Category: Statistics

JAMA Pediatr. 2023 Feb 6. doi: 10.1001/jamapediatrics.2022.5689. Online ahead of print.

ABSTRACT

IMPORTANCE: Infants younger than 1 year have the highest burden of pertussis morbidity and mortality. In 2011, the US introduced tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy to protect infants before vaccinations begin.

OBJECTIVE: To assess the association of maternal Tdap vaccination during pregnancy with the incidence of pertussis among infants in the US.

DESIGN, SETTING, AND PARTICIPANTS: In this ecologic study, a time-trend analysis was performed of infant pertussis cases reported through the National Notifiable Diseases Surveillance System between January 1, 2000, and December 31, 2019, in the US. Statistical analysis was performed from April 1, 2020, to October 31, 2022.

EXPOSURES: Maternal Tdap vaccination during pregnancy.

MAIN OUTCOMES AND MEASURES: Pertussis incidence rates were calculated and compared between 2 periods-the pre-maternal Tdap vaccination period (2000-2010) and the post-maternal Tdap vaccination period (2012-2019)-for 2 age groups: infants younger than 2 months (target group of maternal vaccination) and infants aged 6 months to less than 12 months (comparison group). Incidence rate differences between the 2 age groups were modeled using weighted segmented linear regression. The slope difference between the 2 periods was estimated to assess the association of maternal Tdap vaccination with pertussis incidence among infants.

RESULTS: A total of 57 460 pertussis cases were reported in infants younger than 1 year between 2000 and 2019; 19 322 cases (33.6%) were in infants younger than 2 months. During the pre-maternal Tdap vaccination period, annual pertussis incidence did not change among infants younger than 2 months (slope, 3.29 per 100 000 infants per year; P = .28) but increased slightly among infants aged 6 months to less than 12 months (slope, 2.10 per 100 000 infants per year; P = .01). There was no change in the difference in incidence between the 2 age groups (slope, 0.08 per 100 000 infants per year; P = .97) during the pre-maternal Tdap vaccination period overall. However, in the post-maternal Tdap vaccination period, incidence decreased among infants younger than 2 months (slope, -14.53 per 100 000 infants per year; P = .001) while remaining unchanged among infants aged 6 months to less than 12 months (slope, 1.42 per 100 000 infants per year; P = .29). The incidence rate difference between the 2 age groups significantly decreased during the post-maternal Tdap vaccination period (slope, -14.43 per 100 000 infants per year; P < .001). Pertussis incidence rate differences were significantly different between the pre-maternal and post-maternal Tdap vaccination periods (slope difference, -14.51 per 100 000 infants per year; P = .01).

CONCLUSIONS AND RELEVANCE: In this study, following maternal Tdap vaccine introduction, a sustained decrease in pertussis incidence was observed among infants younger than 2 months, narrowing the incidence gap with infants aged 6 months to less than 12 months. These findings suggest that maternal Tdap vaccination is associated with a reduction in pertussis burden in the target age group (<2 months) and that further increases in coverage may be associated with additional reductions in infant disease.

PMID:36745442 | DOI:10.1001/jamapediatrics.2022.5689

Transl Vis Sci Technol. 2023 Feb 1;12(2):6. doi: 10.1167/tvst.12.2.6.

ABSTRACT

PURPOSE: Artificial intelligence (AI) methods are changing all areas of research and have a variety of capabilities of analysis in ophthalmology, specifically in visual fields (VFs) to detect or predict vision loss progression. Whereas most of the AI algorithms are implemented in Python language, which offers numerous open-source functions and algorithms, the majority of algorithms in VF analysis are offered in the R language. This paper introduces PyVisualFields, a developed package to address this gap and make available VF analysis in the Python language.

METHODS: For the first version, the R libraries for VF analysis provided by vfprogression and visualFields packages are analyzed to define the overlaps and distinct functions. Then, we defined and translated this functionality into Python with the help of the wrapper library rpy2. Besides maintaining, the subsequent versions’ milestones are established, and the third version will be R-independent.

