bluuebunny/crossref_metadata_2025 huggingface dataset:
EZETIMIBE IN HYPERCHOLESTEROLAEMIA
Authors: Farnier M
Published: April 2023

Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors, compounds that effectively block intestinal absorption of dietary and biliary cholesterol, without affecting absorption of fat soluble vitamins or triglycerides. Ezetimibe underwent glucuronidation to a single metabolite and localised at the intestinal wall, where it prevented luminal cholesterol absorption. Pre‐clinical studies demonstrated the lipid‐lowering and antiatherosclerotic properties of ezetimibe. The efficacy and safety of ezetimibe monotherapy have been determined in phase ll/lll studies: in phase II studies, the optimal efficacy was reached with ezetimibe 10 mg per day and the pooled efficacy data have shown that ezetimibe 10 mg has a positive effect on the lipoprotein profile with a significant reduction in LDL‐cholesterol of 18.5%, an increase in HDL‐cholesterol of 3.5% and a trend towards lowering in triglyceride concentrations (‐4.9%). The monotherapy phase III studies have confirmed the efficacy with a decrease in LDL‐C of 17.4% and have demonstrated an excellent safety and tolerability profile. The potential for a pharmacokinetic and/or pharmacodynamic interaction between ezetimibe and various statins and the efficacy and safety or the co‐administration of ezetimibe and statins have been evaluated in different phase l/ll studies: ezetimibe had no significant effect on the pharmacokinetics of simvastatin or atorvastatin. Ezetimibe 10 mg co‐administrated with the starting dose of any statin induced a mean 18% additive LDL‐C lowering effect. This additive 18% reduction in LDL‐C is achieved in one step compared with the three steps necessary with statin monotherapy.
MANAGEMENT OF OSTEOPOROSIS IN AN ORTHOPAEDIC DEPARTMENT: AUDIT IMPROVES PRACTICE
Authors: Charalambous CP , Kumar S , Tryfonides M , Rajkumar P , Hirst P
Published: April 2023

Patients presenting with an osteoporosis‐related fracture are at increased risk of further fractures. We performed a retrospective survey to determine if elderly patients presenting to the orthopaedic unit at Manchester Royal Infirmary with low energy hip or distal radius fractures were being managed appropriately with regards to assessment, investigation and treatment for possible osteoporosis. The initial survey demonstrated that only 16% of elderly female patients with low energy hip fractures and none of those (0%) with distal radius fractures were started on treatment or referred for further investigations for possible osteoporosis. After changes in our practice, 76% (p<0.00001) of patients with hip fractures and 81% (p<0.00001) of those with distal radius fractures were investigated, started on treatment or referred to a consultant physician for the management of osteoporosis.
GIANT SIGMOID DIVERTICULUM CAUSING COLONIC AND URINARY OBSTRUCTION
Authors: Bann SD , Karanjia ND
Published: April 2023

Diverticulosis of the colon is a fairly common disease, but a solitary giant diverticulum is relatively rare. This case presented with symptoms of urinary and bowel obstruction.
A PHARMACOKINETIC COMPARISON OF THE MODIFIED RELEASE CAPSULE AND A PLAIN TABLET FORMULATION OF MEBEVERINE
Authors: Winsemius A , Meuwsen I , Boon C , Van Der Laan A , Brekle A , De Vries M
Published: April 2023

This study was conducted to compare the pharmacokinetic properties of the modified release 200 mg capsule of mebeverine and the plain 135 mg tablet of mebeverine after single and multiple doses in 12 healthy subjects in a randomised, crossover design. Single doses were given on days 1 and 7 and multiple doses (200 mg b.i.d. for the capsule and 135 mg t.i.d. for the tablet) on days 2–6 of the study. The 200 mg modified release capsule of mebeverine has extended release Properties, as indicated by a lower Cmax, a later tmax and a longer elimination half‐life than the plain tablet, while the bioavailability is optimal. No significant accumulation occurs after multiple doses of either formulation. The twice‐daily dosage regimen of the 200 mg modified release capsule is a good alternative to the three times daily dosage regimen of the 135 mg plain tablet, because the reduced daily intake is likely to benefit patient compliance.
A SYSTEMATIC APPROACH TO ERECTILE DYSFUNCTION IN THE CARDIOVASCULAR PATIENT: A CONSENSUS STATEMENT – UPDATE 2002
Authors: Jackson G , Betteridge J , Dean J , Eardley I , Hall R , Holdright D , Holmes S , Kirby M , Riley A , Sever P
Published: April 2023

EXECUTIVE SUMMARY

Sexual activity is no more stressful to the heart when compared with a number of other natural daily activities, e.g. walking one mile on the level in 20 minutes.

The cardiac risk of sexual activity in patients diagnosed with cardiovascular disease is minimal in properly assessed and advised patients.

Erectile dysfunction (ED) is extremely common, affecting over half of men aged 40–70 years, and increases in frequency with age.

ED and cardiovascular disease share many of the same risk factors and commonly coexist.

ED in the otherwise asymptomatic man may be a marker for underlying coronary artery disease.

ED in the diagnosed cardiovascular patient should be identified by routine questioning in general practice. Modern therapies can restore a sexual relationship in the majority of patients with ED and can lead to a substantial improvement in quality of life.

The majority of patients assessed to be at low or intermediate cardiac risk, as defined later in this paper, can be effectively managed in primary care. Primary care treatment for ED in patients defined as high risk can be initiated following a specialist opinion and/or confirmation that the patient's cardiovascular condition is stabilised.

