Savings from the introduction of BPaL and BPaLM regimens at the country level.

BACKGROUND: In 2022, the WHO recommended the 6-month regimens BPaL (bedaquiline + pretomanid + linezolid) and BPaLM (BPaL + moxifloxacin) as treatment options for most forms of drug-resistant TB. SLASH-TB estimates the cost-saving and cost-effectiveness for the healthcare system and patients when a country switches from current standard-of-care treatment regimens to BPaL/BPaLM. METHODOLOGY: Country data from national TB programmes (NTP) are used to calculate the costs for all regimens and treatment outcomes. Where BPaL/BPaLM is not currently used, clinical trial outcomes data are used to estimate cost-effectiveness. DALYs are calculated using the Global Burden of Disease (GBD) database. RESULTS: We present the results of four countries that have used the tool and shared their data. When shorter and longer regimens are replaced with BPaL/BPaLM, the savings per patient treated in Pakistan, the Philippines, South Africa, and Ukraine are $746, $478, $757, and $2,636, respectively. An increased number of patients would be successfully treated with BPaL/BPaLM regimens, with 411, 1,025, 1,371 and 829 lives saved and 20,179, 27,443, 33,384 and 21,924 DALYs averted annually in the four countries, respectively. CONCLUSION: Through BPaL/BPaLM regimens, drug-resistant TB treatment has become more effective, shorter, less burdensome for patients, cheaper for both health systems and patients, and saves more lives.

CONTEXTE: En 2022, l'OMS a préconisé l'utilisation des schémas thérapeutiques (bedaquiline + pretomanid + linezolid) et BPaLM (BPaL + moxifloxacin), d'une durée de 6 mois, comme alternatives pour traiter la plupart des formes de TB résistante aux médicaments. SLASH-TB a réalisé une estimation des économies et de la rentabilité pour le système de santé et les patients lorsqu'un pays décide de passer des schémas thérapeutiques standards actuels au BPaL/BPaLM. MÉTHODOLOGIE: Les programmes nationaux de lutte contre la TB (NTP) utilisent les données nationales pour évaluer les coûts des différents schémas thérapeutiques et des résultats des traitements. Si le BPaL/BPaLM n'est pas utilisé actuellement, les données des essais cliniques sont utilisées pour estimer le rapport coût-efficacité. Les années de vie ajustées sur l'incapacité (DALYs, pour l'anglais « disability-adjusted life-years ¼) sont calculées à l'aide de la base de données Global Burden of Disease (GBD). RÉSULTATS: Nous présentons les résultats de quatre pays qui ont utilisé l'outil et partagé leurs données. Lorsque les schémas plus courts et plus longs sont remplacés par BPaL/BPaLM, les économies par patient traité au Pakistan, aux Philippines, en Afrique du Sud et en Ukraine sont respectivement de 746, 478, 757 et 2 636 dollars. L'utilisation des schémas BPaL/BPaLM permettrait de traiter un plus grand nombre de patients avec succès, ce qui sauverait respectivement 411, 1 025, 1 371 et 829 vies et éviterait 20 179, 27 443, 33 384 et 21 924 DALYs par an dans les quatre pays. CONCLUSION: Les schémas BPaL/BPaLM ont révolutionné le traitement de la tuberculose pharmacorésistante en le rendant plus efficace, plus rapide, moins contraignant pour les patients, plus économique pour les systèmes de santé et les patients, et en sauvant un plus grand nombre de vies.

Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma.

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate.

Patients' perceptions on temporomandibular disorder treatment with hydrostatic oral splints - a pilot study.

OBJECTIVE: To evaluate temporomandibular disorder (TMD) treatment with a prefabricated, hydrostatic oral splint (HOS) based on self-reported patient's symptoms using a standardized questionnaire. METHODS: Two hundred fifty-eight questionnaires from patients diagnosed with TMD and subsequently treated with HOS were collected from two independent private practices. Based on patient's comfort the questionnaire recorded TMD symptoms and symptom regression. Descriptive and comparative statistics was carried out using SPSS. RESULTS: A total of 221 questionnaires were analyzed. Patients reported TMD symptoms such as pain (93.2%), TMJ clicking (66.1%), headache (25.8%), cervical spine disorders (23.5%), restricted mouth opening (22.6%) and tinnitus (11.8%). For most symptoms, improvement was reported mostly after two weeks, except for tinnitus, where positive effects were usually reported after four weeks. CONCLUSION: HOS seem to be effective for immediate treatment of pain and other TMD symptoms. Based on the available data, a treatment period of four weeks can be recommended.

TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

[Expert evidence in whiplash injury: interdisciplinary orthopaedic and biomechanical approach]. / Begutachtung der Halswirbelsäulendistorsion: Interdisziplinärer unfallchirurgisch-orthopädischer und biomechanischer Ansatz.

Considering the controversially discussed issue of whiplash injury a pragmatic approach based on our own experience in the area of forensic expert opinion is presented. Findings of accident analysis and biomechanics are correlated with the individual situation after the accident (initial clinical appearance), the course of the ailment and the indispensable physical examination. The latter leads to determination of the individual vulnerability (not increased/increased) which is important for the evaluation of the physical condition and estimation of the physical stress limit. These limits vary widely between individuals and must be considered carefully when relating dose and effect of accident severity to a possible physical injury. Determination of the accident severity is especially important when there are no objective signs of injury and the existence of a minor whiplash injury (Quebec Task Force degree 1 or 2) is in question.

Donor human milk largely replaces formula-feeding of preterm infants in two urban hospitals.

OBJECTIVE: To determine acceptance of donor human milk (DM) for feeding preterm infants and whether offering DM, alters mothers' milk (MM) feeding. STUDY DESIGN: Infant feeding data were collected from medical records of 650 very preterm infants enrolled between 2006-2011 in two hospital level III neonatal intensive care units (NICUs) in Cincinnati, Ohio. The study was conducted during the implementation of a program offering 14 days of DM. RESULT: From 2006-2011, any DM use increased from 8 to 77% of infants, largely replacing formula for the first 2 weeks of life; provision of MM did not change. DM was more likely to be given in the first 2 weeks of life, if infants never received MM or were >1000 g birth weight, but DM use did not differ by sociodemographic factors. CONCLUSION: Offering DM dramatically increased human milk feeding and decreased formula use, but did not alter MM feeding in hospital.

Avaliação do extrato etanólico de Ottonia martiana Miq. para o controle de duas doenças florestais / Evaluation of Ottonia martiana Miq. alcoholic extract to control two forest diseases

Metabólitos secundários presentes em plantas medicinais apresentam várias propriedades biológicas incluindo a atividade antifúngica. Esse estudo avaliou o potencial antifúngico da planta medicinal Ottonia martiana no controle da pinta-preta em erva-mate (Ilex paraguariensis) e do mofo-cinzento em eucalipto (Eucalyptus dunnii). Extrato etanólico (EBEtOH) dos órgãos totais (raízes, caules, folhas e frutos) foi preparado e testado na concentração de 1000 μg mL-1 contra os patógenos Cylindrocladium spathulatum (pinta-preta) e Botrytis cinerea (mofo-cinzento). Bioensaios in vitro (germinação de esporos e bioautografia direta) e in vivo (teste de patogenicidade em mudas) mostraram que o EBEtOH reduziu o crescimento micelial dos patógenos testados e a germinação dos esporos de C. spathulatum e estimulou a germinação de esporos de B. cinerea. O teste de patogenicidade mostrou que o controle da pinta-preta em erva-mate e do mofo cinzento em eucalipto não é viável usando-se a concentração testada de EBEtOH de O. martiana. Na bioautografia direta, foram detectadas zonas de inibição de crescimento micelial dos fungos e que foram relacionadas com a presença de piperovatina.

Secondary metabolites from medicinal plants have several biological properties, including antifungal activity. This study evaluated the antifungal potential of the medicinal plant Ottonia martiana to control maté leaf spot (Ilex paraguariensis) and eucalypt gray mould (Eucalyptus dunnii). Ethanol extract (EBEtOH) of the total parts (roots, stems, leaves and fruits) was prepared at the concentration of 1000 μg mL-1 and tested against Cylindrocladium spathulatum (maté leaf spot) and Botrytis cinerea (eucalypt gray mould). In vitro bioassays (spore germination and direct bioautography) and in vivo bioassays (pathogenicity test in seedlings) showed that EBEtOH reduced the mycelial growth of the tested pathogens and the germination of C. spathulatum spores and stimulated the germination of B. cinerea spores. The pathogenicity test showed that the control of maté leaf spot and eucalypt gray mould is not viable using the tested concentration of O. martiana EBEtOH. Zones of mycelial growth inhibition were detected in direct bioautography and were related to the presence of piperovatine.

[Challenges in the implementation of electronic health care records and patient cards in Austria]. / Herausforderungen bei der Umsetzung der elektronischen Patientenakte und Gesundheitskarte in Osterreich.

