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1.
J Eur Acad Dermatol Venereol ; 38(7): 1401-1409, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38329222

RESUMO

BACKGROUND: Prurigo nodularis (PN) is characterized by intensely itchy nodules/lesions and skin pain, which can have a substantial impact on health-related quality of life (HRQoL). Treatment benefits on such symptoms and impacts are best assessed in trials using patient-reported outcome (PROs) instruments such as Skin Pain Numerical Rating Scale (NRS), Sleep-NRS and Dermatology Life Quality Index (DLQI). However, no guidance exists for interpreting meaningful changes in scores using these PROs in patients with PN. OBJECTIVES: The main objective was to derive within-patient (responder definition) and between-group improvement thresholds for interpreting Skin Pain-NRS, Sleep-NRS and DLQI total scores in patients with PN. The measurement properties of the three PROs were also evaluated. METHODS: Intention-to-treat (ITT), blinded and pooled data were used from the Phase 3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN. Anchor- and distribution-based methods were applied to derive responder definition and between-group thresholds for Skin Pain-NRS, Sleep-NRS and DLQI. Data were additionally used to examine the instrument measurement properties, including reliability, validity and responsiveness. RESULTS: A total of 311 patients (mean age 49.5 years, 65.3% female) were included in the pooled ITT population. The within-patient improvement threshold for Skin Pain-NRS was estimated as 4.0 points, 2.0 points for Sleep-NRS and 9.0 points for DLQI total score. A 1.5-point improvement in Skin Pain-NRS scores, 1.0-point in Sleep-NRS and 4.0-point in DLQI indicated a between-group meaningful change. Adequate to good psychometric properties were demonstrated for all three instruments. CONCLUSIONS: The results of this study can aid interpretation of Skin Pain-NRS, Sleep-NRS and DLQI scores in patients with PN in both clinical trials and clinical practice to better understand and treat PN-related skin pain and the impact of PN on sleep quality and HRQoL.


Assuntos
Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Prurigo , Qualidade de Vida , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Dor/etiologia , Prurigo/tratamento farmacológico , Prurigo/complicações , Sono
2.
Public Health ; 215: 106-117, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36682079

RESUMO

OBJECTIVE: To assess the effectiveness of prenatal and postnatal home visits (HVs) and women group meetings (WGMs) by paramedical professionals to improve maternal and child health outcomes in low- and middle-income countries (LMICs). STUDY DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic review of trials published till December 2020, as per registered protocol in The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42018091968). Outcomes were neonatal mortality rate (NMR), maternal mortality ratio (MMR), the incidence of low birth weight, and still birth rate (SBR). The Cochrane Pregnancy and Childbirth Group's Trials Register, Cochrane Central Register of Controlled Trials, PubMed, and Excerpta Medica Database (EMBASE) were searched. Pooled results were estimated using random-effects meta-analysis in RevMan version 5.2. RESULTS: Twenty-five trials met the inclusion criteria. HVs were the key intervention in 12, WGMs in 11, and both interventions in 2 trials. The pooled estimates have shown that NMR was significantly reduced by HVs (OR 0.77, confidence interval [CI]: 0.67-0.90, P = 0.0007, I2 = 77%) and WGMs (OR 0.76, CI: 0.65-0.90, P = 0.001, I2 = 71%). SBR was significantly reduced by HVs (OR 0.77, CI: 0.70-0.85; P < 0.001, I2 = 0%). Subgroup analysis of studies in which more than 10% of pregnant women participated in the WGMs showed significant reduction in NMR (OR 0.67, CI 0.58-0.77, P = 0.00001, I2 = 31%) and MMR (OR 0.55, CI 0.36-0.84, P = 0.005, I2 = 27%). Two studies reported improvement in birth weight by HVs. CONCLUSIONS: HVs and WGMs (with >10% pregnant women) by paramedical professionals are effective strategies in reducing the NMR and MMR in LMICs. HVs were also effective in reducing SBR.


