Nevin Manimala

Allergy Asthma Clin Immunol. 2022 Aug 28;18(1):79. doi: 10.1186/s13223-022-00720-z.

ABSTRACT

BACKGROUND: Asthma, allergic rhinitis and eczema have been identified as the most prevalent childhood allergic diseases. However, the prevalence of these allergic diseases can vary in different regions within a country and in the world.

METHODS: The objective of the study was to estimate the prevalence of asthma, allergic rhinitis and eczema in schoolchildren in the Kandy and Anuradhapura districts of Sri Lanka. This was a multicentre cross sectional study carried out among children of age 6-7 years and 13-14 years attending state schools fulfilling the entry criteria of the Global Asthma Network Phase 1 study methodology.

RESULTS: A total of 3673 children of 6-7 years and 4658 children of 13-14 years were recruited. The prevalence of current asthma, allergic rhinitis and eczema were 12% (CI 10.44-13.75), 15.7% (CI 13.94-17.64) and 9.7% (CI 8.30-11.31) among 6-7 years age group and 15.3% (CI 13.66-17.09), 30.5% (CI 28.86-32.74) and 7.3% (CI 6.15-8.65) respectively among the 13-14 age group in Kandy district. The reported prevalence rates of the disease conditions were 9.9% (CI 8.72-11.22), 10.1% (CI 8.90-11.44) and 5.9% (CI 4.98-6.98) among 6-7 years age group and 14.9% (CI 13.67-16.22), 22.5% (CI 21.04-24.03) and 1.8% (CI 1.38-2.34) in the 13-14 years age group in Anuradhapura district. When comparing these prevalence rates, there is relatively a higher prevalence of childhood allergic diseases in Kandy district. This difference is statistically significant in all three allergic disease conditions (P < 0.001).

CONCLUSION: Prevalence of allergic diseases in Anuradhapura is closer to reported data in the previous studies. There is relatively higher prevalence of childhood allergic diseases among children in Kandy district.

PMID:36031628 | DOI:10.1186/s13223-022-00720-z

BMC Med Inform Decis Mak. 2022 Aug 28;22(1):225. doi: 10.1186/s12911-022-01969-5.

ABSTRACT

BACKGROUND AND OBJECTIVE: The automated detection of atrial activations (AAs) recorded from intracardiac electrograms (IEGMs) during atrial fibrillation (AF) is challenging considering their various amplitudes, morphologies and cycle length. Activation time estimation is further complicated by the constant changes in the IEGM active zones in complex and/or fractionated signals. We propose a new method which provides reliable automatic extraction of intracardiac AAs recorded within the pulmonary veins during AF and an accurate estimation of their local activation times.

METHODS: First, two recently developed algorithms were evaluated and optimized on 118 recordings of pulmonary vein IEGM taken from 35 patients undergoing ablation of persistent AF. The adaptive mathematical morphology algorithm (AMM) uses an adaptive structuring element to extract AAs based on their morphological features. The relative-energy algorithm (Rel-En) uses short- and long-term energies to enhance and detect the AAs in the IEGM signals. Second, following the AA extraction, the signal amplitude was weighted using statistics of the AA sequences in order to reduce over- and undersensing of the algorithms. The detection capacity of our algorithms was compared with manually annotated activations and with two previously developed algorithms based on the Teager-Kaiser energy operator and the AF cycle length iteration, respectively. Finally, a method based on the barycenter was developed to reduce artificial variations in the activation annotations of complex IEGM signals.

RESULTS: The best detection was achieved using Rel-En, yielding a false negative rate of 0.76% and a false positive rate of only 0.12% (total error rate 0.88%) against expert annotation. The post-processing further reduced the total error rate of the Rel-En algorithm by 70% (yielding to a final total error rate of 0.28%).

CONCLUSION: The proposed method shows reliable detection and robust temporal annotation of AAs recorded within pulmonary veins in AF. The method has low computational cost and high robustness for automatic detection of AAs, which makes it a suitable approach for online use in a procedural context.

PMID:36031620 | DOI:10.1186/s12911-022-01969-5

J Headache Pain. 2022 Aug 28;23(1):111. doi: 10.1186/s10194-022-01476-y.

ABSTRACT

OBJECTIVE: This study examines changes in utilization and costs trends associated with migraine medications.

BACKGROUND: Migraine attacks are a burden to many patients. There are many pharmacotherapy options available with newer migraine drug classes entering the market in the past decade. Little is known about the use, associated costs, and the impact of the newer agents.

