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Introduction Intracranial aneurysms in children are very rare pathologic entities. (1200 cases presented in literature from 1939-2011). Material and Methods The authors present 51 cases of children (aged: 0-16) operated between January 1999 and December 2023 - 24 years in three neurosurgical centers: “Bagdasar Arseni” Emergency University Hospital (Bucharest), Sanador Clinical Hospital (Bucharest) and Timis County Emergency Hospital (Timisoara). We collected data from many children’s intracranial aneurysms cases because “Bagdasar-Arseni” Emergency University Hospital has the most important pediatric neurosurgical unit in the country. Regarding our series, pediatric aneurysms represent 6.14% (51 cases) of all operated intracranial aneurysms (765 cases). The mean age of the patients was 14.3 years. There were 29 boys (58.7%) and 22 girls (41.2%). The clinical features are dominated by headache (48 cases - 95.7%), neck stiffness (45 cases - 91.4%), vomiting (44 cases - 89.3%), focal neurological deficit (24 cases - 44.6%), an altered level of consciousness (17 cases - 36.1%), seizures (24 cases - 44.6%, fever (20 cases - 34%). The majority of patients were Hunt & Hess Il at admittance (27 cases, 53%). All neuroimagistic investigations were done in the first 48 hours (CT, DSA, MRI). Locations: anterior communicating artery aneurysms (20 cases, 36.1%), followed by middle cerebral artery aneurysms (15 cases, 25.5%) and internal carotid artery bifurcation aneurysms (9 cases, 19.1%) and so on. Many aneurysms were large and giant (18 cases - 31.9%). Microsurgery approach was performed in 48 cases (99.7%) and 3 case (4.4%) were endovascular approached. This represents a new vision because the actual endovascular way is extremely efficient and performant in occluding pediatric intracranial aneurysms. The Glasgow Outcome Scale (GOS) at six months postop. showed GR in 40 cases (78.5%), MD in 9 cases (17.2%), SD in 1 patient (2.1%) and (preoperative) death in 1 patient (2.1%). Conclusions Intracranial aneurysms in children are a very rare pathologic entity. Early microsurgical or endovascular approach is mandatory and has excellent results (good recovery).

Summary This article describes the structures and processes involved in healthcare delivery for sepsis, from the prehospital setting until rehabilitation. Quality improvement initiatives in sepsis may reduce both morbidity and mortality. Positive outcomes are more likely when the following steps are optimized: early recognition, severity assessment, prehospital emergency medical system activation when available, early therapy (antimicrobials and hemodynamic optimization), early orientation to an adequate facility (emergency room, operating theater or intensive care unit), in-hospital organ failure resuscitation associated with source control, and finally a comprehensive rehabilitation program. Such a trajectory of care dedicated to sepsis amounts to a chain of survival and rehabilitation for sepsis. Implementation of this chain of survival and rehabilitation for sepsis requires full interconnection between each link. To date, despite regular international recommendations updates, the adherence to sepsis guidelines remains low leading to a considerable burden of the disease. Developing and optimizing such an integrated network could significantly reduce sepsis related mortality and morbidity.

Summary: This article describes the structures and processes involved in healthcare delivery for sepsis, from the prehospital setting until rehabilitation. Quality improvement initiatives in sepsis may reduce both morbidity and mortality. Positive outcomes are more likely when the following steps are optimized: early recognition, severity assessment, prehospital emergency medical system activation when available, early therapy (antimicrobials and hemodynamic optimization), early orientation to an adequate facility (emergency room, operating theater or intensive care unit), in-hospital organ failure resuscitation associated with source control, and finally a comprehensive rehabilitation program. Such a trajectory of care dedicated to sepsis amounts to a chain of survival and rehabilitation for sepsis. Implementation of this chain of survival and rehabilitation for sepsis requires full interconnection between each link. To date, despite regular international recommendations updates, the adherence to sepsis guidelines remains low leading to a considerable burden of the disease. Developing and optimizing such an integrated network could significantly reduce sepsis related mortality and morbidity. [ABSTRACT FROM AUTHOR]

Abstract Background A subset of Graves’ disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. Methods A prospective cohort study (2018–2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. Results Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves’ ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium–low cumulative dosage group (average

Background: A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. Methods: A prospective cohort study (2018–2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. Results: Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium–low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium–low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD. Conclusion: Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients. [ABSTRACT FROM AUTHOR]

