Transferring inpatients between wards drives large nosocomial COVID-19 outbreaks, Wales, 2020-22: a matched case-control study using routine and enhanced surveillance data.

BACKGROUND: The role of the hospital environment in the spread of COVID-19 is unclear. AIM: To measure associations between ward characteristics and outbreak size to inform mitigations. METHODS: Wards with large (case wards) and small (control wards) outbreaks in three acute hospitals were compared. Cases were healthcare-associated COVID-19 inpatients (positive polymerase chain reaction test ≥8 days post admission). Case wards were adult medical/surgical wards with ≥10 cases within rolling 14-day periods, between April 1st, 2020 and April 30th, 2022. Control wards were equivalents with 2-9 cases. Demographic and laboratory data were extracted from routine surveillance systems. Continuous data were aggregated fortnightly and analysed as binary variables according to median values. Each case ward was compared with two control wards matched on outbreak start date (±14 days) to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) using univariable and conditional multivariable logistic regression. FINDINGS: From 170 outbreaks (median: 5 cases; interquartile range: 2-9), 35 case wards were identified. Community admissions were lower in case wards vs control wards (5 vs 10 median admissions; P<0.01, respectively), whereas transfers between wards within the same hospital were higher (58 vs 29 median transfers; P<0.01, respectively). Wards with more transfers in the preceding fortnight were significantly more likely to experience a large outbreak (≥35 vs <35 transfers; adjusted OR: 9.08; 95% CI: 2.5-33). CONCLUSION: We recommend safely minimizing patient movements, such as by asking clinicians to record the rationale for transfer, to reduce the likelihood of disease transmission.

The Sins of the Parents Are to Be Laid Upon the Children: Biased Humans, Biased Data, Biased Models.

Technological innovations have become a key driver of societal advancements. Nowhere is this more evident than in the field of machine learning (ML), which has developed algorithmic models that shape our decisions, behaviors, and outcomes. These tools have widespread use, in part, because they can synthesize massive amounts of data to make seemingly objective recommendations. Yet, in the past few years, the ML community has been drawing attention to the need for caution when interpreting and using these models. This is because these models are created by humans, from data generated by humans, whose psychology allows for various biases that impact how the models are developed, trained, tested, and interpreted. As psychologists, we thus face a fork in the road: Down the first path, we can continue to use these models without examining and addressing these critical flaws and rely on computer scientists to try to mitigate them. Down the second path, we can turn our expertise in bias toward this growing field, collaborating with computer scientists to reduce the models' deleterious outcomes. This article serves to light the way down the second path by identifying how extant psychological research can help examine and curtail bias in ML models.

Getting back to the "new normal": Autonomy restoration during a global pandemic.

We investigate the psychological recovery process of full-time employees during the 2-week period at the onset of the Coronavirus pandemic (COVID-19). Past research suggests that recovery processes start after stressors abate and can take months or years to unfold. In contrast, we build on autonomy restoration theory to suggest that recovery of impaired autonomy starts immediately even as a stressor is ongoing. Using growth curve modeling, we examined the temporal trajectories of two manifestations of impaired autonomy-powerlessness and (lack of) authenticity-to test whether recovery began as the pandemic unfolded. We tested our predictions using a unique experience-sampling dataset collected over a 2-week period beginning on the Monday after COVID-19 was declared a "global pandemic" by the World Health Organization and a "national emergency" by the U.S. Government (March 16-27, 2020). Results suggest that autonomy restoration was activated even as the pandemic worsened. Employees reported decreasing powerlessness and increasing authenticity during this period, despite their subjective stress-levels not improving. Further, the trajectories of recovery for both powerlessness and authenticity were steeper for employees higher (vs. lower) in neuroticism, a personality characteristic central to stress reactions. Importantly, these patterns do not emerge in a second experience-sampling study collected prior to the COVID-19 crisis (September 9-20, 2019), highlighting how the pandemic initially threatened employee autonomy, but also how employees began to recover their sense of autonomy almost immediately. The present research provides novel insights into employee well-being during the COVID-19 pandemic and suggests that psychological recovery can begin during a stressful experience. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Oral, jaw, and neck injury in infants and children: from abusive trauma or intubation?

