Oxford-AstraZeneca COVID-19 vaccine: need of a reasoned and effective vaccine campaign.

OBJECTIVES: A strong COVID-19 vaccine campaign is needed to reach the herd immunity and reduce this pandemic infection. STUDY DESIGN: In the Foch Hospital, France, in February 2021, 451 healthcare workers were vaccinated by a first dose of AstraZeneca vaccine. METHODS: Adverse effects were reported to our pharmaco-vigilance circuit, by an online and anonymous questionnaire following the first weeks of the vaccinal campaign to healthcare workers. RESULTS: Two hundred seventy-four (60.8%) of them reported multiple adverse effects. Main adverse effects reported were feverish state/chills (65.7%), fatigue/physical discomfort (62.4%), arthralgia/muscle pain (61.0%) and fever (44.5%). CONCLUSIONS: On March 2021 many European countries suspended AstraZeneca vaccine for one week due to safety uncertainty. Thus, confidence in its efficacy is undermined. However, the benefit/risk balance is clearly in favor of vaccination.

A pathway leading to a cation-binding pocket determines the selectivity of the NhaP2 antiporter in Vibrio cholerae1.

The Vc-NhaP2 antiporter from Vibrio cholerae exchanges H+ for K+ or Na+ but not for the smaller Li+. The molecular basis of this unusual selectivity remains unknown. Phyre2 and Rosetta software were used to generate a structural model of the Vc-NhaP2. The obtained model suggested that a cluster of residues from different transmembrane segments (TMSs) forms a putative cation-binding pocket in the middle of the membrane: D133 and T132 from TMS V together with D162 and E157 of TMS VI. The model also suggested that L257, G258, and N259 from TMS IX together with T276, D273, Q280, and Y251 from TMS X as well as L289 and L342 from TMS XII form a transmembrane pathway for translocated ions with a built-in filter determining cation selectivity. Alanine-scanning mutagenesis of the identified residues verified the model by showing that structural modifications of the pathway resulted in altered cation selectivity and transport activity. In particular, L257A, G258A, Q280A, and Y251A variants gained Li+/H+ antiport capacity that was absent in the nonmutated antiporter. T276A, D273A, and L289A variants exclusively exchanged K+ for H+, while a L342A variant mediated Na+/H+ exchange only, thus maintaining strict alkali cation selectivity.

Optimising concentrations of antimicrobial agents in pharmaceutical preparations: Case of an oral solution of glycerol and an ophthalmic solution containing cysteamine.

INTRODUCTION: In the context of current distrust of antimicrobial preservatives, the quantities of these substances in two pharmaceutical formulas were studied: an ophthalmic solution of cysteamine preserved benzalkonium chloride at 1mg/5mL and Glycerotone(®) preserved with sorbic acid at 0.1g/100g. The purpose of this work was to verify that a reduction of the quantities of preservative continues to fulfil the requirements for antimicrobial preservation. MATERIAL AND METHODS: The Test of efficacy of antimicrobial preservation, section 5.1.3 of the 8th edition of the European Pharmacopoeia, was carried out on each formulation prepared with decreasing quantities of preservative. RESULTS: The results show that formulations whose preservative concentration was reduced by a factor of four remained compliant with standards. It is to be noted that in formulas without preservative, fungal growth was observed in both the solution of Glycerotone(®) and the ophthalmic solution containing cysteamine. DISCUSSION: Although there is no question that an antimicrobial preservative is necessary, the quantity of preservative can be reduced without deteriorating the quality of the pharmaceutical product but the minimal effective concentration remains to be determined. CONCLUSION: The formulations of many pharmaceutical products should therefore be examined in order to limit the quantities of preservative while continuing to guarantee patient's safety.

Current discharge management of acute coronary syndromes: baseline results from a national quality improvement initiative.

