Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial.

BACKGROUND: Emergence of drug resistance demands novel antimalarial drugs with new mechanisms of action. We aimed to identify effective and well tolerated doses of ganaplacide plus lumefantrine solid dispersion formulation (SDF) in patients with uncomplicated Plasmodium falciparum malaria. METHODS: This open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial was conducted at 13 research clinics and general hospitals in ten African and Asian countries. Patients had microscopically-confirmed uncomplicated P falciparum malaria (>1000 and <150 000 parasites per µL). Part A identified the optimal dose regimens in adults and adolescents (aged ≥12 years) and in part B, the selected doses were assessed in children (≥2 years and <12 years). In part A, patients were randomly assigned to one of seven groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days; ganaplacide 800 mg plus lumefantrine-SDF 960 mg as a single dose; once a day ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; once a day ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; or twice a day artemether plus lumefantrine for 3 days [control]), with stratification by country (2:2:2:2:2:2:1) using randomisation blocks of 13. In part B, patients were randomly assigned to one of four groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days, or twice a day artemether plus lumefantrine for 3 days) with stratification by country and age (2 to <6 years and 6 to <12 years; 2:2:2:1) using randomisation blocks of seven. The primary efficacy endpoint was PCR-corrected adequate clinical and parasitological response at day 29, analysed in the per protocol set. The null hypothesis was that the response was 80% or lower, rejected when the lower limit of two-sided 95% CI was higher than 80%. This study is registered with EudraCT (2020-003284-25) and ClinicalTrials.gov (NCT03167242). FINDINGS: Between Aug 2, 2017, and May 17, 2021, 1220 patients were screened and of those, 12 were included in the run-in cohort, 337 in part A, and 175 in part B. In part A, 337 adult or adolescent patients were randomly assigned, 326 completed the study, and 305 were included in the per protocol set. The lower limit of the 95% CI for PCR-corrected adequate clinical and parasitological response on day 29 was more than 80% for all treatment regimens in part A (46 of 50 patients [92%, 95% CI 81-98] with 1 day, 47 of 48 [98%, 89-100] with 2 days, and 42 of 43 [98%, 88-100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83-99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93-100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92-100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86-100] with artemether plus lumefantrine). In part B, 351 children were screened, 175 randomly assigned (ganaplacide 400 mg plus lumefantrine-SDF 960 mg once a day for 1, 2, or 3 days), and 171 completed the study. Only the 3-day regimen met the prespecified primary endpoint in paediatric patients (38 of 40 patients [95%, 95% CI 83-99] vs 21 of 22 [96%, 77-100] with artemether plus lumefantrine). The most common adverse events were headache (in seven [14%] of 51 to 15 [28%] of 54 in the ganaplacide plus lumefantrine-SDF groups and five [19%] of 27 in the artemether plus lumefantrine group) in part A, and malaria (in 12 [27%] of 45 to 23 [44%] of 52 in the ganaplacide plus lumefantrine-SDF groups and 12 [50%] of 24 in the artemether plus lumefantrine group) in part B. No patients died during the study. INTERPRETATION: Ganaplacide plus lumefantrine-SDF was effective and well tolerated in patients, especially adults and adolescents, with uncomplicated P falciparum malaria. Ganaplacide 400 mg plus lumefantrine-SDF 960 mg once daily for 3 days was identified as the optimal treatment regimen for adults, adolescents, and children. This combination is being evaluated further in a phase 2 trial (NCT04546633). FUNDING: Novartis and Medicines for Malaria Venture.

Conversion of a Conference Room into a Low-Acuity Inpatient Medical Unit: A Creative Response to Influenza-Related Surge.

The 2017-2018 influenza season was associated with high demand for both emergency department (ED) care and inpatient acute care for influenza-like illness (ILI). This high demand resulted in increased numbers of inpatients and ED patients, including prolonged ED length of stay. A large, urban, academic medical center in a cold-weather region was limited in its ability to expand its footprint to create de novo locations of care, such as temporary outbuildings or tents. As such, a large conference room was rapidly converted and placed in service as a temporary inpatient unit for adults requiring inpatient admission. LOGISTICS AND IMPLEMENTATION: The logistical, infection prevention, safety, information technology, staffing, and other concerns of creating a clinical environment during a high demand scenario is challenging. However, the lessons learned in this study are reproducible despite the complexity of this issue. CONCLUSION: This is believed to be the first published account of successful conversion of a nonclinical area to an operational clinical unit in response to a surge in demand for hospital care and admission. This may be a valid option for hospitals of all sizes as part of a surge or disaster plan.