Patient-centered, interinstitutional digital documentation and communication in the Austrian health care system is a primary goal of Austria health politics. The implementation of the eCard in the year 2005 was a very important step towards digitalization of the Austria health system. The main responsibility of the Ministry of Health (MoH) is coordinating the implementation of the eHealth infrastructure based on international standards. The Austrian electronic health care record (ELGA) should include all relevant multimedia medical and health-related data of a uniquely identified person. A selection of "relevant" documents must be made. The implementation of ELGA will take place in modules. Because of the importance of the federal states and their role in health care, a special commission was set up to represent the most important stakeholders. Thereby they are included in the decision-making process. This is important with regard to the future use of many already existing information systems and for further investments. The most important steps until now were the implementation of a working group for ELGA as an association of the national health commission in the year 2006 and the implementation of a feasibility study as well as a cost-benefit analysis. Data protection and security are considered very important factors and, with respect to these, the roles for health care providers will be defined. To achieve high acceptance from the public and especially from health care providers, it is important to inform them about the benefits of eHealth.

Cultural epidemiology of TB with reference to gender in Bangladesh, India and Malawi.

SETTING: TB control programmes in Bangladesh, India and Malawi. OBJECTIVE: To identify and compare socio-cultural features of tuberculosis (TB) and the distribution of TB-related experiences, meanings and behaviours with reference to gender across cultures in three high-endemic low-income countries. DESIGN: Approximately 100 patients at three sites were interviewed with in-depth semi-structured Explanatory Model Interview Catalogue (EMIC) interviews inquiring about patterns of distress, perceived causes and help-seeking behaviours in the context of illness narratives. RESULTS: Female patients reported more diverse symptoms and men more frequently focused on financial concerns. Most patients reported psychological and emotional distress. Men emphasised smoking and drinking alcohol as causes of TB, and women in Malawi reported sexual causes associated with HIV/AIDS. In Bangladesh, exaggerated concerns about the risk of spread despite treatment contributed to social isolation of women. Public health services were preferred in Malawi, and private doctors in India and Bangladesh. CONCLUSION: Cross-site analysis of these studies has identified features of TB that influence the burden of disease and are likely to affect timely help seeking and adherence to treatment. Health systems benefit from sex-disaggregated epidemiological data complemented by cultural epidemiological study, which together clarify the role of gender and contribute to the knowledge base for TB control at various levels.

Gender and socio-cultural determinants of delay to diagnosis of TB in Bangladesh, India and Malawi.

SETTING: Tuberculosis (TB) control programmes in Bangladesh, India and Malawi. OBJECTIVE: To compare the interval from symptom onset to diagnosis of TB for men and women, and to assess socio-cultural and gender-related features of illness explaining diagnostic delay. DESIGN: Semi-structured Explanatory Model Interview Catalogue (EMIC) interviews were administered to 100 or more patients at each site, assessing categories of distress, perceived causes and help seeking. Based on time from initial symptoms to diagnosis of TB, patients were classified with problem delay (>90 days), timely diagnosis (< or =30 days) or moderate delay. EMIC interview data were analysed to explain problem delay. RESULTS: The median interval from symptom onset to diagnosis was longest in India and shortest in Malawi. With adjustment for confounding, female sex (Bangladesh), and status of married woman (India) and housewife (Malawi) were associated with problem delay. Prominent non-specific symptoms--chest pain (Bangladesh) and breathlessness (Malawi)--were also significant. Cough in India, widely associated with TB, was associated with timely diagnosis. Sanitation as a perceived cause linked to poor urban conditions was associated with delayed diagnosis in India. Specific prior help seeking with circuitous referral patterns was identified. CONCLUSION: The study identified gender- and illness-related features of diagnostic delay. Further research distinguishing patient and provider delay is needed.

Gender and socio-cultural determinants of TB-related stigma in Bangladesh, India, Malawi and Colombia.

SETTING: Tuberculosis (TB) control programmes in Bangladesh, India, Malawi and Colombia. OBJECTIVE: Assess indicators of TB-related stigma and socio-cultural and gender-related features of illness associated with stigma. DESIGN: Semi-structured Explanatory Model Interview Catalogue (EMIC) interviews were administered to 100 or more patients at each site, assessing categories of distress, perceived causes and help seeking. Indicators of self-perceived stigma were analysed individually and in a validated index, which was compared across sites and between men and women at each site. Cultural epidemiological explanatory variables for stigma and interactions with female sex were analysed at each site. Qualitative illness narratives were examined to explain the role and context of explanatory variables. RESULTS: The overall stigma index was highest in India, lowest in Malawi and greater for women in Bangladesh. In India and Malawi, women were more likely to be concerned about impact on marital prospects. Associations with HIV/AIDS were linked to TB stigma in Malawi, where sexual contact as a perceived cause was more associated with stigma for men and less for women. CONCLUSION: Stigma both influences and indicates the effectiveness of TB control. Cultural epidemiological methods clarify cross-cutting and local features of stigma and gender for TB control.