BACKGROUND: Evidence-practice gaps exist in the continuum of care for patients with acute coronary syndromes (ACS), particularly at hospital discharge. AIM: We aimed to describe the methodology and baseline results of the Discharge Management of Acute Coronary Syndromes (DMACS) project, focusing on the prescription of guideline-recommended medications, referral to cardiac rehabilitation and communication between the hospital, patient and their primary healthcare professionals. METHODS: DMACS employed Drug Use Evaluation methodology involving data collection, evaluation and feedback, and targeted educational interventions. Adult patients with ACS discharged during a 4-month period were eligible to participate. Data were collected (maximum 50 patients) at each site through an inpatient medical record review, a general practitioner (GP) postal/fax survey conducted 14 days post discharge and a patient telephone survey 3 months post discharge. RESULTS: Forty-nine hospitals participated in the audit recruiting 1545 patients. At discharge, 57% of patients were prescribed a combination of antiplatelet agent(s), beta-blocker, statin and angiotensin-converting enzyme inhibitor and/or angiotensin II-antagonist. At 3 months post discharge, 48% of patients reported using the same combination. Some 67% of patients recalled being referred to cardiac rehabilitation; of these, 33% had completed the programme. In total, 83% of patients had a documented ACS management plan at discharge. Of these, 90% included a medication list, 56% a chest pain action plan and 54% risk factor modification advice. Overall, 65% of GPs rated the quality of information received in the discharge summary as 'very good' to 'excellent'. CONCLUSIONS: The findings of our baseline audit showed that despite the robust evidence base and availability of national guidelines, the management of patients with ACS can be improved. These findings will inform a multifaceted intervention strategy to improve adherence to guidelines for the discharge management of patients with ACS.

Complete Genome Sequence of Kluyvera sp. CRP, a Cellulolytic Strain Isolated from Red Panda Feces (Ailurus fulgens).

The enterobacterium genus Kluyvera is widely distributed in the environment and a rare source of infection in humans. Kluyvera sp. strain CRP was isolated from feces of a healthy, captive Chinese red panda (Ailurus fulgens), and its complete genome (5,157,963 bp, 54.80% GC content) was established through hybrid assembly.

Isolated fallopian tube torsion: a series of six cases.

Isolated Fallopian tube torsion is a rare gynecological cause of acute lower abdominal pain. Currently, there are no pathognomonic symptoms, clinical findings, imaging or laboratory characteristics for this condition, and the diagnosis can rarely be made before operation. We have identified six cases of isolated Fallopian tube torsion treated over a period of 3 years. It was observed that acute onset of abdominal pain with gastrointestinal symptoms can be the initial presenting features. Clinical and laboratory findings included positive peritoneal signs, fever, tachycardia and leucocytosis. Most of the women had preoperative ultrasound showing tubular adnexal masses of heterogeneous echogenicity with cystic component and the presence of free fluid. In contrast to the belief that isolated Fallopian tube torsion is more common in the right side, in five of our cases it occurred in the left side.

Human COL2A1-directed SV40 T antigen expression in transgenic and chimeric mice results in abnormal skeletal development.

The ability of SV40 T antigen to cause abnormalities in cartilage development in transgenic mice and chimeras has been tested. The cis-regulatory elements of the COL2A1 gene were used to target expression of SV40 T antigen to differentiating chondrocytes in transgenic mice and chimeras derived from embryonal stem (ES) cells bearing the same transgene. The major phenotypic consequences of transgenic (pAL21) expression are malformed skeleton, disproportionate dwarfism, and perinatal/neonatal death. Expression of T antigen was tissue specific and in the main characteristic of the mouse alpha 1(II) collagen gene. Chondrocyte densities and levels of alpha 1(II) collagen mRNAs were reduced in the transgenic mice. Islands of cells which express cartilage characteristic genes such as type IIB procollagen, long form alpha 1(IX) collagen, alpha 2(XI) collagen, and aggrecan were found in the articular and growth cartilages of pAL21 chimeric fetuses and neonates. But these cells, which were expressing T antigen, were not properly organized into columns of proliferating chondrocytes. Levels of alpha 1(II) collagen mRNA were reduced in these chondrocytes. In addition, these cells did not express type X collagen, a marker for hypertrophic chondrocytes. The skeletal abnormality in pAL21 mice may therefore be due to a retardation of chondrocyte maturation or an impaired ability of chondrocytes to complete terminal differentiation and an associated paucity of some cartilage matrix components.