RESULTS: The developed Python package is available as open-source software via the GitHub repository and is ready to be installed from PyPI. Several Jupyter notebooks are prepared to demonstrate and describe the capabilities of the PyVisualFields package in the categories of data presentation, normalization and deviation analysis, plotting, scoring, and progression analysis.

CONCLUSIONS: We developed a Python package and demonstrated its functionality for VF analysis and facilitating ophthalmic research in VF statistical analysis, illustration, and progression prediction.

TRANSLATIONAL RELEVANCE: Using this software package, researchers working on VF analysis can more quickly create algorithms for clinical applications using cutting-edge AI techniques.

PMID:36745440 | DOI:10.1167/tvst.12.2.6

JAMA Intern Med. 2023 Feb 6. doi: 10.1001/jamainternmed.2022.6545. Online ahead of print.

ABSTRACT

IMPORTANCE: Deprescribing is a promising approach to addressing the burden of polypharmacy. Few studies have initiated comprehensive deprescribing in the hospital setting among older patients requiring ongoing care in a postacute care (PAC) facility.

OBJECTIVE: To evaluate the efficacy of a patient-centered deprescribing intervention among hospitalized older adults transitioning or being discharged to a PAC facility.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial of the Shed-MEDS (Best Possible Medication History, Evaluate, Deprescribing Recommendations, and Synthesis) deprescribing intervention was conducted between March 2016 and October 2020. Patients who were admitted to an academic medical center and discharged to 1 of 22 PAC facilities affiliated with the medical center were recruited. Patients who were 50 years or older and had 5 or more prehospital medications were enrolled and randomized 1:1 to the intervention group or control group. Patients who were non-English speaking, were unhoused, were long-stay residents of nursing homes, or had less than 6 months of life expectancy were excluded. An intention-to-treat approach was used.

INTERVENTIONS: The intervention group received the Shed-MEDS intervention, which consisted of a pharmacist- or nurse practitioner-led comprehensive medication review, patient or surrogate-approved deprescribing recommendations, and deprescribing actions that were initiated in the hospital and continued throughout the PAC facility stay. The control group received usual care at the hospital and PAC facility.

MAIN OUTCOMES AND MEASURES: The primary outcome was the total medication count at hospital discharge and PAC facility discharge, with follow-up assessments during the 90-day period after PAC facility discharge. Secondary outcomes included the total number of potentially inappropriate medications at each time point, the Drug Burden Index, and adverse events.

RESULTS: A total of 372 participants (mean [SD] age, 76.2 [10.7] years; 229 females [62%]) were randomized to the intervention or control groups. Of these participants, 284 were included in the intention-to-treat analysis (142 in the intervention group and 142 in the control group). Overall, there was a statistically significant treatment effect, with patients in the intervention group taking a mean of 14% fewer medications at PAC facility discharge (mean ratio, 0.86; 95% CI, 0.80-0.93; P < .001) and 15% fewer medications at the 90-day follow-up (mean ratio, 0.85; 95% CI, 0.78-0.92; P < .001) compared with the control group. The intervention additionally reduced patient exposure to potentially inappropriate medications and Drug Burden Index. Adverse drug event rates were similar between the intervention and control groups (hazard ratio, 0.83; 95% CI, 0.52-1.30).

CONCLUSIONS AND RELEVANCE: Results of this trial showed that the Shed-MEDS patient-centered deprescribing intervention was safe and effective in reducing the total medication burden at PAC facility discharge and 90 days after discharge. Future studies are needed to examine the effect of this intervention on patient-reported and long-term clinical outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02979353.

PMID:36745422 | DOI:10.1001/jamainternmed.2022.6545

J Comput Biol. 2023 Feb 6. doi: 10.1089/cmb.2022.0330. Online ahead of print.

ABSTRACT

Diversification models describe the random growth of evolutionary trees, modeling the historical relationships of species through speciation and extinction events. One class of such models allows for independently changing traits, or types, of the species within the tree, upon which speciation and extinction rates depend. Although identifiability of parameters is necessary to justify parameter estimation with a model, it has not been formally established for these models, despite their adoption for inference. This work establishes generic identifiability up to label swapping for the parameters of one of the simpler forms of such a model, a multitype pure birth model of speciation, from an asymptotic distribution derived from a single tree observation as its depth goes to infinity. Crucially for applications to available data, no observation of types is needed at any internal points in the tree, nor even at the leaves.

