Efectividad de una intervención educativa para acortar el tratamiento antibiótico parenteral en infecciones moderadas y graves en un hospital pediátrico de alta complejidad / Effectiveness of an educational intervention to shorten parenteral antibiotic treatment in moderate and severe infections in a tertiary-care pediatric hospital

Introducción: Las intervenciones destinadas a acortar la duración de los tratamientos antibióticos parenterales son consideradas estrategias de utilidad para reducir complicaciones relacionadas con los tratamientos parenterales prolongados en forma inadecuada, la selección de resistencia y los costos hospitalarios. El objetivo del estudio fue evaluar la efectividad de un programa para reducir la duración del tratamiento antibiótico parenteral innecesario en el tratamiento de infecciones moderadas y severas en niños hospitalizados. Material y Métodos: Estudio antes después sin grupo control. Se incluyeron niños entre 3 meses y 18 años que recibían tratamiento antibiótico parenteral como tratamiento de peritonitis, infección de piel y partes blandas, infección osteoarticular, neumonía neutropenia febril sin foco clínico de infección internados en el Hospital Garrahan. Período Pre-intervención (Pre-I) 2011 vs. Post-intervención 2012. Intervención: talleres interactivos, difusión de algoritmos diagnósticos y de tratamiento de las infecciones consideradas y monitoreo regular de las prescripciones antibióticas parenterales y su duración. Análisis estadístico: STATA version 8.0 software. Resultados: Pre-I vs. post-I se incluyeron un total de 194 vs. 227 pacientes respectivamente. La mediana de edad fue de 49 meses (RIC: 19-92 m) vs. 39 meses (13-108m), respectivamente p>0.05., se obtuvo documentación microbiológica en 52 (27%) vs. 63 (28%), p>0.05. La mediana de días de tratamiento antibiótico parenteral según pre vs. post I fue de 6 días (RIC: 5-7d.) vs. 3 días (RIC 2-4) para Infección de piel y partes blandas, 5 días (RIC: 3-8) vs. 4 días (RIC 3-6) para neumonía, 6 días (RIC:5-8) vs. 4 días (RIC:4-5) para peritonitis, 7 días(RIC: 6-8) vs. 5 días (RIC: 5-7 días) para infecciones osteoarticulares y 5 días (RIC: 4-6) vs. 4 días (RIC: 3-5) para neutropenia febril sin foco clínico de infección. Mediana del total de días de tratamiento antibiótico parenteral pre-I vs. post-I fue 6.5 días (RIC: 5-7) vs. 4 días (RIC: 4-5), p<0.01, la mediana días totales de internación fue de 7(6-8) vs. 5 (5-6) p<0.01. Conclusiones: Se observó una reducción en la duración de los tratamientos endovenosos de infecciones moderadas y graves en el periodo post-intervención generando una mayor disponibilidad de camas en la institución (au)

