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Efficacy of dupilumab in chronic prurigo and chronic idiopathic pruritus: A systematic review of current evidence and analysis of response predictors

J Eur Acad Dermatol Venereol. 2022 May 15. doi: 10.1111/jdv.18221. Online ahead of print.

ABSTRACT

Dupilumab has demonstrated a great reduction on chronic pruritus that is the hallmark of atopic dermatitis (AD). Underscoring relevant pathogenesis similarities emerging from AD, chronic idiopathic pruritus (CIP) and chronic prurigo (CP), several authors suggested the beneficial role of dupilumab in these conditions. The evidence on this subject is limited with no precise data available. In this study, we carried out a systematic literature review in order to evaluate the efficacy of dupilumab on both pruritus and skin manifestations in the two largest retrospective cohorts of patients with CP and CIP and tried to identify potential response predictors. Electronic searches were conducted on 4 databases. Our primary outcome was the improvement in pruritus measured by a reduction in patient’s reported numerical rating scale of itch (NRSI) by > 4. Secondary outcomes included: proportion of patients with complete response at the end of treatment, reduction in the number of lesions by the Investigator Global Assessment (IGA), improvement in numerical rating scale of sleep (NRSS), improvement in quality of life measured by the Dermatology Life Quality Index (DLQI), time until patient perceived any improvement (Time-First) and time until patient reported absence of pruritus (Time-Final). Descriptive statistics were calculated for each demographic and clinical variable. Univariate logistic regression analyses were conducted to explore association between response to dupilumab and potential predictive factors. We included 25 articles in the analysis, counting a total of 153 patients. Based on CP patients’ cohort (n=132), the mean NRSI at baseline was 8.79 ±0.86 and the NRSI final was 2.32 ±1.27. The mean time to first improvement was 5.18 ±3.13 weeks, while the time to complete improvement of pruritus (Time-final) was 13.6 ±12.0 weeks. Ninety patients out of 109 (83%) noticed improvement in pruritus before 4 weeks of dupilumab therapy. At the end of treatment, 18 patients out of 126 (14%) had a complete remission of pruritus and 110 patients out of 123 (89%) had a reduction of NRSI > 4. The reduction in NRSI was significantly greater in patients improving before 4 weeks of treatment (6.57 ±1.71) compared to patients improving in more than 4 weeks (5.49 ±1.39, p<0.001). Patients with history of AD and those who have been previously treated with cyclosporine or methotrexate had a significantly lower reduction in NRSI (e.g. 6.05 ±1.34 vs 7.08 ±1.90 p<0.01 for non-associated AD patients). Based on CIP patient’s cohort (n=21), the mean NRSI at baseline was 8.33 ±0.80 and the NRSI final was 0.95 ±0.59. The mean time to first improvement was 2 ±0 weeks, while the time to complete improvement (Time-final) was 14.6 ±10 weeks. At the end of treatment, 3 patients out of 21 (14%) had a complete remission of pruritus and 100% of patients had a reduction of NRSI > 4. No serious treatment-emergent adverse events were reported. The most common adverse event was mild conjunctivitis (13 cases). We highlight the importance of one early sign of improvement as predictor of the future response to dupilumab: the improvement before 4 weeks of treatment that leads significantly to a greater final reduction in NRSI. Furthermore, patients with the presence or history of atopy appear to be less responsive to dupilumab than non-atopic patients and develop more side effects, in particular conjunctivitis.

PMID:35569006 | DOI:10.1111/jdv.18221

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Impact of screen exposure on pediatric vernal Keratoconjunctivitis: a survey during the COVID-19 pandemic in Italy

Ital J Pediatr. 2022 May 14;48(1):74. doi: 10.1186/s13052-022-01253-2.

ABSTRACT

BACKGROUND: The SARS-CoV-2 outbreak pushed the Italian government to start a strict lockdown, replacing school attendance with long-distance learning. This caused reduced exposure to sunlight but increased exposure to screens. Vernal keratoconjunctivitis (VKC) is a chronic inflammatory ocular condition in which exposure to light plays a cardinal role. We conducted an online survey to evaluate the impact of screen exposure on children with VKC during the COVID-19 lockdown.

METHODS: We performed a survey-based observational study, asking patients followed at the Allergology clinics of Meyer Children’s University Hospital in Florence and of Policlinico Umberto I in Rome to provide grading on 6 subjective ocular clinical manifestations presented during the lockdown and to give an estimate of their hours/day of screen exposure.

RESULTS: Mean scores of signs and symptoms increased homogeneously when studying patients exposed to longer screen time. When comparing scores collected in 2019 to those in 2020, there was not a significant reduction in clinical manifestations, although the situation differed between the two centers due to geographical differences in sunlight exposure.