There is no evidence that currently licensed treatments for ED add to the overall cardiovascular risk in patients with or without diagnosed cardiovascular disease.

If one form of therapy is not effective, follow‐up will identify the need for alternative approaches.

The pro‐active management of ED in the cardiovascular patient provides an ideal and effective opportunity to address other cardiovascular risk factors and improve treatment outcomes.
FEMALE STRESS AND URGE INCONTINENCE IN FAMILY PRACTICE: INSIGHT INTO THE LOWER URINARY TRACT
Authors: Viktrup L
Published: April 2023

As many as 25% of all women are affected by urinary incontinence, but only a few are treated. This frequent, often medically unrecognised, condition occurs in women of all ages. The continence mechanism is based on bladder detrusor control, intact anatomical structures in and around the urethra, correct positioning of the bladder neck and a comprehensive innervation of the lower urinary tract. Age and childbearing are established risk factors for the development of urinary incontinence, but other factors are currently suggested. The evaluation of urinary incontinence should include history, gynaecological examination, urine test, frequency‐volume diary and a pad‐weighing test. Female urinary incontinence can be treated in general practice by simple means, e.g. pelvic floor muscle training, bladder training, electrostimulation, drug therapy, or a combination of these approaches. This review updates the knowledge of the continence mechanism and summarises the epidemiology, risk factors, assessment and treatment of urinary incontinence in general practice.
TYPE 2 DIABETES MELLITUS AND THYROTOXICOSIS PRESENTING CONCURRENTLY
Authors: Shah D , Turnbull CJ
Published: April 2023

The symptoms of thyrotoxicosis and diabetes mellitus can be quite similar, and in patients presenting with diabetes, thyrotoxicosis could be missed unless specifically tested for. There are few reports of the two conditions presenting at the same time. We report on two such cases. In a patient who is diagnosed as having both conditions concurrently, an oral glucose tolerance test should be repeated after successful treatment of thyrotoxicosis before a diagnosis of diabetes mellitus is made.
DONEPEZIL: TOLERABILITY AND SAFETY IN ALZHEIMER'S DISEASE
Authors: Pratt RD , Perdomo CA , Surick IW , Ieni JR
Published: April 2023

The tolerability and safety of donepezil HCI in patients with mild to moderate Alzheimer's disease (AD) were examined in an integrated analysis of phase ll/lll placebo‐controlled trials. Patients with mild to moderately severe AD (n=1920) were randomised to receive donepezil (n=1291) or placebo (n=629). Adverse events, physical examinations and clinical laboratory tests were assessed. A high completion rate (79%) was achieved in these trials. Of the 1291 patients receiving donepezil only, 142 (11%) withdrew because of an adverse event compared with 43 of the 629 (7%) placebo patients. The most common adverse events included nausea, diarrhoea, headache, insomnia, dizziness, rhinitis, vomiting, asthenia/fatigue and anorexia. Donepezil had no clinically significant effect on any laboratory evaluations and was not associated with hepatotoxicity. These results demonstrate that donepezil is well tolerated and has a favourable safety profile at clinically effective, once‐daily doses of 5 mg and 10 mg.
GUIDEWIRE‐INDUCED DISSECTION OF THE RIGHT CORONARY ARTERY AND ADJACENT AORTIC WALL DURING PERCUTANEOUS CORONARY ANGIOPLASTY
Authors: Hung M‐J , Kuo L‐T , Wang C‐H , Cherng W‐J
Published: April 2023

We describe two patients in whom right coronary artery dissection and retrograde dissection of the sinus of Valsalva occurred during guidewire advancement for percutaneous coronary angioplasty. Both patients were treated successfully by coronary stenting. These cases illustrate that contrast medium injection can detect early complications during guidewire advancement for coronary intervention.
ACUTE CEREBELLAR ATAXIA ASSOCIATED WITH CHICKENPOX
Authors: Saab M , Wadhwa V
Published: April 2023

A case of a child with acute cerebellar ataxia associated with chickenpox virus infection is described. Acute cerebellar ataxia associated with chickenpox is a well‐recognised complication and the pertinent features of this condition are discussed.
IS DAILY MVI REQUIRED IN PATIENTS RECEIVING PARENTERAL NUTRITION?
Authors: Firdose R , Chalekson J , Leonard J , Smith M , Elamin EM
Published: April 2023

Between November 1996 and January 1999 there was a nationwide shortage of intravenous multivitamins (MVI) in the US. We investigated whether patients who received parenteral nutrition (PN) with MVI three times per week instead of daily developed clinical manifestations of vitamin deficiency during that period. Five patients were enrolled in the study. All received home PN as their sole source of nutrition for at least six months. None of these patients showed clinical manifestations of vitamin deficiency. In addition, compared to daily MVI administration, supplementation with MVI three times per week saved $1000 per patient per year. This preliminary study raises the question of how much MVI is needed to prevent vitamin deficiency. Using MVI three days a week instead of daily would substantially reduce the cost of treatment and might reduce the risk of infections for these patients.
SHOCK WAVES DO MORE THAN JUST CRUSH STONES: EXTRACORPOREAL SHOCK WAVE THERAPY IN PLANTAR FASCIITIS
Authors: Rajkumar P , Schmitgen GF
Published: April 2023