Introduction: Interventions to shorten parenteral antibiotic treatment are considered useful strategies to reduce complications related to inadequately long parenteral treatment, resistance, and hospital costs. The aim of this study was to assess the effectiveness of a program for the reduction of unnecessary parenteral antibiotic treatment in the management of hospitalized children with moderate and severe infections. Material and methods: A before-and-after study without control group. Children between 3 months and 18 years of age receiving parental antibiotics for the treatment of peritonitis, skin and soft tissue infection, osteoarticular infection, pneumonia, and febrile neutropenia without a clear focus of infection admitted to the Garrahan Hospital were included in the study. Pre-intervention period (Pre-I) 2011 vs. post-intervention period 2012. Intervention: Interactive workshops, diffusion of diagnostic and treatment algorithms for infections used, and regular monitoring of prescriptions for parenteral antibiotics and their duration. Statistical analysis: STATA version 8.0 software. Results: In the pre-I vs. post-I a total of 194 vs. 227 patients were included, respectively. Median age was 49 months (IQR: 19-92 m) vs. 39 months (13-108 m), respectively, p>0.05. Microbiological documentation was obtained in 52 (27%) vs. 63 (28%) patients, p>0.05. Median days of parenteral antibiotic treatment in the pre vs. post I period was 6 days (IQR: 5-7 d) vs. 3 days (IQR: 2-4 d) for skin and soft tissue infection, 5 days (IQR: 3-8) vs. 4 days (IQR: 3-6) for pneumonia, 6 days (IQR: 5-8) vs. 4 days (IQR: 4-5) for peritonitis, 7 days (IQR: 6-8) vs. 5 days (IQR: 5-7 days) for osteoarticular infections, and 5 days (IQR: 4-6) vs. 4 days (IQR: 3-5) for febrile neutropenia without a clear focus of infection. Median total days of parenteral antibiotic treatment in the pre vs. post I period was 6.5 days (IQR: 5-7) vs. 4 days (IQR: 4-5), p<0.01 and the median total days of length of hospital stay was 7 (IQR: 6-8) vs. 5 (IQR: 5-6), p<0.01. Conclusions: A decrease in the duration of intravenous treatment duration for moderate and severe infections was observed in the post-intervention period leading to an improved availability of beds at the institution (AU)

Phototherapy during treadmill training improves quadriceps performance in postmenopausal women.

OBJECTIVE: To evaluate the effects of infrared-light-emitting diode (LED) during treadmill training on functional performance. METHODS: Thirty postmenopausal women aged 50-60 years were randomly assigned to one of three groups and successfully completed the full study. The three groups were: (1) the LED group, which performed treadmill training associated with phototherapy (n = 10); (2) the exercise group, which carried out treadmill training only (n = 10); and (3) the sedentary group, which neither performed physical training nor underwent phototherapy (n = 10). Training was performed over a period of 6 months, twice a week for 45 min per session at 85-90% of maximal heart rate, which was obtained during progressive exercise testing. The irradiation parameters were 100 mW, 39 mW/cm(2) and 108 J/cm(2) for 45 min. Quadriceps performance was measured during isokinetic exercise testing at 60°/s and 300°/s. RESULTS: Peak torque did not differ amongst the groups. However, the results showed significantly higher values of power and total work for the LED group (∆ = 21 ± 6 W and ∆ = 634 ± 156 J, p < 0.05) when compared to both the exercise group (∆ = 13 ± 10 W and = 410 ± 270 J) and the sedentary group (∆ = 10 ± 9 W and ∆ = 357 ± 327 J). Fatigue was also significantly lower in the LED group (∆ = -7 ± 4%, p < 0.05) compared to both the exercise group (∆ = 3 ± 8%) and the sedentary group (∆ = -2 ± 6%). CONCLUSIONS: Infrared-LED during treadmill training may improve quadriceps power and reduce peripheral fatigue in postmenopausal women.

Multiple sclerosis in Italy: cost-of-illness study.

This study estimates the direct costs of multiple sclerosis (MS) in Italy from the perspective of the National Health System. Patients diagnosed with MS for ≥1 year prior to study entry were included in the analysis; neurological disability was assessed using the Expanded Disability Status Scale (EDSS). Cost variables were analyzed according to: MS phenotype, disease course over the previous year and EDSS rating. A total of 510 patients were included in the analysis. Overall costs were significantly higher for relapsing-remitting MS and secondary progressive MS than for primary progressive MS (P < 0.05). Costs were higher for EDSS scores 0.0-3.5 and 4.0-6.0 than for scores > 6.0 (P < 0.05). The extrapolated data gave an estimated annual direct cost of MS per patient of 18,030. In conclusion, relapsing-remitting MS or secondary progressive MS phenotypes and lower estimated EDSS scores appear to be associated with higher costs.

Mitoxantrone treatment in patients with early relapsing-remitting multiple sclerosis.