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Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was =1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio = 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio =1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Intracranial aneurysms in children are very rare pathologic entities. (1200 cases presented in literature from 1939-2011). MATERIAL AND METHODS: The authors present 51 cases of children (aged: 0-16) operated between January 1999 and December 2023 - 24 years in three neurosurgical centers: "Bagdasar Arseni" Emergency University Hospital (Bucharest), Sanador Clinical Hospital (Bucharest) and Timis County Emergency Hospital (Timisoara). We collected data from many children's intracranial aneurysms cases because "Bagdasar-Arseni" Emergency University Hospital has the most important pediatric neurosurgical unit in the country. Regarding our series, pediatric aneurysms represent 6.14% (51 cases) of all operated intracranial aneurysms (765 cases). The mean age of the patients was 14.3 years. There were 29 boys (58.7%) and 22 girls (41.2%). The clinical features are dominated by headache (48 cases - 95.7%), neck stiffness (45 cases - 91.4%), vomiting (44 cases - 89.3%), focal neurological deficit (24 cases - 44.6%), an altered level of consciousness (17 cases - 36.1%), seizures (24 cases - 44.6%, fever (20 cases - 34%). The majority of patients were Hunt & Hess Il at admittance (27 cases, 53%). All neuroimagistic investigations were done in the first 48 hours (CT, DSA, MRI). Locations: anterior communicating artery aneurysms (20 cases, 36.1%), followed by middle cerebral artery aneurysms (15 cases, 25.5%) and internal carotid artery bifurcation aneurysms (9 cases, 19.1%) and so on. Many aneurysms were large and giant (18 cases - 31.9%). Microsurgery approach was performed in 48 cases (99.7%) and 3 case (4.4%) were endovascular approached. This represents a new vision because the actual endovascular way is extremely efficient and performant in occluding pediatric intracranial aneurysms. The Glasgow Outcome Scale (GOS) at six months postop. showed GR in 40 cases (78.5%), MD in 9 cases (17.2%), SD in 1 patient (2.1%) and (preoperative) death in 1 patient (2.1%). CONCLUSIONS: Intracranial aneurysms in children are a very rare pathologic entity. Early microsurgical or endovascular approach is mandatory and has excellent results (good recovery). [ABSTRACT FROM AUTHOR]

In 2022, three antiviral drugs—molnupiravir, remdesivir and nirmatrelvir/ritonavir—were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the involvement of 1118 patients, with complete follow-up data, treated between the 5th of January and the 3rd of October 2022 at Santa Maria Goretti's hospital in Latina, Central Italy. A univariable and a multivariable analysis were performed on clinical and demographic data and composite outcome, the persistence of symptoms at 30 days and time to negativization, respectively. The three antivirals showed a similar effectiveness in containing the progression of the infection to severe COVID-19 and a good tolerability in the absence of serious adverse effects. Persistence of symptoms after 30 days was more common in females than males and less common in patients treated with molnupiravir and nirmatrelvir/r. The availability of different antiviral molecules is a strong tool and, if correctly prescribed, they can have a significant role in changing the natural history of infection for frail persons, in which vaccination could be not sufficient for the prevention of severe COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: Below we report our experience in the use of molnupiravir, the first antiviral drug against SARS-CoV-2 available to us, in the treatment of patients with COVID-19. Materials and Methods: We enrolled patients diagnosed with COVID-19 and comorbidities who were candidates for antiviral drug therapy. All patients received molnupiravir (800 mg twice daily). Blood chemistry checks were carried out at T0 and after 7/10 days after starting therapy (T1). Results: There were enrolled within the cohort 100 patients. There was 100.0% compliance with the antiviral treatment. No patient required hospitalization due to worsening of respiratory function or the appearance of serious side effects. The median downtime of viral load was ten days (IQR 8.0–13.0), regardless of the type of vaccination received. The patients who had a shorter distance from vaccination more frequently presented vomiting/diarrhea. During baseline and T1 we found significant differences in the median serum concentrations of the main parameters, in particular of platelets, RDW CV, neutrophils and lymphocytes, the eGFR, liver enzymes, as well as of the main inflammatory markers, CRP and Ferritin. Conclusion: Participants treated with molnupiravir, albeit in risk categories, demonstrated early clinical improvement, no need for hospitalization, and a low rate of adverse events. [ABSTRACT FROM AUTHOR]

IntroductionAggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.MethodsThis was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150–200 mg/m2). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h-scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.ResultsThe study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6–14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h-scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h-score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.ConclusionEarly initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.

