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Bronquiectasia , Humanos , Bronquiectasia/microbiología , Masculino , Femenino , Persona de Mediana Edad , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/diagnóstico , Estudios Retrospectivos , Adulto , Mycobacterium tuberculosis/aislamiento & purificación , Anciano , Antituberculosos/administración & dosificación , Antituberculosos/uso terapéuticoRESUMEN
BACKGROUND & RATIONALE: In prior work using non-speech stimuli, children with hearing loss show impaired perception of binaural cues and no significant change in cortical responses to bilateral versus unilateral stimulation. Aims of the present study were to: 1) identify bilateral responses to envelope and spectral components of a speech syllable using the frequency-following response (FFR), 2) determine if abnormalities in the bilateral FFR occur in children with hearing loss, and 3) assess functional consequences of abnormal bilateral FFR responses on perception of binaural timing cues. METHODS: A single-syllable speech stimulus (/dα/) was presented to each ear individually and bilaterally. Participants were 9 children with normal hearing (MAge = 12.1 ± 2.5 years) and 6 children with bilateral hearing loss who were experienced bilateral hearing aid users (MAge = 14.0 ± 2.6 years). FFR temporal and spectral peak amplitudes were compared between listening conditions and groups using linear mixed model regression analyses. Behavioral sensitivity to binaural cues were measured by lateralization responses as coming from the right or left side of the head. RESULTS: Both temporal and spectral peaks in FFR responses increased in amplitude in the bilateral compared to unilateral listening conditions in children with normal hearing. These measures of "bilateral advantage" were reduced in the group of children with bilateral hearing loss and associated with decreased sensitivity to interaural timing differences. CONCLUSION: This study is the first to show that bilateral responses in both temporal and spectral domains can be measured in children using the FFR and is altered in children with hearing loss with consequences to binaural hearing.
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Estimulación Acústica , Señales (Psicología) , Percepción del Habla , Humanos , Niño , Masculino , Femenino , Adolescente , Estudios de Casos y Controles , Pérdida Auditiva Bilateral/fisiopatología , Pérdida Auditiva Bilateral/psicología , Pérdida Auditiva Bilateral/diagnóstico , Audífonos , Factores de Tiempo , Personas con Deficiencia Auditiva/psicología , Factores de Edad , Localización de Sonidos , Audición , Acústica del Lenguaje , Potenciales Evocados Auditivos , ElectroencefalografíaRESUMEN
BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Neoplasias Endometriales , Paclitaxel , Humanos , Femenino , Carboplatino/administración & dosificación , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Método Doble Ciego , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/mortalidad , Supervivencia sin Progresión , Anticuerpos Monoclonales HumanizadosRESUMEN
PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/mortalidad , Anciano , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Temozolomida/uso terapéutico , Adulto , Antineoplásicos Alquilantes/uso terapéutico , Factores de Edad , Terapia Combinada , Resultado del Tratamiento , Manejo de la EnfermedadRESUMEN
Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We were successful in identifying biomarkers that were predictive of high hallucinations and of high delusions states, and of future psychiatric hospitalizations related to them, more so when personalized by gender and diagnosis. Top biomarkers for hallucinations that survived discovery, prioritization, validation and testing include PPP3CB, DLG1, ENPP2, ZEB2, and RTN4. Top biomarkers for delusions include AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA. The top biological pathways uncovered by our work are glutamatergic synapse for hallucinations, as well as Rap1 signaling for delusions. Some of the biomarkers are targets of existing drugs, of potential utility in pharmacogenomics approaches (matching patients to medications, monitoring response to treatment). The top biomarkers gene expression signatures through bioinformatic analyses suggested a prioritization of existing medications such as clozapine and risperidone, as well as of lithium, fluoxetine, valproate, and the nutraceuticals omega-3 fatty acids and magnesium. Finally, we provide an example of how a personalized laboratory report for doctors would look. Overall, our work provides advances for the improved diagnosis and treatment for schizophrenia and other psychotic disorders.