Patients' perceptions of nasopharyngeal aspiration in the emergency department of a teaching hospital in Hong Kong.

Nasopharyngeal aspiration (NPA) is the preferred method for collecting specimens for viral culture in patients with respiratory tract infection. As virus identification may influence admission and treatment decisions, it is important to perform NPA in the emergency department. The test may be uncomfortable and poorly tolerated. This prospective study investigated patients' perceptions of NPA. Patients in the emergency department with upper respiratory tract infection undergoing NPA between 9 March 2005 and 12 August 2005 were included. 86 patients (mean (SD) age 47 (23) years; 49 women) were recruited. 22 (26%) patients complained that NPA was very uncomfortable, 59 (69%) reported that it was mildly uncomfortable and 5 (6%) patients reported no discomfort. On a 10-point scale, the median discomfort score was 4. 29 (34%) patients stated that NPA was more uncomfortable than blood taking, 19 (22%) patients felt that both were similar and 38 (44%) patients felt that NPA was less uncomfortable (p value not significant). NPA performed in the emergency department is well tolerated and should be considered in emergency departments when results may influence patient management.

Modification of human beta-globin locus PAC clones by homologous recombination in Escherichia coli.

We report here modifications of human beta-globin PAC clones by homologous recombination in Escherichia coli DH10B, utilising a plasmid temperature sensitive for replication, the recA gene and a wild-type copy of the rpsL gene which allows for an efficient selection for plasmid loss in this host. High frequencies of recombination are observed even with very small lengths of homology and the method has general utility for introducing insertions, deletions and point mutations. No rearrangements were detected with the exception of one highly repetitive genomic sequence when either the E.COLI: RecA- or the lambdoid phage encoded RecT and RecE-dependent recombination systems were used.

Laparoscopic surgery for common surgical emergencies: a population-based study.

BACKGROUND: Despite being controversial in the past, many reports on the safe use of laparoscopic surgery in emergency settings have been published. The aim of this study was to investigate the diffusion of laparoscopic surgery in three common surgical emergency operations, namely, appendectomy, cholecystectomy, and simple repair of perforated peptic ulcer (PPU), in a stable population. METHODS: This was a retrospective analysis of the central database of the Hospital Authority (HA) in Hong Kong. Data for patients managed in 14 HA hospitals from 1998 to 2002 were studied. The operation record and discharge record of each patient were also investigated to verify the data. RESULTS: A total of 12,708 patients underwent appendectomy, 2631 patients underwent cholecystectomy, and 2260 patients had simple repair of PPU performed. During the study period, 37.2% of appendectomies, 46.5% of cholecystectomies, and 23.1% of simple repairs of PPU were performed laparoscopically. More than a two-fold increase in the proportion of laparoscopic surgery was observed in each of these three operations. By the end of 2002, the percentage of laparoscopic surgery had increased to 53.5% for appendectomies, 61.3% for cholecystectomies, and 32.9% for simple repairs of PPU. Significantly lower hospital mortality rates and shorter postoperative hospital stay were consistenty observed in patients with laparoscopic surgery of the three emergencies. A wide variation in the use of laparoscopic surgery, ranging from 3.7% to 73.1%, was observed among the 14 HA hospitals. However, there was no correlation in the use of laparoscopic surgery with the volume of operation performed in each hospital (p = 0.933). CONCLUSION: A high diffusion rate on the use of laparoscopic surgery for common surgical emergency was observed in Hong Kong. However, there was also a wide variation in the diffusion rate among the 14 HA hospitals. Efforts to reduce hospital variation for the better dissemination of safe laparoscopic technique may be warranted.

Gallbladder cancer presenting with acute cholecystitis: a population-based study.

