Calculating Route: Functional Trajectories and Long-Term Outcomes in Survivors of Severe COVID-19.

OBJECTIVES: We investigated functional trajectories after severe COVID-19 and estimated their associations with adverse outcomes (falls, rehospitalizations, institutionalization, or death), cognition and post COVID-19 condition within 1-year of hospital discharge. DESIGN: Prospective cohort study. SETTING: A large academic medical center in Sao Paulo, Brazil. PARTICIPANTS: Survivors of COVID-19 admissions to an intensive care unit. INTERVENTIONS: None. MEASUREMENTS: We evaluated participants' disability status before hospital admission and three, six, nine, and twelve months after discharge using 15 activities of daily living. During follow-up, cognition and post COVID-19 condition (defined as persistent symptoms with duration ≥2 months) were assessed. A latent class growth analysis was performed to investigate functional trajectories after discharge. RESULTS: We included 422 participants (median age 63 years, 13.5% were frail before COVID-19). Four distinct functional trajectories could be identified: "minimal disability trajectory" (37.4% of participants), "mild disability trajectory" (37.9%), "moderate disability trajectory" (16.8%), and "severe disability trajectory" (7.8%). Compared with minimal disability trajectory, the odds ratios (95% confidence interval) for 1-year adverse outcomes were 2.28 (1.38-3.76) for minor disability trajectory; 4.21 (2.10-8.42) for moderate disability trajectory; and 4.16 (1.51-11.46) for severe disability trajectory, even after adjustments. The occurrence of post COVID-19 condition was 67.5% and associated with functional trajectories (p=0.004). Cognition was also associated with functional trajectories. CONCLUSION: Severe COVID-19 survivors can experience diverse functional trajectories, with those presenting higher levels of disability at increased risk for long-term adverse outcomes. Further investigations are essential to confirm our findings and assess the effectiveness of rehabilitation interventions, aiming to improve health outcomes in those who survived severe COVID-19 and other causes of sepsis.

Evaluating the menopausal transition with the STRAW + 10 in a Brazilian cohort of women with HIV, 2015-2016.

BACKGROUND: Menopausal transition is a physiological process encompassing hormonal and body changes that impact women's health and life quality. This period may be characterized by the Stages of Reproductive Aging Workshop (STRAW + 10) criteria using menstrual patterns. Use of the STRAW + 10 is uncertain in HIV infection. We aimed to characterize menopausal transition in women with HIV (WWH) using the STRAW + 10 criteria, hormonal measures and menopause symptoms. METHODS: We performed a cross-sectional study, nested to the HIV-Infected Women's Cohort, in Rio de Janeiro, Brazil. Eligible women included those aged 30 years or older, without clinical or surgical menopause, hormonal contraception, replacement therapy and ovarian disorders. We conducted face-to-face interviews and collected blood samples for follicle stimulating hormone (FSH) and estradiol measures. RESULTS: We enrolled 328 WWH (28.3% of women in the cohort). The distribution of age, hormonal levels and reported symptoms per each STRAW + 10 stage was consistent with the expected distribution in the menopausal transition. Age and FSH significantly increased and estradiol decreased from stage -2 (7 + days of menstrual delay) to stage +2 (8 + years of amenorrhea). CONCLUSIONS: The present results support use of the STRAW + 10 to characterize the menopausal transition of WWH with good clinical and immunological control.

Improving hand hygiene adherence in an endoscopy unit.

BACKGROUND AND STUDY AIMS: Although hand hygiene is the most important measure in preventing infection transmission in healthcare settings, adherence to recommendations among healthcare workers is low. We implemented and assessed the impact of a World Health Organization-recommended educational intervention to improve hand hygiene adherence at the endoscopy unit of a Brazilian tertiary hospital. PATIENTS AND METHODS: Hand hygiene adherence and techniques used by healthcare workers of the endoscopy unit in the course of their duties were observed unobtrusively by four nurses from the infection control unit. Data were collected at every opportunity for hand hygiene. Evaluations were carried out before and 1 and 10 months after an educational intervention. The intervention consisted of task-orientated training sessions, with live demonstrations of the multitude of opportunities for hand hygiene and the appropriate techniques. In addition to assessing hand hygiene practices, we also evaluated staff knowledge through standardized questionnaires administered before and after the education intervention. Adherence was defined as hand hygiene/disinfection at an opportunity for hand hygiene. RESULTS: Adherence improved from 21.4 % before the intervention to 63.3 % 1 month and 73.5 % 10 months after the educational intervention. Correct answers to the questionnaire were 82.1 % on pre-intervention test and 85.7 % on post-intervention test. CONCLUSION: Hand hygiene rates were low before the education intervention and improved significantly after it. Against expectations, adherence to hand hygiene practices had increased further at 10 months after the intervention, reinforcing the intervention's positive impact.