Deep sclerectomy for the management of uncontrolled uveitic glaucoma: preliminary data.

BACKGROUND: If medical treatment fails in uveitic glaucoma a surgical approach should be considered. Classical trabeculectomy is known to have a less favourable outcome in uveitis. Our intention is to report the first series of uveitis patients with glaucoma resistant to medical therapy who were treated with deep sclerectomy (DS). PATIENTS AND METHODS: Fourteen eyes of 13 patients (mean age 39.0 +/- 18.5 years; range 8 to 76 years) with chronic uveitis underwent non-penetrating filtering surgery from 1995 to 2003. All patients had their uveitis controlled before and after surgery by immunomodulatory therapy. Non-penetrating filtering surgery consisted of DS with collagen implant (Staar(R)) in 4 eyes, DS with draining device (T-Flux Ioltech(R)) in 2 patients, DS without implant in 7 patients and with viscocanalostomy in 1 patient. Nine eyes (65 %) received mitomycin C peri-operatively. RESULTS: Intra-ocular pressure (IOP) was reduced from a mean pre-operative value of 42.8 +/- 13.6 mmHg to a 1-year mean post-operative value of 12.1 +/- 4.0 (71.7 % reduction). Eleven of the 14 eyes completed 12 months of follow-up, resulting in complete success in 5 (45.4 %) and in qualified success in 5 (45 %) and in failure in one patient (9.2 %), later controlled by a second operation. Anti-glaucomatous medication was reduced from a mean of 3.7 +/- 0.5 medications preoperatively to 1.2 +/- 0.8 medications (71.4 % reduction) at the 12 month follow-up. Nine of the 14 patients achieved a 24 month follow-up with a mean IOP of 14.1 +/- 3.8 mmHg and mean of anti-glaucomatous medications of 1.6. Four patients have been examined 4 years after the DS: mean IOP was 13.2 +/- 2.2 mmHg and mean medication 1.7 +/- 1.0. Post-operative complications included one case of lens opacity and 2 cases of hypotony lasting for five months and four weeks after the intervention respectively. CONCLUSION: Non-penetrating filtering surgery controlled the intra-ocular pressure in 90 % of eyes with uveitic glaucoma resistant to medical therapy at 12 months. Surgical complications were low which may explain the high success rate of the procedure, compared to classical penetrating surgery.

Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints.

The "Workshop on Regulatory Use of (Q)SARs for Human Health and Environmental Endpoints," organized by the European Chemical Industry Council and the International Council of Chemical Associations, gathered more than 60 human health and environmental experts from industry, academia, and regulatory agencies from around the world. They agreed, especially industry and regulatory authorities, that the workshop initiated great potential for the further development and use of predictive models, that is, quantitative structure-activity relationships [(Q)SARs], for chemicals management in a much broader scope than is currently the case. To increase confidence in (Q)SAR predictions and minimization of their misuse, the workshop aimed to develop proposals for guidance and acceptability criteria. The workshop also described the broad outline of a system that would apply that guidance and acceptability criteria to a (Q)SAR when used for chemical management purposes, including priority setting, risk assessment, and classification and labeling.

Avaliação da atividade antibacteriana de Ottonia martiana Miq., Piperaceae / Evaluation of antibacterial activity of Ottonia martiana Miq., Piperaceae

Ottonia martiana Miq., arbusto da família Piperaceae, é conhecida na medicina popular brasileira como "anestésica". Raízes e partes aéreas são utilizadas em alcoolaturas para aliviar dores de dente, devido à ação anestésica sobre a mucosa bucal. Avaliou-se a atividade antibacteriana "in vitro" dos extratos desta planta medicinal contra duas bactérias presentes na placadentária: Staphylococcus aureus (ATCC 6538) e Staphylococcus epidermis (ATCC 12228). Extratos de caules e raízes de Ottonia martiana exibiram uma baixa atividade inibitória sobre o crescimento de Staphylococcus aureus, não apresentaram ação antimicrobiana sobre a outra bactéria testada e exibiram frações que inibiram o desenvolvimento de Staphylococcus aureus.