A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19.

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).

Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial.

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.

Validation study of a new dry self-sampling device for detection of human papilloma virus in cervical cancer screening / Estudio de validación de un nuevo dispositivo de automuestreo en seco para la detección del virus del papiloma humano en el cribado del cáncer cervical

Objective: To evaluate the efficiency of IUNETEST(R) self-sampling device by comparing f-HPVtypingTM and Cobas(R) 4800 HPV detection techniques in gynecological cytology and self-sampling up-take. Material and methods: A total of 196 patients were included: Fifty percent (50%) for routine cervical cancer screening (n=98) and the other half presented an abnormal cytology (n=98). Two samples for patient were evaluated. Results: Both sample up-takes showed high concordance for HPV detection (Cohen's kappa > 0.85). Equal sensitivity between molecular techniques was detected in Gynecological cytology up-takes (77.3%). In self-sampling, sensiti-vity was higher in f-HPVtypingTM than in Cobas(R) 4800 (77.3% vs. 75.5%). Roche presented better specificity thanf-HPVtypingTM: 82.3 and 80.7% vs. 79.2 and 78.5% in self-sample and gynecological up-takes. Negative predictive value was similar: 87.3 and 87.7% vs. 87.2 and 86.7% in self-sample and gynecological up-take by Roche and in f-HPVtyping, respectively. The most prevalent types were HPV-16, followed by 52, 39, 58 and 66. Conclusions: Self-sample up-takes may be as good as physician collected samples for screening diagnostic. Both HPV detection methods present a high correlation for both sample collections. The high acceptability of IUNETEST(R) self-sample device, may encourage screening in non-attenders, increasing screening coverage

Objetivo: evaluar la eficiencia del dispositivo de autotoma IUNETEST(R) comparando las técnicas de detección de HPV, f-HPVtypingTM y Cobas(R) 4800 en la citología ginecológica y la toma de auto-muestreo. Material y métodos: se incluyeron un total de 196 pacientes: cincuenta por ciento (50%) para la detección de cáncer de cuello uterino de rutina (n=98) y la otra mitad presentaba una citología anormal (n=98). Se evaluaron dos muestras por paciente. Resultados: ambas tomas de muestras mostraron una alta concordancia para la detección del VPH (kappa de Cohen> 0,85). Igual sensibilidad entre las técnicas moleculares se detectó en tomas de citología ginecológica (77,3%). En el auto-muestreo, la sensibilidad fue mayor en f-HPVtypingTM que en Cobas(R) 4800 (77,3% vs. 75,5%). Roche presentó una mejor especificidad que f-HPVtypingTM: 82,3 y 80,7% vs. 79,2 y 78,5% en muestras de autotoma y ginecológicas. El valor predictivo negativo fue similar: 87,3 y 87,7% vs. 87,2 y 86,7% en la autotoma y la captación ginecológica de Roche y en f-HPVtyping, respectivamente. Los tipos más prevalentes fueron HPV-16, seguido de 52, 39, 58 y 66. Conclusiones: Las tomas de muestras por autotoma pueden ser tan buenas como las muestras recolectadas por el médico para el diagnóstico de detección del HPV. Ambos métodos de detección de HPV presentan una alta correlación para ambas colecciones de muestras. La alta aceptabilidad del dispositivo de auto-muestra IUNETEST(R) puede alentar la detección en personas que no asisten, aumentando la cobertura del screening

True osseous metaplasia of the endometrium: the bone is not from a fetus.

OBJECTIVE: To identify the origin of calcified tissue in endometrial ossification. DESIGN: DNA analyses from the ossified tissue and from the woman were studied to compare both genotypes. SETTING: University and general hospitals. PATIENT(S): A 27-year-old infertile woman diagnosed of osseous metaplasia of the endometrium. INTERVENTION(S): Hysteroscopic resection of the endometrial osseous metaplasia for DNA analysis. MAIN OUTCOME MEASURE(S): DNA comparison between the patient and the osseous tissue extracted from the uterus. RESULT(S): All markers produced the same allele length for both blood and endometrial biopsy (including bones), thus confirming the same genetic origin. CONCLUSION(S): Endometrial ossification is derived from the patient, resulting in a true osseous metaplasia.

Rapid prenatal diagnosis by QF-PCR: evaluation of 30,000 consecutive clinical samples and future applications.

Rapid prenatal diagnoses of major chromosome abnormalities can be performed on a large scale using highly polymorphic short tandem repeats (STRs) amplified by the quantitative fluorescent polymerase chain reaction (QF-PCR). The assay was introduced as a preliminary investigation to remove the anxiety of the parents waiting for the results by conventional cytogenetic analysis using amniotic fluid or chorionic cells. However, recent studies, on the basis of the analyses of several thousand samples, have shown that this rapid approach has a very high rate of success and could reduce the need for cytogenetic investigations. Its high efficiency, for example, allows early interruption of affected fetuses without the need of waiting for completion of fetal karyotype. The main advantages of the QF-PCR are its accuracy, speed, automation, and low cost that allows very large number of samples to be analyzed by few operators. Here, we report the results of using QF-PCR in a large series of consecutive clinical cases and discuss the possibility that, in a near future, it may even replace conventional cytogenetic analyses on selected samples.

Rapid prenatal diagnosis of aneuploidies and zygosity in multiple pregnancies by amniocentesis with single insertion of the needle and quantitative fluorescent PCR.

OBJECTIVE: To investigate amniotic fluid (AF) samples retrieved in multiple pregnancies by single insertion of the needle, for rapid assessment of chromosome copy number, zygosity, and cross-contamination between fetuses, using Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR) amplification of highly polymorphic microsatellite markers. METHODS: Fifty-two multiple pregnancies were selected (47 twins, 5 triplets) and 108 samples of amniotic fluid were sampled between 12 to 20 weeks of gestation (mean 15.5) using the single-needle technique. Aneuploidy screening by QF-PCR amplification of short tandem repeats (STRs) on chromosomes X, Y, 21, 13, and 18 was carried out within 24 h of collection. Owing to the sampling procedure, the eventual presence of contamination between fetuses was also evaluated in every case. RESULTS: Normal and aneuploid fetuses were readily identified by QF-PCR. Fetal reduction was made available, for trisomic fetuses, without further waiting for completion of fetal karyotyping. In twin gestations, the ultrasound examination of chorionicity was always in agreement with the molecular assessment of zygosity. Contamination between fetuses due to the sampling procedure with a single puncture was never observed. CONCLUSION: Rapid prenatal diagnosis of aneuploidies by QF-PCR is a sensitive, efficient, and reliable assay. When applied in multiple pregnancies, it has the added value of allowing the assessment of zygosity in all cases, independently of chorionicity and fetal sex.