Heel pain is a common orthopaedic problem, The cause of this clinical entity remains an enigma. The overall prognosis is good, however, and the symptoms generally settle well with time. There appears to be little evidence of the effectiveness of local steroid injections and dorsiflexion night splints. Extracorporeal shock wave therapy (ECSW) has been used in orthopaedics since the 1980s. With this, a new tool has become available for the treatment of plantar fasciitis, achillis tendinitis, shoulder pain and tendinosis of the elbow. In our pilot study we found good results with the use of ECSW therapy in resistant plantar fasciitis. Additional controlled studies are required to define the precise role of this new modality in the treatment of chronic plantar fasciitis.
19. MALE BREAST CANCER: AETIOLOGY, GENETICS AND CLINICAL MANAGEMENT
Authors: Tischkowitz MD , Hodgson SV , Fentiman IS
Published: April 2023

Male breast cancer (MBC) is a rare disease with an older average age of presentation than in women. Predisposing factors include increased exposure to oestrogen and being a carrier of a BRCA2 mutation. Most MBC is ductal and the majority are oestrogen receptor positive. Modified radical mastectomy is the treatment of choice for local disease and adjuvant radio‐, hormonal and chemotherapy should all be considered. Stage for stage, the prognosis for MBC is similar to that for female breast cancer. Despite a wealth of small retrospective studies on MBC, its rarity means there is a lack of prospective randomised controlled treatment trials, which needs to be addressed if significant advances are to be made in the treatment of this unusual and challenging disease.
20. ORAL CONTRACEPTIVES, HORMONE REPLACEMENT THERAPY AND BREAST CANCER
Authors: Fentiman IS
Published: April 2023

Both oral contraceptives (OCs) and hormone replacement therapy (HRT) are widely used by healthy women, so that any increase in breast cancer has to be considered in relation to the avoidance of either pregnancy or menopausal symptoms. Use of OCs for more than four years before first full term pregnancy leads to a small but significant increase in risk of breast cancer (6.5 extra cases per 10,000 women aged 20–29) that persists for 10 years after cessation. Risk is not amplified by a positive family history and OC‐induced breast cancers are more likely to be localised to the breast. For those taking HRT there is an increased relative risk of breast cancer of 2.3% per year, similar to the increase in risk for each extra year spent in a premenopausal state. The increase in risk disappears five years after cessation. HRT does not lead to any increase in risk of dying of breast cancer. Some breast cancer patients can safely take HRT, and it is possible that some formulations may reduce the subsequent risk of relapse.
HIGH DENSITY LIPOPROTEIN: GUARDIAN OF THE VASCULAR SYSTEM?
Authors: Packard C , Nunn A , Hobbs R ,   members of the Future Forum Editorial Board*
Published: April 2023

The role of low‐density lipoprotein in the development of coronary heart disease (CHD) is well recognised. There is also growing evidence that high‐density lipoprotein cholesterol (HDL‐C) is a powerful inverse predictor for premature CHD and that maintaining a high HDL‐C level may guard against atherosclerosis. Patients with low HDL‐C levels often also have central obesity, insulin resistance and other features of the metabolic syndrome. This syndrome is both increasingly common and strongly implicated in the growing worldwide epidemic of type 2 diabetes. HDL‐C may be increased by lifestyle changes, e.g. weight loss, physical activity and smoking cessation. Pharmacological agents such as fibrates, niacin and statins have also been shown significantly to elevate HDL‐C. Although current guidelines are beginning to recognise the protective role of HDL‐C level in preventing coronary events, HDL‐C should be adopted soon as a target for intervention in its own right.
A HYALURONAN PREPARATION (500–730 KDA) IN THE TREATMENT OF OSTEOARTHRITIS: A REVIEW OF CLINICAL TRIALS WITH HYALGAN®
Authors: Maheu E , Ayral X , Dougados M
Published: April 2023

The purpose of this paper is to review the intra‐articular treatment of osteoarthritis (OA) of the knee with the hyaiuronan preparation 500–730 kDa (Hyalgan®). Reviewing the results of 24 clinical trials, it can be concluded that 3–5 weekly injections of Hyalgan significantly improve the pain and functional status of patients with OA. Although the onset of improvement is delayed by 3–4 weeks, the effect can last at least six months and up to one year after treatment cessation. The benefits of Hyalgan compared with intra‐articular corticosteroids are also addressed. The potential for Hyalgan to have a structure‐modifying action by retarding stuctural progression in OA of the knee is considered. However, further studies of Hyalgan in OA in other joints, and in damaged joints in rheumatoid arthritis, are needed.
DOUBLE DISLOCATION OF THE PROXIMAL AND DISTAL INTERPHALANGEAL JOINTS OF THE LITTLE FINGER
Authors: Charalambous CP , Rajkumar P , Samarj1 R
Published: April 2023

A 32‐year‐old amateur goalkeeper sustained simultaneous dislocation of the proximal and distal interphalangeal joints following a hyperextension injury. This was reduced under a digital nerve block. Neighbour finger strapping and early mobilisation achieved a full range of movements at both joints when reviewed three weeks after the initial injury.
ORBITAL CELLULITIS: A REVIEW OF 21 CASES FROM IBADAN, NIGERIA
Authors: Bekibele CO , Onabanjo OA
Published: April 2023