Introduction: Aggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking. Methods: This was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150–200 mg/m2). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h -scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders. Results: The study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6–14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h -scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h -score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response. Conclusion: Early initiation of TMZ therapy, functional tumors, and low MGMT h -score predict a favorable response to TMZ in APAs. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn's disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients' concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication. [ABSTRACT FROM AUTHOR]

Objectives: Below we report our experience in the use of molnupiravir, the first antiviral drug against SARS-CoV-2 available to us, in the treatment of patients with COVID-19. Materials and Methods: We enrolled patients diagnosed with COVID-19 and comorbidities who were candidates for antiviral drug therapy. All patients received molnupiravir (800 mg twice daily). Blood chemistry checks were carried out at T0 and after 7/10 days after starting therapy (T1). Results: There were enrolled within the cohort 100 patients. There was 100.0% compliance with the antiviral treatment. No patient required hospitalization due to worsening of respiratory function or the appearance of serious side effects. The median downtime of viral load was ten days (IQR 8.0–13.0), regardless of the type of vaccination received. The patients who had a shorter distance from vaccination more frequently presented vomiting/diarrhea. During baseline and T1 we found significant differences in the median serum concentrations of the main parameters, in particular of platelets, RDW CV, neutrophils and lymphocytes, the eGFR, liver enzymes, as well as of the main inflammatory markers, CRP and Ferritin. Conclusion: Participants treated with molnupiravir, albeit in risk categories, demonstrated early clinical improvement, no need for hospitalization, and a low rate of adverse events.

nvasive candidiasis is an extremely important problem for severe patients in intensive care units. The high rates of attributive mortality are associated not only with the severity of the patient’s condition, but also with a delayed therapy due to not always available or not validated early diagnostic tests, limitations of conventional microbiological studies, and a non-specific clinical picture which prevent clinicians from suspecting a systemic Candida infection. The development of prognostic rules to identify patients with high or low invasive candidiasis risk based on microbiological and/or clinical characteristics seems to be the most available approach which has been confirmed in the prospective studies. This article describes the common prognostic rules and discusses the possible options of their implementation in clinical practice.

A new tuberculosis model with health education and early therapy is introduced. The early therapy is available for both detected latent and infective individuals. The basic reproduction number R 0 $R_0$ is derived by the next generation matrix. Mathematical analyses show that the disease free equilibrium is globally asymptotically stable if R 0 < 1 $R_0<1$ , and the endemic equilibrium is globally asymptotically stable if R 0 > 1 $R_0>1$. Numerical simulations are also carried out to illustrate our analytical results. Our results show that both health education and early therapy have the positive impact in reducing burden of tuberculosis. [ABSTRACT FROM AUTHOR]

BackgroundWestern blot (WB) assay is considered the gold standard test for HIV infection confirmation. However, it requires technical expertise and is quite time-consuming. WHO recommends blood-based rapid diagnosis to achieve same-day test and treatment. However, this rapid testing strategy has not been promoted worldwide due to inadequate research evaluating the effectiveness of rapid tests (RTs) as an alternative confirmatory HIV test for WB. This study aims to compare the diagnostic performance of rapid HIV tests compared with WB.MethodsPubMed and Web of Science were searched for publications on rapid HIV tests using blood specimen. A meta-analysis was performed to quantitatively evaluate the diagnostic performance of rapid HIV tests compared with the WB assay in terms of pooled sensitivity, specificity, area under summary receiver operating characteristic (SROC) curve, and diagnostic odds ratio (DOR).ResultsTwenty articles involving 27,343 fresh specimens for rapid HIV tests were included in the meta-analysis. Regarding Capillus HIV-1/HIV-2, the pooled sensitivity, specificity, area under SROC curve, and DOR derived from six studies were 0.999 (95% CI, 0.956–1.000), 0.999 (95% CI, 0.991–1.00), 1.00 (95% CI, 0.99–1.00), and 1.0 × 106 (95% CI, 2.6 × 104–3.9 × 107) compared with the WB assay, respectively. With respect to Determine HIV-1/2, the pooled sensitivity, specificity area under SROC, and DOR derived from eight studies were 1.00 (95% CI, 0.789–1.000), 0.992 (95% CI, 0.985–0.996), 1.00 (95% CI, 0.99–1.00), and 1.8 × 106 (95% CI 406.049–7.8 × 109) compared with the WB assay, respectively. Regarding two-step serial RTs, the pooled sensitivity, specificity area under SROC, and DOR derived from eight studies were 0.998 (95% CI, 0.991–1.000), 0.998 (95% CI, 0.994–0.999), and 1.00 (95% CI 0.99–1.00) compared with the WB assay, respectively.ConclusionOur meta-analysis results may provide evidenced-based support for substituting RT for WB. Blood-based rapid HIV tests have comparable sensitivity and specificity to WB for HIV early therapy.

