Tag: statistics

Sci Transl Med. 2023 Jan 4;15(677):eadc9606. doi: 10.1126/scitranslmed.adc9606. Epub 2023 Jan 4.

ABSTRACT

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT^-/- mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor β1 (TGFβ1) and collagen (COL1A1) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.

PMID:36599005 | DOI:10.1126/scitranslmed.adc9606

J Pediatr Hematol Oncol. 2023 Jan 1;45(1):e26-e30. doi: 10.1097/MPH.0000000000002575. Epub 2022 Oct 20.

ABSTRACT

Children with cancer often present with general and nonspecific symptoms leading to initial diagnostic workup inclusive of clinical imaging. Various sequences of magnetic resonance imaging (MRI) are becoming more available for diagnostic imaging. However, there is currently a dearth of literature quantifying the sensitivity and specificity of whole-body MRI in identifying pediatric malignancy. In this study, a retrospective analysis was performed of pediatric whole-body MRI inclusive of short tau inversion recovery sequence conducted at an academic pediatric medical center from 2013 to 2018. Kappa statistics were used to evaluate the diagnostic agreement between MRI results and the gold standard diagnostic study of the respective final diagnosis. Sensitivity, specificity, false-positive, and false-negative estimates were provided with joint 90% confidence regions. One hundred forty-two patients received a whole-body MRI during the study period. The sensitivity of whole-body MRI in detecting malignancy was found to be 93.8% with a specificity of 93.4%. The positive and negative predictive values were determined to be 65.2% and 99.1%, respectively. Our findings suggest that whole-body MRI may be of value as an initial diagnostic tool for pediatric malignancy. Larger multicenter collaboration will be needed to further support these data.

PMID:36598963 | DOI:10.1097/MPH.0000000000002575

J Pediatr Hematol Oncol. 2023 Jan 1;45(1):25-28. doi: 10.1097/MPH.0000000000002600. Epub 2022 Nov 24.

ABSTRACT

PURPOSE: Central venous lines (CVL) in children with acute lymphoblastic leukemia (ALL) provide comfortable administration of intensive chemotherapy and blood sampling. The optimal time for the insertion of CVL in patients with ALL during induction therapy is controversial. This study aimed to investigate the frequency of CVL-related complications in children with ALL concerning the time of CVL insertion.

PATIENTS AND METHODS: We reviewed the records of 52 pediatric ALL patients with CVL. CVL placement before or on treatment day 15 was defined as “early insertion”, and after treatment day 15 was defined as “late insertion”. Demographics, preoperative blood counts, type of central line, time of CVL placement, CVL-related complications, and blood counts during complications were all noted. All the data were collected from those with the first catheter use.

RESULTS: CVL was placed ≤15 days in 26 patients (50%) and after 15 days in 26 patients (50%). Regarding the infection rates, no statistical difference was found between early and late CVL-inserted groups (P=n.s.). Five patients developed thrombosis, and risk was found to be similar between early and late CVL-inserted groups (P=n.s.). Catheter-related mechanical complications were recorded in 7 patients (3 in early and 4 in late CVL-inserted group, (P=n.s.).

CONCLUSION: The present study showed no relation between the timing of CVL placement during induction therapy and the occurrence of infection and thrombosis. Our results suggest that CVL can be placed safely at the time of diagnosis or early induction treatment to provide a comfortable administration of chemotherapy and decrease painful blood samplings.

PMID:36598960 | DOI:10.1097/MPH.0000000000002600

Proc Natl Acad Sci U S A. 2023 Jan 10;120(2):e2123182120. doi: 10.1073/pnas.2123182120. Epub 2023 Jan 4.

