Protocol-Driven Intensive Outpatient Management of Pregnant Patients With Symptomatic Coronavirus Disease 2019.

BACKGROUND: Reports of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have focused on pregnant women hospitalized due to moderate to severe coronavirus disease 2019 (COVID-19) or asymptomatic women diagnosed through universal screening at the time of obstetric admission. Many pregnant women who have symptomatic SARS-CoV-2 infection may not meet criteria for hospitalization; however, whether and how these women can be managed safely in outpatient setting is not well described. METHODS: We sought to describe the time to symptom and viral clearance and to identify predictors of hospitalization to better understand the safety of monitoring pregnant patients with symptomatic COVID-19 in the outpatient setting. We performed a retrospective cohort study of pregnant patients with symptomatic, confirmed COVID-19 illness at a large, academic medical center. Patients had systematic telehealth follow up by a clinician team to assess for symptoms, provide virtual prenatal care, and arrange in-person visits when appropriate in a dedicated outpatient center. Data were collected via chart abstraction. RESULTS: Of 180 pregnant patients presenting with symptoms and undergoing reverse-transcription polymerase chain reaction (RT-PCR) testing, 67 patients with confirmed COVID-19 infection were identified during the study period. Nineteen (28%) required acute care given worsening of COVID-19 symptoms, and 95% of these were directed to this acute care setting due to symptom severity telehealth evaluation. Nine women (13%) were admitted to the hospital given worsening symptoms, 3 required intensive care unit care, 2 required ventilatory support, and 2 required delivery. Women with the presenting symptoms of fever, cough, shortness of breath, chest pain, or nausea and vomiting were more likely to require admission. The median duration from initial positive test to RT-PCR viral clearance was 26 days. Disease progression, time to viral clearance, and duration of symptoms did not vary significantly by trimester of infection. CONCLUSIONS: Management of the majority of pregnant women with symptomatic COVID-19 illness can be accomplished in the outpatient setting with intensive and protocol-driven monitoring for symptom progression.

The optic nerve lamina region is a neural progenitor cell niche.

Retinal ganglion cell axons forming the optic nerve (ON) emerge unmyelinated from the eye and become myelinated after passage through the optic nerve lamina region (ONLR), a transitional area containing a vascular plexus. The ONLR has a number of unusual characteristics: it inhibits intraocular myelination, enables postnatal ON myelination of growing axons, modulates the fluid pressure differences between eye and brain, and is the primary lesion site in the age-related disease open angle glaucoma (OAG). We demonstrate that the human and rodent ONLR possesses a mitotically active, age-depletable neural progenitor cell (NPC) niche, with unique characteristics and culture requirements. These NPCs generate both forms of macroglia: astrocytes and oligodendrocytes, and can form neurospheres in culture. Using reporter mice with SOX2-driven, inducible gene expression, we show that ONLR-NPCs generate macroglial cells for the anterior ON. Early ONLR-NPC loss results in regional dysfunction and hypomyelination. In adulthood, ONLR-NPCs may enable glial replacement and remyelination. ONLR-NPC depletion may help explain why ON diseases such as OAG progress in severity during aging.

Gross motor skills of South African preschool-aged children across different income settings.

OBJECTIVES: No studies have investigated gross motor skill (GMS) proficiency of preschool-aged children across different income settings in South Africa. Research from high-income countries suggests that children from low-income settings display poorer GMS proficiency compared to higher-income peers. This study aimed to (1) describe GMS proficiency of preschool-aged children in urban high-income (UH), urban low-income (UL) and rural low-income (RL) settings; and (2) explore differences in proficiency between income settings and sex. DESIGN: Descriptive cross-sectional study. METHODS: The Test of Gross Motor Development-Edition 2 (TGMD-2) was used to assess GMS. The TGMD-2 gross motor quotient, standardised scores and raw scores were used to describe proficiency. RESULTS: GMS proficiency was assessed in n=259 3-6-year-old children (n=46 UH, n=91 UL, n=122 RL). Overall, 93% of the children were classified as having 'average' or better GMS. According to TGMD-2 standardised scores, the RL children performed significantly better than UH and UL children (p=0.028 and p=0.009, respectively). RL children were significantly more proficient than UH and UL children in the strike and horizontal jump when comparing raw scores. Overall, boys performed significantly better than girls in the strike, stationary dribble, kick and leap when comparing raw scores (all p<0.001). CONCLUSIONS: This study reports high GMS proficiency in preschool-aged children across income settings in South Africa. The factors associated with higher GMS in low-income settings are not immediately obvious. Thus, future research should explore potential factors and identify opportunities to ensure that GMS proficiency is capitalised on as preschool-aged children enter formal schooling.

