A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth.

BACKGROUND: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches. METHODS: 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma. FINDINGS: Children who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, ßtreatment group x study week (95% CI) = 0.002 (0.001, 0.003); P = 0.004]. They also had elevated fecal abundances of Agathobacter faecis, Blautia massiliensis, Lachnospira and Dialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjusted P < 0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention. INTERPRETATION: MDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development. FUNDING: This work was supported by the BMGF (Grants OPP1134649/INV-000247).

Follow-up assessment of visceral leishmaniasis treated patients and the impact of COVID-19 on control services in Nepal.

BACKGROUND: Follow-up assessment of visceral leishmaniasis (VL) treated cases is important to monitor the long term effectiveness of treatment regimens. The main objective of this study was to identify the gaps and challenges in the follow-up of treated VL cases, to monitor treatment outcome and to assess the impact of COVID-19 on VL elimination services and activities. METHODS: Clinicians treating VL patients, district focal persons for VL, and patients treated for VL in seven high endemic districts in Nepal during 2019-2022 were interviewed to collect data on challenges in the follow-up of VL treated patients as per national strategy. RESULTS: Follow up status was poor in two districts with the largest number of reported cases. The majority of cases were children under 10 years of age (44.2%). Among 104 VL treated cases interviewed, 60.6% mentioned that clinicians had called them for follow-up but only 37.5% had complied. Among 112 VL treated cases followed up, 8 (7.14%) had relapse and 2 (1.8%) had PKDL. Among 66 cases who had VL during the COVID-19 lock down period, 32 (48.5%) were diagnosed within 1 week; however, 10 (15.1%) were diagnosed only after 4 weeks or more. During the COVID-19 pandemic, there was no active search for VL because of budget constraints and lack of diagnostic tests, and no insecticide spraying was done. CONCLUSION: Relapses and PKDL are challenges for VL elimination and a matter of concern. Successful implementation of the national strategy for follow up of treated VL cases requires addressing elements related to patients (awareness, transport, communication) clinicians (compliance) and organization of service delivery (local health worker training and deployment). COVID-19 did not have much impact on VL diagnosis and treatment; however, public health programmes including active case detection and insecticide spraying for vector control were severely reduced.

Influence of MRI Follow-Up on Treatment Decisions during Standard Concomitant and Adjuvant Chemotherapy in Patients with Glioblastoma: Is Less More?

MRI is the gold standard for treatment response assessments for glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, a reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy at 2-3 month intervals actually benefits patients and how it influences clinical decision making about the continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans post-chemoradiotherapy (post-CCRT), after three cycles of adjuvant chemotherapy [TMZ3/6], and after the completion of treatment [TMZ6/6]), and of unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in an early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p < 0.001). Perfusion MRI caused less diagnostic uncertainty (p = 0.021) but did not influence treatment consequences (p = 0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.

The Role of FDG-PET in the Evaluation of Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by nodules, comedones, and sinus tracts that often leave prominent scarring. In recent years, non-invasive imaging techniques have been used to assess the inflammatory activity, vascularization, and treatment response of lesions. Specifically, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans may aid in identifying systemic inflammation in patients with HS, improving diagnosis. Inflamed hypermetabolic tissues exhibit a greater uptake of FDG due to increased glucose uptake and vascularity. A systematic review was conducted to summarize the utility of nuclear imaging techniques in the diagnosis and treatment follow-up of HS. PubMed, Scopus, and ScienceDirect databases were utilized for relevant articles discussing the utility of PET scans in managing HS. A total of 51 citations were identified in the initial search. Following the review of titles, abstracts, and duplicates, 43 articles were excluded, leaving a total of eight articles for analysis. Data were extracted from each article, encompassing the number of patients, imaging techniques employed, and final results. An analysis of the data demonstrated that FDG-PET showed evidence of identifying subclinical lesions of the disease, improving the visualization of HS, and providing an objective method of assessing severity.

Effectiveness and implementation of models of cancer survivorship care: an overview of systematic reviews.