Assuntos
Países em Desenvolvimento , Mulheres , Recém-Nascido , Gravidez , Humanos , Feminino , Criança , Visita Domiciliar , Recém-Nascido de Baixo Peso , Vitaminas , Avaliação de Resultados em Cuidados de Saúde
3.
Morphologie ; 107(358): 100592, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36781317

RESUMO

OBJECTIVES: The present study was proposed to assess if the online search behavior for Anatomy dissection was affected by actual dissection being performed in the labs. The interest in dissection was ascertained and compared between pre-pandemic, pandemic, and current times. METHODS: Online web search behavior for key terms related to "Anatomy dissection" was noticed worldwide using Google Trends Tool. Relative search volume (RSV) was downloaded for these keywords worldwide using all categories, and web search settings during a period from January 1, 2018, to July 31, 2022. RESULTS: There was almost a similar google trend for the first three months in years 2018 and 2020, with a slightly lower RSV in March and a noticeable RSV decrease from April onwards in 2020. During the pre-pandemic period, the peak for RSV in the month of May was noticed. These peaks were missing in 2020 and 2021. In May 2022, RSV again increased. The top five countries with the highest search hit for "Anatomy Dissection" web were the Philippines, the United States, Canada, Australia, and India. CONCLUSIONS: There was lower search trend for "Anatomy dissection" during the pandemic period as compared to pre-pandemic period. The search trends may be associated with the closure of dissection labs and it may be concluded that Anatomy learners search for this term more often, if they are actually performing the dissections. The future integrated multi-country data and analysis from different set-ups about their ways of dissection and labs before and after the pandemic may further clarify.


Assuntos
Pandemias , Ferramenta de Busca , Estados Unidos/epidemiologia , Austrália
4.
Br J Dermatol ; 186(4): 633-641, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34358343

RESUMO

BACKGROUND: Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75-55·97; P < 0·001) and had ≥ 3-point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26-55·34; P < 0·001) and ≥ 4-point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69-45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment-emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. CONCLUSIONS: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile.


Assuntos
Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais Humanizados , China , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Int J Technol Assess Health Care ; 38(1): e61, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35761433

RESUMO

OBJECTIVES: Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence. METHODS: The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone's risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter's regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA. RESULTS: Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR = 1.4 (95 percent confidence interval [CI]: .95-2.05) and 1.42 (95 percent CI: 1.03-1.97)], the comprehensive data set reached the decision threshold 36 months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set. CONCLUSIONS: Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3 years earlier.


Assuntos
Viés de Publicação , Humanos , Rosiglitazona/uso terapêutico
6.
Br J Dermatol ; 184(5): 857-870, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32969489

RESUMO

BACKGROUND: Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16-week, randomized, placebo-controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)-4/IL-13 signalling, significantly improved signs and symptoms with acceptable safety; longer-term safety and efficacy data are lacking. OBJECTIVES: To report the pharmacokinetic profile and long-term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. METHODS: Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study and subsequent open-label extension (OLE) study. Patients received single-dose dupilumab 2 or 4 mg kg-1 followed by 8-week pharmacokinetic sampling, then 2 or 4 mg kg-1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration-time profile and treatment-emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP-NRS) score. RESULTS: Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target-mediated pharmacokinetics characterized dupilumab concentrations (week 24-48 mean serum concentrations: 2 mg kg-1 , 61-77 mg L-1 ; 4 mg kg-1 , 143-181 mg L-1 ). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg-1 , 47%; 4 mg kg-1 , 56%) and AD exacerbation (29% and 13%, respectively). Single-dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP-NRS improved by -37%/-33% and -17%/-20% at week 2 (phase IIa) and -92%/-84% and -70%/-58% at week 52 (OLE), respectively. CONCLUSIONS: These safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe AD.


Assuntos
Dermatite Atópica , Anticorpos Monoclonais Humanizados , Criança , Estudos de Coortes , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Humanos , Índice de Gravidade de Doença , Resultado do Tratamento
7.
BMC Pregnancy Childbirth ; 21(1): 389, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011316