We investigated the clinical and MRI effects of mitoxantrone (MITOX) administered to 45 patients during the first five years of highly active relapsing-remitting multiple sclerosis. Differences occurring between the end of treatment and follow-up (clinical mean: 3.6 years; brain MR: 1.8 years) with respect to baseline variables (EDSS, annualized relapse rate, active T2 lesions, new T1 lesions and number of Gd-enhancing lesions) were analysed using parametric and non-parametric tests. One patient developed leukemia four months after the end of the treatment; no other serious adverse events occurred during treatment and the follow-up period. A clinically relevant reduction in the annualized relapse rate ( P < 0.0001 at end of treatment and P < 0.0001 at follow-up) and improvement in the EDSS (P < 0.0001 at end of treatment and P = 0.0005 at follow-up) was found. At the end of treatment, 53% of patients experienced no increase in active T2 lesions, while 73% showed no increase in the number of new T1 lesions. At follow-up, 41 out of 45 (91%) patients showed a stable MRI pattern and were active-scan free. Despite potential serious adverse events, MITOX may be considered an option in selected patients with very active early MS.

Investigating the role of brain-derived neurotrophic factor in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well-known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain-derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing-remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educational-level matched healthy subjects. We found that in the RRMS group, the BDNF Met-allele was significantly associated with the lower volume of cerebral grey matter (GM) (P = 0.005). Furthermore, a significant (P = 0.013) interaction effect between 'MS-status' and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met-allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF-related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met-allele might have a negative prognostic effect on cortical morphometry in RRMS patients.

Interferon after 10 years in patients with multiple sclerosis.

Multiple sclerosis (MS) is a life-long disease that typically affects young adults. The introduction of disease-modifying therapy has changed the clinical and social burden of the disease. Safety, tolerability and efficacy profiles of Interferon beta (IFNbeta) therapy in MS have been widely highlighted both in trial settings and in daily clinical practice. However, there is a relative lack of information on the long-term period: all pivotal trials must be considered short-term in a disease with an average duration of 30-40 years and post-marketing studies suffer from some limitations. Moreover, current available IFNbeta preparations are only partially effective and are difficult to administer, which has led to poor patient compliance. Over the treatment period, a problem could be the development of neutralising antibodies (NAbs) against the drug, which have been related to lessening treatment benefits. Despite these restrictions, IFNbeta still remains the first choice treatment in MS.

Sex hormones modulate brain damage in multiple sclerosis: MRI evidence.

BACKGROUND: Sex related differences in the course and severity of multiple sclerosis (MS) could be mediated by the sex hormones. OBJECTIVE: To investigate the relation between serum sex hormone concentrations and characteristics of tissue damage on conventional magnetic resonance imaging (MRI) in men and women suffering from relapsing-remitting MS. RESULTS: Serum testosterone was significantly lower in women with MS than in controls. The lowest levels were found in women with a greater number of gadolinium enhancing lesions. A positive correlation was observed between testosterone concentrations and both tissue damage on MRI and clinical disability. In men, there was a positive correlation between oestradiol concentrations and brain damage. CONCLUSIONS: The hormone related modulation of pathological changes supports the hypothesis that sex hormones play a role in the inflammation, damage, and repair mechanisms typical of MS.

Longitudinal evaluation of depression and anxiety in patients with clinically isolated syndrome at high risk of developing early multiple sclerosis.

We investigated the relationship between emotional changes, brain lesion burden and development of multiple sclerosis (MS). Thirty-seven consecutive patients with clinically isolated syndrome (CIS) were prospectively assessed with the Expanded Disability Status Scale (EDSS), the 21-item Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI) and gadolinium enhanced (Gd+) MRI scans. BDI and STAI were also administered to 36 age-matched controls. Conversion to MS was defined as the occurrence of a clinical relapse. CIS patients were more likely to endorse symptoms of anxiety and depression than controls. Baseline scores for depression and anxiety did not correlate with the total lesion load (i.e., volume of Gd+, T2 and T1 lesions) and the number of Gd+ lesions during the first six months of follow-up. A positive correlation was found between severity of depressive scores and the lesion load in the right temporal region (P = 0.005). After 33+/-6 months of the study entry, patients who had a clinical relapse were more frequently depressed (P = 0.001) than those relapse free. Emotional disturbances are frequently observed in CIS patients and show a tendency towards a normalization in relapse-free patients. The increased rate of depressive symptoms observed in patients who developed MS seems to result from a combination of psychological and organic features. The lesion load in the right temporal region is confirmed as a key area for developing depressive symptoms, even in the early phase of the disease.