BACKGROUND: The role of laparoscopic cholecystectomy (LC) in acute cholecystitis remains controversial. The aim of the present study was to determine the incidence, clinicopathological characteristics, and outcome of patients with gallbladder cancer presenting with acute cholecystitis. METHODS: We performed a retrospective analysis of patients with gallbladder cancer who presented with acute cholecystitis and were treated at the public hospitals in Hong Kong between 1998 and 2002. RESULTS: Among 2,700 patients with acute cholecystitis managed with cholecystectomy (1,347 open and 1,353 LC), 63 patients (2.3%) were found to have gallbladder cancer. There were 44 women and 19 men with a mean age of 74.7 (+/-12.8) years. Adenocarcinoma (90.5%) was the most common cancer. The overall median survival was 5 months (95% CI = 2.6-7.4). The 5-year survival rate was 20.8%. Laparoscopic cholecystectomy was attempted in 11 patients and was completed successfully in six of them. There was no difference between the LC and open groups in the complication rate, hospital mortality rate, or survival rate. CONCLUSIONS: In the ethnic Chinese population of Hong Kong, the incidence of gallbladder cancer presenting with acute cholecystitis is higher than the same finding in patients undergoing elective cholecystectomy for cholelithiasis. Long-term survival is possible because such patients may be diagnosed at an early stage of the disease.

A double-blind, randomized study of three antimicrobial regimens in the prevention of infections after elective colorectal surgery.

The objective of this study was to assess the prophylactic efficacy of cefoxitin, ceftizoxime, and metronidazole-gentamicin in colorectal surgery. A double-blind, randomized prospective clinical trial design was used in a Canadian tertiary care teaching hospital. Patients were randomized to one of three treatment groups and received three doses of a study drug (30 min preoperative and 2 postoperative doses at 12 and 24 h). Cefoxitin and ceftizoxime were given as 1000-mg doses. Metronidazole-gentamicin was given as 500 mg of metronidazole plus 120 mg of gentamicin in a minibag. High-risk patients (bowel ischemia, diabetic, current steroid use, etc.) received 10 postoperative doses. Patients with infections, prior antibiotics, or study drug allergies were excluded. Over 30 months, 153 patients were enrolled. Thirty-one patients were excluded for protocol violations. Of the 122 evaluable patients (38 ceftizoxime, 45 metronidazole-gentamicin, 39 cefoxitin), there was no difference across groups regarding sex, age, weight, preoperative Apache II score, and prior history of bowel surgery. Groups were equivalent regarding surgeon, nursing unit, high-risk status (six ceftizoxime, seven metronidazole-gentamicin, seven cefoxitin), bowel preparation, and procedure (including blood loss, drains, organ injury, intraoperative complications). Clinically significant infection requiring systemic antibiotics (7-day hospital and 30-day follow-up) was identified in 0% of ceftizoxime, 15% of metronidazole-gentamicin, and 26% of cefoxitin receiving patients (p = 0.005). Mean ASEPSIS scores for each group were 2.3 (range 0-15) for ceftizoxime, 9.2 (range 0-45) for metronidazole-gentamicin, and 10.4 (range 0-75) for cefoxitin (p = 0.01). Ceftizoxime patients tended to have a shorter total hospital stay (12.2 days versus 19.7 days for cefoxitin versus 13.9 days for metronidazole-gentamicin; p = 0.04), although the procedure to discharge interval was not significantly different (p = 0.09). There was no difference in clinical outcome according to risk status. Anaerobic bacteria were observed more commonly in the ceftizoxime and cefoxitin groups, whereas enteric Gram-negative aerobes were observed most often in the metronidazole-gentamicin group. The study regimens were generally well tolerated. Drug costs were equivalent between ceftizoxime and cefoxitin and lowest with the metronidazole-gentamicin regimen. Ceftizoxime appears to be more effective for the prevention of infection in colorectal surgery than either cefoxitin or metronidazole-gentamicin in the dosage regimens studied.

Cost analysis of an adult outpatient parenteral antibiotic therapy (OPAT) programme. A Canadian teaching hospital and Ministry of Health perspective.

BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) programmes have become prevalent over the past 2 decades. From the US perspective, these programmes have been shown to reduce healthcare costs. No comprehensive analysis has been published from the Canadian perspective. OBJECTIVE: To describe a Canadian OPAT programme for the 3-year period since its inception and to conduct a treatment cost analysis. DESIGN AND METHODS: Demographics and resource utilisation data (health professional labour, laboratory and diagnostic tests, antimicrobials, delivery, home nursing care, catheters and catheter placement) were prospectively collected for enrollees in the OPAT programme over the evaluation period. Avoided hospital resource utilisation was estimated via retrospective chart review by the investigators. Costs were retrospectively assigned to each resource and total cost avoidance by the OPAT programme was determined from each perspective. PERSPECTIVE: A teaching hospital and a provincial Ministry of Health (MOH). MAIN OUTCOME MEASURES AND RESULTS: 140 treatment courses were initiated for 117 adult patients (mean age 54 years) who were enrolled into the programme. Mean pre-OPAT length of hospital stay was 12 days, and mean OPAT duration was 22.5 days. Bone/joint (39%), skin and soft tissue (16%), cardiac (13%) and respiratory tract (12%) infections were the most common infections managed. The most commonly used antimicrobials were vancomycin (29%), cloxacillin +/- gentamicin (22%) and ceftriaxone +/- gentamicin (11%) 85% of enrollees successfully completed their planned antimicrobial treatment regimens. Premature discontinuation of antimicrobial therapy for various reasons occurred in the remaining 15% of courses. The mean cost per treatment course of OPAT was 1910 Canadian dollars ($Can) from the hospital perspective and $Can6326 from the MOH perspective. Assuming that patients would have otherwise completed their antimicrobial therapy in hospital, the mean cost per treatment course was estimated to be $Can14,271. The overall cost avoidance of the OPAT programme was $Can1,730,520 (hospital perspective) and $Can1,009,450 (MOH perspective) over the 3-year assessment period. Sensitivity analyses revealed the results to be robust to plausible changes. CONCLUSIONS: This analysis supports the premise that an adult OPAT programme can substantially reduce healthcare costs in the Canadian healthcare setting.

What is the relationship between the Glasgow coma scale and airway protective reflexes in the Chinese population?

AIM: To describe the relationship of gag and cough reflexes to Glasgow coma score (GCS) in Chinese adults requiring critical care. METHOD: Prospective observational study of adult patients requiring treatment in the trauma or resuscitation rooms of the Emergency Department, Prince of Wales Hospital, Hong Kong. A long cotton bud to stimulate the posterior pharyngeal wall (gag reflex) and a soft tracheal suction catheter were introduced through the mouth to stimulate the laryngopharynx and elicit the cough reflex. Reflexes were classified as normal, attenuated or absent. RESULTS: A total of 208 patients were recruited. Reduced gag and cough reflexes were found to be significantly related to reduced GCS (p=0.014 and 0.002, respectively). Of 33 patients with a GCS≤8, 12 (36.4%) had normal gag reflexes and 8 (24.2%) had normal cough reflexes. 23/62 (37.1%) patients with a GCS of 9-14 had absent gag reflexes, and 27 (43.5%) had absent cough reflexes. In patients with a normal GCS, 22.1% (25/113) had absent gag reflexes and 25.7% (29) had absent cough reflexes. CONCLUSIONS: Our study has shown that in a Chinese population with a wide range of critical illness (but little trauma or intoxication), reduced GCS is significantly related to gag and cough reflexes. However, a considerable proportion of patients with a GCS≤8 have intact airway reflexes and may be capable of maintaining their own airway, whilst many patients with a GCS>8 have impaired airway reflexes and may be at risk of aspiration. This has important implications for airway management decisions.

Population-based information on emergency colorectal surgery and evaluation on effect of operative volume on mortality.

INTRODUCTION: Population-based information on emergency surgery for colorectal conditions was limited. The present study was designed to review comprehensively the outcomes of emergency colectomy in Hong Kong population and evaluate the effect of case load on mortality after considering case mixes. METHODS: All adult patients older than aged 18 years who underwent emergency colectomy in 2003 in all 15 Hong Kong public hospitals were included. Demographics and perioperative variables were reviewed and analyzed. Hospitals were classified into low, middle, or high operative volume groups according to their yearly caseloads, and their performance in terms of mortality were compared by using CR-POSSUM. RESULTS: A total of 864 patients with a mean age of 67.8 years were included. Bowel obstruction and peritonitis were the two major clinical indications for the surgery. The crude in-hospital mortality rate was 18.9%; individual hospitals varied from 8.7% to 33.3%. With the risk adjusted model, all hospital groups performed within 95% confidence limits of prediction. There was no statistical difference for mortality of hospitals of different case volume. CONCLUSION: A crude in-hospital mortality of 18.9% after emergency colorectal surgery was observed in Hong Kong public hospitals. Higher hospital case load is not significantly associated with better outcomes in emergency colectomy.