RESUMO

BACKGROUND: Since 2005, India has experienced an impressive 77% reduction in maternal mortality compared to the global average of 43%. What explains this impressive performance in terms of reduction in maternal mortality and improvement in maternal health outcomes? This paper evaluates the effect of household wealth status on maternal mortality in India, and also separates out the performance of the Empowered Action Group (EAG) states and the Southern states of India. The results are discussed in the light of various pro-poor programmes and policies designed to reduce maternal mortality and the existing supply side gaps in the healthcare system of India. Using multiple sources of data, this study aims to understand the trends in maternal mortality (1997-2017) between EAG and non EAG states in India and explore various household, economic and policy factors that may explain reduction in maternal mortality and improvement in maternal health outcomes in India. METHODS: This study triangulates data from different rounds of Sample Registration Systems to assess the trend in maternal mortality in India. It further analysed the National Family Health Surveys (NFHS). NFHS-4, 2015-16 has gathered information on maternal mortality and pregnancy-related deaths from 601,509 households. Using logistic regression, we estimate the association of various socio-economic variables on maternal deaths in the various states of India. RESULTS: On an average, wealth status of the households did not have a statistically significant association with maternal mortality in India. However, our disaggregate analysis reveals, the gains in terms of maternal mortality have been unevenly distributed. Although the rich-poor gap in maternal mortality has reduced in EAG states such as Bihar, Odisha, Assam, Rajasthan, the maternal mortality has remained above the national average for many of these states. The EAG states also experience supply side shortfalls in terms of availability of PHC and PHC doctors; and availability of specialist doctors. CONCLUSIONS: The novel contribution of the present paper is that the association of household wealth status and place of residence with maternal mortality is statistically not significant implying financial barriers to access maternal health services have been minimised. This result, and India's impressive performance with respect to maternal health outcomes, can be attributed to the various pro-poor policies and cash incentive schemes successfully launched in recent years. Community-level involvement with pivotal role played by community health workers has been one of the major reasons for the success of many ongoing policies. Policy makers need to prioritise the underperforming states and socio-economic groups within the states by addressing both demand-side and supply-side measures simultaneously mediated by contextual factors.


Assuntos
Disparidades nos Níveis de Saúde , Renda/estatística & dados numéricos , Mortalidade Materna , Pobreza/estatística & dados numéricos , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Mortalidade Materna/tendências , Fatores Socioeconômicos , Adulto Jovem
8.
J Eur Acad Dermatol Venereol ; 35(2): 464-475, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32893393

RESUMO

BACKGROUND: Dupilumab has demonstrated efficacy and acceptable safety in adults and children (aged 6-17 years) with moderate-to-severe atopic dermatitis (AD), but effective systemic therapy with a favorable risk-benefit profile in younger children remains a significant unmet need. OBJECTIVES: To determine the pharmacokinetics, safety and efficacy of single-dose dupilumab in children with severe AD aged ≥6 months to <6 years. METHODS: This open-label, multicenter, phase 2, sequential, two-age cohort, two-dose level study (LIBERTY AD PRE-SCHOOL; NCT03346434) included an initial cohort of older children aged ≥2 to <6 years, followed by a younger cohort aged ≥6 months to <2 years. Pharmacokinetic sampling, safety monitoring and efficacy assessments were performed during the 4-week period after a single subcutaneous injection of dupilumab, in two sequential dosing groups (3 mg/kg, then 6 mg/kg). The use of standardized, low-to-medium potency topical corticosteroids was allowed. RESULTS: Forty patients were enrolled (20/age cohort, 10/dose level within a cohort) between December 20, 2017 and July 22, 2019. Within each age cohort, pharmacokinetic exposures after a single injection of dupilumab increased in a greater than dose-proportional manner. At week 3, treatment with 3 and 6 mg/kg dupilumab reduced scores of mean Eczema Area and Severity Index by -44.6% and -49.7% (older cohort) and -42.7% and -38.8% (younger cohort), and mean Peak Pruritus NRS scores by -22.9% and -44.7% (older cohort) and -11.1% and -18.2% (younger cohort), respectively. At week 4, improvements in most efficacy outcomes diminished in both age groups, particularly with the lower dose. The safety profile was comparable to that seen in adults, adolescents and children. CONCLUSIONS: Single-dose dupilumab was generally well tolerated and substantially reduced clinical signs/symptoms of AD. Slightly better responses were seen in older than younger children. The pharmacokinetics of dupilumab were non-linear, consistent with previous studies in adults and adolescents.