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Biomarcadores , Farmacogenética , Medicina de Precisión , Trastornos Psicóticos , Humanos , Medicina de Precisión/métodos , Trastornos Psicóticos/genética , Trastornos Psicóticos/tratamiento farmacológico , Farmacogenética/métodos , Biomarcadores/sangre , Masculino , Femenino , Alucinaciones/genética , Antipsicóticos/uso terapéutico , Deluciones/genética , Adulto , Medición de Riesgo/métodos , Esquizofrenia/genética , Esquizofrenia/tratamiento farmacológicoRESUMEN
In animal communication, functionally referential alarm calls elicit the same behavioral responses as their referents, despite their typically distinct bioacoustic traits. Yet the auditory forebrain in at least one songbird species, the black-capped chickadee Poecile atricapillus, responds similarly to threat calls and their referent predatory owl calls, as assessed by immediate early gene responses in the secondary auditory forebrain nuclei. Whether and where in the brain such perceptual and cognitive equivalence is processed remains to be understood in most other avian systems. Here, we studied the functional neurogenomic (non-) equivalence of acoustic threat stimuli perception by the red-winged blackbird Agelaius phoeniceus in response to the actual calls of the obligate brood parasitic brown-headed cowbird Molothrus ater and the referential anti-parasitic alarm calls of the yellow warbler Setophaga petechia, upon which the blackbird is known to eavesdrop. Using RNA-sequencing from neural tissue in the auditory lobule (primary and secondary auditory nuclei combined), in contrast to previous findings, we found significant differences in the gene expression profiles of both an immediate early gene, ZENK (egr-1), and other song-system relevant gene-products in blackbirds responding to cowbird vs. warbler calls. In turn, direct cues of threats (including conspecific intruder calls and nest-predator calls) elicited higher ZENK and other differential gene expression patterns compared to harmless heterospecific calls. These patterns are consistent with a perceptual non-equivalence in the auditory forebrain of adult male red-winged blackbirds in response to referential calls and the calls of their referents.
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Passeriformes , Pájaros Cantores , Animales , Masculino , Vocalización Animal/fisiología , Pájaros Cantores/fisiología , Prosencéfalo/fisiología , Transcriptoma , Percepción Auditiva/fisiologíaRESUMEN
PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Estudios Prospectivos , Dacarbazina/efectos adversos , Supervivencia sin Enfermedad , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Antineoplásicos Alquilantes/efectos adversosRESUMEN
Furan is a naturally forming compound found in heat-processed foods such as coffee, canned meats, and jarred baby food. It is concurrently found with analogues including 2-methylfuran (2-MF) and 3-methylfuran (3-MF), and toxicity studies demonstrate all are potent liver toxins. Toxicity studies found 3-MF is more toxic than either furan, or 2-MF. The present analysis assesses the transcriptional response in liver samples taken from male Fischer (F344) rats exposed to furan or 3-MF from 0 to 2.0 and 0-1.0 mg/kg bw/day, respectively, for 90 days. Transcriptional analyses found decreased liver function and fatty acid metabolism are common responses to both furan and 3-MF exposure. Furan liver injury promotes a ductular reaction through Hippo and TGFB signalling, which combined with increased immune response results in ameliorating perturbed bile acid homeostasis in treated rats. Failure to activate these pathways in 3-MF exposed rats and decreased p53 activity leads to cholestasis, and increased toxicity. Finally, BMD analysis indicate many of the most sensitive pathways affected by furan and 3-MF exposure relate to metabolism - malate dehydrogenase and glucose metabolism with BMDLs of 0.03 and 0.01 mg/kg bw/day for furan and 3-MF exposure, respectively, which agrees with BMDLs previously reported for apical and microarray data.
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Furanos , Hígado , Ratas , Masculino , Animales , Ratas Endogámicas F344 , Furanos/análisis , Hígado/metabolismo , GenómicaRESUMEN
Background Non-union, chronic pain, functional disability, and infection are all things that have been associated with open fractures with severe soft tissue damage leading to the need for additional hospitalization, and sometimes even subsequent surgeries and weeks or months of rehabilitation. Open fractures and severe musculoskeletal injuries are occasionally treated with hyperbaric oxygen therapy (HBOT) in an effort to reduce the risk of complications and increase the likelihood of a successful recovery. Methods A prospective randomized controlled study was done between January 2019 and August 2022 at a tertiary health care center including 60 patients with a severe soft tissue injury (Grade II and III) divided into two groups - group-CT (30 patients who received conventional treatment) and group HT (30 patients, who received HBOT in addition to conventional treatment). The outcome was measured according to the Bates-Jensen Wound Assessment Tool. Results The wound size, depth, and granulation were significantly reduced in group-HT patients. In the final session, the patient's severity of the wound in group-HT was significantly reduced (P = 0.0001) compared to group-CT. Conclusions Patients who received HBOT reported a significant improvement in their wounds.