'Gender gap' in multiple sclerosis: magnetic resonance imaging evidence.

The authors evaluated the gender difference in the magnetic resonance imaging characteristics of the lesions occurring in the brain of 413 multiple sclerosis (MS) patients. Men had fewer contrast-enhancing lesions (P = 0.01), but a higher proportion of lesions evolving into 'black holes' (P = 0.001), when compared with women. Thus, our data indicate that men with MS are prone to develop less inflammatory, but more destructive lesions than women. This study results provides support for a modulation of the MS pathological changes by gender.

A 6-year clinical and MRI follow-up study of patients with relapsing-remitting multiple sclerosis treated with Interferon-beta.

There are few long-term clinical and magnetic resonance imaging (MRI) data on patients treated with interferon-beta (IFN-beta) for relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to provide clinical and MRI data on 68 patients with RRMS treated over a 6-year period and to investigate whether a baseline MRI predicts their long-term clinical and MRI outcome. Six MRI scans were performed monthly before treatment and a further 13 scans were performed during treatment with IFN-beta, the last of which 6 years after commencement of treatment. The relapse rate, disability as measured by the Expanded Disability Status Scale (EDSS), and MRI parameters, including Gd-enhancing lesion load (Gd-LL), T2 hyperintense lesion load (T2-LL) T1 hypointense lesion load (T1-LL) and supratentorial brain volume (SBV) were measured throughout the study. The mean annual relapse rate over the 6 years was 0.52 (SD 0.67), which is significantly lower (68.6%) than the mean annual relapse rate of 1.6 observed during the 2-year period before the commencement of treatment (P < 0.01). The median EDSS score increased from 2 to 2.5, remaining stable in 60% of the patients. From the baseline scan to the final scan, there was a median increase of 7% in the T2-LL and 23.9% in the T1-LL, whilst SBV decreased by 2.7%. The increase in the EDSS over the course of the study was significantly correlated with a reduction in brain volume (r = 0.46, P = 0.001). Greater brain damage at baseline, as measured by both T2-LL and T1-LL, was significantly associated with an increase in disability over the 6 years (r = 0.44, P = 0.0009; r = 0.50, P = 0.0007, respectively). This study shows a sustained effect of IFN-beta on the relapse rate, which is lower than during the 2 years before treatment commencement. More than half the patients showed an improvement or stabilization in the EDSS score. The increment in disability was correlated with the development of brain atrophy but not with increases in lesion burden. Finally, the finding that the extent of lesion burden at the baseline was a strong predictor of increasing disability suggests that IFN-beta treatment might have a moderate effect in modifying the multiple sclerosis (MS) disease course over 6 years unless preventive treatment is started early.

MRI brain volume changes in relapsing-remitting multiple sclerosis patients treated with interferon beta-1a.