Assuntos
Dermatite Atópica , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Criança , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Humanos , Lactente , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Br J Dermatol ; 182(1): 85-96, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31595499

RESUMO

BACKGROUND: Dupilumab (monoclonal antibody inhibiting IL-4/IL-13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate-to-severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16-week, randomised, placebo-controlled phase III trial in adolescents (NCT03054428). OBJECTIVES: To characterize the pharmacokinetics of dupilumab, and long-term safety and efficacy in adolescents. METHODS: This was a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study with a phase III open-label extension (OLE) in adolescents with moderate-to-severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg-1 or 4 mg kg-1 ) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8-week safety follow-up. Patients then enrolled in the OLE, continuing 2 mg kg-1 or 4 mg kg-1 dupilumab weekly. Primary end points were dupilumab concentration-time profile and incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI). RESULTS: Forty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target-mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L-1 and 161 ± 60 mg L-1 for 2 mg kg-1 and 4 mg kg-1 , respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg-1 ], 47% [4 mg kg-1 ]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction -34% ± 20% (2 mg kg-1 ) and -51% ± 29% (4 mg kg-1 )]. With continuing treatment, EASI scores improved further [week 52: -85% ± 12% (2 mg kg-1 ) and -84% ± 20% (4 mg kg-1 )]. CONCLUSIONS: In adolescents with moderate-to-severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52-week safety and efficacy data support long-term use of dupilumab in this patient population. What's already known about this topic? Adolescents with moderate-to-severe atopic dermatitis (AD) have high unmet medical need, with significant disease burden and limited treatment options. Dupilumab (monoclonal antibody against interleukin-4 receptor α) is approved for the treatment of adolescents with moderate-to-severe AD who are inadequately responsive to standard of care (U.S.A.) or candidates for systemic therapy (European Union). A 16-week, randomized, placebo-controlled phase III trial in adolescents demonstrated significant improvements in AD signs/symptoms with an acceptable safety profile. What does this study add? These studies demonstrate the long-term safety and efficacy of dupilumab in adolescents with moderate-to-severe AD for up to 52 weeks of treatment, thus extending and reinforcing the findings from the 16-week dupilumab phase III trial. The data from these studies also support the use of dupilumab in combination with current standard of care (topical corticosteroids), which was not evaluated in the 16-week phase III monotherapy trial.


Assuntos
Dermatite Atópica , Eczema , Adolescente , Anticorpos Monoclonais Humanizados , Estudos de Coortes , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Humanos , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Morphologie ; 104(346): 147-150, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32518047

RESUMO

The pandemic Covid-19 is responsible for a major education crisis globally and has a drastic impact on medical training as well. The objective of the present study was to envision the present and future impact of Covid-19 on anatomy learning and research. The virtual education is the only mode of teaching in current scenario. Every anatomist is unlocking technology to deliver best education however understanding of the subject without dissections or other practical teaching aids like bones, specimens, embryology models, microscopic slides etc. is challenging. This approach misses the feel and human visual impacts. Potential educational disruption is felt currently and will be experienced even after the pandemic is over due to scarcity of cadavers. As the body donor may be carrier or died of Covid-19 and there is no proven screening to rule out this infection in donor, so the acceptance of body donations is not advisable for the safety of medical students and health care workers. To conclude, anatomy education is cadaverless currently due to Covid-19 lockdown and it is prophesied that after the pandemic, real cadavers will be replaced by virtual cadavers because of paucity of cadavers. Research in the field of anatomy will also be adversely affected.


Assuntos
Anatomia/educação , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Treinamento por Simulação/métodos , Anatomia/tendências , COVID-19 , Cadáver , Dissecação/educação , Cirurgia Geral/educação , Cirurgia Geral/tendências , Humanos , Internato e Residência , SARS-CoV-2 , Treinamento por Simulação/tendências , Estudantes de Medicina
12.
J Hum Nutr Diet ; 31(5): 612-624, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30073712