Background: Western blot (WB) assay is considered the gold standard test for HIV infection confirmation. However, it requires technical expertise and is quite time-consuming. WHO recommends blood-based rapid diagnosis to achieve same-day test and treatment. However, this rapid testing strategy has not been promoted worldwide due to inadequate research evaluating the effectiveness of rapid tests (RTs) as an alternative confirmatory HIV test for WB. This study aims to compare the diagnostic performance of rapid HIV tests compared with WB. Methods: PubMed and Web of Science were searched for publications on rapid HIV tests using blood specimen. A meta-analysis was performed to quantitatively evaluate the diagnostic performance of rapid HIV tests compared with the WB assay in terms of pooled sensitivity, specificity, area under summary receiver operating characteristic (SROC) curve, and diagnostic odds ratio (DOR). Results: Twenty articles involving 27,343 fresh specimens for rapid HIV tests were included in the meta-analysis. Regarding Capillus HIV-1/HIV-2, the pooled sensitivity, specificity, area under SROC curve, and DOR derived from six studies were 0.999 (95% CI, 0.956–1.000), 0.999 (95% CI, 0.991–1.00), 1.00 (95% CI, 0.99–1.00), and 1.0 × 106 (95% CI, 2.6 × 104–3.9 × 107) compared with the WB assay, respectively. With respect to Determine HIV-1/2, the pooled sensitivity, specificity area under SROC, and DOR derived from eight studies were 1.00 (95% CI, 0.789–1.000), 0.992 (95% CI, 0.985–0.996), 1.00 (95% CI, 0.99–1.00), and 1.8 × 106 (95% CI 406.049–7.8 × 109) compared with the WB assay, respectively. Regarding two-step serial RTs, the pooled sensitivity, specificity area under SROC, and DOR derived from eight studies were 0.998 (95% CI, 0.991–1.000), 0.998 (95% CI, 0.994–0.999), and 1.00 (95% CI 0.99–1.00) compared with the WB assay, respectively. Conclusion: Our meta-analysis results may provide evidenced-based support for substituting RT for WB. Blood-based rapid HIV tests have comparable sensitivity and specificity to WB for HIV early therapy. [ABSTRACT FROM AUTHOR]

BackgroundThe World Health Organization (WHO) Consolidated antiretroviral therapy (ART) guidelines set the CD4+ T-cell counts threshold to 500 cells/mm3 in 2013, and 2015 guidelines recommend treating all HIV-infected adults regardless of their CD4+ T-cell counts. To inform the decision-making around ART guidelines for people living with HIV, we systematically reviewed the literature to estimate differences in clinical benefits between individuals starting treatment with baseline CD4+ T-cell counts ≥500 cells/mm3 (early initiation) as compared to