OBJECTIVES: The objective of this study was to identify the incidence of oral, jaw, and neck injury secondary to endotracheal intubation in young children. METHODS: This prospective observational study was conducted in the pediatric intensive care unit at a level 1 trauma center. From October 1998 to January 1999 and November 2007 to April 2008, all intubated patients younger than 3 years with no prior oral procedures were examined within 24 hours of intubation. A standardized form was used to record injuries. Separately, medical records were reviewed for prior injuries. Chi-square/Fisher exact test was used for statistical analysis. RESULTS: Of 105 patients included in the study, 12 had oral, jaw, or neck injury. One patient had a hard palate injury from a pen cap in his mouth during a seizure. Another broke a tooth biting the laryngoscope blade (the only injury directly attributable to intubation). The remaining 10 patients were determined to be those who experienced abusive trauma. The overall incidence of injury directly from intubation was 0.9%. Oral, jaw, and neck injuries were all significantly associated with abusive trauma (P < 0.001). Eleven patients had difficult intubations: 9 had no injuries, 1 experienced abusive trauma and the second was the patient who broke his tooth during intubation. CONCLUSIONS: Oral, jaw, or neck injury in young children is rarely caused by endotracheal intubation, regardless of difficulty during the procedure.

Development of hexadecyloxypropyl tenofovir (CMX157) for treatment of infection caused by wild-type and nucleoside/nucleotide-resistant HIV.

CMX157 is a lipid (1-0-hexadecyloxypropyl) conjugate of the acyclic nucleotide analog tenofovir (TFV) with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. CMX157 was consistently >300-fold more active than tenofovir against multiple viruses in several different cell systems. CMX157 was active against all major subtypes of HIV-1 and HIV-2 in fresh human peripheral blood mononuclear cells (PBMCs) and against all HIV-1 strains evaluated in monocyte-derived macrophages, with 50% effective concentrations (EC(50)s) ranging between 0.20 and 7.2 nM. The lower CMX157 EC(50)s can be attributed to better cellular uptake of CMX157, resulting in higher intracellular levels of the active antiviral anabolite, TFV-diphosphate (TFV-PP), inside target cells. CMX157 produced >30-fold higher levels of TFV-PP in human PBMCs exposed to physiologically relevant concentrations of the compounds than did TFV. Unlike conventional prodrugs, including TFV disoproxil fumarate (Viread), CMX157 remains intact in plasma, facilitating uptake by target cells and decreasing relative systemic exposure to TFV. There was no detectable antagonism with CMX157 in combination with any marketed antiretroviral drug, and it possessed an excellent in vitro cytotoxicity profile. CMX157 is a promising clinical candidate to treat wild-type and antiretroviral drug-resistant HIV, including strains that fail to respond to all currently available nucleoside/nucleotide reverse transcriptase inhibitors.

Evaluation of hexadecyloxypropyl-9-R-[2-(Phosphonomethoxy)propyl]- adenine, CMX157, as a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections.

9-R-[2-(Phosphonomethoxy)propyl]-adenine (tenofovir) is an acyclic nucleoside phosphonate with antiviral activity against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV). Tenofovir is not orally bioavailable but becomes orally active against HIV-1 infection as the disoproxil ester (tenofovir disoproxil fumarate [Viread]). We have developed an alternative strategy for promoting the oral availability of nucleoside phosphonate analogs which involves esterification with a lipid to form a lysolecithin mimic. This mimic can utilize natural lysolecithin uptake pathways in the gut, resulting in high oral availability. Since the mimic is not subject to cleavage in the plasma by nonspecific esterases, it remains intact in the circulation and facilitates uptake by target cells. Significant drops in apparent antiviral 50% effective concentrations (EC(50)s) of up to 3 logs have been observed in comparison with non-lipid-conjugated parent compounds in target cells. We have applied this technology to tenofovir with the goal of increasing oral availability, decreasing the apparent EC(50), and decreasing the potential for nephrotoxicity by reducing the exposure of the kidney to the free dianionic tenofovir. Here we report that, in vitro, the hexadecyloxypropyl ester of tenofovir, CMX157, is 267-fold more active than tenofovir against HIV-1 and 4.5-fold more active against HBV. CMX157 is orally available and has no apparent toxicity when given orally to rats for 7 days at doses of 10, 30, or 100 mg/kg/day. Consequently, CMX157 represents a second-generation tenofovir analog which may have an improved clinical profile.

Biochemical and mechanistic basis for the activity of nucleoside analogue inhibitors of HIV reverse transcriptase.

HIV encodes an RNA directed DNA polymerase (reverse transcriptase, RT) that is an essential enzyme in the viral replication cycle. This enzyme catalyzes the synthesis of double stranded proviral DNA from single stranded genomic RNA via a bireactant-biproduct mechanism. The functional enzyme purified from virus particles is a complex consisting of two polypeptides of molecular weight 66,000 and 51,000. Two of the four classes of currently approved anti-HIV drugs, the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs), act by inhibiting this enzyme. In this review each step of DNA synthesis catalyzed by the RT is described and the mechanism of inhibition of catalysis and termination of DNA synthesis by NRTIs is detailed. The individual steps in the catalytic cycle and the effects that the NRTIs have on them have been examined using transient kinetic analysis. The impact of stereoisomerism and resistance mutations on the rate of NRTI triphosphate incorporation (k(pol)), binding in the catalytic complex (K(d)) and the overall efficiency of incorporation (k(pol)/K(d)) are summarized for lamivudine, coviracil and zalcitabine. The results provide insight into the molecular forces and structural features that make these molecules effective inhibitors.