This study was set up to review cases of orbital cellulitis admitted to the eye ward of our hospital between 1994 and 1998, and to compare the findings with similar studies. Twenty‐one (14 males, 7 females, age range 45 days to 50 years [mean 13 years]) of 35 patients with an initial diagnosis of orbital cellulitis were reviewed (14 patients were excluded from the final analysis). Most of the cases were associated with pansinusitis, the commonest organism isolated being Staphylococcus aureus. All the patients were co‐managed with ortorhinolaryngologists, and sometimes also with bacteriologists and paediatricians. Seventy‐five per cent of the patients made a full recovery. Complications included orbital abscess (28.6%), optic atrophy (10%), cornea opacities (10%) and seizures (5%). Orbital cellulitis remains a childhood infection with potentially devastating consequences. There appears to have been a reduction not only in the number of cases admitted to the eye ward but also in the number and severity of complications. Prompt treatment and a multidisciplinary approach to management may be partly responsible for the improved outcome. This approach therefore needs to be encouraged.
QUALITY OF LIFE AFTER USE OF THE PATIENT ACTIVATED ATRIAL DEFIBRILLATOR
Authors: Spurrell P , Mitchell A , Kamalvand K , Sulke N
Published: April 2023

The aim of the study was to evaluate the effects of long‐term use of the patient‐activated atrial defibrillator for recurrent persistent atrial fibrillation (AF) on quality of life (QOL). Fifteen patients were implanted with the Medtronic Jewel AF 7250 device (dual chamber atrial and ventricular defibrillator) for AF only. AF recurrences were treated by out‐of‐hospital patient‐activated atrial defibrillation shocks following the self‐administration of oral sedation. QOL was assessed at pre‐implant and up to one year with SF36, symptom checklist and HADS questionnaires. A total of 238 (median 10) out‐of‐hospital patient‐activated atrial defibrillation shocks were performed. The SF36 demonstrated a trend toward improvement over the 12‐month period compared with baseline values. There was no significant change in the symptom frequency or severity scores. Pre‐implant levels of both anxiety and depression were within the predefined range of normality (6±3 and 3±2, respectively) and no significant change was seen at 6 months (5±4 and 3±3) or 12 months post implant (5±4 and 2±2, respectively). After one year of follow‐up, 13 (87%) patients said they would have the device implanted again (two were undecided). The study demonstrates that patient‐activated atrial defibrillation is a well tolerated therapeutic strategy for maintaining sinus rhythm.
ARIPIPRAZOLE: A REVIEW OF ITS PHARMACOLOGY AND CLINICAL USE
Authors: Taylor DM
Published: April 2023

Atypical antipsychotics generally have a lower propensity for extrapyramidal side‐effects (EPSE), hyperprolactinaemia and tardive dyskinesia than that associated with typical antipsychotics but may still produce troublesome side‐effects, such as weight gain, cardiac rhythm changes and impaired glucose tolerance. Aripiprazole is a new atypical antipsychotic with a unique receptor binding profile that combines partial agonist activity at D2 and 5HT1A receptors with potent antagonism at 5HT2A receptors. Clinical studies in acute schizophrenic relapse, chronic schizophrenia and acute mania show it is robustly more effective than placebo. Once‐daily aripiprazole 15–30 mg is as effective as haloperidol 10 mg/day and risperidone 6 mg/day in short‐term treatment of schizophrenia and more effective than haloperidol 7–10 mg/day in maintenance of response in chronic schizophrenia. Aripiprazole appears to be well tolerated, with most studies suggesting a frequency of adverse effects similar to placebo. Aripiprazole seems not to cause significant EPSE, hyperprolactinaemia, excessive weight gain or cardiac rhythm disturbance. Limited data suggest that aripiprazole is not associated with impaired glucose tolerance.
UPPER AIRWAY OBSTRUCTION IN A YOUNG ADULT
Authors: Hayward H , McParland P , Schuster‐Bruce M , Vassallo M
Published: April 2023

Acute epiglottitis is a potentially rapidly fatal illness. Although commonly thought of as a disease affecting children, it is increasingly being diagnosed in adults. We report a case of upper airway obstruction due to epiglottitis in a 37‐year‐old female. The need for early diagnosis because of the risk of a fatal outcome is highlighted.
THE EXPRESS STUDY: PRELIMINARY RESULTS
Authors:   Preliminary results presented at the 17th International Congress on Thrombosis in Bologna, Italy, 26–30 October 2002, Eriksson Bengt , Ansell Jack , Agnelli Giancarlo , Dahl Ola , Owen Olwen Glynn
Published: April 2023

The phase III trial EXPRESS was a randomised, double‐blind comparison of two anticoagulant therapies used as prophylaxis against venous thromboembolism (VTE) during major elective orthopaedic surgery. The investigational treatment was ximelagatran/melagatran (Exanta), a new direct thrombin inhibitor in both its oral and subcutaneously injectable forms; the comparator was the low molecular weight heparin enoxaparin. Results showed ximelagatran/melagatran was highly statistically significantly superior to enoxaparin in preventing VTE with a relative risk reduction in proximal deep vein thrombosis plus pulmonary embolism of 63.3% (p<0.000002). The relative risk reduction for total VTE was 23.6% (p<0.0003). There were no differences in clinically important bleeding events (fatal bleeding, critical organ bleeding and bleeding requiring reoperation) but excess bleeding assessed subjectively was more common in the ximelagatran group than in the enoxaparin group.
MANAGEMENT OF LIFE‐THREATENING EPISTAXIS IN A JEHOVAH'S WITNESS
Authors: Stark RD , Coatesworth AP , Tucker AG
Published: April 2023