RESUMO

BACKGROUND: Necrotising enterocolitis (NEC) is one of the most common life-threatening emergencies of the gastrointestinal tract in preterm neonates. The present study aimed to determine the efficacy of oropharyngeal colostrum with respect to reducing NEC in preterm neonates. METHODS: A literature search was conducted for various randomised control trials by searching the Cochrane Central Register of Controlled Trials, PubMed, EMBASE and ongoing clinical trials. Randomised or quasi-randomised trials comparing oropharyngeal colostrum versus placebo in neonates (birthweight ≤ 1500 g or gestational age ≤ 32 weeks) were included in the review. The methodological quality of each trial was independently reviewed by the authors. For categorical and continuous variables, typical estimates for relative risk and typical estimates for weighted mean difference were calculated, respectively. A random effect model was assumed for meta-analysis. RESULTS: In total, four eligible trials were included in the review. Oropharyngeal colostrum therapy was not associated with a statistically significant reduction in the incidence of NEC stage ≥2 [typical relative risk (RR) = 0.64; 95% confidence interval (CI) = 0.27-1.49], mortality from any cause (typical RR = 0.86; 95% CI = 0.15-4.80) and time to reach full feed [typical weighted mean difference (WMD) = -3.26; 95% CI = -8.87 to 2.35]. Duration of hospital stay was significantly less in the control group (typical WMD = 9.77; 95% CI = 3.96-15.59). CONCLUSIONS: The current evidence is insufficient for recommending oropharyngeal colostrum as a routine clinical practice in the prevention of NEC. We emphasise the need for large randomised controlled trials with an adequate sample size and validated clinical outcomes in preterm neonates.


Assuntos
Colostro/imunologia , Enterocolite Necrosante/prevenção & controle , Imunoterapia/métodos , Recém-Nascido de muito Baixo Peso/imunologia , Enterocolite Necrosante/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Tempo de Internação , Masculino , Orofaringe/imunologia , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Dis Esophagus ; 30(9): 1-8, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28859356

RESUMO

Chemoprevention and risk-stratification studies in Barrett's esophagus (BE) rely on biomarkers but the variability in their temporal and spatial expression is unknown. If such variability exists, it will impact sampling techniques and sample size calculations. Specimens from three levels of biopsies over two serial endoscopies in nondysplastic BE patients were analyzed for aneuploidy, proliferation markers (Ki67, Mcm2), and cell cycle markers (cyclin A and cyclin D1). A modification of the image cytometry technique, where cytokeratin staining automatically distinguished epithelial and stromal cells, measured aneuploidy on whole tissue sections. Other biomarkers were studied by immunohistochemistry. Coefficient of variability (SD/mean) was calculated; a value <10% indicated low variability. A total of 120 specimens (20 subjects each with three biopsy levels at two time points) from nondysplastic BE patients (71 ± 8.8 years, all Caucasian, 90% males, C5.1M7.5 ± 3.4 cm) were analyzed. The mean interval between endoscopies was 32.8 ± 8.4 months. Aneuploidy had a spatial variability of 6.8% at visit 1 (mean diploid index: 1.1 ± 0.09) and 7.9% at visit 2 (mean diploid index: 1.1 ± 0.06) and a temporal variability of 7.0-8.1% for the three levels. For other biomarkers, the spatial variability ranged from ∼5 to 30% at visit 1 and 11-92% at visit 2 and the temporal variability ranged from 0 to 77%. To conclude, of all the biomarkers, only aneuploidy had both spatial and temporal variability of <10%. Spatial and temporal variability were biomarker dependent and could be as high as 90% even without progression. These data will be useful to design chemoprevention and risk-stratification studies in BE.


Assuntos
Aneuploidia , Esôfago de Barrett/genética , Esôfago de Barrett/metabolismo , Esôfago/metabolismo , Idoso , Esôfago de Barrett/patologia , Biomarcadores/metabolismo , Biópsia , Proliferação de Células , Ciclina A/metabolismo , Ciclina D1/metabolismo , Esofagoscopia , Esôfago/patologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Análise Espaço-Temporal , Fatores de Tempo
16.
Clin Exp Immunol ; 184(2): 237-47, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26646713

RESUMO

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19⁺ B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD⁺ subsets. Within memory subsets, a higher frequency of CD21⁺ CD38⁻ B cells (> 20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15-10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.


Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Subpopulações de Linfócitos B/imunologia , Síndrome de Fadiga Crônica/imunologia , Glicoproteínas de Membrana/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Adolescente , Adulto , Idoso , Antígenos CD19/metabolismo , Antígenos CD20/imunologia , Biomarcadores , Antígeno CD24/imunologia , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina D/imunologia , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Receptores de Complemento 3d/imunologia , Rituximab/uso terapêutico , Adulto Jovem
17.
Int J Sports Med ; 37(9): 748-53, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27487432