Evaluation of various POSSUM models for predicting mortality in patients undergoing elective oesophagectomy for carcinoma.

BACKGROUND: The aim of the study was to validate the use of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), Portsmouth (P) POSSUM and upper gastrointestinal (O) POSSUM models in patients undergoing elective thoracic oesophagectomy for carcinoma. METHODS: The observed in-hospital mortality rates in 545 patients undergoing elective thoracic oesophagectomy for squamous cell carcinoma of the oesophagus in all public hospitals in Hong Kong was compared with rates predicted by POSSUM, P-POSSUM and O-POSSUM. The discriminatory power of these models was assessed using receiver-operator characteristic (ROC) curve analysis. RESULTS: The observed mortality rate was 5.5 per cent, whereas rates predicted by POSSUM, P-POSSUM and O-POSSUM were 15.0, 4.7 and 10.9 per cent respectively. P-POSSUM showed no lack of fit (P = 0.814), but POSSUM (P < 0.001) and O-POSSUM (P = 0.002) showed lack of fit against observed mortality. POSSUM overpredicted mortality across nearly all risk groups, whereas O-POSSUM overpredicted mortality in patients with low physiological scores and in older patients. POSSUM (area under ROC curve 0.776) and P-POSSUM (0.776) showed equally good discriminatory power but O-POSSUM (0.676) was inferior. CONCLUSION: P-POSSUM provided the most accurate prediction of in-hospital mortality in this group of patients who had elective oesophagectomy.

Types of optometric testing emphasized in different practice modes.

BACKGROUND: In order to determine if tests performed in an examination vary with practice settings, we surveyed all 5,200 California licensed optometrists and asked them to identify their primary mode of practice and the percentage of time and/or frequency that certain test procedures were done in an eye examination. METHODS: We restricted our analysis to three practice modes: private, corporate, and nonprofit/health maintenance organization (NP/HMO). We received a 66.4 percent response rate. To determine any trends in emphasis of testing by the three practice modes and to establish relationships between the three, we compared each mode of practice to the other. The combinations were private vs. corporate, corporate vs. NP/HMO, and private vs. NP/HMO. The three combinations were compared to the frequency of performing case history, stereo acuity testing, binocular vision testing, biomicroscopy, dilated fundus examination, tonometry and perimetry. RESULTS AND CONCLUSIONS: We found the following relationships in the frequency/emphasis of testing as statistically significant: 1) For stereopsis testing: private practices performed it more often than corporate; 2) For binocular vision testing: private practices performed it more than did either corporate or NP/HMO, corporate performed it more than NP/HMO; 3) For tonometry: corporate performed it slightly more than NP/HMO; 4) For dilation: NP/HMO performed it more than both private and corporate; and 5) For perimetry: private performed it more than both corporate and NP/HMO.

Vancomycin-induced acute interstitial nephritis.

OBJECTIVE: To report a case of acute interstitial nephritis (AIN) related to administration of vancomycin for the treatment of Staphylococcus aureus sternal wound infection, osteomyelitis, and infective endocarditis. CASE SUMMARY: Reports in the literature regarding vancomycin-induced AIN are scarce. We describe the fifth known case of AIN, in a 64-year-old white man who developed fever, maculopapular rash, acute renal failure, eosinophilia, and eosinophiluria after approximately 1 month of vancomycin treatment. The results of the renal biopsy were consistent with an allergic drug reaction. Four months after his initial episode of AIN, the patient was rechallenged with vancomycin for the treatment of S. aureus septic arthritis. One day after initiation of vancomycin, serum eosinophils started to rise, his urine tested positive for eosinophils, but his serum creatinine remained stable. CONCLUSIONS: Our case report and others from the literature suggest vancomycin causes allergic AIN. Clinicians should be aware of this adverse effect in an era of increasing use of vancomycin for treatment of resistant gram-positive organisms.