PMID:36745414 | DOI:10.1089/cmb.2022.0330

Minerva Gastroenterol (Torino). 2023 Feb 6. doi: 10.23736/S2724-5985.23.03323-5. Online ahead of print.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is the most common rhythm disturbance seen in clinical practice. Evidence emerged that suggested inflammation was associated with risk of AF. Helicobacter pylori (HP) cause gastric and esophageal inflammation, as well as systemic and vascular inflammation. These local and systemic inflammatory effects may increase the risk of AF. The pathogenesis of atrial fibrillation (AF) remains unknown. However, many recent studies point to an association between AF and inflammation because of a demonstrable significant correlation between the dysrhythmia and various biomarkers of inflammation. Given the suggested involvement of inflammation with this dysrhythmia, an initiating factor for inflammation has been sought. Chronic bacterial infection is the most likely event to initiate and maintain an inflammatory process. Recently, bacterial infections have been hypothesized to be involved in the pathogenesis of AF, and Helicobacter pylori and Chlamydia pneumoniae are two bacteria that have aroused interest. The aim of this study was to compare the prevalence of H. Pylori infection, proven by gastric biopsy, between AF patients and control group and the role of CRP, MPV, age and sex in patients with HP associated AF.

METHODS: We investigated one hundred eighty patients with HP in whom gastroscopy was done and/or urea breathe test because of dyspepsia and epigastric discomfort for eventual detecting the presence of H. pylori infection, and the prevalence of fibrillation in patients with HP, and whether age, sex, inflammatory markers are different in the two groups. The study was enrolled in the Department of Internal Medicine, Ziv Medical Center, Safed, Israel, from 2015 until 2019.

RESULTS: The prevalence is more pronounced in men with both atrial fibrillation and H. pylori, in terms of age we see that the incidence of atrial fibrillation is more relative in the older age P<0.001. There is no statistically significant difference in the inflammatory marker MPV between the two groups P<0.005. The levels of high-sensitivity C-reactive protein (hs-CRP) have been shown to be higher among patients with H. pylori with AF compared with the control group HP without AF statistically significant P<0.001.

CONCLUSIONS: There is a correlation between HP and AF, AF is more related to age and to an increased inflammation marker CRP in patients diagnosed with HP.

PMID:36745411 | DOI:10.23736/S2724-5985.23.03323-5

J Drugs Dermatol. 2023 Feb 1;22(2):165-173. doi: 10.36849/JDD.6910.

ABSTRACT

BACKGROUND: There is a paucity of data on usage of topical medications in patients with darker phototypes. This single-center, randomized, double-blinded, vehicle-controlled clinical study investigated the efficacy of a combination calcipotriene/betamethasone dipropionate (Cal/BD) aerosol foam 0.005%/0.064% in the treatment of psoriasis vulgaris in Fitzpatrick skin types IV to VI.

METHODS: 25 adult subjects were randomized 4:1 to Cal/BD foam or foam vehicle once daily for 4 weeks followed by 4 weeks of open label treatment. From week 4 to week 8, subjects randomized to Cal/BD foam once daily switched to Cal/BD foam twice weekly for 4 weeks, while those randomized to vehicle applied Cal/BD foam once daily.

RESULTS: At week 4, 4/19 (21%) of Cal/BD foam patients achieved clear/almost clear Investigator Global Assessment (IGA) status with &ge;2 grade improvement compared with 0/5 (0%) of vehicle patients (P=0.54). 12/19 (63%) of Cal/BD foam patients achieved a 50% reduction in Psoriasis Area and Severity Index (PASI 50) at week 4, compared with 0/5 (0%) of vehicle patients (P=0.04). Mean changes in melanin index at week 4 indicate a trend toward increased pigmentation in Cal/BD foam patients and decreased pigmentation in foam vehicle patients (P=0.30). All adverse events were mild and deemed unrelated to treatment by the investigators.