ABSTRACT

Early-life experience enduringly sculpts thalamocortical (TC) axons and sensory processing. Here, we identify the very first synaptic targets that initiate critical period plasticity, heralded by altered cortical oscillations. Monocular deprivation (MD) acutely induced a transient (<3 h) peak in EEG γ-power (~40 Hz) specifically within the visual cortex, but only when the critical period was open (juvenile mice or adults after dark-rearing, Lynx1-deletion, or diazepam-rescued GAD65-deficiency). Rapid TC input loss onto parvalbumin-expressing (PV) inhibitory interneurons (but not onto nearby pyramidal cells) was observed within hours of MD in a TC slice preserving the visual pathway – again once critical periods opened. Computational TC modeling of the emergent γ-rhythm in response to MD delineated a cortical interneuronal gamma (ING) rhythm in networks of PV-cells bearing gap junctions at the start of the critical period. The ING rhythm effectively dissociated thalamic input from cortical spiking, leading to rapid loss of previously strong TC-to-PV connections through standard spike-timing-dependent plasticity rules. As a consequence, previously silent TC-to-PV connections could strengthen on a slower timescale, capturing the gradually increasing γ-frequency and eventual fade-out over time. Thus, ING enables cortical dynamics to transition from being dominated by the strongest TC input to one that senses the statistics of population TC input after MD. Taken together, our findings reveal the initial synaptic events underlying critical period plasticity and suggest that the fleeting ING accompanying a brief sensory perturbation may serve as a robust readout of TC network state with which to probe developmental trajectories.

PMID:36598942 | DOI:10.1073/pnas.2123182120

PLoS One. 2023 Jan 4;18(1):e0280050. doi: 10.1371/journal.pone.0280050. eCollection 2023.

ABSTRACT

PURPOSE: We aimed to quantify life course-specific associations between death in hospital and 30 chronic conditions, and comorbidity among them, in adults (aged 20+ years) during their first acute care hospitalization with a confirmed or suspected COVID-19 diagnosis in Canada.

METHODS: We identified 35,519 first acute care hospitalizations with a confirmed or suspected COVID-19 diagnosis in the Discharge Abstract Database as of March 31, 2021. For each of five life-course age groups (20-34, 35-49, 50-64, 65-79, and 80+ years), we used multivariable logistic regression to examine associations between death in hospital and 30 chronic conditions, comorbidity, period of admission, and pregnant status, after adjusting for sex and age.

RESULTS: About 20.9% of hospitalized patients with COVID-19 died in hospital. Conditions most strongly associated with in-hospital death varied across the life course. Chronic liver disease, other nervous system disorders, and obesity were statistically significantly associated (α = 0.05) with in-hospital death in the 20-34 to 65-79 year age groups, but the magnitude of the associations decreased as age increased. Stroke (aOR = 5.24, 95% CI: 2.63, 9.83) and other inflammatory rheumatic diseases (aOR = 4.37, 95% CI: 1.64, 10.26) were significantly associated with in-hospital death among 35 to 49 year olds only. Among 50+ year olds, more chronic conditions were significantly associated with in-hospital death, but the magnitude of the associations were generally weaker except for Down syndrome in the 50 to 64 (aOR = 8.49, 95% CI: 4.28, 16.28) and 65 to 79 year age groups (aOR = 5.19, 95% CI: 1.44, 20.91). Associations between comorbidity and death also attenuated with age. Among 20 to 34 year olds, the likelihood of death was 19 times greater (aOR = 18.69, 95% CI: 7.69, 48.24) in patients with three or more conditions compared to patients with none of the conditions, while for 80+ year olds the likelihood of death was two times greater (aOR = 2.04, 95% CI: 1.70, 2.45) for patients with six or more conditions compared to patients with none of the conditions.

CONCLUSION: Conditions most strongly associated with in-hospital death among hospitalized adults with COVID-19 vary across the life course, and the impact of chronic conditions and comorbidity attenuate with age.

PMID:36598923 | DOI:10.1371/journal.pone.0280050

PLoS One. 2023 Jan 4;18(1):e0280051. doi: 10.1371/journal.pone.0280051. eCollection 2023.

ABSTRACT

BACKGROUND: Cardiovascular diseases are the leading cause of death and disability worldwide. Little is known about the organizational priorities of patients and clinicians involved in primary cardiovascular care. This study aimed to identify their shared top priorities and explore on which aspects their perspectives differed.

METHODS: A three-round modified online Delphi study was carried out with patients and clinicians in seven academic primary care settings from metropolitan, suburban and small-town areas in Quebec, Canada. Patient partners experienced in the mobilization of their experiential knowledge also participated in the study. Following an “open” round, the items elicited were assessed by a combined rating and ranking approach. Items achieving an initial consensus level ≥70% were reassessed and then rank-ordered based on their final scores. Levels of consensus achieved among patients and clinicians were compared using Fisher’s Exact tests.