The religious beliefs of Jehovah's Witnesses forbid them to receive blood or blood products. We report a case of life‐threatening epistaxis in a Jehovah's Witness, causing severe anaemia (Hb 2.7 g/dl). The successful management of this case and literature relating to this are discussed.
Morphology‐controlled therapeutic activity of cerium oxide nanoparticles for mild traumatic brain injury
Authors: Youn Dong Hyuk , Tran Ngoc Minh , Nguyen Thanh Nhan , Cho Sung Min , Jung Harry , Lee Aran , Kim Jinhee , Kim Nayoung , Jeon Jin Pyeong , Yoo Hyojong
Published: April 2023

The design and optimization of nanostructures with unique morphologies and properties are at the forefront of biomedical nanotechnology. Cerium oxides are widely used to investigate the effect of morphology on performance. However, elucidating the morphology–activity relationship of cerium oxide nanocrystals in biomedical applications remains challenging. Herein, the therapeutic effects of cerium oxide nanoparticles with different morphologies: cerium oxide nanorods with two different aspect ratios (CeOx NRs_A and CeOx NRs_B), cerium oxide nanopolyhedra (CeOx NPs), and cerium oxide nanocubes (CeOx NCs) are investigated in in vivo and in vitro mild traumatic brain injury (TBI) models. Cerium oxide nanoparticles inhibit oxidative stress and inflammation after mild TBI, alleviating cognitive impairment; furthermore, the therapeutic effect is significantly affected by their morphology. Owing to the higher Ce3+/Ce4+ ratio, exposure of more active crystal surfaces, and greater number of exposed oxygen vacancies, CeOx NRs show better activity than CeOx NPs and CeOx NCs for mild TBI. Among the two investigated types of cerium oxide nanorods, CeOx NRs_A, with a higher Ce3+/Ce4+ ratio on the surface, appear to spread better than CeOx NRs_B in the injured lesions. The factors causing morphology‐controlled biomedical performance, such as Ce3+/Ce4+ molar ratio, surface area, and aspect ratio, are discussed.
Impact of the COVID‐19 pandemic on the glycemic control in people with diabetes mellitus: A retrospective cohort study
Authors: Ohkuma Kanako , Sawada Mika , Aihara Masakazu , Doi Shunsuke , Sekine Rie , Usami Satoshi , Ohe Kazuhiko , Kubota Naoto , Yamauchi Toshimasa
Published: April 2023

Aim

To investigate the impact of the COVID‐19 pandemic and its preventive measures on the glycemic and lipid control in people with diabetes mellitus (DM).

Materials and methods

We conducted this retrospective cohort study from April 2019 to March 2021; we termed the period from April 2019 to March 2020 as the pre‐COVID‐19 period, and the period from April 2020 to March 2021 as the COVID‐19 period, and divided each of these two periods into four quarters.

Results

In the 1st quarter of the COVID period, when the Japanese government declared the first public health emergency, 3,465 people with diabetes mellitus were receiving treatment, which was 10.4% lower than that in the pre‐COVID period. The annual mean HbA1c level was significantly elevated in the COVID‐19 period. The annual mean total cholesterol (TC) and triglyceride (TG) levels were also significantly higher in the COVID‐19 period. Although there were no significant differences in the glycemic control or annual medication between the two periods in people with type 1 diabetes mellitus, the annual mean HbA1c, TC, and TG levels were significantly higher in the COVID‐19 period in people with type 2 diabetes mellitus. Furthermore, a significant increase in the percentage of prescriptions for glinides, biguanides, sodium‐glucose cotransporter 2 inhibitors, and glucagon‐like peptide‐1 receptor agonists for people with type 2 diabetes mellitus was observed in the COVID period.

Conclusions

It appears from our study that COVID‐19 and its preventive measures had a negative impact on the glycemic and lipid control in people with diabetes mellitus.
Detecting Differential Item Functioning in CAT Using IRT Residual DIF Approach
Authors: Lim Hwanggyu , Choe Edison M.
Published: April 2023

The residual differential item functioning (RDIF) detection framework was developed recently under a linear testing context. To explore the potential application of this framework to computerized adaptive testing (CAT), the present study investigated the utility of the RDIFR statistic both as an index for detecting uniform DIF of pretest items in CAT and as a direct measure of the effect size of uniform DIF. Extensive CAT simulations revealed RDIFR to have well‐controlled Type I error and slightly higher power to detect uniform DIF compared with CATSIB, especially when pretest items were calibrated using fixed‐item parameter calibration. Moreover, RDIFR accurately estimated the amount of uniform DIF irrespective of the presence of impact. Therefore, RDIFR demonstrates its potential as a useful tool for evaluating both the statistical and practical significance of uniform DIF in CAT.
Chinese expert consensus on the application of live combined Bifidobacterium, Lactobacillus, and Enterococcus powder/capsule in digestive system diseases (2021)
Authors: Fang Jingyuan , Yang Yunsheng , Xie Weifen
Published: April 2023

Background and Aim

Disturbance of gut microbiota is associated with pathological change in multiple diseases. Probiotics can improve symptoms and exert clinical effects via regulation of gastrointestinal microecological environments, and a probiotic product commonly dispensed by Chinese physicians is a combination of live Bifidobacterium, Lactobacillus, and Enterococcus in powder/capsule form. It contains three strains—of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis—which can act synergistically to balance the microbiome, regulate immunity, and repair the gut barrier. Although this product has been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat digestive system diseases. To date, there have been no reference standards to guide clinical practice and no relevant expert consensus on this product, in China.