CONCLUSION: During the lockdown, there was a reduction in sunlight exposure but conversely an increase in the time spent in front of screens that correlated with the worsening of VKC signs and symptoms in direct proportion to the hours/day of screen exposure. Our results also showed a statistically significant difference in the relative impact of long-distance learning on VKC clinical manifestations in the different Italian regions.

PMID:35568956 | DOI:10.1186/s13052-022-01253-2

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Circulating 25-hydroxyvitamin D levels and hypertension risk after adjusting for publication bias

Clin Hypertens. 2022 May 15;28(1):15. doi: 10.1186/s40885-022-00196-4.

ABSTRACT

BACKGROUND: Previous systematic reviews reported that serum vitamin D deficiency was associated with risk of hypertension. The aim was to conduct a meta-epidemiological analysis for evaluating the potential effects of publication bias.

METHODS: The selection criterion was defined as a follow-up study for evaluating the association between circulating 25-hydroxyvitam D level and hypertension risk in adults. A funnel plot and Egger’s test were used to detect a publication bias. If a publication bias was identified, trim-and-fill analysis (TFA) with linear estimator was performed to estimate a summary relative risk (sRR).

RESULTS: The meta-analysis of 13 cohorts resulted in the lower the vitamin D, the higher the risk of hypertension statistically significant (sRR, 1.22; 95% confidence interval [CI], 1.05 to 1.41). But The P-value of Egger’s test (=0.015) and asymmetry of the funnel plot showed that there was a publication bias. TFA resulted in that statistical significance disappeared in the association between vitamin D level and hypertension risk in total cohorts (filled sRR, 1.03; 95% CI, 0.89 to 1.18) as well as men and women cohorts.

CONCLUSIONS: The publication bias-adjusted results by TFA had no statistically significant association between vitamin D levels and the risk of hypertension. The significant results in previous systematic reviews might be interpreted as due to publication bias.

PMID:35568961 | DOI:10.1186/s40885-022-00196-4

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Circulating miRNAs in extracellular vesicles related to treatment response in patients with idiopathic membranous nephropathy

J Transl Med. 2022 May 14;20(1):224. doi: 10.1186/s12967-022-03430-7.

ABSTRACT

BACKGROUND: Extracellular vesicle (EV)-microRNAs (miRNAs) are potential biomarkers for various renal diseases. This study attempted to identify the circulating EV-miRNA signature not only for discriminating idiopathic membranous nephropathy (IMN) from idiopathic nephrotic syndrome (INS), but also to predict the treatment response of patients with IMN.

METHODS: We prospectively enrolled 60 participants, including those with IMN (n = 19) and INS (n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum EV-miRNA profiles of all participants. To identify the EV-miRNAs predictive of treatment response in IMN, we also analyzed EV-miRNAs among patients with IMN with and without clinical remission.

RESULTS: The expression levels of 3 miRNAs differed between IMN patients, INS patients and HVs. In addition, compared to HVs, RNA sequencing revealed differential expression of 77 and 44 EV-miRNAs in patients with IMN without and with remission, respectively. We also identified statistically significant (|fold change ≥ 2, p < 0.05) differences in the expression levels of 23 miRNAs in IMN without remission. Biological pathway analysis of miRNAs in IMN without remission indicated that they are likely involved in various pathways, including renal fibrosis.

CONCLUSION: Our study identified EV-miRNAs associated with IMN as well as those associations with therapeutic response. Therefore, these circulating EV-miRNAs may be used as potential markers for the diagnosis and prediction of treatment response in patients with IMN.

PMID:35568952 | DOI:10.1186/s12967-022-03430-7

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Link between unmet need and economic status in Bangladesh: gap in urban and rural areas

BMC Womens Health. 2022 May 14;22(1):176. doi: 10.1186/s12905-022-01752-8.

ABSTRACT

BACKGROUND: Unmet need for family planning (FP) is a core concept in designing FP programmes and reduction of unmet need for FP can improve reproductive and maternal health services. Bangladesh is still away from achieving the target regarding unmet need for FP. This study aimed to explore the composite effect of economic status and place of residence on unmet need for FP among currently married women of reproductive age in Bangladesh after controlling the effect of other selected covariates.

METHODS: The study used the data extracted from the Bangladesh Demographic and Health Survey (BDHS) 2017-2018, which is a nationally representative survey implemented using a stratified two-stage cluster sample design. A total of 13,031 currently married women of reproductive age were included in the final analysis. Binary logistic regression model has been employed to identify the factors influencing the unmet need for FP. Model-I investigated the effect of composite variable place-wealth on unmet need for FP and Model-II examined the effect of place-wealth on unmet need for FP after adjusting for the effect of other selected covariates. The Odds Ratios with p-values were reported to identify significant covariates.