PURPOSE: To critically assess the effectiveness and implementation of different models of post-treatment cancer survivorship care compared to specialist-led models of survivorship care assessed in published systematic reviews. METHODS: MEDLINE, CINAHL, Embase, and Cochrane CENTRAL databases were searched from January 2005 to May 2021. Systematic reviews that compared at least two models of cancer survivorship care were included. Article selection, data extraction, and critical appraisal were conducted independently by two authors. The models were evaluated according to cancer survivorship care domains, patient and caregiver experience, communication and decision-making, care coordination, quality of life, healthcare utilization, costs, and mortality. Barriers and facilitators to implementation were also synthesized. RESULTS: Twelve systematic reviews were included, capturing 53 primary studies. Effectiveness for managing survivors' physical and psychosocial outcomes was found to be no different across models. Nurse-led and primary care provider-led models may produce cost savings to cancer survivors and healthcare systems. Barriers to the implementation of different models of care included limited resources, communication, and care coordination, while facilitators included survivor engagement, planning, and flexible services. CONCLUSIONS: Despite evidence regarding the equivalent effectiveness of nurse-led, primary care-led, or shared care models, these models are not widely adopted, and evidence-based recommendations to guide implementation are required. Further research is needed to address effectiveness in understudied domains of care and outcomes and across different population groups. IMPLICATIONS FOR CANCER SURVIVORS: Rather than aiming for an optimal "one-size fits all" model of survivorship care, applying the most appropriate model in distinct contexts can improve outcomes and healthcare efficiency.

Post-treatment effects of topiramate on alcohol-related outcomes: A combined analysis of two placebo-controlled trials.

Topiramate reduces drinking and alcohol-related problems and is increasingly being used to treat alcohol use disorder (AUD). In a randomized controlled trial (RCT) of topiramate, rs2832407, a single nucleotide polymorphism (SNP) in the GRIK1 gene moderated topiramate's effects (Study 1). However, a second RCT (Study 2) did not replicate the SNP's moderating effect during treatment. The current analysis combines data from these two studies to examine topiramate's effects on alcohol-related outcomes and on its pharmacogenetic moderation during a 6-month post-treatment period. This analysis includes 308 individuals with problematic alcohol use (67% male; mean age = 51.1; topiramate: 49%, placebo: 51%). It uses generalized linear mixed models to examine changes in self-reported alcohol consumption and alcohol-related problems and concentrations of the liver enzyme γ-glutamyltransferase. The report combines published 3- and 6-month follow-up data from Study 1 with similar, unpublished data from Study 2. Despite robust effects of topiramate on drinking during treatment, the overall multivariate medication effects on outcomes during 3- and 6-month follow-up were not significant (p = 0.08 and p = 0.26, respectively). The moderating effect of the SNP on primary treatment outcomes was also not significant during either follow-up period (p = 0.13 and p = 0.16, respectively). However, during the 3-month post-treatment period, drinks per day was significantly lower in the topiramate group than the placebo group in the rs2832407*CC-genotype group. The robust effects of topiramate on alcohol-related outcomes during treatment diminish substantially once the medication is discontinued. Research is needed both to determine the optimal treatment duration and to identify clinically useful pharmacogenetic moderators of topiramate for treating AUD.

Improvement of SCD morbimortality in children: experience in a remote area of an African country.

BACKGROUND: Sickle cell disease (SCD) is a public health problem in the Democratic Republic of Congo. While reference sickle cell centers have been implemented in capital cities of African countries and have proven to be beneficial for SCD patients. In the Democratic Republic of Congo, they have never been set up in remote areas for families with low or very low sources of income. METHOD: A cohort of 143 children with SCD aged 10 years old (IQR (interquartile range): 6-15 years) (sex ratio male/female = 1.3) were clinically followed for 12 months without any specific intervention aside from the management of acute events, and then for 12 months with a monthly medical visit, biological follow-up, and chemoprophylaxis (folic acid/penicillin), adequate fluids and malaria prevention. RESULTS: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1-5). The implementation of standardized and regular follow-ups in a new sickle cell reference center in a remote city showed an increase in the annual mean hemoglobin level from 50 to 70 g/L (p = 0.001), and a decrease in the lymphocyte count and spleen size (p < 0.001). A significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes of vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes were also observed. CONCLUSIONS: The creation of a sickle cell reference center and the regular follow-up of children with sickle cell disease are possible and applicable in the context of a remote city of an African country and represent simple and accessible measures that can reduce the morbimortality of children with sickle cell disease.

Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients.

BACKGROUND: Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency. METHODS: ER+ HER2- MBC patients were included in a prospective observational cohort before treatment initiation. Tumor response was assessed by radiological evaluation (RECIST v1.1) every 3 months. Plasma samples were collected before treatment (baseline), at day 15 (D15), at day 30 (D30), and at disease progression. We searched for somatic mutations from archived tumor tissues by targeted deep sequencing. For patients with somatic mutations identified, circulating tumor DNA (ctDNA) was tracked using digital droplet PCR. Ratios of ctDNA levels ([D15/baseline] and [D30/baseline]) were then correlated with prospectively registered patient characteristics and outcomes. RESULTS: Twenty-five of the 61 patients enrolled had a somatic mutation testable in plasma (NPIK3CA = 21, NTP53 = 2, NAKT1 = 2). At baseline, 84% of patients had detectable ctDNA levels but ctDNA levels had no prognostic impact on PFS (p = 0.10). Among those patients, ctDNA was still detected in 82% at D15 and 68% at D30. ctDNA clearance observed at day 30 was associated with longer PFS (HR = 7.2, 95% CI = 1.5-32.6, p = 0.004). On the contrary, a [D30/baseline] ctDNA ratio > 1 was associated with a shorter PFS (HR = 5.1, 95% CI = 1.4-18.3, p = 0.02) and all 5 patients with increased ctDNA levels at D30 showed disease progression after 3 months under palbociclib-fulvestrant. Finally, at the time of radiological tumor progression, ctDNA was detected in all patients tested. CONCLUSION: Our study demonstrates that the efficiency of palbociclib and fulvestrant can be monitored by serial analyses of ctDNA before radiological evaluation and that early ctDNA variation is a prognostic factor of PFS.

Representações sociais da terapia antirretroviral para pessoas vivendo com HIV / Las representaciones sociales de la terapia antirretroviral para las personas que viven con el VIH / Social representations of antiretroviral therapy for people living with HIV

Objetivo: analisar a representação social da terapia antirretroviral para pessoas vivendo com HIV. Método: estudo qualitativo, com a utilização da teoria das representações sociais. A coleta de dados incluiu 50 participantes, sendo realizada de fevereiro a setembro de 2020, utilizando um questionário de caracterização sociodemográfica e um formulário para evocações livres. O cenário do estudo foi uma unidade de tratamento de HIV na região metropolitana do Rio de Janeiro. A análise dos dados foi realizada pelo software EVOC. Resultados: o núcleo central da representação da terapia antirretroviral reforça o controle do HIV e a imagem do medicamento como algo bom. Conclusão: a estrutura representacional sugere que o grupo tende à normalização da terapia antirretroviral, fazendo referência a um medicamento que controla o HIV. O estudo possibilitou reconhecer os diferentes conteúdos representacionais da terapia antirretroviral para o grupo estudado, além da variada complexidade entre as imagens identificadas.

Objective: analyzing the social representation of antiretroviral therapy for people living with HIV. Method: a qualitative study using the Theory of Social Representations. Data collection included 50 participants, being performed from February to September 2020 using a sociodemographic characterization questionnaire and a form for free evocations. The study scenario was an HIV treatment unit in the metropolitan region of Rio de Janeiro. Data analysis was performed by the EVOC software. Results: the central nucleus of the representation of antiretroviral therapy reinforces HIV control and the image of the drug as something good. Conclusion: the representational structure suggests that the group tends to normalize antiretroviral therapy, referring to a drug that controls HIV. The study made it possible to recognize the different representational contents of antiretroviral therapy for the studied group, in addition to the varied complexity among the images identified.