METHODS: This retrospective, cross-sectional study examined 2017-2020 administrative claims from a large national pharmacy benefits manager. Patients aged ≥ 18 years enrolled in commercial, Medicare, Medicaid, or health insurance exchange insurance plans who filled ≥ 2 prescription claims for triptans, ergotamines, isometheptenes, gepants, ditans, and CGRP mABs were included. A two-sample t-test was conducted to estimate whether differences in mean utilization and costs between 2017 and 2020 were statistically significant for migraine drug classes, except for CGRP mABs, which were estimated between 2018 and 2020.

RESULTS: The sample ranged from 161,369 (2017) to 240,330 (2020) patients. 84.5% (n = 203,110; 2020) of patients were women. The number of 30-day adjusted prescription fills for prophylaxis remained stable over the four-year period, except for CGRP mABs, which increased from 0.5% (n = 0.007; 2018) to 5.3% (n = 0.075; 2020). Antiepileptics, antidepressants and beta blockers were the most common prophylaxes, while triptans, non-steroidal anti-inflammatory drugs/non-narcotic analgesics and opioids were the most common treatments utilized. CGRP mABs were the most expensive, while utilization of triptans were the highest. CGRP mABs had the largest increase in utilization (177.5%) and costs (166.3%) PPPM in 2020 ($291.17) compared to 2018 ($109.35), the year they were first available (p < 0.001). Between 2018 and 2020, costs increased overall and for commercial and Medicare enrollees, but remained unchanged for Medicaid and HIX members.

CONCLUSION: Our study demonstrates a shift in migraine medication utilization from 2017-2020, where increased use of CGRP mABs had a significant contribution to increased costs. These increased pharmacy costs must be weighed against the improved tolerability of these agents likely resulting in other healthcare and indirect cost savings.

PMID:36031609 | DOI:10.1186/s10194-022-01476-y

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Mar;38(2):113-118. doi: 10.12047/j.cjap.6220.2022.023.

ABSTRACT

Objective: To investigate the effects of intrathecal injection of IRF8 SiRNA on the pain threshold and activation of spinal cord microglia in rats with postoperative persistent pain. Methods: One hundred and twenty male Sprague-Dawley rats were randomly divided into sham group (SH, n=12), SMIR group (SM, n=48), SMIR + DEPC group (SD, n=12) and SMIR + irf8 SiRNA group (SS, n=48). In the SM group, the persistent postsurgical pain(PPsP) model was established according to the skin/muscle incision and retraction (SMIR), and the SH group was only incised without retracted. The SD group and SS group received intrathecal catheterization one week before SMIR, the SS group was injected with 20 μl of IRF8 SiRNA solution (dissolved in DEPC-treated water, 150 pmol) intrathecally on the 5^th and 6^th day after SMIR, and the SD group was injected with the same amount of DEPC-treated water. The paw withdrawal threshold (PWT) of each group was measured and recorded before SMIR and on the 1^st, 3^rd, 7^th, 12^th, 22^nd and 33^rd days after SMIR. Western blot was used to detect the expression of Iba-1 in the dorsal horn of spinal cord on the 12^th days after SMIR, and the saphenous nerves in the SH group and SM group were collected to observe their ultrastructural changes under electron microscope. The flow cytometry was used to detect the activation of microglia in spinal cord dorsal horn before SMIR and on the 1^st, 3^rd, 7^th, 12^th, 22^nd and 33^rd days after SMIR in the SM group and SS group. Results: Compared with D0, the PWT of SM group was decreased on the 1^th to 22^nd day after SMIR (P＜0.05 or P＜0.01), and returned to normal level on the 33^rd day after SMIR (P＞ 0.05). Compared with the SH group, the PWT of the SM group was decreased on the 1^th to 22^nd day after SMIR (P＜0.05 or P＜ 0.01). However, compared with the SD group, the PWT of the SS group was increased on the 7^th to 22^nd day after SMIR (P＜0.05 or P＜0.01). Compared with SH group, the PWT of SS group was decreased on the 7^th to 22^nd day after SMIR (P＜0.05 or P＜0.01). The average thickness of saphenous nerve myelin was (377.0 3±69.60) nm in the SH group and (369.50±73.26) nm in the SM group, and there was no significant difference between the two groups (P＞0.05). Compared with the SH group, the expression level of Iba-1 was increased significantly (P＜0.01) in the SM group. Compared with the SD group, the expression of Iba-1 was inhibited (P＜0.05) in the SS group, and compared with the SH group, the expression of Iba-1 was also statistically different (P＜0.05) in the SS group, while the expression of Iba-1 was not statistically significant between the SM group and the SD group (P＞0.05). Compared with D0, the activation ratio of microglia was increased significantly on the 3^rd to 22^nd day after SMIR (P＜0.01) in the SM group , while the activation of microglia reached a peak on 3rd day after SMIR (P＜0.01) in the SS group. After intrathecal administration, the activation rate of microglia in the spinal dorsal horn of the SS group was decreased significantly, and compared with the SM group, it was decreased significantly on the 7^th to 12^th day after SMIR (P＜0.01). Conclusion: The significant and persistent mechanical hyperalgesia in PPsP induced by SMIR was caused non-obvious peripheral nerve injury, which may be mediated by the activation of microglia in the dorsal horn of the spinal cord. IRF8 SiRNA administrated by intrathecal injection could inhibit the activation of microglia and reverse SMIR-induced hyperalgesia.