The aim of this study was to investigate changes of brain volume as measured by magnetic resonance imaging (MRI) in relapsing-remitting multiple sclerosis (MS) patients under treatment with interferon beta-1a. Moreover, the relationship between brain volume changes and standard MR or clinical outcome variables was determined. After a 6-month pretreatment period, 52 patients with relapsing-remitting MS were assigned to receive interferon beta-1a (Rebif-Serono) during a 24-month treatment period MRI scans were performed monthly during the 6-month pretreatment period and for the first 9 months of the treatment period. A final MRI scan was also performed at the end of the 12- and 24-month treatment period. Over 24 months of IFNbeta-1a treatment, a significant decrease of hyperintense lesion volume was found (-18.0%; p<0.0001) compared to the last pretreatment scan, while T1 hypointense volume showed a slight nonsignificant increase (+2.2%), and brain volume showed a significant decrease (-2.2%; p<0.0001). The mean volume of enhancing lesions over the 6-month pretreatment period was significantly related to absolute (p=0.02; r=-0.32) and per cent change (p=0.03; r=-0.30) of brain volume during 24-month treatment period. No correlations between changes in brain volume and changes in T2 hyperintense volume or T1 hypointense volume were observed. Neither was there a relationship between brain volume and changes of Expanded Disability Status Scale (EDSS) or frequency in clinical relapses. Of the group in whom was detected a significant decrease of brain volume, 13 out of 26 (50%) had a sustained change in EDSS while in the group that did not have a significant decrease of brain volume, only 3 out of 26 (11.5%) had a sustained EDSS change (p=0.02). In this study a decrease of brain volume was found in relapsing-remitting MS patients treated with IFNbeta-1a over 2 years. The only parameter that predicted brain volume decrease by 2 years of IFNbeta-1a treatment was the mean volume of enhancing lesions over the 6-month pretreatment period.

Satellite potentials on EMG: neurophysiologic evidence of axonal transection in MS?

To detect signs of axonal damage in MS, the authors investigated the occurrence in EMG of motor unit action potentials with satellite potentials (SP-MUAP) in the upper limb muscles in 10 consecutive patients with MS with cervical spinal cord demyelinating lesions and 10 control subjects. Subjects' SP-MUAP rate was 0 to 2.5% (median 0%) in the control group, and 0 to 17.5% (median 7.5%) in the MS group (p < 0.01). Motor unit remodeling secondary to axonal transection of spinal motor neurons traversing cervical demyelinating lesions may be hypothesized.

A comparison of the sensitivity of MRI after double- and triple-dose Gd-DTPA for detecting enhancing lesions in multiple sclerosis.

We compared the number and volume of enhancing lesions detected in patients with multiple sclerosis (MS) seen on post-contrast T(1)-weighted scans obtained after the injection of different gadolinium-DTPA (Gd) doses. Enhanced magnetic resonance imaging (MRI) scans were obtained from 16 patients with relapsing remitting or secondary progressive MS on two different occasions separated by an interval of approximately 24 h. On the first occasion, enhanced scans were obtained 15 min after the injection of a double dose of Gd (0.2 mmol/Kg), on the second 15 min after the injection of a triple dose (0.3 mmol/Kg) of Gd. Scans were assessed by consensus in a random order by two observers unaware of the dose of Gd used. We counted the same 30 enhancing lesions on both double dose and triple dose scans from 9 patients. The mean (SD) volumes of enhancing lesions were 1.7 (2.7) mL on double dose and 1.9 (3.4) mL on triple-dose scans. This difference was not statistically significant. This study demonstrated that double dose of Gd has a sensitivity for detecting MS activity similar to that of a triple dose, with the advantage of a significant cost saving.

MRI of spinal cord in MS.

Over the last 10 - 15 years, magnetic resonance imaging techniques have had a major impact in understanding and managing multiple sclerosis. The present review briefly summarises the current usefulness of spinal cord MRI in MS disease, examining the frequency, distribution and main characteristics of spine MS plaques; the differential diagnosis with other spinal cord disease was also described. Finally we considered how newer imaging sequences when added to semi-automated quantitative methods, may give us a putative tool to reliably quantify subtle changes which develop on the spinal cord of MS patients over time.

Antinuclear antibodies and response to IFNbeta-1a therapy in relapsing-remitting multiple sclerosis.