Background: The World Health Organization (WHO) Consolidated antiretroviral therapy (ART) guidelines set the CD4+ T-cell counts threshold to 500 cells/mm³ in 2013, and 2015 guidelines recommend treating all HIV-infected adults regardless of their CD4+ T-cell counts. To inform the decision-making around ART guidelines for people living with HIV, we systematically reviewed the literature to estimate differences in clinical benefits between individuals starting treatment with baseline CD4+ T-cell counts ≥500 cells/mm³ (early initiation) as compared to <500 cells/mm³ (deferred initiation). Methods: We systematically searched the electronic databases and abstracts for randomized controlled trials (RCT) and observational studies. Outcomes were mortality, AIDS progression, AIDS or death, immunologic recovery, and virologic suppression. We pooled data across studies and performed analyses of effect sizes. Results: We identified 13 studies comparing early and deferred treatment. The pooled risk ratio (RR) of mortality of 11 observational studies was 0.90 (95% CI 0.82-0.99), with moderate heterogeneity (I² = 53%). The pooled RR for progression to AIDS from two observational studies was 0.77 (95% CI 0.47-1.24). Five observational studies found a pooled RR of death or AIDS of 0.94 (95% CI 0.93-0.95). For the outcome of immuno- logic recovery, defined as CD4+ T-cell counts reaching at least 800 cells/mm³ after ART, one observational study found early initiation of ART had an HR (hazard ratio) of 2.39 (95% CI 1.93-2.96). The pooled RR of viral suppression (a viral load <50 copies/ml) after 9 months from one cohort was 1.04 (95% CI 0.99-1.09). Conclusion: Mortality risk and risk for AIDS appear to be reduced among people living with HIV with early initiation of ART, based on current WHO guidelines, as compared to those with deferred initiation of ART (<500 cells/mm³). [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods: Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥ 5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results: Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion: Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and achieved PsARC response more rapidly than late PsA. In this cohort, comedication with csDMARDs was beneficial over 2 years. [ABSTRACT FROM AUTHOR]

For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection.In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized. [ABSTRACT FROM AUTHOR]

Zusammenfassung Frühkindliche Entwicklung, ihre Varianzen und insbesondere krankhafte Abweichungen sind zentraler Fokus der Frühdiagnostik, denn nur daraus lässt sich eine effektive individuelle Frühtherapie ableiten. Die etablierten Entwicklungstests verfolgen aus ihrer jeweiligen Historie heraus unterschiedliche Ansätze und führen entsprechend den untersuchten Testinhalten zu jeweils spezifischen Ergebnissen. Die Eigenschaften der Entwicklungstests sollten auch dem Therapeuten bekannt sein, ebenso auch der strukturierte Untersuchungsgang und die Interpretation der Ergebnisse. Early childhood development, its variances and especially the pathological deviations are focal point of early clinical diagnostics in infants and are prerequisite for an effective individual early therapy. A number of developmental tests are well-established. Because of their different history they have varying approaches and lead to different results. The specific characteristics of the developmental tests as well as the structured clinical examination and its exact interpretation should be well known by therapists. [ABSTRACT FROM AUTHOR]

Background: Evidence for early intensive behavioural interventions (EIBI) by therapists as an effective treatment for children with an Autism Spectrum Disorder (ASD) is growing. High-intensity and sustained delivery of quality EIBI is expensive. The TOBY (Therapy Outcomes by You) Playpad is an App-based platform delivering EIBI to facilitate learning for young children with ASD, while enabling parents to become co-therapists. Intervention targets include increasing joint attention, imitation and communication of children with ASD. The primary aim of the study presented in this protocol is to determine the effectiveness of the TOBY App in reducing ASD symptoms when used as a complement to conventional EIBI. The secondary aim is to examine parental attributes as a result of TOBY App use. Methods and design: Children aged less than 4;3 years diagnosed with ASD and parents will be recruited into this single-blind, randomised controlled trial using a pragmatic approach. Eligible participants will be randomised to the treatment group 'TOBY therapy + therapy as usual' or, the control group 'therapy as usual' for six months. The treatment will be provided by the TOBY App and parent where a combination of learning environments such as on-iPad child only (solo), partner (with parent) and off-iPad - Natural Environment (with parent) Tasks will be implemented. Parents in the treatment group will participate in a TOBY training workshop. Treatment fidelity will be monitored via an App-based reporting system and parent diaries. The primary outcome measure is the Autism Treatment Evaluation Checklist. The secondary outcome measures involve diagnostics, functional and developmental assessments, including parent questionnaires at baseline (T0), three months (T1) and six months (T2). Discussion: This trial will determine the effectiveness of the TOBY App as a therapeutic complement to other early interventions children with ASD receive. The trial will also determine the feasibility of a parent delivered early intervention using the iPad as an educational platform, and assess the impact of the TOBY App on parents' self-efficacy and empowerment in an effort to reduce children's ASD symptoms. The outcomes of this trial may have EIBI services implications for newly diagnosed children with ASD and parents. [ABSTRACT FROM AUTHOR]