Methods

Following a literature search, evidence was graded and classified according to the grading of recommendations assessment, development, and evaluation (GRADE) system and consensus was secured from a panel of 52 experts.

Results

An expert consensus has been formed, on the clinical application of live combined Bifidobacterium, Lactobacillus, and Enterococcus in various digestive system diseases, to provide reference for its clinical use.

Conclusions

Bifidobacterium triple viable powder/capsule may offer benefits, by regulating the balance of intestinal microecology. It can be used for the treatment and prevention of various digestive system diseases with good overall safety; further research is needed to confirm its application in other contexts. The recommendations in this consensus will be confirmed or refined in light of future research and clinical practice.
Revisiting Real Wage Rigidity
Authors: ELLINGTON MICHAEL , MARTIN CHRIS , WANG BINGSONG
Published: April 2023

In this paper, we provide empirical evidence that real wage rigidity is not a major cause of unemployment volatility. We argue that there is a disconnect between the theoretical and empirical literatures on this topic. While theoretical studies define real wage rigidity as the response of wages to changes in unemployment following productivity shocks, the empirical literature measures real wage rigidity as the estimated semi‐elasticity of wages with respect to unemployment, averaged over all shocks. We show that averaging over shocks gives a biased measure of real wage rigidity, as the impact of other shocks confounds the response to productivity shocks. Our results indicate that the estimated semi‐elasticity with respect to productivity shocks is twice as large as the estimated semi‐elasticity averaged over all shocks. This implies that one cannot attribute unemployment volatility to real wage rigidity.
Diversity under the microscope: Lessons for building belonging in interdisciplinary spaces from the Women in Imaging + Industry bootcamp
Authors: Esbin Meagan , Blackmon Lena
Published: April 2023

As scientific projects and labs benefit from increasingly interdisciplinary expertise, students and trainees find themselves navigating a myriad of academic spaces, each with its own workplace culture and demographics. A clear example is the interdisciplinary field of optics and biological microscopy which bridges biology, physics and engineering. While Biology PhDs are now >50% women, men in physics and engineering fields still significantly outnumber women, resulting in an imbalance of gender representation among microscopists and other ‘tool innovators’ in the interdisciplinary field of biological microscopy and biomedical optics. In addition to the cultural and cognitive whiplash that results from disparate representation between fields such as Biology, Engineering, and Physics, indifference from institutional leaders to implement equity‐focused initiatives further contributes to cultures of exclusion, rather than belonging, for women. Here we elaborate on the motivation, structure, and outcomes of building a specific affinity‐based bootcamp as an intervention to create an inclusive, welcoming learning environment for women in optics. Considering the presence of nonbinary, trans and other gender minoritised scientists, we recognise that women are not the only gender group underrepresented in biological microscopy and biomedical optics; still, we focus our attention on women in this specific intervention to improve gender parity in biological microscopy and biomedical optics. We hope that these strategies exemplify concrete paths forward for increasing belonging in interdisciplinary fields, a key step towards improving and diversifying graduate education.
An innovative phase 2 proof‐of‐concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy
Authors: Querol Luis , Lewis Richard A. , Hartung Hans‐Peter , Van Doorn Pieter A. , Wallstroem Erik , Luo Xiaodong , Alonso‐Alonso Miguel , Atassi Nazem , Hughes Richard A. C.
Published: April 2023

Background and Aims

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune‐mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open‐label phase 2 study (NCT04658472) evaluating efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in CIDP.

Methods

This phase 2, proof‐of‐concept, multicenter, open‐label trial will evaluate the efficacy, and safety of SAR445088 in 90 patients with CIDP across three groups: (1) currently treated with standard‐of‐care (SOC) therapies, including immunoglobulin or corticosteroids (SOC‐Treated); (2) refractory to SOC (SOC‐Refractory); and (3) naïve to SOC (SOC‐Naïve). Enrolled participants undergo a 24‐week treatment period (part A), followed by an optional treatment extension for up to an additional 52 weeks (part B).

In part A, the primary endpoint for the SOC‐Treated group is the percentage of participants with a relapse after switching from SOC to SAR445088. The primary endpoint for the SOC‐Refractory and SOC‐Naïve groups is the percentage of participants with a response, compared to baseline. Secondary endpoints include safety, tolerability, immunogenicity, and efficacy of SAR445088 during 12‐week overlapping period (SOC‐Treated). Part B evaluates long‐term safety and durability of efficacy. Data analysis will be performed using Bayesian statistics (predefined efficacy thresholds) and historical data‐based placebo assumptions to support program decision‐making.

Interpretation

This innovative trial design based on patient groups and Bayesian statistics provides an efficient paradigm to evaluate new treatment candidates across the CIDP spectrum and can help accelerate development of new therapies.
Associations between temporomandibular disorders, pain, jaw and masticatory function in dentofacial deformity patients: A cross‐sectional study
Authors: Madhan Sivaranjani , Nascimento Gustavo G. , Ingerslev Janne , Cornelis Marie , Pinholt Else Marie , Cattaneo Paolo M. , Svensson Peter
Published: April 2023

Background and objective

Patients with dentofacial deformity often present with impaired masticatory function, orofacial pain and temporomandibular disorders (TMD). This study investigates the relationship between TMD, pain, jaw and masticatory function at different stages of orthognathic surgical (OS) treatment.