Low and Decreasing Prevalence and Rate of False Positive HIV Diagnosis - Chókwè District, Mozambique, 2014-2017.

In 2017, rapid human immunodeficiency virus (HIV) testing services enabled the HIV diagnosis and treatment of approximately 15.3 million persons with HIV infection in sub-Saharan Africa with life-saving antiretroviral therapy (ART) (1). Although suboptimal testing practices and misdiagnoses have been reported in sub-Saharan Africa and elsewhere, trends in population burden and rate of false positive HIV diagnosis (false diagnosis) have not been reported (2,3). Understanding the population prevalence and trends of false diagnosis is fundamental for guiding rapid HIV testing policies and practices. To help address this need, CDC analyzed data from 57,655 residents aged 15-59 years in the Chókwè Health and Demographic Surveillance System (CHDSS) in Mozambique to evaluate trends in the rate (the percentage of false diagnoses among retested persons reporting a prior HIV diagnosis) and population prevalence of false diagnosis. From 2014 to 2017, the observed rate of false diagnosis in CHDSS decreased from 0.66% to 0.00% (p<0.001), and the estimated population prevalence of false diagnosis decreased from 0.08% to 0.01% (p = 0.0016). Although the prevalence and rate of false diagnosis are low and have decreased significantly in CHDSS, observed false diagnoses underscore the importance of routine HIV retesting before ART initiation and implementation of comprehensive rapid HIV test quality management systems (2,4,5).

From identical S- and P-wave p T spectra to maximally distinct polarizations: probing NRQCD with χ states.

A global analysis of ATLAS and CMS measurements reveals that, at mid-rapidity, the directly-produced χ c 1 , χ c 2 and J/ ψ mesons have differential cross sections of seemingly identical shapes, when presented as a function of the mass-rescaled transverse momentum, p T / M . This identity of kinematic behaviours among S- and P-wave quarkonia is certainly not a natural expectation of non-relativistic QCD (NRQCD), where each quarkonium state is supposed to reflect a specific family of elementary production processes, of significantly different p T -differential cross sections. Remarkably, accurate kinematic cancellations among the various NRQCD terms (colour singlets and octets) of its factorization expansion can lead to a surprisingly good description of the data. This peculiar tuning of the NRQCD mixtures leads to a clear prediction regarding the χ c 1 and χ c 2 polarizations, the only observables not yet measured: they should be almost maximally different from one another, and from the J/ ψ polarization, a striking exception in the global panorama of quarkonium production. Measurements of the difference between the χ c 1 , χ c 2 and J/ ψ polarizations, complementing the observed identity of momentum dependences, represent a decisive probe of NRQCD.

Dynamics of Resilient and Non-resilient Mood.

Individuals with affective disorders show losses in the complexity of their mood variation. We hypothesized that this complexity is a mechanism by which resilient individuals respond to everyday-life adversity, a response that would be disrupted in patients with affective disorders. Participants were outpatients with affective disorders (N=17) and matched controls (N=10) who self-recorded their daily mood over a mean duration of 233 days. Complexity was measured by sample entropy. The load of adversity was conveyed by the proportion of severely negative-affective days. Results showed that, in both controls and patients, complexity increased with adversity but patients displayed substantial disruptions in this complexity response by: (a) weaker associations between complexity and adversity (Pearson's r=0.54 to 0.59 vs. 0.59 to 0.70);(b) lower complexity for the same load of adversity (ANCOVA, p<0.01), representing losses of up to 29% of the complexity expected from controls (Mann-Whitney, p<0.005). We concluded that patients with affective disorders fail to increase the complexity of their mood variation to the same extent as resilient individuals when exposed to the same load of adversity, and propose that rigid emotion regulation processes may be causing this attenuated response. Resilience implies complex mood for complicated lives.

Conservative treatment of intraosseous hemangiomas in the mandible: case report with a 17-year follow-up period.