Objetivo: analizar la representación social de la terapia antirretroviral para las personas que viven con el VIH. Método: un estudio cualitativo utilizando la Teoría de las Representaciones Sociales. La recolección de datos incluyó a 50 participantes, realizándolos de febrero a septiembre de 2020 utilizando un cuestionario de caracterización sociodemográfica y un formulario para evocaciones libres. El escenario del estudio fue una unidad de tratamiento del VIH en la región metropolitana de Río de Janeiro. El análisis de los datos fue realizado por el software EVOC. Resultados: el núcleo central de la representación de la terapia antirretroviral refuerza el control del VIH y la imagen del fármaco como algo bueno. Conclusión: la estructura representacional sugiere que el grupo tiende a normalizar la terapia antirretroviral, refiriéndose a un fármaco que controla el VIH. El estudio ha permitido reconocer los diferentes contenidos representacionales de la terapia antirretroviral para el grupo estudiado, además de la variada complejidad entre las imágenes identificadas.

Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up.

BACKGROUND: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. METHODS: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. RESULTS: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963-0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929-0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956-0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980-0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947-0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. CONCLUSIONS: The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.

Association between attendance at outpatient follow-up appointments and blood pressure control among patients with hypertension.

OBJECTIVE: The aim of this study was to assess the impact of regularity in treatment follow-up appointments on treatment outcomes among hypertensive patients attending different healthcare settings in Islamabad, Pakistan. Additionally, factors associated with regularity in treatment follow-up were also identified. METHODS: A cross-sectional study was undertaken in selected primary, secondary and tertiary healthcare settings between September, 2017 and December, 2018 in Islamabad, Pakistan. A structured data collection form was used to gather sociodemographic and clinical data of recruited patients. Binary logistic regression analyses were undertaken to determine association between regularity in treatment follow-up appointments and blood pressure control and to determine covariates significantly associated with regularity in treatment follow-up appointments. RESULTS: A total of 662 patients with hypertension participated in the study. More than half 346 (52%) of the patients were females. The mean age of participants was 54 ± 12 years. Only 274 (41%) patients regularly attended treatment follow-up appointments. Regression analysis found that regular treatment follow-up was an independent predictor of controlled blood pressure (OR 1.561 [95% CI 1.102-2.211; P = 0.024]). Gender (OR 1.720 [95% CI 1.259-2.350; P = 0.001]), age (OR 1.462 [CI 95%:1.059-2.020; P = 0.021]), higher education (OR 1.7 [95% CI 1.041-2.778; P = 0.034]), entitlement to free medical care (OR 3.166 [95% CI 2.284-4.388; P = 0.0001]), treatment duration (OR 1.788 [95% CI 1.288-2.483; P = 0.001]), number of medications (OR 1.585 [95% CI 1.259-1.996; P = 0.0001]), presence of co-morbidity (OR 3.214 [95% CI 2.248-4.593; P = 0.0001]) and medication adherence (OR 6.231 [95% CI 4.264-9.106; P = 0.0001]) were significantly associated with regularity in treatment follow-up appointments. CONCLUSION: Attendance at follow-up visits was alarmingly low among patients with hypertension in Pakistan which may explain poor treatment outcomes in patients. Evidence-based targeted interventions should be developed and implemented, considering local needs, to improve attendance at treatment follow-up appointments.

Recurrent disease after treatment for cervical intraepithelial neoplasia-The importance of a flawless definition of residual disease and length of follow-up.