Ionotropic but not metabotropic glutamatergic receptors in the locus coeruleus modulate the hypercapnic ventilatory response in unanaesthetized rats.

AIM: Central chemoreceptors are important to detect changes of CO2/H(+), and the Locus coeruleus (LC) is one of the many putative central chemoreceptor sites. Here, we studied the contribution of LC glutamatergic receptors on ventilatory, cardiovascular and thermal responses to hypercapnia. METHODS: To this end, we determined pulmonary ventilation (V(E)), body temperatures (T(b)), mean arterial pressure (MAP) and heart rate (HR) of male Wistar rats before and after unilateral microinjection of kynurenic acid (KY, an ionotropic glutamate receptor antagonist, 10 nmol/0.1 µL) or α-methyl-4-carboxyphenylglycine (MCPG, a metabotropic glutamate receptor antagonist, 10 nmol/0.1 µL) into the LC, followed by 60 min of air breathing or hypercapnia exposure (7% CO2). RESULTS: Ventilatory response to hypercapnia was higher in animals treated with KY intra-LC (1918.7 ± 275.4) compared with the control group (1057.8 ± 213.9, P < 0.01). However, the MCPG treatment within the LC had no effect on the hypercapnia-induced hyperpnea. The cardiovascular and thermal controls were not affected by hypercapnia or by the injection of KY and MCPG in the LC. CONCLUSION: These data suggest that glutamate acting on ionotropic, but not metabotropic, receptors in the LC exerts an inhibitory modulation of hypercapnia-induced hyperpnea.

Opioid µ-receptors in the rostral medullary raphe modulate hypoxia-induced hyperpnea in unanesthetized rats.

AIM: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid µ-receptors have been found in the MR, we studied the putative role of opioid µ-receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. METHODS: We measured pulmonary ventilation (VE) and the body temperatures (Tb) of male Wistar rats before and after the selective opioid µ-receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, cyclic, 0.1 µg per 0.1 µL) was microinjected into the rMR during normoxia or after 60 min of hypoxia. RESULTS: The animals treated with intra-rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia (430 ± 86 mL kg(-1) min(-1)) compared with the control group (790 ± 82 mL kg(-1) min(-1) ) (P < 0.05). No differences in the Tb were observed between groups during hypoxia. CONCLUSION: These data suggest that opioids acting on µ-receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.

Coagulopathy following lethal and non-lethal envenoming of humans by the South American rattlesnake (Crotalus durissus) in Brazil.

The South American tropical rattlesnake (Crotalus durissus subspp) is responsible for approximately 10% of bites from venomous snakes in Brazil. We studied 24 victims of bites by this species over 3 years, in south-eastern Brazil, particularly investigating haemostatic alterations. Thirteen patients were defined as moderately envenomed and 11 as severe. There were two deaths, which were not attributed to venom-induced haemostatic disturbances. However, envenoming by C. durissus is frequently associated with haemostatic disorders, which are probably attributable mainly to the action of the thrombin-like enzyme, with possible additional effects secondary to the powerful myotoxic activity of the venom.

South American rattlesnake bite (Crotalus durissus SP) without envenoming: insights on diagnosis and treatment.

A South American rattlesnake bite without clinical manifestations of envenoming (termed 'dry-bite') has not been recognized to occur by the Brazilian Ministry of Health, which recommends the administration of antivenom to all bitten patients. During 36 months of an observational study on South American rattlesnake bites in Minas Gerais, Brazil, 12% of 41 patients with fang marks at the bite-site did not present clinical or laboratory features of envenoming and had no plasma venom detected before specific serotherapy, fulfilling the criteria for the diagnosis of true 'dry-bite'. Data from these preliminary observations suggest that these patients should be correctly diagnosed since they should not be treated with unnecessary and sometimes hazardous and expensive serotherapy.

Tourniquet ineffectiveness to reduce the severity of envenoming after Crotalus durissus snake bite in Belo Horizonte, Minas Gerais, Brazil.

Clinical and laboratory data from patients who applied a tourniquet (tourniquet group, n = 45) and who did not apply it (non-tourniquet group, n = 52) after being bitten by Crotalus durissus were compared. The patients were treated with 100-200 ml of Crotalus durissus antivenom. The gender, age, time elapsed between bite and hospital admission, dose of antivenom and the frequency of local paresthesia, myalgia and palpebral ptosis did not differ between the two groups. Plasma creatine kinase enzyme activity and partial thromboplastin time, plasma whole venom and crotoxin concentrations and the frequency of acute renal and respiratory failure and number of deaths also did not differ between both groups. Data from this study show the ineffectiveness of tourniquet applied by patients in the fields to reduce the severity of Crotalus durissus envenoming.

[Liver transplantation from living related donors] / Transplante hepático com doador vivo familiar.