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BACKGROUND: There is a lack of understanding of the barriers reported by healthcare providers when evaluating beta-lactam allergies, but knowledge of these barriers is required for practical and effective implementation interventions. METHODS: Twenty-five healthcare providers, consisting of physicians, nurses and pharmacists practicing in the areas of intensive care, emergency medicine, infectious disease and general hospital practice, were interviewed between September 2021 and July 2023. Twenty-three of these providers were practising in the USA. A semi-structured interview guide grounded in the Theoretical Domain Framework was used for the interviews. Deductive and inductive analysis was performed on the interview transcripts, and translated into intervention recommendations using the Behaviour Change Wheel. RESULTS: Widely held beliefs included a lack of clear policy for the evaluation of allergies, confusing or missing documentation of allergy information, confidence in their own and their colleagues' ability to evaluate allergies when information is available, and pharmacists as the provider most equipped to evaluate beta-lactam allergies. CONCLUSIONS: Health systems should adopt and disseminate policies for the evaluation of beta-lactam allergies, and promote the use of pharmacists in the evaluation of drug allergies when possible. Allergy sections of electronic health records should be reworked to encourage unambiguous documentation of allergy reactions and support using previously tolerated beta-lactam antibiotics.
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Hipersensibilidad a las Drogas , Hipersensibilidad , Humanos , beta-Lactamas/efectos adversos , Antibacterianos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , FarmacéuticosRESUMEN
Pregnancy initiates a temporary transition in the maternal physiological state, with a shift in the oral microbiome and a potential increase in frequency of oral diseases. The risk of oral disease is higher among populations of Hispanic and Black women and those with lower socioeconomic status (low SES), demonstrating a need for intervention within these high-risk populations. To further our understanding of the oral microbiome of high-risk pregnant women, we characterized the oral microbiome in 28 nonpregnant and 179 pregnant low-SES women during their third trimester living in Rochester, New York. Unstimulated saliva and supragingival plaque samples were collected cross-sectionally, followed by assessment of the bacterial (16S ribosomal RNA) and fungal (18S ITS) microbiota communities. Trained and calibrated dentists performed oral examinations to determine the number of decayed teeth and plaque index. Initially, plaque from 28 nonpregnant women and 48 pregnant women were compared; these data showed significant differences in bacterial abundances based on pregnancy status. To further our understanding of the oral microbiome within the pregnant population, we next examined the oral microbiome within this population based on several variables. Streptococcus mutans, Streptococcus oralis, and Lactobacillus were associated with a greater number of decayed teeth. The composition of fungal communities differed between plaque and saliva, demonstrating 2 distinct "mycotypes" that were represented by a greater abundance of Candida in plaque and Malassezia in saliva. Veillonella rogosae, a common oral bacterium, was negatively associated with both plaque index and salivary Candida albicans colonization by culture data. This was further emphasized by in vitro inhibition of C. albicans by V. rogosae. Identification of interactions between the bacterial or fungal oral communities revealed that V. rogosae was positively associated with the oral commensal Streptococcus australis and negatively with the cariogenic Lactobacillus genus, suggesting V. rogosae as a potential biomarker of a noncariogenic oral microbiome.
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Caries Dental , Placa Dental , Microbiota , Humanos , Femenino , Embarazo , Caries Dental/microbiología , Saliva/microbiología , Placa Dental/microbiología , Candida albicans , Lactobacillus , Streptococcus mutansRESUMEN
This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.
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Carcinoma Hepatocelular , Neoplasias Gastrointestinales , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Guías de Práctica Clínica como AsuntoRESUMEN
Anxiety disorders are increasingly prevalent, affect people's ability to do things, and decrease quality of life. Due to lack of objective tests, they are underdiagnosed and sub-optimally treated, resulting in adverse life events and/or addictions. We endeavored to discover blood biomarkers for anxiety, using a four-step approach. First, we used a longitudinal within-subject design in individuals with psychiatric disorders to discover blood gene expression changes between self-reported low anxiety and high anxiety states. Second, we prioritized the list of candidate biomarkers with a Convergent Functional Genomics approach using other evidence in the field. Third, we validated our top biomarkers from discovery and prioritization in an independent cohort of psychiatric subjects with clinically severe anxiety. Fourth, we tested these candidate biomarkers for clinical utility, i.e. ability to predict anxiety severity state, and future clinical worsening (hospitalizations with anxiety as a contributory cause), in another independent cohort of psychiatric subjects. We showed increased accuracy of individual biomarkers with a personalized approach, by gender and diagnosis, particularly in women. The biomarkers with the best overall evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4. Finally, we identified which of our biomarkers are targets of existing drugs (such as a valproate, omega-3 fatty acids, fluoxetine, lithium, sertraline, benzodiazepines, and ketamine), and thus can be used to match patients to medications and measure response to treatment. We also used our biomarker gene expression signature to identify drugs that could be repurposed for treating anxiety, such as estradiol, pirenperone, loperamide, and disopyramide. Given the detrimental impact of untreated anxiety, the current lack of objective measures to guide treatment, and the addiction potential of existing benzodiazepines-based anxiety medications, there is a urgent need for more precise and personalized approaches like the one we developed.