Intraosseous hemangiomas in the jaws are rare lesions and may lead to several complications. The authors present a case of a 12-year-old girl with a radiolucent periapical lesion between tooth 35 and 36 where nocturnal exsanguinating bleeding started to occur from periodontal sulcus during orthodontic treatment. Diagnosis of an intraosseous hemangioma in the mandible was based on positive needle aspiration for blood, computed tomography and arteriography. At first the family chose to only follow-up the lesion but episodes of nocturnal hemorrhage were becoming more frequent and a treatment was requested. Embolization and dental extraction were performed in order to treat the lesion. After a follow-up period of 17 years no more cases of hemorrhage occurred and lesion regressed.

Diagnostic accuracy of C-reactive protein and procalcitonin in the early detection of infection after elective colorectal surgery - a pilot study.

BACKGROUND: Colorectal surgery is associated with postoperative infectious complications in up to 40% of cases, but the diagnosis of these complications is frequently misleading, delaying its resolution. Several biomarkers have been shown to be useful in infection diagnosis. METHODS: We conducted a single-centre, prospective, observational study segregating patients submitted to elective colorectal surgery with primary anastomosis, CRP and PCT were measured daily. We compared infected and non-infected patients. RESULTS: From October 2009 to June 2011, a total of 50 patients were included. Twenty-one patients developed infection. PCT and CRP before surgery were equally low in patients with or without postoperative infectious complications. After surgery, both PCT and CRP increased markedly. CRP time-course from the day of surgery onwards was significantly different in infected and non-infected patients (P = 0.001) whereas, PCT time-course was almost parallel in both groups (P = 0.866). Multiple comparisons between infected and non-infected patients from 5th to 9th postoperative days (POD) were performed and CRP concentration was significantly different (P < 0.01, Bonferroni correction), on the 6th, 7th and 8th POD. A CRP concentration > 5.0 mg/dl at the D6 was predictive of infection with a sensitivity of 85% and a specificity of 62% (positive likelihood ratio 2.2, negative likelihood ratio 0.2). CONCLUSIONS: After a major elective surgical insult both CRP and PCT serum levels increased independently of the presence of infection. Besides serum CRP time-course showed to be useful in the early detection of an infectious complication whereas PCT was unhelpful.

Bowel complications of deep endometriosis during pregnancy or in vitro fertilization.

OBJECTIVE: To review bowel complications caused by deep endometriosis during pregnancy or in vitro fertilization (IVF). DESIGN: Three case reports and a systematic review. SETTING: A tertiary referral center for deep endometriosis surgery. PATIENT(S): Three case reports of bowel perforation or occlusion during pregnancy caused by deep endometriosis. INTERVENTION(S): A PubMed search was conducted to identify complications of deep endometriosis during pregnancy or IVF. The literature search identified 13 articles. According to these, 12 articles described 12 bowel complications caused by progression of deep endometriosis during pregnancy, and 1 article described six cases of bowel occlusion during IVF. RESULT(S): In 12 of 15 women, complications occurred during the third trimester of pregnancy, whereas 3 of 15 women presented with complications in the postpartum period. All complications during IVF occurred during stimulation. No specific factors that could predict these complications were identified, leading to the conclusion that endometriosis complications that occur in pregnancy or in IVF patients are probably underreported. CONCLUSION(S): Bowel complications during pregnancy or IVF stimulation may occur in women with deep endometriosis. This suggests that the endocrine environment of pregnancy does not prevent progression, at least in some women. These complications are rare, although probably underreported.

Rotation-invariant relations in vector meson decays into fermion pairs.

The covariance properties of angular momentum eigenstates imply the existence of a rotation-invariant relation among the parameters of the difermion decay distribution of inclusively observed vector mesons. This relation is a generalization of the Lam-Tung identity, a result specific to Drell-Yan production in perturbative QCD, here shown to be equivalent to the dynamical condition that the dilepton is always produced transversely polarized with respect to quantization axes belonging to the production plane.

J / psi polarization from fixed-target to collider energies.