RESULTS: Thirty panelists completed the study (9 clinic patients, 7 patient partners and 14 clinicians). Out of 41 organizational aspects generated, six top priorities were shared by patients and clinicians. These related to listening and tailoring care to each patient, provision of personalized information, rapid response in the event of a problem, keeping professional training up-to-date, and relational and informational continuity of care. Statistically significant differences were found between patients’ and clinicians’ perspectives regarding the importance of offering healthy lifestyle and prevention activities at the clinic (lower for patients), timely access to the treating physician (higher for patients), and effective collaboration with specialist physicians (higher for patients).

CONCLUSION: Although their views differ on some organizational aspects, patients and clinicians share a small set of top priorities for primary cardiovascular care that may be transferable to other chronic diseases. These top priorities should remain a central focus of clinical settings, alongside other primary care reform goals.

PMID:36598919 | DOI:10.1371/journal.pone.0280051

PLoS One. 2023 Jan 4;18(1):e0280031. doi: 10.1371/journal.pone.0280031. eCollection 2023.

ABSTRACT

BACKGROUND: The WHO recommends pregnant women attend antenatal clinic at least three times during pregnancy; during the first, second and third trimesters. During these visits, an array of clinical and laboratory tests is conducted. The information obtained plays an important role not only in the management and care of pregnancy, but also guides policies targeted at addressing pregnancy-induced health challenges. This study therefore presents laboratory and clinical information of pregnant women at their first antenatal visits.

METHODS: The study was cross-sectional in design which retrospectively reviewed laboratory and clinical data of pregnant women attending their first antenatal clinic (ANC) at the Comboni Hospital, Volta region, Ghana. The data reviewed included information on hemoglobin level, hemoglobin phenotype, malaria diagnostics, Human Immunodeficiency Virus test (HIV), glucose-6-phosphate dehydrogenase (G6PD) deficiency, Hepatitis C Virus (HCV) test, Hepatitis B Virus (HBV) test, Syphilis test, blood pressure, age, urine glucose, and urine protein. The hemoglobin level was assayed with a hemoglobinometer. Qualitative lateral flow chromatographic immunoassay techniques were used to diagnose the HIV, HCV, HBV, syphilis, and malaria status of the pregnant women. Urine dipstick was used assay for the urine protein and urine glucose, whilst the methemoglobin test was used for the G6PD deficiency and alkaline hemoglobin electrophoresis for hemoglobin phenotype. Data on demographic, anthropometric and vital signs such as age, weight and blood pressure were also collected. Descriptive statistics were performed. Frequency and percentages were used to describe the categorical variables and means and standard deviations used to describe the continuous variables.

RESULTS: Hemoglobin S(Hb S) was found in 12.8% of the women with 73.4% having hemoglobin levels below 11.5g/dl. On G6PD deficiency, 1.6% and 0.8% were partially and fully defective respectively. Also, urine protein (1.2%) and glucose (0.4%) were detected. The prevalence of HBV, HCV and malaria were 4.4%, 3.6% and 2.4%, respectively.

CONCLUSION: Anemia in pregnancy was high among the study sample. Malaria and hepatitis infections were observed in the study sample. Policies on maternal health should be targeted at providing better nutritional options, that can enhance the hemoglobin level during pregnancy. Pregnant women should benefit from enhanced surveillance for HIV, HBV, HCV, and syphilis.

PMID:36598908 | DOI:10.1371/journal.pone.0280031

PLoS One. 2023 Jan 4;18(1):e0279180. doi: 10.1371/journal.pone.0279180. eCollection 2023.

ABSTRACT

BACKGROUND: Despite the potential detrimental consequences for individuals’ health and discrimination from covid-19 symptoms, the outcomes have received little attention. This study examines the relationships between having personally experienced discrimination based on the symptoms of covid-19 (during the first wave of the pandemic), mental health, and emotional responses (anger and sadness). It was predicted that covid-19 discrimination would be positively related to poor mental health and that this relationship would be mediated by the emotions of anger and sadness.