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Farmacogenética , Medicina de Precisión , Humanos , Femenino , Medicina de Precisión/métodos , Calidad de Vida , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/psicología , Biomarcadores , Medición de Riesgo , Benzodiazepinas , Proteínas de Transporte de Serotonina en la Membrana PlasmáticaRESUMEN
This pilot study assessed the feasibility and potential effectiveness of a single-session workshop in modifying parental beliefs/knowledge about attention-deficit/hyperactivity disorder (ADHD) in children and impact on treatment acceptance/utilization. Concerns raised by school professionals about lack of treatment follow-through after ADHD diagnosis and parental misinformation about medication usage catalyzed this project. A single-group pre-post quasi-experimental design was used. Sixty-eight parents completed ADHD knowledge/belief scales and stress inventories, and pre-ADHD and post-ADHD information workshop. Follow-up calls were made after the workshop to assess treatment utilization. Parents/caregivers experienced significant knowledge and belief changes regarding medication efficacy, willingness to accept physician treatment recommendations, and rejection of non-empirically based treatments. Follow-up data showed that 41% of contacted participants met with physicians to discuss medication utilization and behavioral treatments. Brief, one-session psycho-educational workshops were feasible and impacted parental beliefs and behaviors regarding scientifically supported interventions for ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/terapia , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Proyectos Piloto , Responsabilidad Parental , Padres , Instituciones AcadémicasRESUMEN
INTRODUCTION: Early childhood caries (ECC) is a complex oral disease that is prevalent in US children. OBJECTIVES: The purpose of this 2-y prospective cohort study was to examine baseline and time-dependent risk factors for ECC onset in initially caries-free preschool children. METHODS: A cohort of 189 initially caries-free children aged 1 to 3 y was recruited. At each 6-mo study visit, children were examined using the ICDAS index; salivary samples were collected to assess mutans streptococci (MS), lactobacilli, Candida species, salivary cortisol (prior and after a stressor), and salivary IgA. Diet and oral health behavior were assessed from parent report. Child and family stress exposure was assessed from measures of psychological symptoms, stressful life event exposure, family organization and violence exposure, and social support. Sociodemographic factors were also considered. A Kaplan-Meier estimator of survival function of time to ECC and a Cox proportional hazards model were used to identify predictors of ECC onset. RESULTS: Onset of ECC was associated with high salivary MS levels at baseline (log-rank test, P < 0.0001). Cox proportional hazards regression showed that the risk of dental caries significantly increased with salivary MS in log scale over the 6-mo period (hazard ratio, 1.08; P = 0.01). Other risk factors in the model did not reach statistical significance. CONCLUSION: Our results provide prospective evidence that an increase in salivary MS predicts ECC onset in young, initially caries-free children, confirming that a high salivary MS count likely plays a causal role in ECC onset, independent of covariates. KNOWLEDGE TRANSFER STATEMENT: These results suggest that we must focus on reducing salivary MS counts in young children and preventing or delaying MS colonization in infants and young children determined to be at risk for ECC.
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Caries Dental , Lactante , Humanos , Preescolar , Estudios Prospectivos , Estudios Longitudinales , Caries Dental/epidemiología , Streptococcus mutans , Modelos de Riesgos ProporcionalesRESUMEN
Trials to assess differences in PRWE (Patient Related Wrist Evaluation) over time, for both surgical and non-surgical interventions post DRFs (distal radius fractures) are rare. The DASH (Disabilities of the Arm, Shoulder and Hand) questionnaire has been shown to be improved by a greater margin in the medium term for surgical interventions, than non surgical interventions. However, a study found that PRWE can be considered superior to the DASH questionnaire for DRFs, due to greater specificity to wrist pain and function. Conflicting data makes it difficult to determine surgical vs non-surgical superiority for DRF's over time with PRWE as a recovery metric. PubMed and Cochrane were searched for randomised controlled trials up to 31.8.23, reporting PRWE over 3, and 12 months. Data was extracted by 2 researchers. The differences in PRWE over time post surgical and non-surgical interventions was assessed using unpaired T testing. 1226 records were screened. 4 studies enrolling 817 participants met the eligibility criteria and were analysed. Significantly lower PRWE in surgical intervention has been identified at the 3 month mark (p<0.001). There was greater significant change in non-surgical intervention between months 3 and 12 (p<0.001). Change in PRWE over time may be a good indicator of functional outcomes in DRFs post surgical or non-surgical interventions. This could inform future clinical trial design and surgical decision-making. Further work is required to design even more user-friendly and digital patient- reported outcomes specifically for DRFs.