OBJECTIVE: To evaluate adherence to national guidelines for follow-up, and assess residual and recurrent disease after treatment for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). STUDY DESIGN: In a case-series design women aged 25-69 years treated for primary CIN2+ in 2006-2011 (n = 752) were followed through August 9, 2019 for residual or recurrent disease, i.e., CIN2+ diagnosed before or after, respectively, two consecutive, normal post-treatment cytology results. We used the Chi-Square test to assess predictive factors of adherence to post-treatment follow-up and residual disease, and survival analyses to assess the cumulative incidence of residual and recurrent disease. RESULTS: Strict adherence to post-treatment follow-up was low . However, 702 (95 %) women attended at least one post-treatment follow-up visit within the suggested time window. Forty-two women (5.6%) were diagnosed with residual disease, 38 (91 %) of whom were diagnosed within 2 years of treatment. Among the 637 (85 %) women with two consecutive, normal post-treatment cytology results, cumulative incidence of recurrent disease was 1.0 (95 % confidence interval [CI]: 0.2-1.8) and 2.5 (95 % CI: 1.2-3.8) per 100 women-years within 42 and 78 months of treatment, respectively. Three women with residual and two with recurrent disease were diagnosed with cervical cancer within 78 months of treatment. Women with not-free resection margins at treatment had a significantly increased risk of residual and recurrent disease. Using a 2-year definition for residual disease would misclassify 3 of 5 cancer cases as recurrent disease when they were true cases of residual disease. CONCLUSIONS: This study emphasizes the importance of properly distinguishing between residual and recurrent disease after treatment for CIN2 + . Many women with residual disease could benefit from an earlier colposcopy, cervical biopsy, or diagnostic conization during post-treatment follow-up in order to detect occult cervical cancer. The cumulative incidence of recurrent disease within 78 months of treatment was low.

Monitoring of Phenylalanine Levels in Patients with Phenylketonuria Using Dried Blood Spots: a Comparison of Two Methods

Abstract Phenylketonuria (PKU) is caused by deficient activity of phenylalanine hydroxylase (PAH), responsible for the conversion of phenylalanine (Phe) to tyrosine (Tyr). Monitoring of patients with PKU requires the measurement of Phe in plasma using high-performance liquid chromatography (HPLC) or in dried blood spots (DBS) using different techniques to adjust treatment strategy. The objective of this study was to evaluate Phe levels in DBS measured by two different methods and compare them with Phe levels measured in plasma by HPLC. We analyzed 89 blood samples from 47 PKU patients by two different methods: fluorometric method developed in-house (method A) and the commercially available PerkinElmer® Neonatal Phenylalanine Kit (method B) and in plasma by HPLC. The mean Phe levels by method A, method B, and HPLC were 430.4±39.9μmol/L, 439.3±35.4μmol/L, and 442.2±41.6μmol/L, respectively. The correlation values between HPLC and methods A and B were 0.990 and 0.974, respectively (p < 0.001 for both). Our data suggest that methods A and B are useful alternatives for monitoring Phe levels in patients with PKU, with method A being in closer agreement with the reference standard (HPLC).

Functional Results after Larynx-Preserving Treatment of Laryngeal Cancer. Suggestions for follow-up.

ntroduction: Laryngeal cancer and its treatment are associated with both short- and long-term side effects, affecting laryngeal functions and having an impact on the quality of life. Material and methods: Retrospective analysis of the medical records of patients receiving surgical or non-surgical, larynx- -preserving treatment for laryngeal cancer. R esults: After termination of the treatment, the highest proportion of patients with bad voice quality was in the glottic carcinoma group (both in early and late phase), with swallowing dysfunction in the transglottic carcinoma group. Compared to the situation before the treatment, the proportion of patients with impaired voice quality (bad voice quality and loss of voice) initially decreased among all groups (except for supraglottic carcinomas), and during the first post-treatment year either increased or did not change. The proportion of patients with no swallowing dysfunction increased in the supraglottic, subglottic and transglottic carcinoma groups. D iscussion: We consider necessary the implementation of a standard pre- and post-treatment monitoring of the voice and swallowing function in the management of patients with laryngeal cancer.

Efficacy of intensity-modulated radiation therapy for optic nerve sheath meningioma.