Methods

A total of 120 OS patients were prospectively recruited and grouped as pre‐orthodontic (group 1), pre‐surgery (group 2), 4‐month post‐surgery (group 3), 24‐month post‐surgery (group 4), in addition to 30 controls (group 0). Outcomes were assessed using: Jaw Function Limitation Scale (JFLS), McGill pain questionnaire, DC/TMD instrument, voluntary maximum bite force (MVBF), and masticatory efficiency (ME) using two‐coloured chewing gum. Data were analysed using structural equation modelling.

Results

The prevalence of non‐painful TMD did not differ between groups (p = .827). However, the prevalence of painful TMD differed between groups (p = .001). Among the painful TMDs, the highest prevalence was observed for masseter myalgia in group 2 (p = .031), and importantly group 4 did not differ from group 0 (p = .948). The MPQ score was significantly higher in group 1 (p = .001) compared to group 0, and the JFLS score was significantly higher in groups 1, 2 and 3 compared to group 0. Notably, MPQ (p = .756) and JFLS (p = .572) scores in group 4 were not different from group 0. However, MVBF (p = .996) and ME (p = .991) did not differ between groups 1 and 4. The association of self‐reported pain and jaw function with the masticatory function was observed in OS patients.

Conclusion

OS was not associated with a negative impact on TMD. Jaw function and pain levels were similar to controls at the 24‐month follow‐up. The masticatory function was further affected by the surgery and seems to require a longer recovery time. Moreover, it was confirmed that pain and TMD were associated with limitations in jaw function and impacts on masticatory function.
Effects of pork fat and linseed oil as additives on gel quality of fish cake
Authors: Liu Yu , Huang Yizhen , Zhang Lin , Li Shengjie , Cheng Qiaofen , Zhu Beiwei , Dong Xiuping
Published: April 2023

Pork fat (PF) is a necessary ingredient in making traditional fish cakes (TFCs), which contains saturated fatty acids with potential health concerns. While linseed oil (LO) containing α‐linolenic acid is a potential nutrient‐enhancing fat substitute. In this study, the effect of pork fat and linseed oil level on gel quality, sensory characteristics, microstructure, and protein conformation of TFCs were characterized. Results showed that the TFCs with 30% pork fat (wt/wt) had the highest gel strength. Additionally, sensory evaluation determined that TFCs with 30% pork fat scored the best by a sensory panel with high gel strength, water‐holding capacity, and fresh and sweet taste. The gel strength, chewiness, and hardness of nutrient‐enriched fish cakes with 20% linseed oil replaced for pork fat were higher than that only with pork fat (wt/wt) without changing in tenderness and elasticity. Visual results showed that the network was uniform at a moderate level of linseed oil addition (20% LO/PF replacement ratio). The results of this study provided technical guidelines for standardizing the TFC manufacture processes, and useful insight for the development of fish cakes with reduced animal fat content for additional health benefits for consumers.
Concurrent chronic lymphocytic leukemia and primary hyperparathyroidism in a mule
Authors: Townsend Kile S. , Johnson Philip J. , Donnelly Lindsay L. , LaCarrubba Alison M. , Lattimer James C. , Havis Brett , Springer Nora L. , Kim Dae Y.
Published: April 2023

A 26‐year‐old mule gelding was evaluated for chronic weight loss and decreased appetite. The mule had been losing weight and intermittently hypophagic for approximately 7 months. Laboratory analysis of whole blood and plasma identified severe total hypercalcemia, marked hypophosphatemia, markedly increased parathyroid hormone concentration, and marked lymphocytosis. A sestimibi scan intended to identify parathyroid gland tissue was nondiagnostic. Results of flow cytometry and PCR for antigen receptor rearrangement (PARR) were consistent with a B cell lymphoproliferative disorder, likely chronic lymphocytic leukemia (CLL). Although not previously described concurrently, these conditions may sometimes arise together, complicating definition of the underlying mechanism for weight loss and hypercalcemia in aged equids.
Weak antagonistic fitness effects can maintain an inversion polymorphism
Authors: Pei Yifan , Forstmeier Wolfgang , Knief Ulrich , Kempenaers Bart
Published: April 2023

The study of chromosomal inversion polymorphisms has received much recent attention, particularly in cases where inversions have drastic effects on phenotypes and fitness (e.g. lethality of homozygotes). Less attention has been paid to the question of the maintenance of inversion polymorphisms that show only weak effects. Here, we study the maintenance of such an inversion polymorphism that links 250 genes on chromosome Tgu11 in the zebra finch (Taeniopygia guttata). Based on data from over 6000 captive birds, we estimated the effects of this inversion on a wide range of fitness‐related traits. We found that, compared with the ancestral allele A, the inverted allele D had small additive beneficial effects on male siring success and on female fecundity. These fitness‐enhancing effects may explain the initial spread of the derived D allele (allele frequency 53%). However, individuals that were homozygous for D had a slightly lower survival rate, which may explain why the D allele has not spread to fixation. We used individual‐based simulations to examine how an inversion polymorphism with such antagonistic fitness effects behaves over time. Our results indicate that polymorphisms become stabilized at an intermediate allele frequency if the inversion links an additively beneficial allele of small effect size to a recessive weakly deleterious mutation, overall resulting in weak net heterosis. Importantly, this conclusion remains valid over a wide range of selection coefficients against the homozygous DD (up to lethality), suggesting that the conditions needed to maintain the polymorphism may frequently be met. However, the simulations also suggest that in our zebra finch populations, the estimated recessive deleterious effect of the D allele (on survival in captivity) is not quite large enough to prevent fixation of the D allele in the long run. Estimates of fitness effects from free‐living populations are needed to validate these results.
Simulating the effects of long‐distance dispersal and landscape heterogeneity on the eco‐evolutionary outcomes of range expansion in an invasive riverine fish, Tench (Tinca tinca)
Authors: Bernos Thaïs A. , Day Casey , Hill Jaclyn , Morissette Olivier , Jeffries Kenneth M. , Mandrak Nicholas E.
Published: April 2023