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Fracturas de la Muñeca , Muñeca , Humanos , Extremidad Superior , Articulación de la Muñeca , ManoRESUMEN
OBJECTIVE: Lung cancer in never-smokers represents a growing proportion of patients. The relationship between smoking status, symptom appraisal and help-seeking behaviour is complex. Little is known about cancer symptom-related health behaviours according to smoking status. The aim of the study was to explore lung cancer patients' experiences of a lung cancer diagnosis, identifying differences by smoking history. METHOD: This was a qualitative study involving telephone interviews with 40 lung cancer patients (20 never smokers, 11 former smokers and 9 current smokers). We used framework analysis to analyse the data using the Common Sense Model of Illness Self-Regulation as a theoretical framework, developed after initial analysis. RESULTS: All patients were likely to delay seeking help for symptoms in primary care regardless of smoking history, but for different reasons. Smoking history was instrumental to how individuals perceived and responded to early symptoms of lung cancer. Differences in interpretation and coping responses to new symptoms seemed to be caused by the higher presence of comorbidities due to smoking, and perceptions of the current state of health. Individuals with a smoking history reported acting with urgency in seeking help and follow up, whereas patients who experienced low levels of concern were more easily reassured by clinicians, resulting in delays. CONCLUSIONS: Never and former smokers perceive, interpret, and respond to symptoms of lung cancer differently to smokers. However, few people attribute their lung symptoms to cancer initially, even with a smoking history. Interventions that drive increased urgency and vigilance in never smokers may be effective.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Fumar/epidemiología , Investigación Cualitativa , ComorbilidadRESUMEN
OBJECTIVE: To determine if preterm birth is associated with adaptation of the hypothalamic-pituitary-adrenal (HPA) axis and whether HPA axis programming relates to the degree of prematurity (defined as extremely preterm birth at <28 weeks or very preterm birth at 28-32 weeks gestation). DESIGN: This study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured prevaccination and postvaccination, and in the morning and evening, at 4 months chronological age. SETTING: Infants born at a single Scottish hospital. PARTICIPANTS: 45 term-born, 42 very preterm and 16 extremely preterm infants. OUTCOMES: Cortisol stress response to vaccination (postvaccination minus prevaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values) and mean log-transformed daily cortisol. RESULTS: Compared with infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8 nmol/L vs 13.1 nmol/L, difference in means: -7.3 nmol/L, 95% CI -14.0 to -0.6) and a flattened diurnal slope (difference in geometric means: -72.9%, 95% CI -87.1 to -42.8). In contrast, the cortisol response to vaccination (difference in means -2.7 nmol/L, 95% CI -7.4 to 2.0) and diurnal slope at 4 months (difference in geometric means: -33.6%, 95% CI -62.0 to 16.0) did not differ significantly in infants born very preterm compared with infants born at term. CONCLUSIONS: Infants born extremely preterm have blunted cortisol reactivity and a flattened diurnal slope. These patterns of HPA axis regulation are commonly seen after childhood adversity and could contribute to later metabolic and neurodevelopmental phenotypes observed in this population.
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Hidrocortisona , Nacimiento Prematuro , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Recien Nacido Extremadamente Prematuro , Recién Nacido , Sistema Hipófiso-Suprarrenal/metabolismo , Estudios Prospectivos , SalivaRESUMEN
BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis adaptation is a potential mechanism linking early life exposures with later adverse health. This study tested the hypothesis that preterm birth is associated with adaptation of diurnal cortisol regulation across infancy. METHODS: A secondary analysis was conducted of saliva cortisol measured morning, midday and evening, monthly, across infancy, as part of a birth cohort conducted in Linköping, Sweden. Diurnal cortisol regulation of infants born extremely preterm (n=24), very preterm (n=27) and at term (n=130) were compared across infancy through random coefficients regression models. RESULTS: Compared with infants born at term, infants born extremely preterm (-17.2%, 95% CI: -30.7 to -1.2), but not very preterm (1.7%, 95% CI: -14.1 to 20.4), had a flattened diurnal slope across infancy. CONCLUSIONS: Extremely preterm birth is associated with a flattened diurnal slope in infancy. This pattern of cortisol regulation could contribute to adverse metabolic and neurodevelopmental phenotypes observed in this population.