LIMITATIONS: The sample size was small and underpowered to detect statistically significant changes in most endpoints.

CONCLUSION: Cal/BD foam was safe and well tolerated in plaque psoriasis patients with skin of color. Larger studies involving skin of color populations with psoriasis are warranted. Pigmentary changes (hyper- and hypopigmentation) in lesional skin were observed. J Drugs Dermatol. 2023;22(2): 165-173.doi:10.36849/JDD.6910.

PMID:36745370 | DOI:10.36849/JDD.6910

J Drugs Dermatol. 2023 Feb 1;22(2):197-202. doi: 10.36849/JDD.7151.

ABSTRACT

Calcipotriol, a vitamin D analogue is widely used in the treatment of psoriasis. However, poor adherence to topical therapy has led to an ineffective use of the medication and built a barrier to the treatment’s success. A water-free lipid-based formulation system has been developed to improve dosage and cosmetic properties along with patient compliance. This study was conducted to evaluate the efficacy and cutaneous safety of water-free lipid-based formulations containing calcipotriol (50 &mu;g/g) as compared to their corresponding vehicles and marketed calcipotriol formulations in a psoriasis plaque test. In total, 24 subjects with chronic psoriasis vulgaris were enrolled in this single-center, randomized, vehicle, and comparator-controlled clinical trial and treated once daily over a 12-day period (10 applications). The anti-psoriatic effect was evaluated by sonographic measurement of psoriatic infiltrate and investigators’ clinical efficacy assessments. The mean reduction in psoriatic infiltrate from baseline to day 12 (end of trial) with lipid-based calcipotriol formulations (-34% and -37%) was statistically significant (P&lt;0.0001) when compared to their corresponding vehicles (6% and -4%) but not when compared with marketed calcipotriol solution and cream (-34% and -49% respectively). Mean total clinical assessment scores of these lipid-based calcipotriol formulations (1.7 each) were between those of the two comparators – greater than marketed calcipotriol solution (1.3) but lower than cream (2.0). Overall, nine mild non-serious treatment-emergent adverse effects related to all calcipotriol formulations were reported in four subjects, but all recovered at the follow-up visit. Therefore, novel lipid-based formulations of calcipotriol were clearly more efficacious than their corresponding vehicles and considered as safe therapy against psoriasis vulgaris. J Drugs Dermatol. 2023;22(2):197-202. doi:10.36849/JDD.7151Citation:&nbsp;Holmb&auml;ck J, Carlsson A, Rinwa P. Efficacy and safety of water-free lipid formulation system containing calcipotriol against psoriasis vulgaris. J Drugs Dermatol. 2023;22(2):197-202. doi:10.36849/JDD.7151 &nbsp.

PMID:36745360 | DOI:10.36849/JDD.7151

Spine Deform. 2023 Feb 6. doi: 10.1007/s43390-023-00641-w. Online ahead of print.

ABSTRACT

PURPOSE: Although the pediatric population typically has a high union rate, the cervical spine has a reputation for frequent pseduarthrosis, as high as 38% in some prior series. Our purpose was to examine the rate and risk factors for pseudarthrosis in pediatric cervical spine fusions.

METHODS: Retrospective review of all patients with ≥ 2 years follow-up undergoing cervical spinal fusion between January 2004 and December 2019 at a tertiary pediatric hospital. Pseudarthrosis was defined as an absence of radiographic union as assessed by the attending surgeon for which revision surgery was performed.