RESULTS: The rate of unmet need for FP was 15.48%. The composite factor of economic status and place of residence had significant influence on unmet need for FP in both models. Generally, rural women were significantly more likely to have unmet need for FP than their urban counterparts. In particular, women from rural areas and belong to rich families had the highest likelihoods of unmet need for FP. The other selected covariates also had significant influence on unmet need for FP.

CONCLUSION: This study shows that rural women had higher odds of unmet need for FP than urban women. The healthcare providers and stakeholders should take necessary actions to motivate women to use contraceptive specially the women who are residing in the rural areas.

PMID:35568941 | DOI:10.1186/s12905-022-01752-8

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Organisational and staff-related effects on cultural competence in the hospital setting: a cross-sectional online survey of nursing and medical staff

BMC Health Serv Res. 2022 May 14;22(1):644. doi: 10.1186/s12913-022-07947-x.

ABSTRACT

BACKGROUND: Cultural competence is considered a core qualification for dealing with socio-cultural diversity and balancing disparities in health care.

OBJECTIVES: To explore features supporting and inhibiting cultural competence in the hospital at both organisational and staff levels.

DESIGN: Cross-sectional online survey in the form of a full census from May to November 2018.

SETTING: Two organisations that run a total of 22 hospitals in Germany.

PARTICIPANTS: Eight hundred nursing and medical professionals [nurses: n = 557; doctors: n = 243].

METHODS: Using the Short Form Cultural Intelligence SCALE (SFCQ), cultural competence was measured and its relation to potential influencing factors at staff level and organisational level examined, using bivariate (t-Test, one-way ANOVA, Pearson and Spearman correlations) and multivariate (multiple linear regression) approaches. Model 1 examined features at organisational level, Model 2 at individual level and Model 3 included organisational and individual features.

RESULTS: The mean cultural competence measured was 3.49 [min.: 1.3; max.: 5.0]. In the bivariate and isolated multivariate models [Models 1 and 2], factors on both organisational and individual levels were significantly related to the hospital staff’s cultural competence. The multivariate overview [Model 3], however, revealed that individual features at staff level were the statistically relevant predictors. Positive influencing features included staff’s assessment of the importance of cultural competence in their professional context [B: 0.368, 95% confidence interval 0.307; 0.429], participation in competence training [B: 0.193; 95% confidence interval 0.112; 0.276] and having a migration background [B: 0.175; 95% confidence interval 0.074; 0.278], while negative features included length of medical service [B: -0.004; 95% confidence interval -0.007; -0.001].

CONCLUSIONS: The development and practice of cultural competence appear to be determined less by organisational features and more on the level of individual actors. In addition to staff development, adequate organisational structures and an economic incentive system are required to promote sociocultural diversity in hospitals.

PMID:35568939 | DOI:10.1186/s12913-022-07947-x

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Effect of radical lymphadenectomy in colorectal cancer with para-aortic lymph node metastasis: a systematic review and meta-analysis

BMC Surg. 2022 May 14;22(1):181. doi: 10.1186/s12893-022-01631-x.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) with para-aortic lymph node metastasis (PALNM) is an intractable clinical situation, and the role of radical lymphadenectomy in the treatment of CRC with PALNM is still controversial. The aim of the current system review and meta-analysis is to evaluate the clinical efficacy and safety of radical lymphadenectomy in CRC patients with PALAN.

METHODS: We performed a systematic search of PubMed, Embase, Cochrane Library and other online databases up to 31 October 2021. The clinical data including overall survival and postoperative complications were screened and analyzed after data extraction. Odds ratios (ORs) were applied to analyze these dichotomous outcomes with a fixed effects model.

RESULTS: A total of 7 available retrospective clinical studies involving 327 patients were finally included. CRC patients with PALNM who underwent radical lymphadenectomy showed significantly overall survival (OR: 6.80, 95% CI: 3.46-13.38, P < 0.01; I2 = 0%) when compared to those who did not receive radical lymphadenectomy. Moreover, in terms of postoperative complications (OR: 0.71, 95% CI: 0.35-1.44, P = 0.48; I2 = 0%), there was no statistical difference between radical lymphadenectomy treatment and control groups.

CONCLUSIONS: The radical lymphadenectomy treatment has showed the expected clinical efficacy in prolonging overall survival time of CRC patients with PALAN. Moreover, the preemptive radical lymphadenectomy could not cause additional postoperative complications.

PMID:35568938 | DOI:10.1186/s12893-022-01631-x

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Response surface optimization of a vortex-assisted dispersive liquid-liquid microextraction method for highly sensitive determination of repaglinide in environmental water by HPLC/UV

BMC Chem. 2022 May 14;16(1):33. doi: 10.1186/s13065-022-00826-w.