OBJECTIVES: To present the experience with the first 12 living related liver transplants performed at Hospital Sírio-Libanês in São Paulo. METHODS: The donors were the fathers (6) and the mothers (6) with age ranging from 30 to 48 years. All candidates for donation were submitted to a full informed consent form, clinical and radiological evaluation and had blood withdrawn for autotransfusion. Recipient age ranged from 7 months to 10 years whereas recipient weight varied from 6.3 to 34 kg. Six patients were considered as high risk due to complications of advanced liver disease and were submitted to urgent transplantation. RESULTS: Mean donor hospital stay was 10 days with no mortality. Technical complications were observed in 4 recipients. Seven patients presented at least one episode of bacterial, viral or fungal infection. One or more biopsy proven rejection episodes were disclosed in 7 patients. Overall recipient survival was 67%, being 83% for elective cases and 50% for urgent cases. Long term follow up ranged from 8 to 25 months. Seven out of 8 survivors present excellent quality of life and normal liver function. The other patient is currently under reduced immunosuppression due to Epstein-Barr virus infection.CONCLUSIONS: These results demonstrate the safety and viability of living related liver transplantation which, in face of the current donor scarcity, should be considered as a valid option for the treatment of children with end stage liver disease.

Time factor in the detection of circulating whole venom and crotoxin and efficacy of antivenom therapy in patients envenomed by Crotalus durissus.

Thirty-seven patients envenomed by Crotalus durissus were classified into three groups according to the interval between the bite and hospital admission (delta T): group 1 (n = 14, delta T < 4 hr), group 2 (n = 14, delta T > 4 hr < 8 hr) and group 3 (n = 9, delta T > 8 hr). Venous blood from these patients was sampled for biochemical and hematological analysis and for whole venom, crotoxin and antivenom enzyme-linked immunosorbent assays before antivenom treatment (T0) and at 1 hr (T1), 6 hr (T6), 12 hr (T12) and 24 hr (T24) after the start of antivenom therapy. The patients were treated with 100-200 ml (10-20 ampules) of C. durissus antivenom. Whole venom and crotoxin were detected in 13 (92.8%) and 11 (78.6%) of 14 group 1 patients, respectively, in 11 (78.6%) and six (42.9%) of 14 group 2 patients, respectively, and in two (22.2%) and one (11.1%) of nine group 3 patients, respectively, before antivenom treatment. Data from this study show that whole venom and crotoxin were not detected in most of patients when the time elapsed between the bite and hospital admission was greater than 8 hr, and crotoxin was not detected in most of the patients who were admitted to the hospital at times ranging from 4 to 8 hr after the snakebite. Plasma whole venom, crotoxin and antivenom levels measured over time in these patients show the efficacy of antivenom treatment, since circulating venom and crotoxin were no longer detected 1 hr after antivenom therapy and high antivenom titers persisted for at least 24 hr after serotherapy.

Efficacy of antivenom therapy for neutralizing circulating venom antigens in patients stung by Tityus serrulatus scorpions.

Enzyme-linked immunosorbent assays for detection of Tityus serrulatus venom antigen and of horse anti-T. serrulatus venom antibodies were carried out before antivenom treatment and at 1, 6, 12, and 24 hr after antivenom therapy in 18 patients with systemic manifestations following T. serrulatus scorpion sting. Increased levels of circulating venom antigens were detected in the patients before antivenom treatment, but were no longer detected 1 hr after specific antivenom therapy. High titers of antivenom persisted for at least 24 hr after treatment with antivenom. The evolution of clinical and laboratory manifestations of envenoming showed that vomiting and local pain decreased within 1 hr and hyperglycemia was no longer detected 12 hr after antivenom therapy. The cardiorespiratory manifestations disappeared 6-24 hr after the administration of antivenom and all patients recovered completely. This study demonstrates the efficacy of antivenom therapy in neutralizing circulating venom antigens and supports the prompt administration of a potent antivenom to patients with systemic manifestations of envenoming.

Standardization of an enzyme linked immunosorbent assay (ELISA) for detecting circulating toxic venom antigens in patients stung by the scorpion Tityus serrulatus.

The sensitivity and specificity of an enzyme-linked immunosorbent assay (ELISA) for the detection of circulating antigens from toxic components of Tityus serrulatus scorpion venom was determined in patients stung by T. serrulatus before antivenom administration. Thirty-seven patients were classified as mild cases and 19 as moderate or severe cases. The control absorbance in the venom assay was provided by serum samples from 100 individuals of same socioeconomic group and geographical area who had never been stung by scorpions or treated with horse antisera. The negative cutoff value (mean + 2 SD) corresponded to a venom concentration of 4.8 ng/ml. Three out of the 100 normal sera were positive, resulting in a specificity of 97%. The sensitivity of the ELISA when all cases of scorpion sting were included was 39.3%. When mild cases were excluded, the sensitivity increased to 94.7%. This study showed that this ELISA can be used for the detection of circulating venom toxic antigens in patients with systemic manifestations following. T. serrulatus sting but cannot be used for clinical studies in mild cases of envenoming since the test does not discriminate mild cases from control patients.

