genetic engineering has empowered repurposing at scale, allowing long-lasting repeating clinical trials to be automated within a much shorter time-frame, by adjusting existing protocols. This is particularly important during sanitary emergencies as the ones caused by the 2014 West African Ebola outbreak, the Zika virus rapid spread in both South and North America in 2015, followed by Asia in 2016, and the pandemic caused by the SARS-CoV-2, which has infected more than 187 million people and caused more than 4 million deaths, worldwide, as per July 2021 statistics. In this scenery, this chapter presents a novel fully automated strategy to handle antigenic variability in immunisation protocols. The methodology comprises of two major steps (1) nanopore sequencing of infectious agent variants – the focus is on the SARS-CoV-2 and its variants; followed by (2) mRNA vector design for immunotherapy. This chapter presents the nanopore sequencing step and Chapter 17 introduces a protocol for mRNA vector design.

PMID:36301483 | DOI:10.1007/978-1-0716-2716-7_16

Chin J Integr Med. 2022 Oct 27. doi: 10.1007/s11655-022-3688-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).

METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12.

RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred.

CONCLUSIONS: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

PMID:36301456 | DOI:10.1007/s11655-022-3688-3

Chin J Integr Med. 2022 Oct 27. doi: 10.1007/s11655-022-3685-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.

METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.

RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).

CONCLUSION: Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

PMID:36301455 | DOI:10.1007/s11655-022-3685-6

J Ultrasound. 2022 Oct 27. doi: 10.1007/s40477-022-00728-6. Online ahead of print.

ABSTRACT

PURPOSE: Respiratory distress syndrome (RDS), also known as hyaline membrane disease, is the most common clinical syndrome encountered among preterm infants, and the complications of the disease account for substantial mortality. Diagnosis of RDS is based on the clinical status of patients in correlation with laboratory parameters and chest X-ray. Lung ultrasound despite its wide use still is not incorporated into diagnostic algorithms. The aim of the study was to evaluate the diagnostic ability of lung ultrasound in diagnosing respiratory distress syndrome as well as in the monitoring of the response to treatment. A secondary aim was to propose a modified ultrasound grading scale.

METHODS: The prospective study included 150 neonates with clinical and radiographic signs of neonatal respiratory distress syndrome within the first 24 h of life, with different gestational age (≤ 35 weeks). Lung ultrasound was performed by two radiologists and correlated with a chest X-ray. Two gradation scales (ultrasound and X-ray) were compared and each scale was correlated with the patient’s clinical data.

RESULTS: In comparison between ultrasound findings and X-ray results showed a statistically significant difference in a favor of ultrasound. Based on the presence of subpleural consolidations, further differentiation of ultrasound profiles were made into subgroups and new ultrasound classification have been proposed.

CONCLUSION: Our study showed that lung ultrasound enables the diagnosing of respiratory distress syndrome in premature neonates and also shows a significant correlation with chest X-ray, which is considered as a radiological method of choice for the diagnosis of RDS.

PMID:36301438 | DOI:10.1007/s40477-022-00728-6

Pharmacoeconomics. 2022 Oct 27. doi: 10.1007/s40273-022-01209-8. Online ahead of print.

ABSTRACT

Fenfluramine, tradename Fintepla^®, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as Technology Appraisal 808. Within the STA process, the company (Zogenix International) provided NICE with a written submission and a mathematical health economic model, summarising the company’s estimates of the clinical effectiveness and cost-effectiveness of fenfluramine for patients with Dravet syndrome (DS). This company submission (CS) was reviewed by an evidence review group (ERG) independent of NICE. The ERG, Kleijnen Systematic Reviews in collaboration with Maastricht University Medical Centre, produced an ERG report. This paper presents a summary of the ERG report and the development of the NICE guidance. The CS included a systematic review of the evidence for fenfluramine. From this review the company identified and presented evidence from two randomised trials (Study 1 and Study 1504), an open-label extension study (Study 1503) and ‘real world evidence’ from a prospective and retrospective study. Both randomised trials were conducted in patients up to 18 years of age with DS, whose seizures were incompletely controlled with previous anti-epileptic drugs. A Bayesian network meta-analysis was performed to compare fenfluramine with cannabidiol plus clobazam. There was no evidence of a difference between any doses of fenfluramine and cannabidiol in the mean convulsive seizure frequency (CSF) rate during treatment. However, fenfluramine increased the number of patients achieving ≥ 50% reduction in CSF frequency from baseline compared to cannabidiol. The company used an individual-patient state-transition model (R version 3.5.2) to model cost-effectiveness of fenfluramine. The CSF and convulsive seizure-free days were estimated using patient-level data from the placebo arm of the fenfluramine registration studies. Subsequently, a treatment effect of either fenfluramine or cannabidiol was applied. Utility values for the economic model were obtained by mapping Pediatric Quality of Life Inventory data from the registration studies to EuroQol-5D-3L Youth (EQ-5D-Y-3L). The company included caregiver utilities in their base-case, as the severe needs of patients with DS have a major impact on parents and caregivers. There were several key issues. First, the company included caregiver utilities in the model in a way that when patients in the economic model died, the corresponding caregiver utility was also set to zero. Second, the model was built in R statistical software, resulting in transparency issues. Third, the company assumed the same percentage reduction for convulsive seizure days as was estimated for CSF. Fourth, during the final appraisal committee meeting, influential changes were made to the model that were not in line with the ERG’s preferences (but were accepted by the appraisal committee). The company’s revised and final incremental cost effectiveness ratio (ICER) in line with committee preferences resulted in fenfluramine dominating cannabidiol. Fenfluramine was recommended as an add-on to other antiepileptic medicines for treating seizures associated with DS in people aged 2 years and older in the National Health Service (NHS).

PMID:36301414 | DOI:10.1007/s40273-022-01209-8

Obes Surg. 2022 Oct 27. doi: 10.1007/s11695-022-06328-x. Online ahead of print.

ABSTRACT

PURPOSE : Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB.

METHOD: We used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery.

RESULTS: RYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls.

CONCLUSION: The postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.

PMID:36301409 | DOI:10.1007/s11695-022-06328-x