The Michigan Risk Score to predict peripherally inserted central catheter-associated thrombosis.

Essentials How best to quantify thrombosis risk with peripherally inserted central catheters (PICC) is unknown. Data from a registry were used to develop the Michigan Risk Score (MRS) for PICC thrombosis. Five risk factors were associated with PICC thrombosis and used to develop a risk score. MRS was predictive of the risk of PICC thrombosis and can be useful in clinical practice. SUMMARY: Background Peripherally inserted central catheters (PICCs) are associated with upper extremity deep vein thrombosis (DVT). We developed a score to predict risk of PICC-related thrombosis. Methods Using data from the Michigan Hospital Medicine Safety Consortium, image-confirmed upper-extremity DVT cases were identified. A logistic, mixed-effects model with hospital-specific random intercepts was used to identify factors associated with PICC-DVT. Points were assigned to each predictor, stratifying patients into four classes of risk. Internal validation was performed by bootstrapping with assessment of calibration and discrimination of the model. Results Of 23 010 patients who received PICCs, 475 (2.1%) developed symptomatic PICC-DVT. Risk factors associated with PICC-DVT included: history of DVT; multi-lumen PICC; active cancer; presence of another CVC when the PICC was placed; and white blood cell count greater than 12 000. Four risk classes were created based on thrombosis risk. Thrombosis rates were 0.9% for class I, 1.6% for class II, 2.7% for class III and 4.7% for class IV, with marginal predicted probabilities of 0.9% (0.7, 1.2), 1.5% (1.2, 1.9), 2.6% (2.2, 3.0) and 4.5% (3.7, 5.4) for classes I, II, III, and IV, respectively. The risk classification rule was strongly associated with PICC-DVT, with odds ratios of 1.68 (95% CI, 1.19, 2.37), 2.90 (95% CI, 2.09, 4.01) and 5.20 (95% CI, 3.65, 7.42) for risk classes II, III and IV vs. risk class I, respectively. Conclusion The Michigan PICC-DVT Risk Score offers a novel way to estimate risk of DVT associated with PICCs and can help inform appropriateness of PICC insertion.

Postnatal growth of the human optic nerve.

PurposeAlthough the length of the average human adult optic nerve (ON) is known, the average length of the normal full-term, newborn ON has never been adequately evaluated, nor has the in vivo growth rate of the human ON been determined. We wanted to identify both the average length of the newborn human ON and its rate of anteroposterior growth.Patients and methodsUsing MRIs from a newly generated set of normal newborn infants rescanned at 1 year, and from different aged groups, we calculated average newborn ON length and growth rate.ResultsThe newborn human ON is 25.3±0.3 mm in length from globe to chiasm, and grows by 80% in length after birth, with maximum speed of elongation occurring in the first 3 years of life, attaining full length by 15 years of age.ConclusionThe human ON grows dramatically in the first 3 years of life, and continues to grow for the first two decades. These data are relevant for pediatric treatments that may impede or alter orbital growth in infants, and maximal susceptibility to oncological procedures in early childhood.

Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.

CONTEXT: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. OBJECTIVE: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. DESIGN: This was a cross-sectional case control study. SETTING: The study was conducted at a clinical research center. PARTICIPANTS: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. INTERVENTIONS: Blood samples and anthropometric measures were obtained. MAIN OUTCOME MEASURES: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. RESULTS: Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. CONCLUSION: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.

Inhibition of Escherichia coli in cultivated cattle manure.