RESULTS: 64 patients (mean age: 8.4 ± 4.7 years) met inclusion criteria. Mean follow-up was 63.3 ± 41.4 months (range: 24-187 months). 28 fusions (44%) included the occiput. 41 patients (64%) had instrumentation, while 23 patients (36%) had uninstrumented fusions. 48 (75%) patients had a halo for a mean of 97.6 ± 49.5 days. The incidence of pseudarthrosis was as follows: overall = 8/64 (12.5%); posterior fusion = 14.8% (8/54); anterior fusions = 0% (0/4); and anteroposterior fusions = 0% (0/6). The rate of pseudarthrosis was over 8 times higher in fusions involving the occiput (occipitocervical fusion: 25.0%; 7/28 vs. cervical alone: 2.8%; 1/36; p = 0.02). Although not statistically significant, the rate of pseudarthrosis was 3 times higher in uninstrumented fusions (21.7%; 5/23) than instrumented fusions (7.3%; 3/41) (p = 0.12). In patients with uninstrumented fusion to the occiput, pseudarthrosis rate was 35.7% (5/14), which was higher compared to those who did not (6.0%; 3/50) (p = 0.01). Incidence of pseudarthrosis was similar in patients who received autograft (13.0%; 7/54) compared to allograft alone (10.0%; 1/10) (p > 0.999).

CONCLUSIONS: The pseudarthrosis rate in pediatric cervical spine fusions remained high despite frequent use of halo immobilization and autograft. Patients with uninstrumented occipitocervical fusions are at particularly high risk with more than 1 in 3 developing a pseudarthrosis.

STUDY DESIGN: Retrospective, Comparative.

LEVEL OF EVIDENCE: III.

PMID:36745301 | DOI:10.1007/s43390-023-00641-w

J Mol Neurosci. 2023 Feb 6. doi: 10.1007/s12031-023-02103-4. Online ahead of print.

ABSTRACT

Regardless of shifts in levels of individual transcripts, it remains elusive whether natural variability in cell-specific transcriptomes within the cerebral cortex is limited in aggregate. It is also unclear whether cortical cell-specific transcriptomes might change dynamically in absence of cell number changes. Total variation in neuron- and glia-specific in-aggregate transcriptomes could be identified in a model-free way via glia-neuron ratio approach, by univariate median-to-median ratios comparing integral levels of cell-specific transcripts within a tissue sample. When deleterious, regenerative or developmental events affecting cortical cell numbers were subtle, median-to-median ratios demonstrated within-group variability not exceeding <20-25% in most cases. These levels of total variability might be explained in part by limited (~5-10%) circadian and stress-induced shifts in cell-specific cortical transcriptomes. Relevant in-aggregate transcriptomic alterations were identified after shifts in cell numbers induced by well-validated deleterious events including ischemia, traumatic injury, microglia’s activation/depletion or specific mutations. Cortical median-to-median ratios also follow naturally occurring changes in the numbers of excitatory, inhibitory neurons and glial cells during perinatal brain development. These findings characterize cortical cell-specific transcriptomes as subjects to circadian shifts and lifetime events, urging the importance of reporting full details on an origin of any transcriptomic sample collected in vivo.

PMID:36745298 | DOI:10.1007/s12031-023-02103-4

MAGMA. 2023 Feb 6. doi: 10.1007/s10334-022-01058-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the origin of compartment size overestimation in double diffusion encoding MRI (DDE) in vivo experiments in the human corticospinal tract. Here, the extracellular space is hypothesized to be the origin of the DDE signal. By exploiting the DDE sensitivity to pore shape, it could be possible to identify the origin of the measured signal. The signal difference between parallel and perpendicular diffusion gradient orientation can indicate if a compartment is regular or eccentric in shape. As extracellular space can be considered an eccentric compartment, a positive difference would mean a high contribution to the compartment size estimates.

MATERIALS AND METHODS: Computer simulations using MISST and in vivo experiments in eight healthy volunteers were performed. DDE experiments using a double spin-echo preparation with eight perpendicular directions were measured in vivo. The difference between parallel and perpendicular gradient orientations was analyzed using a Wilcoxon signed-rank test and a Mann-Whitney U test.

RESULTS: Simulations and MR experiments showed a statistically significant difference between parallel and perpendicular diffusion gradient orientation signals ([Formula: see text]).

CONCLUSION: The results suggest that the DDE-based size estimate may be considerably influenced by the extra-axonal compartment. However, the experimental results are also consistent with purely intra-axonal contributions in combination with a large fiber orientation dispersion.

PMID:36745290 | DOI:10.1007/s10334-022-01058-8