METHODS: The study was conducted using an online questionnaire from January to June 2020 (the Covistress network; including 44 countries). Participants were extracted from the COVISTRESS database (Ntotal = 280) with about a half declaring having been discriminated due to covid-19 symptoms (N = 135). Discriminated participants were compared to non-discriminated participants using ANOVA. A mediation analysis was conducted to examine the indirect effect of emotional responses and the relationships between perceived discrimination and self-reported mental health.

RESULTS: The results indicated that individuals who experienced discrimination based on the symptoms of covid-19 had poorer mental health and experienced more anger and sadness. The relationship between covid-19 personal discrimination and mental health disappeared when the emotions of anger and sadness were statistically controlled for. The indirect effects for both anger and sadness were statistically significant.

DISCUSSION: This study suggests that the covid-19 pandemic may have generated discriminatory behaviors toward those suspected of having symptoms and that this is related to poorer mental health via anger and sadness.

PMID:36598901 | DOI:10.1371/journal.pone.0279180

PLoS One. 2023 Jan 4;18(1):e0266985. doi: 10.1371/journal.pone.0266985. eCollection 2023.

ABSTRACT

PURPOSE: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.

METHODS: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.

RESULTS: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).

CONCLUSION: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

PMID:36598895 | DOI:10.1371/journal.pone.0266985

PLoS One. 2023 Jan 4;18(1):e0279163. doi: 10.1371/journal.pone.0279163. eCollection 2023.

ABSTRACT

OBJECTIVES: Understand the continuity and changes in headache not-otherwise-specified (NOS), migraine, and post-traumatic headache (PTH) diagnoses after the transition from ICD-9-CM to ICD-10-CM in the Veterans Health Administration (VHA).

BACKGROUND: Headache is one of the most commonly diagnosed chronic conditions managed within primary and specialty care clinics. The VHA transitioned from ICD-9-CM to ICD-10-CM on October-1-2015. The effect transitioning on coding of specific headache diagnoses is unknown. Accuracy of headache diagnosis is important since different headache types respond to different treatments.

METHODS: We mapped headache diagnoses from ICD-9-CM (FY 2014/2015) onto ICD-10-CM (FY 2016/2017) and computed coding proportions two years before/after the transition in VHA. We used queries to determine the change in transition pathways. We report the odds of ICD-10-CM coding associated with ICD-9-CM controlling for provider type, and patient age, sex, and race/ethnicity.

RESULTS: Only 37%, 58% and 34% of patients with ICD-9-CM coding of NOS, migraine, and PTH respectively had an ICD-10-CM headache diagnosis. Of those with an ICD-10-CM diagnosis, 73-79% had a single headache diagnosis. The odds ratios for receiving the same code in both ICD-9-CM and ICD-10-CM after adjustment for ICD-9-CM and ICD-10-CM headache comorbidities and sociodemographic factors were high (range 6-26) and statistically significant. Specifically, 75% of patients with headache NOS had received one headache diagnoses (Adjusted headache NOS-ICD-9-CM OR for headache NOS-ICD-10-CM = 6.1, 95% CI 5.89-6.32. 79% of migraineurs had one headache diagnoses, mostly migraine (Adjusted migraine-ICD-9-CM OR for migraine-ICD-10-CM = 26.43, 95% CI 25.51-27.38). The same held true for PTH (Adjusted PTH-ICD-9-CM OR for PTH-ICD-10-CM = 22.92, 95% CI: 18.97-27.68). These strong associations remained after adjustment for specialist care in ICD-10-CM follow-up period.

DISCUSSION: The majority of people with ICD-9-CM headache diagnoses did not have an ICD-10-CM headache diagnosis. However, a given diagnosis in ICD-9-CM by a primary care provider (PCP) was significantly predictive of its assignment in ICD-10-CM as was seeing either a neurologist or physiatrist (compared to a generalist) for an ICD-10-CM headache diagnosis.

CONCLUSION: When a veteran had a specific diagnosis in ICD-9-CM, the odds of being coded with the same diagnosis in ICD-10-CM were significantly higher. Specialist visit during the ICD-10-CM period was independently associated with all three ICD-10-CM headaches.

PMID:36598881 | DOI:10.1371/journal.pone.0279163