PMID:36031567 | DOI:10.12047/j.cjap.6220.2022.023

Eur Urol Focus. 2022 Aug 25:S2405-4569(22)00175-4. doi: 10.1016/j.euf.2022.08.006. Online ahead of print.

ABSTRACT

BACKGROUND: Erectile dysfunction (ED) increases with age. Remarkably, the relationship between age and the risk of ED has only been described in crude categories, such as risk for men aged 50-59 yr, without taking comorbidities into account.

OBJECTIVE: To understand how the risk of patient-reported ED varies according to age and comorbidity status.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a cohort of 17 250 patients with prostate cancer who completed the International Index of Erectile Function erectile function domain (IIEF-EF) questionnaire before any prostate treatment.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We created a logistic regression model to predict the probability of ED using age and comorbidities such as cardiovascular disease, diabetes, and hypertension as predictors. We used age as a nonlinear term to allow a curvilinear relationship between age and ED.

RESULTS AND LIMITATIONS: The prevalence of patient-reported ED among men without any comorbidities increased from 10% to 79% from the age of 40 and 80 yr. The risk of ED increased sharply with comorbidity: the probability of ED for 50- and 75-yr-old individuals was 20% and 68% for healthy men, but 41% and 85% for those with hypertension, obesity, and diabetes. Men with several comorbidities have the same risk of ED as that of healthy men 15-25 yr older. Limitations include a healthier-than-average patient group and lack of information about some comorbidities and the severity of comorbidities.

CONCLUSIONS: Our results allow us to better understand how the risk of ED changes with age and comorbidities. Further research should evaluate the impact of other risk factors not considered in the present study and should take risk factor severity into account.

PATIENT SUMMARY: Our study shows how the probability of erectile dysfunction (ED) changes with increasing age, analyzed alone and when taking into account the presence of other risk factors for this condition (eg, diabetes, high blood pressure, and cardiovascular disease). Our results help in better understanding the probability of ED for men with and without comorbidities.

PMID:36031560 | DOI:10.1016/j.euf.2022.08.006

Vet Anaesth Analg. 2022 Jul 21:S1467-2987(22)00108-8. doi: 10.1016/j.vaa.2022.07.005. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare dexmedetomidine and fentanyl constant rate infusions in anesthetic protocols for septic dogs with pyometra, using microcirculatory, hemodynamic and metabolic variables.

STUDY DESIGN: Randomized clinical study.

ANIMALS: A total of 33 dogs with pyometra with two or more systemic inflammatory response syndrome variables undergoing ovariohysterectomy.

METHODS: Dogs were randomized into two groups: group DG, dexmedetomidine (3 μg kg^-1 hour^-1; 17 dogs) and group FG, fentanyl (5 μg kg^-1 hour^-1; 16 dogs) infused during isoflurane anesthesia and mechanical ventilation. Microcirculation flow index (MFI), total vessel density and De Backer score were assessed using orthogonal polarization spectral imaging at the sublingual site. Heart rate, invasive blood pressure, temperature, arterial blood gas analysis and lactate concentration were obtained at various time points. Variables were recorded at baseline (BL), immediately before (T0), 30 (T30) and 60 (T60) minutes after infusion, and 60 minutes after surgery. Data were analyzed using the Shapiro-Wilk test. To compare variables between groups, the unpaired Student t test was used. Comparison between evaluation time points was performed with two-way anova for repeated measures. Where statistical significance was detected, the Bonferroni post hoc test was used.