Magnitude and "sign" of the measured J / psi polarization crucially depends on the reference frame used in the data analysis: a full understanding of the polarization phenomenon requires measurements reported in two "orthogonal" frames, such as the Collins-Soper and helicity frames. Moreover, the azimuthal anisotropy can be, in certain frames, as significant as the polar one. The seemingly contradictory results reported by the experiments E866, HERA-B, and CDF can be consistently described assuming that the most suitable axis for the measurement is along the direction of the relative motion of the colliding partons, and that directly produced J / psi's are longitudinally polarized at low momentum and transversely polarized at high momentum. We make specific predictions that can be tested on existing CDF data and by LHC measurements, which should show a full transverse polarization for direct J / psi's of p_{T} > 25 GeV / c.

[Information and communication technologies in health institutions: the inevitable encounter]. / Tecnologias de Informação e de Comunicação nas Instituições de Saúde: Encontro Inevitável.

It is widely known that the health sector is a complex area within the socio-political context of a country, and we all, as citizens, have something to say about this topic. In a way, our health depends partly on the correct use of Information and Communication Technologies. This work seeks to introduce and promote the impact of information technologies on health organisations, leading them to feel the need to update their procedures, equipment and applications. This scientific article should allow the reader to understand the importance of technological innovations and the provision of technical support in improving the quality of health.

Prevalência da habilidade dos movimentos da língua em 839 indivíduos / Prevalence of the ability of tongue movements in 839 individuals

Neste trabalho avaliaram-se 839 indivíduos quanto à sua habilidade de movimentação lingual. Após a análise clínica dos indivíduos, constituíram-se oito grupos experimentais para a identificação de cada um dos seguintes movimentos linguais: para fora, para fora-nariz, para fora-mento, para fora-ápice dobrado, palato mole, palato duro, úvula, orofaringe, canaleta, rotação e filtrum. Os indivíduos foram analisados seguindo-se uma metodologia clínica padronizada. Os resultados permitem-nos afirmar que: 1) os movimentos linguais para fora, para os lados-externo, palato duro e dentro para-cima, foram realizados por quase todos os indivíduos; 2) os movimentos linguais para fora-mento, para fora-nariz, úvula e rotação foram pouco freqüentes e devem otimizar as funções linguais ou propiciar condições especiais para algumas habilidades; 3) os movimentos linguais para a orofaringe e úvula foram incomuns e sua verdadeira função ou vantagem não são conhecidas, elas podem denotar potencial de movimentos musculares que possivelmente possam ser requeridos em protocolos para exercícios fisioterapêuticos específicos; 4) a habilidade dos movimentos linguais não é explorada por todos os indivíduos e muitos se constrangem com a sua detecção ou com a sua exposição para com outros indivíduos; 5) a maioria dos indivíduos não foi capaz de relatar a história familiar da habilidade dos movimentos linguais. Apenas 26.46% relataram um caráter familiar para o desenvolvimento da habilidade de movimentação lingual; 6) a faixa etária interfere na habilidade determinados movimentos linguais, especialmente o movimento denominado canaleta, em que se observa a sua formação por meio da união das bordas laterais da língua; 7) o gênero e a cor da pele não interferem na habilidade de movimentação lingual; 8) os movimentos linguais necessitam serem melhores definidos quanto à sua natureza, se hereditária ou se adquirida. Os resultados obtidos sugerem que os movimentos linguais são passíveis de aprendizados ou ainda serem desenvolvidos por meio de protocolos constando de fisioterapia específica com a finalidade de reabilitação do indivíduo; 9) por fim, consideramos que a abordagem fisioterapêutica da língua em casos de perda tecidual ou função motora comprometida deve ser fundamentada em bases anatômicas e funcionais abrindo novas perspectivas na recuperação dos indivíduos acometidos

Língua: aspectos do terço posterior e implicaçäo clínica / Tongue: aspects of posterior third and clinical implication

Ao examinar sua língua e compará-la com as dos demais membros da família, uma paciente preocupou-se com as suas estruturas normais do terço posterior. Isso aconteceu pela maior extensibilidade lingual em direção anterior. As estruturas que a preocupavam eram as papilas valadas e a superfície irregular do terço posterior, geralmente não visíveis a um exame rotineiro da boca; ela acreditava ser portadora de câncer bucal. A paciente recobrou sua tranqüilidade após ser conscientizada de que sua língua era normal, mas que apresentava uma capacidade maior de estendê-la para fora da boca