We determined whether positive ANA was related to response to rIFNss-1a in 62 relapsing-remitting MS patients. According to the presence of antinuclear antibodies (ANA) at baseline and during the first 6 months of treatment, patients were sorted in different groups. The clinical and MRI outcome during short-term (6 months) and long-term (24 months) treatment period was not statistically different between the groups. Therefore, the response to IFNbeta-1a seems not to be influenced by ANA occurrence either before or during treatment. When the analysis was extended to other autoantibodies (i. e. antithyroid, anticardiolipin) similar results were obtained.

Brain atrophy in relapsing-remitting multiple sclerosis: relationship with 'black holes', disease duration and clinical disability.

Recent MRI studies in multiple sclerosis have highlighted the potential role of brain atrophy evaluation as a putative marker of disease progression. In the present study, we evaluated the supratentorial and infratentorial brain volume in patients with relapsing remitting multiple sclerosis (RR MS) and in healthy subjects. Moreover, we determined whether brain volumes of MS patients are associated with different aspects of brain MRI abnormalities and clinical findings. Two-dimensional acquired MRI was performed on 52 relapsing-remitting multiple sclerosis and 30 healthy subjects. The volume of supratentorial and infratentorial structures was measured in selected representative slices. Gd-enhancement, T2 hyperintense, T1 hypointense (i.e. 'black holes') total lesion load, as well as the area of corpus callosum was calculated in the MS group and related to brain volume measures. Correlations between MRI parameters and clinical features were also considered. MS patients had significantly lower supratentorial, infratentorial brain volume and corpus callosum area than healthy subjects (P<0.01). Supratentorial brain volume was significantly related to corpus callosum area (r=0.58; P<0.01) and T1 hypointense lesion load (r=0.48; P<0.01), but not with T2 hyperintense lesion load. Infratentorial/supratentorial ratio was significantly associated with disease duration and EDSS score (r=-0.34; P=0.02 and r=-0.49; P<0.01, respectively). This study documents that brain atrophy is an early MRI finding in RR MS and it is closely related to 'black holes' burden. The use of relative values (infratentorial/supratentorial ratio) may increase the conspicuity of correlation between clinical and MRI findings.

Interferon-beta-1a in relapsing-remitting multiple sclerosis: effect on hypointense lesion volume on T1 weighted images.

OBJECTIVE: Recently, a strong correlation between the increase in hypointense lesion load on T1 weighted spin echo images, and the increase in disability was reported. Although the effect of interferon-beta has been demonstrated both in reducing exacerbation rate, frequency of enhancing lesions, and accumulation of disease burden on T2 weighted images, the impact on the accumulation of hypointense lesions has not yet been evaluated. The aims of the present study were: (a) to assess for the first time the effect of interferon-beta-1a on T1 weighted MRI hypointense lesion volume; and (b) to evaluate the relation between changes on hypointense, hyperintense, and enhancing lesion volume before and during interferon-beta-1a treatment in relapsing-remitting multiple sclerosis. METHODS: After a baseline scan and 6 month pretreatment period, 67 patients with relapsing-remitting multiple sclerosis were treated with interferon-beta-1a by subcutaneous injection three times a week during a 12 month treatment period. All patients had MRI every month during the 6 month pretreatment period and for the first 9 months of the treatment period. A final MRI was also performed at the end of the 12 month treatment period. RESULTS: There was a significant increase in the mean hyperintense lesion volume during the pretreatment phase (6 months) and a slight decrease during the treatment period (12 months), whereas the hypointense lesion volume increased significantly before treatment and remained substantially stable during treatment. There was a significant correlation between changes in hypointense and hyperintense lesion volume during the observation period, but not during treatment. The monthly mean volume of Gadolinium-DTPA enhancing lesions was significantly higher during the pretreatment than the treatment period, and the enhancing lesion volume correlated with changes of hyperintense and hypointense lesion volumes only during the observation period. CONCLUSION: These data suggest that interferon-beta-1a has a stabilising effect on T1 weighted hypointense lesion volume.