RESULTS: MFI was significantly higher in group FG at T30. Mean arterial pressure at T30 was higher in group DG (89 ± 15 mmHg) than in group FG (72 ± 13 mmHg). Lactate concentrations were not significantly different between groups at each time point. Both groups had similar clinical outcomes (mortality, extubation time and occurrence of hypotension and bradyarrhythmias).

CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine (3 μg kg^-1 hour^-1) without a loading dose can be included in the maintenance of anesthesia in dogs with pyometra and sepsis without compromising microcirculation and hemodynamic values when compared with fentanyl (5 μg kg^-1 hour^-1).

PMID:36031557 | DOI:10.1016/j.vaa.2022.07.005

J Integr Med. 2022 Aug 13:S2095-4964(22)00090-5. doi: 10.1016/j.joim.2022.08.002. Online ahead of print.

ABSTRACT

OBJECTIVE: Appraisal of treatment outcomes in integrative medicine is a challenge due to a gap between the concepts of Western medicine (WM) disease and traditional Chinese medicine (TCM) syndrome. This study presents an approach for the appraisal of integrative medicine that is based on targeted metabolomics. We use non-alcoholic fatty liver disease with spleen deficiency syndrome as a test case.

METHODS: A patient-reported outcome (PRO) scale was developed based on literature review, Delphi consensus survey, and reliability and validity test, to quantitatively evaluate spleen deficiency syndrome. Then, a metabonomic foundation for the treatment of non-alcoholic fatty liver disease with spleen deficiency syndrome was identified via a longitudinal interventional trial and targeted metabolomics. Finally, an integrated appraisal model was established by identifying metabolites that responded in the treatment of WM disease and TCM syndrome as positive outcomes and using other aspects of the metabonomic foundation as independent variables.

RESULTS: Ten symptoms and signs were included in the spleen deficiency PRO scale. The internal reliability, content validity, discriminative validity and structural validity of the scale were all qualified. Based on treatment responses to treatments for WM disease (homeostasis model assessment of insulin resistance) or TCM syndrome (spleen deficiency PRO scale score) from a previous randomized controlled trial, two cohorts comprised of 30 participants each were established for targeted metabolomics detection. Twenty-five metabolites were found to be involved in successful treatment outcomes to both WM and TCM, following quantitative comparison and multivariate analysis. Finally, the model of the integrated appraisal system was exploratively established using binary logistic regression; it included 9 core metabolites and had the prediction probability of 83.3%.

CONCLUSION: This study presented a new and comprehensive research route for integrative appraisal of treatment outcomes for WM disease and TCM syndrome. Critical research techniques used in this research included the development of a TCM syndrome assessment tool, a longitudinal interventional trial with verified TCM treatment, identification of homogeneous metabolites, and statistical modeling.

PMID:36031542 | DOI:10.1016/j.joim.2022.08.002

Cardiovasc Res. 2022 Aug 29:cvac135. doi: 10.1093/cvr/cvac135. Online ahead of print.

ABSTRACT

AIM: Evidence for the effect of elevated blood pressure on the risk of venous thromboembolism (VTE) has been conflicting. We sought to assess the association between systolic blood pressure and the risk of VTE.

METHODS AND RESULTS: Three complementary studies comprising an observational cohort analysis, a one-sample and two-sample Mendelian randomization were conducted using data from 5,588,280 patients registered in the Clinical Practice Research Datalink (CPRD) dataset and 432,173 UK Biobank participants with valid genetic data. Summary statistics of International Network on Venous Thrombosis (INVENT) genome-wide association meta-analysis was used for two-sample Mendelian randomization. The primary outcome was the first occurrence of VTE event, identified from hospital discharge reports, death registers, and/or primary care records. In the CPRD cohort, 104,017 (1.9%) patients had a first diagnosis of VTE during the 9.6-year follow-up. Each 20 mmHg increase in systolic blood pressure was associated with a 7% lower risk of VTE (hazard ratio 0.93, 95% CI [0.92 to 0.94]). Statistically significant interactions were found for sex and body mass index, but not for age and subtype of VTE (pulmonary embolism and deep venous thrombosis). Mendelian randomization studies provided strong evidence for the association between systolic blood pressure and VTE, both in the one-sample (odds ratio [OR]: 0.69 [95% CI 0.57 to 0.83] and two-sample analyses (OR 0.80, 95% CI [0.70 to 0.92]).