PURPOSE: The present study examined the efficacy and complications associated with intensity-modulated radiation therapy (IMRT) for optic nerve sheath meningioma (ONSM) in 15 cases and compared visual function before and after treatment. METHODS: Consecutively diagnosed patients with ONSM treated with IMRT were evaluated from 2012 to 2017. We categorized ONSM with three growth patterns (diffuse, fusiform, or globular). Visual acuity, visual fields, and optic disc findings were assessed before and after IMRT. Ocular and systemic complications were evaluated during and after treatment. RESULTS: The 15 patients selected for analysis ranged in age from 33 to 77 years. Post-treatment observation periods were 8 to 57 months. After IMRT, tumor enlargement was not detected in any eyes, and tumor reduction was seen in 2 eyes. At final post-treatment follow-up, eyes with fusiform and globular growth maintained better visual acuity compared with pre-treatment, whereas 2 of 5 eyes with diffuse growth showed reduced vision. Five eyes with no apparent optic disc abnormality maintained better visual acuity compared with pre-treatment, whereas 8 of 10 eyes with disc edema and atrophy remained stable or showed reduced vision. Improvements were seen in all 5 eyes with optic discs negative for pre-treatment abnormalities. Final post-treatment visual field abnormalities improved in 11 eyes. All adverse events identified during IMRT improved rapidly during the treatment period. CONCLUSION: IMRT for the treatment of ONSM achieved improvement and preserved visual function. In particular, early treatment with IMRT before the appearance of optic disc abnormalities can be more effective for improving visual function.

The challenging problem of disease staging in human African trypanosomiasis (sleeping sickness): a new approach to a circular question.

Human African trypanosomiasis (HAT), also known as sleeping sickness, puts millions of people at risk in sub-Saharan Africa and is a neglected parasitic disease that is almost always fatal if untreated or inadequately treated. HAT manifests itself in two stages that are difficult to distinguish clinically. The problem of staging in HAT is extremely important since treatment options, some of which are highly toxic, are directly linked to the disease stage. Several suggested investigations for disease staging have been problematic because of the lack of an existing gold standard with which to compare new clinical staging markers. The somewhat arbitrary current criteria based on the cerebrospinal fluid (CSF) white blood cell (WBC) count have been widely used, but the new potential biomarkers are generally compared with these, thereby making the problem somewhat circular in nature. We propose an alternative 'reverse' approach to address this problem, conceptualised as using appropriate statistical methods to test the performance of combinations of established laboratory variables as staging biomarkers to correlate with the CSF WBC/trypanosomes and clinical features of HAT. This approach could lead to the use of established laboratory staging markers, potentially leading to a gold standard for staging and clinical follow-up of HAT.

Brazilian guidelines for the clinical management of paracoccidioidomycosis

Abstract Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.

Principles of follow-up assessments in patients with breast cancer after radical treatment.

A follow-up assessment plan after radical treatment is a part of a comprehensive approach to treating patients with breast cancer. Because breast cancer is the most frequent cancer both worldwide and in Poland, adequate follow-up is important not only for patients but also for economic reasons. Herein, we review current recommendations for follow-up assessments in patients with breast cancer. The main aim of such assessment is detection of early recurrence or tumor presence in the other breast, observation of long-term treatment complications, and creation of multidisciplinary infrastructure that will allow to reduce the risk of recurrence and alleviate physical, mental, and social consequences of treatment.

French women's representations and experiences of the post-treatment management of breast cancer and their perception of the general practitioner's role in follow-up care: A qualitative study.

BACKGROUND: In France, the Cancer Plan II 2009-2013 was launched to improve post-cancer management and promote greater involvement of general practitioners (GPs) in follow-up care. OBJECTIVES: We investigated how women experienced the post-treatment management of breast cancer and perceived the role of the GP in follow-up care. DESIGN: We conducted a qualitative study based on semi-structured interviews with women with breast cancer in remission. The interviews were transcribed and analysed in accordance with the principles of thematic analysis. SETTING AND PARTICIPANTS: We interviewed 21 patients aged between 30 and 86. Eighteen breast cancer survivors were recruited from GP practices and five from a patients' association. RESULTS: Four themes emerged from the thematic analysis: that breast cancer is a life-changing event; how patients managed the effects of treatment; how patients viewed the future; and patients' expectations of their GP. DISCUSSION AND CONCLUSION: French survivors of breast cancer perceived the physical changes caused by their illness to impact their womanhood, leading to difficulties with sexual relations, a diminished sense of self and fears for the future. They felt abandoned at the end of treatment and desired support. They appreciated the ease of contacting their GP but considered follow-up care outside their remit. They agreed to be followed up by their GP, provided that they co-operated closely with a cancer specialist. This is in accordance with the French Cancer Plan II 2009-2013, which recommends greater involvement of GPs in a monitoring protocol shared with cancer specialists.