ABSTRACT

A vortex-assisted dispersive liquid-liquid microextraction (DLLME) method, mated to chemometrics and combined with HPLC/UV detection was optimized and validated for enrichment and determination of repaglinide in environmental samples using nateglinide as an internal standard (IS). A phosphate buffer (10 mM, pH 2.5): acetonitrile (45:55, v/v) was used as a mobile phase with a flow rate of 1 mL/min in an isocratic elution mode. Chemometrics-assisted optimization was performed using a quadratic integrated D-optimal design. The developed model assessed the statistical significance of the independent variables and their interactions to attain the optimum conditions revealing that extractant type, extractant volume and pH are the most influential factors. Optimization of the extraction procedures was performed with the aid of Design Expert 8® software, which suggested 58 different experiments. The optimal conditions were 30 µL of 1-octanol as extractant, 100 µL of acetonitrile as a disperser at pH 8. Under the optimized conditions, the method showed linearity over the range of 1-100 ng/mL with a limit of detection of 0.4 ng/mL. The accuracy, the intra- and inter-day precision were assessed, the %recoveries were found to be between 98.48 and 100.81% with %RSD lower than 1.3. Using chemometrics in method optimization helped achieve the maximum possible enrichment with the least effort, time, and reagents while considering all possible interactions between variables.

PMID:35568922 | DOI:10.1186/s13065-022-00826-w

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A descriptive survey of substance use treatment facilities in Uasin Gishu County Kenya

BMC Health Serv Res. 2022 May 14;22(1):645. doi: 10.1186/s12913-022-08051-w.

ABSTRACT

BACKGROUND: Substance use disorders are a major problem in Uasin Gishu County, Kenya. The objective of this study was to describe the existing resources within substance use treatment facilities in the County, with the aim of guiding policy and interventions.

METHODS: This was a cross-sectional study. We collected data from six substance use treatment facilities within Uasin Gishu County between August and November 2021. We used a researcher-designed questionnaire to collect information on: availability of in-patient and out-patient services; facility ownership (private-for-profit vs government-run); bed capacity; mode of payment for services; cost of services; availability of medicines for substance use treatment; and staffing characteristics. Descriptive statistics were used to summarize the data.

RESULTS: One facility was run by the National government and the rest were private-for-profit. Uasin Gishu County government had no substance use treatment facility of its own. The total number of beds available within the six facilities was 174 against a population of 1.1 million. All six facilities had stocked at least one medication for substance use disorder treatment. None of the facilities had buprenorphine, buprenorphine naloxone, or methadone. Out-of pocket was the most common mode of payment for services with patients paying using this mode in all the six facilities. Only one facility was accredited by the National Hospital Insurance Fund (NHIF). All facilities had at least one certified addiction counselor and at least one psychologist. Half of the facilities did not have a nurse and two did not have a doctor. The qualification held by most staff was addiction counseling with 41.3% of them having achieved this qualification.

CONCLUSION: The facilities were well staffed with psychologists and addiction counselors. Gaps were found as regards bed capacity, use of pharmacotherapy, insurance coverage and availability of nursing staff and doctors. We recommend that the County government in collaboration with key stakeholders invests in substance use treatment in order to address the high burden of substance use disorders in Uasin Gishu County.

PMID:35568902 | DOI:10.1186/s12913-022-08051-w

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Association between early ondansetron administration and in-hospital mortality in critically ill patients: analysis of the MIMIC-IV database

J Transl Med. 2022 May 14;20(1):223. doi: 10.1186/s12967-022-03401-y.

ABSTRACT

BACKGROUND: While ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose.

METHODS: The MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings.

RESULTS: In total, 51,342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63-0.89, p < 0.001]. In the circulatory system group, the early OND administration was associated with improved in-hospital mortality in ICU patients (OR 0.48, 95% CI 0.34-0.66; P < 0.001). The risk of in-hospital mortality was also lower in early OND users than in non-OND users both in the medical admission group and the surgical ICU admission group, and ORs were 0.57 (95% CI 0.42-0.76; P < 0.001) and 0.79 (95% CI 0.62-0.91; P < 0.001), respectively. A positive role of daily low- and moderate-dose OND treatment in early-stage was showed on the in-hospital mortality in PSM cohort, and the ORs were 0.75 (95% CI 0.62-0.90; P < 0.001) and 0.63 (95% CI 0.43-0.91; P < 0.001), respectively. The relationship between the daily low- and moderate-dose of OND and in-hospital mortality was also significant in ICU patients with cardiovascular diseases, and ORs were 0.51(95% CI 0.36-0.73; P < 0.001), and 0.26(95% CI 0.11-0.65; P < 0.001), respectively. Daily low-to-moderate dose of OND was also associated with in-hospital mortality in ICU entire cohort.

CONCLUSIONS: Early OND use is closely associated with lower in-hospital mortality in ICU patients. Daily low-to-moderate dose of OND application is protective against in-hospital mortality. This association is more evident in the circulatory system group.

PMID:35568908 | DOI:10.1186/s12967-022-03401-y