CONCLUSIONS: We found an increased risk of VTE with lower blood pressure and this association was independently confirmed in two Mendelian randomization analyses. The benefits of blood pressure reduction are likely to outweigh the harms in most patient groups, but in people with predisposing factors for VTE, further blood pressure reduction should be made cautiously.

TRANSLATIONAL PERSPECTIVE: In a large-scale population cohort, with over 100,000 first episodes of VTE and a median follow-up of about 10 years, we found a 7% higher risk of VTE for each 20 mmHg lower systolic blood pressure. The association was comparable when we examined pulmonary embolism and deep venous thrombosis separately, and persisted after taking into account age and other factors, including anticoagulant treatment during follow-up. These results were confirmed using two independent Mendelian randomization studies. Although the beneficial effects of blood pressure-lowering are likely to outweigh any harms in most patient groups, clinicians should be aware of the potential risk of VTE from antihypertensive therapy, in particular in people who have predisposing factors for VTE.

PMID:36031541 | DOI:10.1093/cvr/cvac135

J Orthop Sci. 2022 Aug 25:S0949-2658(22)00191-9. doi: 10.1016/j.jos.2022.07.010. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to assess the impact of delay between admission and surgery on the postoperative outcomes such as mortality and related complications in elderly patients with acute hip fractures.

METHODS: 840 patients aged ≥65 years from January 2009 to September 2015 were included in this retrospective study. According to the interval from admission to surgery, the patients were divided into four groups: group A (surgery within 24 h), group B (surgery within 24 h-48 h), group C (surgery within 48 h-72 h), and group D (surgery later than 72 h). Postoperative complications during hospitalization and mortality at different follow-up time points were compared.

RESULTS: A total of 763 cases were successfully followed up, with an average follow-up time of 30.4 ± 13.1 months. The mean age of the patients was 79.4 ± 6.8 years. The difference in gross postoperative complications among groups was statistically significant in terms of pressure sore (P = 0.02), respiratory complications (P = 0.001), and urological complications (P < 0.001). The multivariate logistic regression analysis identified 3 factors independently associated with the postoperative morbidity, including age (odds ratio [OR] = 1.040), postoperative drainage volume (OR = 1.002) and time from admission to surgery (OR = 1.108). The difference in postoperative mortality among groups was statistically significant at 1 year (P = 0.046) after operation. The multivariate logistic regression analysis identified that age, postoperative drainage volume and time from admission to surgery were independently associated with mortality at 1 year postsurgery.

CONCLUSION: The incidence of postoperative morbidity and mortality in elderly patients with hip fracture is usually the result of multiple factors, surgeons should pay attention to the patient’s age, postoperative wound status and surgical delay time, which may significantly affect the outcome of the treatment.

PMID:36031534 | DOI:10.1016/j.jos.2022.07.010

J Microbiol Immunol Infect. 2022 Aug 17:S1684-1182(22)00135-9. doi: 10.1016/j.jmii.2022.08.006. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Urinary tract infections (UTIs) are the most common bacterial infection in young children. This study aimed to formulate nomogram plots for clinicians to predict UTIs in children aged <3 years by evaluating the risk factors for UTIs in these children.

METHODS: This retrospective study was conducted at a tertiary medical center from December 2017 to November 2020. Children less than three years of age were eligible for the study if they had undergone both urine culture and urinalysis during the study period. Mixed-effects logistic regression models with a stepwise procedure were used to determine the relationship between outcome (positive/negative UTI) and covariates of interest (e.g., weight percentile, laboratory) for each patient. Nomogram plots were constructed on the basis of significant factors. We repeated the analysis thrice to adapt it to three different medical settings: medical centers, regional hospitals, and local clinics.

RESULTS: In the medical center setting, the two most significant factors were urine leukocyte count ≥100 (OR =8.87; 95% CI (Confidence Interval), 4.135-19.027) and urine nitrite level (OR =8.809; 95% CI, 5.009-15.489). The two factors showed similar significance at the regional hospital and local clinic settings. Abnormal renal echo findings were positively correlated with UTI in the medical center setting (OR =2.534; 95% CI 1.757-3.655). Three nomogram plots for the prediction of UTIs were drawn for medical centers, regional hospitals, and local clinics.

CONCLUSION: Using the three nomogram plots, frontline doctors can formulate the probabilities of pediatric UTIs for better decision-making.

PMID:36031532 | DOI:10.1016/j.jmii.2022.08.006