Synthesis of (-)-DAPD.

A new synthesis of (-)-DAPD, suitable for large scale development, is described.

New synthesis of L-FMAU from L-arabinose.

A new synthesis of 2'-deoxy-2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil (13, L-FMAU) was achieved in 10 steps from L-arabinose.

Hypoparathyroidism, intracranial calcification, and seizures 61 years after thyroid surgery.

Though hypocalcemic symptoms from hypoparathyroidism following thyroidectomy most often occur in the immediate postoperative period, hypoparathyroidism can present itself many years after the thyroid surgery with nonspecific symptoms. We present herein the case of a 74-year-old woman with previously undiagnosed hypoparathyroidism who had tonic-clonic seizures and intracranial calcification 61 years after her thyroidectomy. This case is unusual because of the long latency between thyroidectomy and clinical presentation.

Factors influencing the accuracy of home blood pressure measurement.

BACKGROUND: Hypertension is a common disorder, affecting approximately 50 million Americans. Because many people have this disorder and its sequela, it is important not only to detect hypertension but also to monitor adequacy of control. Over the past few years, blood pressure monitoring devices (BPMDs) have become available for individuals to measure their blood pressure (BP) in the convenience of their home. These instruments are touted as being accurate. METHODS: We conducted a study with volunteers who use BPMDs to see how they are used and to assess their accuracy. A BP reading was considered accurate if the differences between the volunteers' and technicians' systolic and diastolic readings were both 10 mm Hg or less. RESULTS: Of 91 patients, 31 (34%) obtained inaccurate readings. The inaccuracy could not be attributed to the type of the instrument, the cost of the instrument, the educational level of the user, or the age of the instrument. CONCLUSIONS: This study shows, despite other studies purporting accuracy, that a significant number of inaccurate readings are obtained by patients using BPMDs. Supervision of their use needs to be incorporated into the physician follow-up to ensure that there is a reasonable correlation between values obtained using the mercury sphygmomanometer and the BPMD.

Some haematological parameters in Malawian neonates.

Studies of haematological parameters were performed on 366 (177 male and 189 female) normal Malawian neonates with mean +/- s.d. birthweight of 2.99 +/- 0.37 (range 2.1-4.0) kg using a Nova Cell Track, Model Nova CT11. Cord anaemia (Cord Hb < 13.5g dl-1) was detected in 100 (27.3%) of the neonates. It was also shown that although the male babies had a significantly higher erythrocyte protoporphyrin level (p < 0.001) than the females, there were no significant differences (p > 0.05) in the red cell, white cell and platelet indices between the two sexes. When the haematological parameters of the 266 (72.7%) non-anaemic (Cord Hb > 13.5g dl-1) neonates were analysed, the mean +/- s.d. values which may serve as local reference standards were: Hb 16.0 +/- 1.7 (range 13.5-21.3) g dl-1, Hct 47.0 +/- 6.0 (range 36.5-67.5) percent, MCV 112.6 +/- 8.9 (range 72.2-131.0) fl, MCH 31.9 +/- 5.5 (range 24.4-48.5) pg, MCHC 33.5 +/- 2.8 (range 29.1-48.9) g dl-1 reticulocyte count 6.9 +/- 3.6 (range 1.2-25.0) percent, free erythrocyte protoporphyrin 3.3 +/- 0.9 (range 1.9-7.7) mgs ZPP gm-1 Hb, platelet count 269.9 +/- 57.7 (range 134.0-454.0) x 10(9) l-1 and total leucocyte count 12.3 +/- 4.8 (range 5.5-35.3) x 10(9) l-1. Further analysis of the differential wbc count disclosed normal levels of eosinophils and neutrophils similar to those given in standard haematology textbooks for Caucasian neonates; thus strengthening the belief that eosinophilia and relative neutropenia previously reported in adult Africans is not of genetic origin, but rather an acquired phenomena.

Case report: the anticardiolipin (antibody) syndrome.