A common practice on Israeli dairy barns comprises daily cultivation of the manure. Cultivation is a mechanical process used to break up and till the manure bedding and it results in a drier and aerated bedding and cleaner cows, which consequently reduces the incidence of mastitis. Cultivation was associated with a shorter survival of Escherichia coli in cultivated manure as compared with noncultivated manure. The objective of the current study was to elucidate the mechanism responsible for the shorter survival duration of E. coli in the cultivated manure. We hypothesized that microorganisms that are antagonistic to E. coli, developing in the cultivated manure, are responsible for this phenomenon. A cow manure derived E. coli strain expressing the green fluorescence protein and antibiotic resistance markers was used to inoculate cow manure in 1.5-L jars. Manure treatments included cultivated and noncultivated manure. Half the jars of each cultivation treatment were autoclave sterilized at 121°C for 1 h on 3 successive days to eliminate from the manure antagonistic microorganisms. Each cultivation-sterilization treatment was performed in triplicate jars. Following sterilization, E. coli numbers in the cultivated and noncultivated manure were comparable, while in the nonsterilized manure the numbers were lower in the cultivated compared with the noncultivated manure. Several fungi isolated from the cultivated manure samples displayed inhibition effect on the tagged E. coli. Antagonistic fungi were also isolated from large-scale cultivated manure samples collected on several dairy farms in Israel. These findings support the notion that manure cultivation might facilitate the development of microorganisms that are antagonistic to E. coli, thus contributing to the general hygiene of the cattle. Identifying the mechanisms by which the antagonistic fungi affect the survival of E. coli in manure could be exploited for improvement of the animal health and for limiting the transmission of zoonotic pathogens to food and water.

[Practical aspects for minimizing errors in the cross-cultural adaptation and validation of quality of life questionnaires]. / Cómo minimizar errores al realizar la adaptación transcultural y la validación de los cuestionarios sobre calidad de vida: aspectos prácticos.

BACKGROUND: The development and validation of questionnaires for evaluating quality of life (QoL) has become an important area of research. However, there is a proliferation of non-validated measuring instruments in the health setting that do not contribute to advances in scientific knowledge. AIMS: To present, through the analysis of available validated questionnaires, a checklist of the practical aspects of how to carry out the cross-cultural adaptation of QoL questionnaires (generic, or disease-specific) so that no step is overlooked in the evaluation process, and thus help prevent the elaboration of insufficient or incomplete validations. METHODS: We have consulted basic textbooks and Pubmed databases using the following keywords quality of life, questionnaires, and gastroenterology, confined to «validation studies¼ in English, Spanish, and Portuguese, and with no time limit, for the purpose of analyzing the translation and validation of the questionnaires available through the Mapi Institute and PROQOLID websites. RESULTS: A checklist is presented to aid in the planning and carrying out of the cross-cultural adaptation of QoL questionnaires, in conjunction with a glossary of key terms in the area of knowledge. The acronym DSTAC was used, which refers to each of the 5 stages involved in the recommended procedure. In addition, we provide a table of the QoL instruments that have been validated into Spanish. CONCLUSIONS: This article provides information on how to adapt QoL questionnaires from a cross-cultural perspective, as well as to minimize common errors.

A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213.

BACKGROUND: Rituximab-hyper-CVAD alternating with rituximab-high-dose methotrexate and cytarabine is a commonly utilized regimen in the United States for mantle cell lymphoma (MCL) based on phase II single institutional data. To confirm the clinical efficacy of this regimen and determine its feasibility in a multicenter study that includes both academic and community-based practices, a phase II study of this regimen was conducted by SWOG. PATIENTS AND METHODS: Forty-nine patients with advanced stage, previously untreated MCL were eligible. The median age was 57.4 years (35-69.8 years). RESULTS: Nineteen patients (39%) did not complete the full scheduled course of treatment due to toxicity. There was one treatment-related death and two cases of secondary myelodysplastic syndrome (MDS). There were 10 episodes of grade 3 febrile neutropenia, 19 episodes of grade 3 and 1 episode of grade 4 infection. With a median follow-up of 4.8 years, the median progression-free survival was 4.8 years (5.5 years for those ≤ 65 years) and the median overall survival (OS) was 6.8 years. CONCLUSIONS: Although this regimen is toxic, it is active for patients ≤ 65 years of age and can be given both at academic centers and in experienced community centers.

The effect of caprine arthritis encephalitis virus infection on production in goats.