RESUMO

The current study aimed to measure perioperative changes in driving performance following arthroscopic shoulder surgery using a validated driving simulator.21 patients who underwent arthroscopic surgery for rotator cuff or labral pathology were tested on a driving simulator preoperatively, and 6 and 12 weeks postoperatively. An additional 21 subjects were tested to establish driving data in a control cohort. The number of collisions, centerline crossings, and off-road excursions were recorded for each trial. VAS and SPADI scores were obtained at each visit.The mean number of collisions in the study group significantly increased from 2.05 preoperatively to 3.75 at 6 weeks (p<0.001), and significantly decreased to 1.95 at 12 weeks (p<0.001). Centerline crossings and off-road excursions did not significantly change from preoperative through 12 weeks, although centerline crossings were statistically different from the controls at each time point (p<0.001). Surgery on the dominant driving arm resulted in greater collisions at 6 weeks than surgery on the non-dominant driving arm (p<0.001).Preliminary data shows that driving performance is impaired for at least 6 weeks postoperatively, with a return to normal driving by 12 weeks. Driving is more profoundly affected in conditions that require avoiding a collision and when the dominant driving arm is involved.


Assuntos
Artroscopia , Condução de Veículo , Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Acidentes de Trânsito , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Adulto Jovem
19.
Occup Med (Lond) ; 65(5): 398-401, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25941211

RESUMO

BACKGROUND: Despite a 2007 national and regional training programme, there was poor implementation of a post-exposure prophylaxis (PEP) programme to prevent occupational transmission of HIV in health care workers (HCWs) in Delhi. A new initiative was therefore launched by the Delhi State AIDS Control Society in 2010 to improve uptake of PEP in HCWs. AIMS: To assess the implementation and efficacy of the PEP programme in Delhi. METHODS: The initiative included a PEP poster and a telephone helpline together with a workshop for senior doctors of 46 public hospitals nominated as PEP supervisors. Data concerning use of the PEP help line and number of HCWs enrolling for PEP between January 2011 and May 2014 were analysed. RESULTS: Until September 2010, only 61% (28) of Delhi hospitals had PEP drugs and medical supervisors to manage the programme and reports concerning the programme were not sent. After roll-out of the PEP helpline, 4057 HCWs accessed the helpline, all public hospitals started implementing the programme and sent monthly reports. During the same period, 1450 HCWs suffered from occupational exposures, 15% were started on PEP drugs of who 98% completed the full course of prophylaxis. CONCLUSIONS: The PEP helpline is probably the first in a developing country and has been helpful for the effective implementation of the national PEP programme in Delhi.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Exposição Ocupacional/prevenção & controle , Profilaxia Pós-Exposição/organização & administração , Serviços Preventivos de Saúde/métodos , Adulto , Feminino , Infecções por HIV/transmissão , Educação em Saúde/métodos , Pessoal de Saúde/educação , Linhas Diretas , Humanos , Masculino , Pessoa de Meia-Idade , Pôsteres como Assunto , Avaliação de Programas e Projetos de Saúde , Adulto Jovem
20.
Med J Armed Forces India ; 71(Suppl 2): S327-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26843747

RESUMO

BACKGROUND: Dental implant insertion torque is crucial for the success of the implant and the prosthesis. This in-vivo study was undertaken to determine the average insertion torque being applied to the dental implant while surgically placing it with a non-calibrated manual ratchet. METHODS: Three dental surgeons placed a total of 45 dental implants (Touareg, ADIN, Afula, Israel) in 42 selected patients. Each surgeon placed 15 implants. Standardised protocols were followed to prepare the site to place the dental implant. Each implant was placed using a manual non-calibrated implant ratchet first. Once the implant was nearly placed, a manual calibrated torque gauge ratchet was used to place the implant in its final position and at that instance, the maximum final torque applied was noted on the torque gauge scale. RESULTS: The mean dental implant insertion torque applied by three surgeons using a non-calibrated manual ratchet was estimated to be 63.26 Ncm with a standard error of 6.80 i.e. (63.26 + 6.8), which was significantly higher than the baseline of 35 Ncm (p < 0.0001). The mean dental implant torque applied by Surgeon 1, 2 and 3, respectively, was 65.93 Ncm, 62.60 Ncm and 62.13 Ncm and this difference amongst them was found to be statistically insignificant (p > 0.05) and each of them had reached more than the baseline level of 35 Ncm individually and significantly (p < 0.0001). CONCLUSION: Without the use of torque measuring devices, an average surgeon may achieve an average insertion torque of 63.26 + 6.8 Ncm.

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