The anticardiolipin antibody syndrome is relatively uncommon. It should be suspected mostly in young people with unexplained embolic or thrombotic events. A young patient with an abnormal prothrombin time, partial thromboplastin time, or venereal disease research lab test with one of the above noted vascular events would be a suspect for this disorder. Though an antibody test that will qualitatively and quantitatively measure antiphospholipid antibodies is available, its clinical application is not entirely clear. The presence of the antibody will support a diagnosis but cannot be used alone for diagnosis or treatment.

Which plasma factors bring about disturbance of endothelial function in pre-eclampsia?

The characteristic pathophysiological changes in pre-eclampsia are thought to be related to abnormalities of the maternal vascular endothelium. We suggest that the blood components that affect the risk of such damage are very-low-density lipoproteins (VLDL), which injure the endothelium, and toxicity-preventing activity (the pl 5.6 form of plasma albumin), which protects against VLDL-induced injury.

The use of beta-galactosidase fusion proteins encoding the early region 1 transforming proteins of adenovirus type 12 to examine the humoral response in tumour-bearing animals.

Sera from 26 rats bearing tumours induced by wild-type (wt) and mutant human adenovirus type 12 (Ad12), or by cells transformed with these viruses, were analysed for antibodies against the early region 1 (E1) transforming proteins. Six Ad12-beta-galactosidase fusion proteins encoding different regions of the Ad12 E1 proteins were constructed. The sera from the tumour-bearing animals reacted most strongly with the fusion protein encoding the N terminus of the E1A protein. Tumour-bearing rats exposed to the E1B 54K and 19K proteins showed strong reactions with the N terminus of the 54K protein and the C terminus of the 19K protein. Monospecific polyclonal antisera were raised against five of the fusion proteins by immunization of rats and rabbits; these sera cross-reacted with the purified native protein. No antibodies could be obtained which recognized a fusion protein containing amino acids 136 to 268 of the 54K protein. The fusion proteins were also used to purify monospecific antisera from tumour-bearer sera using affinity chromatography.

The expression of the retinoblastoma gene product Rb1 in primary and adenovirus-transformed human cells.

Polyclonal antibodies to the human retinoblastoma gene product (Rb1) have been produced in rats by immunisation with a fusion protein comprising part of Rb1 together with the E. coli beta-Gal sequence. We have used these antibodies in Western blotting studies to screen a number of human foetal tissues and organs and found approximately similar levels of expression of Rb1 in all of them. The protein seems to be somewhat more abundant in some cell lines produced by transfection of human embryo retinal (HER) cells with adenovirus 12 early region 1 (Ad 12 E1), Ad 5 E1, Ad 2 E1A + mutant N-ras or SV40 DNA. Using co-immunoprecipitation followed by Western blotting we have shown that the Rb1 protein binds to Ad 12 E1A 266 and 235 amino acid proteins. This interaction is ionic strength dependent but is unaffected by non-ionic detergent up to a concentration of at least 1%. In Ad 12 infected human cells it appears that less E1A is bound to Rb1 than in the transformants. These results are discussed in view of the known similarities and differences between the amino acid sequences of Ad 12 and Ad 5 E1A proteins.

Immunomodulatory activity in regional lymph nodes.

This study is, to our knowledge, the first attempt to evaluate cellular immune mechanisms in regional lymph nodes of patients with head and neck cancer. Twenty lymph nodes from eight patients with stage III-IV squamous cell carcinoma were evaluated using an in vitro culture system. The T-cell mitogenic (concanavalin A) response of patients' peripheral blood mononuclear cells was modulated by the addition of cells from regional lymph nodes removed at neck dissection. Modulatory activity showing augmentation was significantly correlated with the size of the primary tumor and histopathologic grade of the tumor. Modulatory activity did not correlate with the histologic pattern of lymph node reactivity. Although these relationships suggest that regional immunity may be important in tumor-host interactions, further study is necessary to establish their biologic and prognostic importance.

Single agent chemotherapy for head and neck cancers. The murine subrenal capsule assay.

The murine subrenal capsule assay was used to determine chemotherapeutic sensitivities of metastatic, primary, or recurrent head and neck cancers. Tumor fragments (1 cu mm) were implanted under the renal capsule of 2- to 4-month-old normal female C57 BL/6 X DBA/2 F1 hybrid mice. Xenografts included 20 squamous cell carcinomas (SCCs), one mucoepidermoid carcinoma, one adenoid cystic carcinoma, and two melanomas. Groups of tumor-bearing mice were treated with chemotherapy daily for five days. Sensitivities of the tumor were assessed on day 6 by comparison of final implant size with initial implant size. Significant oncolytic activity was detected against 16 of 24 tumors (14 of 20 SCCs and both melanomas). Correlations between the in vivo assay and clinical studies are needed to determine its predictive value.