Three consecutive years of monitoring 248 goats in the same flock, found that the first lactation milk yield was significantly higher in seronegative (578L) than in seropositive (447L) animals but this difference disappeared in the subsequent second to fourth lactations. No significant differences were found in the proportions of seronegative and seropositive does in the flock, the percentage of animals culled, the number of offspring, or in the number of cases of udder bacterial infection, irrespective of age. Removal of kids from their dams before suckling and the feeding of pasteurised colostrum resulted in reduced numbers of seropositive animals. Nevertheless, by approximately 24 months of age, 76.9% of these initially seronegative animals were seropositive, a factor that significantly contributed to flock seropositivity. This finding could be attributed to lateral virus transmission from seropositive to seronegative kids because of lack of segregation within the flock.

Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study.

BACKGROUND: We previously reported results of the phase 2, multicenter PINNACLE study, which confirmed the substantial single-agent activity of bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL). MATERIALS AND METHODS: We report updated time-to-event data, in all patients and by response to treatment, after extended follow-up (median 26.4 months). RESULTS: Median time to progression (TTP) was 6.7 months. Median time to next therapy (TTNT) was 7.4 months. Median overall survival (OS) was 23.5 months. In responding patients, median TTP was 12.4 months, median duration of response (DOR) was 9.2 months, median TTNT was 14.3 months, and median OS was 35.4 months. Patients achieving complete response had heterogeneous disease characteristics; among these patients, median TTP and DOR were not reached, and median OS was 36.0 months. One-year survival rate was 69% overall and 91% in responding patients. Median OS from diagnosis was 61.1 months, after median follow-up of 63.7 months. Activity was seen in patients with refractory disease and patients relapsing following high-intensity treatment. Toxicity was generally manageable. CONCLUSIONS: Single-agent bortezomib is associated with lengthy responses and notable survival in patients with relapsed or refractory MCL, with considerable TTP and TTNT in responding patients, suggesting substantial clinical benefit.

Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma.

BACKGROUND: Given the significant activity and tolerability of gemcitabine in patients with relapsed Hodgkin's lymphoma (HL), the critical role that nuclear factor kappa B (NF-kappaB) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-kappaB activity, and laboratory studies suggesting synergistic antitumor effects of gemcitabine and bortezomib, we hypothesized that this combination would be efficacious in patients with relapsed or refractory HL. PATIENTS AND METHODS: A total of 18 patients participated. Patients received 3-week cycles of bortezomib 1 mg/m(2) on days 1, 4, 8, and 11 plus gemcitabine 800 mg/m(2) on days 1 and 8. RESULTS: The overall response rate for all patients was 22% (95% confidence interval 3% to 42%). Three patients developed grade III transaminase elevation: one was removed from the study and two had doses of gemcitabine held. Almost all patients exhibited inhibition of proteasome activity with treatment. CONCLUSIONS: The combination of gemcitabine and bortezomib is a less active and more toxic regimen in relapsed HL than other currently available treatments. It poses a risk of severe liver toxicity and should be pursued with caution in other types of cancer.

The utilization of intraluminal formalin for intractable rectal haemorrhage in advanced rectal cancer: a case report.

A patient with a metastatic fixed low rectal carcinoma presented severe rectal bleeding requiring massive transfusion over with a 36-hour period. Bleeding was controlled with the instillation of a 4% intrarectal formalin solution permitting the completion of a course of neoadjuvant chemoradiotherapy. This technique has been reserved for intractable transfusion-dependent radiation proctitis and is presented as a primary alternative in severe rectal bleeding from inoperable rectal cancer.

Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. RESULTS: An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. CONCLUSION: Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Phase I study for poor-prognosis lymphoma: augmentation of the "BEAM" regimen with escalating dose melphalan using amifostine cytoprotection and autologous hematopoietic stem cell transplantation--a preliminary report.