Predicting how quickly populations expand their range and whether they will retain genetic diversity when they are introduced to new regions or track environmental conditions suited to their survival is an important applied and theoretical challenge. The literature suggests that long‐distance dispersal, landscape heterogeneity and the evolution of dispersal influence populations' expansion rates and genetic diversity. We used individual‐based spatially explicit simulations to examine these relationships for Tench (Tinca tinca), an invasive fish expanding its geographical range in eastern North America since the 1990s. Simulated populations varied greatly in expansion rates (1.1–28.6 patches year−1) and genetic diversity metrics, including changes in observed heterozygosity (−19 to +0.8%) and effective number of alleles (−0.32 to −0.01). Populations with greater dispersal distances expanded faster than those with smaller dispersal distances but exhibited considerable variation in expansion rate among local populations, implying less predictable expansions. However, they tended to retain genetic diversity as they expanded, suggesting more predictable evolutionary trajectories. In contrast, populations with smaller dispersal distances spread predictably more slowly but exhibited more variability among local populations in genetic diversity losses. Consistent with empirical data, populations spreading in a longer, narrower dispersal corridor lost more neutral genetic variation to the stochastic fixation of alleles. Given the unprecedented pace of anthropogenic environmental change and the increasing need to manage range‐expanding populations, our results have conservation ramifications as they imply that the evolutionary trajectories of populations characterised by shorter dispersal distances spreading in narrower landscapes are more variable and, therefore, less predictable.
Practical wisdom in medicine through the eyes of medical students and physicians
Authors: Kaldjian Lauris C. , Yoon John , Ark Tavinder K. , Shinkunas Laura , Jotterand Fabrice
Published: April 2023

Background

Practical wisdom is considered a multidimensional virtue of enduring relevance to medicine. Though it has received increasing attention in recent years, proposed frameworks for practical wisdom can differ, and little is known about how medical students and physicians describe its dimensions and relevance.

Methods

We used structured interviews, employing open‐ended and closed‐ended questions, to describe how medical students and physicians understand practical wisdom and identify the kinds of clinical situations they believe require practical wisdom. We interviewed 102 participants at two US medical schools in 2021, comprising a voluntary response sample of 40 pre‐clinical medical students and 40 clinical medical students and a purposive sample of 22 nominated physicians. Interviews were conducted by videoconference using a structured interview guide. Open‐ended responses were coded using qualitative content analysis (directed and conventional) and tabulated; closed‐ended responses were tabulated. Quotations provided qualitative illustrations, and frequencies were used for summative results.

Results

Participants considered practical wisdom clinically meaningful, broadly relevant and multidimensional. Most described it as deliberative, goal‐directed, context‐sensitive, integrated with ethics and marked by integrity and motivation to act. Many described it as experience‐based, person‐centred or problem‐solving. Participants also selected an average of 15.6 (SD = 4.9) additional virtues as being essential for practical wisdom in medicine and described a broad range of clinical situations that require practical wisdom in medicine.

Conclusions

Participants described practical wisdom as a multidimensional capacity that entails deliberation, depends on a constellation of other virtues and is broadly applicable to medicine. Most agreed it is goal‐directed and context‐sensitive and involves ethics, integrity and motivation. Efforts to teach practical wisdom in medical education should clarify its dimensions and highlight its relationship to virtue ethics, professionalism, clinical judgement and the individualised care of patients as persons.
Interventions for supporting parents of infants requiring neonatal inter‐hospital transport: A systematic review
Authors: Mason Libuse , Marufu Takawira C. , Warren Inga , Nelson David , Cooke Samuel , Laparidou Despina , Manning Joseph C.
Published: April 2023

Background

Neonatal inter‐hospital transport is associated with heightened stress for parents whose needs may remain unmet around this time.

Aim

To identify interventions which are used to support parents whose infants require neonatal inter‐hospital transport.

Study Design

A systematic literature review approach was used. Six online databases (CINAHL, EMBASE, EMCARE, Medline, PsycINFO, Web of Science) were searched up to February 2022. The eligibility criteria included interventional studies published in the English language. Methodological quality was assessed by the Critical Appraisal Skills Programme checklists. Data were extracted using a predefined framework and synthesized narratively because of heterogeneity of reported outcomes.

Results

A total of 671 articles were screened, with five meeting the eligibility criteria. Three interventions were reported within the five studies: a communication‐based intervention before transport represented by 223 parents in one study, Kangaroo Care during transport, which was carried out with 136 infants in three studies, and video calls after transport evaluated by one study in seven parents versus a control group. The effectiveness of the interventions could not be reliably determined. Neonatal nurses were the main providers of all the interventions pre‐, peri‐, and post‐transport.

Conclusions

Limited evidence of mixed quality and inconsistent outcome measurements is available. Future research should focus on developing a contemporary intervention, determining the optimum timing for its implementation, and evaluating it using a robust study design.

Relevance to Clinical Practice

Neonatal nurses need to be aware of the importance of their role in supporting parents through the distressing time of neonatal transport.