Children with adrenergic manifestations of envenomation after Tityus serrulatus scorpion sting are protected from early anaphylactic antivenom reactions.

The incidence of early anaphylactic reactions to scorpion antivenom given i.v. after Tityus serrulatus scorpion sting was evaluated in 103 children aged up to 15 years in Belo Horizonte, Brazil. Patients without adrenergic manifestations (Group 1, n = 28) were compared with those who presented systemic involvement that included adrenergic manifestations (Group 2, n = 75). Data were recorded on a proforma and the presence or absence of early anaphylactic reaction was cross-tabulated according to clinical features, sex, age and volume of antivenom used in the treatment. Unpaired Student's t-test was used to calculate significance of differences in age and volume of antivenom used. Multivariate logistic regression was used to determine the effects of clinical features and volume of antivenom as predictors of early anaphylactic reaction to antivenom treatment. Twelve (42.9%) of 28 children included in Group 1 presented early anaphylactic reactions compared with 6 (8%) of 75 children of Group 2 (OR = 8.63; 95% CI: 2.88, 25.7). The reactions were more severe in Group 1. There were no significant differences with respect to age and sex. After adjusting for clinical form, volume of antivenom was not significantly associated with presence of reactions (OR = 1.11; 95% CI: 0.70, 2.80 for each 5.0 ml of antivenom administered). The results show that children with adrenergic manifestations after T. serrulatus scorpion sting had significantly lower anaphylactic reactions to antivenom than those without these manifestations.

Application of genomic DNA subtyping by pulsed field gel electrophoresis and restriction enzyme analysis of plasmid DNA to characterize methicillin-resistant Staphylococcus aureus from two nosocomial outbreaks.

Pulsed-field gel electrophoresis (PFGE) and restriction enzyme analysis of plasmid DNA (REAP) were applied to study the epidemiologic relationship among methicillin-resistant Staphylococcus aureus (MRSA) isolates from outbreaks in two hospitals in São Paulo, Brazil: 82 MRSA isolates, 73 from a university hospital and nine from a general adult intensive care unit of a private hospital, were collected from 62 patients: 95% of the MRSAs were also resistant to gentamicin and ciprofloxacin. REAP subtyping of both collections identified six different subtypes: 55 (72.6%) MRSAs from the university hospital and nine isolates from the private hospital shared the same epidemic REAP subtype. Discrimination by restriction of genomic DNA with Sma I followed by PFGE enabled the identification of 14 DNA subtypes. Based on the combined REAP-genomic DNA subtype, the predominant subtype in the university hospital was A/A (44 isolates) whereas the epidemic subtype in the private hospital was A/M (seven isolates). The application of two typing methods showed better discrimination among MRSAs than did either method alone.

In-vitro activity of cefoperazone-sulbactam against Bacteroides species.

The in-vitro activity of two combinations of sulbactam and cefoperazone against 187 strains of Bacteroides fragilis were evaluated; their activity was compared with that of the drugs alone, and correlated with the production of beta-lactamase by the bacterial strains. The results indicated that both combinations had a synergistic effect: the addition of 8 mg/l of sulbactam to the MIC of cefoperazone reduced the percentage of resistant strains from 58% to 0.5%; while the combination of two parts of cefoperazone to one pact of sulbactam lowered the resistance rate to 1%. Synergy was observed most frequently with beta-lactamase positive strains, but it also occurred among beta-lactamase negative strains.

Activity of cefotetan against anaerobic bacteria.

The in vitro activity of cefotetan, a new cephamycin, was compared with that of cefoxitin, cefotaxime, moxalactam, and piperacillin against 368 strains of anaerobic bacteria. Cefotetan was similar to cefoxitin, moxalactam, and piperacillin in its activity against B. fragilis, B. vulgatus, Bacteroides species, anaerobic gram-positive cocci, Fusobacterium and Clostridium species. High resistance rates for cefotetan, however, were demonstrated among B. thetaiotaomicron-ovatus group and B. distasonis. Increasing inoculum concentrations had little effect on the activity of cefotetan.

In vitro activity of cefbuperazone against Bacteroides spp.

The activity of cefbuperazone was tested in vitro against 287 clinical isolates of Bacteroides spp. Cefbuperazone showed good activity against B. fragilis, B. vulgatus, and other Bacteroides species, comparable to that of cefoxitin. It was relatively ineffective against B. distasonis and the B. thetaiotaomicron-ovatus group and was not active against cefoxitin-resistant Bacteroides spp.