We and others have previously shown that the use of amifostine (Ethyol; MedImmune Inc, Gaithersburg, MD) can ameliorate certain regimen-related toxicities of high-dose melphalan (HD-MEL) in the autologous hematopoietic stem cell transplant setting. Our recent experience indicated that the maximum tolerated dose of HD-MEL plus autologous hematopoietic stem cell transplant could be increased from approximately 200 mg/m2 to at least 280 mg/m2 with amifostine. Although a dose-limiting toxicity was not clearly identified, atrial fibrillation was noted in several patients. Phase II trials using this regimen have been reported in lymphoma and myeloma. Nonetheless, it is unlikely that single agent therapy, regardless of dose, will be highly curative in advanced hematologic malignancy. Thus, we used amifostine to permit dose escalation of HD-MEL within the BEAM (BCNU/etoposide/arabinosylcytosine/HD-MEL) combination chemotherapy regimen before autologous hematopoietic stem cell transplant in selected patients with lymphoma. Patient entry at the starting dose (ie, HD-MEL 140 mg/m2) has been completed without the development of severe regimen-related toxicities. This trial is ongoing.

Quality of life of patients with chronic stable angina before and four years after coronary revascularisation compared with a normal population.

OBJECTIVE: To assess the impact of coronary revascularisation on the health related quality of life (HRQOL) of patients with chronic stable angina compared with data from "community" norms four years following revascularisation. DESIGN: Prospective survey and review of medical records. SETTING: Seven of the eight public Swedish heart centres that performed coronary artery interventions. SUBJECTS: 827 patients aged 55-79 years with chronic stable angina who underwent coronary artery revascularisation in 1994 or 1995 and completed the four year HRQOL survey. MAIN OUTCOME MEASURES: Five components of the Swedish quality of life survey. RESULTS: Compared with age and sex adjusted population norms, patients at baseline had significantly lower mean scores on all five functioning and wellbeing scales (p < 0.001). Four years after revascularisation, the mean levels of functioning and wellbeing were similar to those in the normative population (p > 0.05) except for quality of sleep (p < 0.001). The improvements were the same across age groups and for men and women. However, 36% of men and 55% of women were not completely free from angina by four years (p < 0.001). Men without angina after four years had better HRQOL than their community norms (p < 0.001) on all dimensions except quality of sleep (p > 0.05). Women without angina had less pain (p < 0.01) and better general health perception (p < 0.05) but similar physical functioning, quality of sleep, and emotional wellbeing compared with their community counterparts. Both men and women who had suffered at least one anginal attack during the preceding four weeks had significantly worse HRQOL by four years than their community norms (p < 0.01). CONCLUSIONS: By four years following revascularisation, three fifths of patients with chronic stable angina were free of angina and their HRQOL was the same as or better than that of the general Swedish population. However, fewer than half of all women and two thirds of men who underwent revascularisation were angina-free after four years. Among patients with new or persistent angina, the HRQOL was worse than that in community norms.

The provisional fixation TC-100 plating system: a new surgical tool for fracture management.

A new surgical plating system that allows for temporary fixation of the plate onto bone while maintaining fracture reduction during screw delivery is presented. The primary advantage of this system is that the use of bone clamps can be avoided, which may decrease the amount of soft-tissue exposure. The technique, clinical applications, and mechanical properties are discussed, and a representative case example is presented.

Sensitivity and specificity of the RAND/UCLA Appropriateness Method to identify the overuse and underuse of coronary revascularization and hysterectomy.

There is no empirical evidence on the sensitivity and specificity of methods to identify the possible overuse and underuse of medical procedures. To estimate the sensitivity and specificity of the RAND/UCLA Appropriateness Method. Parallel three-way replication of the RAND/UCLA Appropriateness Method for each of two procedures, coronary revascularization and hysterectomy. Maximum likelihood estimates of the sensitivity and specificity of the method for each procedure. These values were then used to re-calculate past estimates of overuse and underuse, correcting for the error rate in the appropriateness method. The sensitivity of detecting overuse of coronary revascularization was 68% (95% confidence interval 60-76%) and the specificity was 99% (98-100%). The corresponding values for hysterectomy were 89% (85-94%) and 86% (83-89%). The sensitivity and specificity of detecting the underuse of coronary revascularization were 94% (92-95%) and 97% (96-98%), respectively. Past applications of the appropriateness method have overestimated the prevalence of the overuse of hysterectomy, underestimated the prevalence of the overuse of the coronary revascularization, and provided true estimates of the underuse of revascularization. The sensitivity and specificity of the RAND/UCLA Appropriateness Method vary according to the procedure assessed and appear to estimate the underuse of procedures more accurately than their overuse.