bluuebunny/crossref_metadata_2025 huggingface dataset:
First‐in‐human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS‐penetrant soluble guanylyl cyclase stimulator
Authors: van Kraaij Sebastiaan J. W. , Gal Pim , Borghans Laura G. J. M. , Klaassen Erica S. , Dijkstra Francis , Winrow Christopher , Glasser Chad , Groeneveld Geert Jan
Published: April 2023

Soluble guanylate cyclase (sGC) and its product, cyclic guanosine monophosphate, play a role in learning and memory formation. Zagociguat (CY6463) is a novel stimulator of sGC being developed for the treatment of neurodegenerative disease. Single zagociguat doses of 0.3, 1, 3, 10, 20, 30, and 50 mg were administered once to healthy participants in a single‐ascending‐dose phase; then zagociguat 2, 5, 10, and 15 mg was administered q.d. for 14 days in a multiple‐ascending‐dose phase; and, finally, zagociguat 10 mg was administered once in both fed and fasted state in a food‐interaction phase. Safety of zagociguat was evaluated by monitoring treatment‐emergent adverse events, suicide risk, vital signs, electrocardiography, and laboratory tests. Pharmacokinetics of zagociguat were assessed through blood, urine, and cerebrospinal fluid sampling. Pharmacodynamic effects of zagociguat were evaluated with central nervous system (CNS) tests and pharmaco‐electroencephalography. Zagociguat was well‐tolerated across all doses evaluated. Zagociguat exposures increased in a dose‐proportional manner. Median time to maximum concentration ranged from 0.8 to 5 h and mean terminal half‐life from 52.8 to 67.1 h. CNS penetration of the compound was confirmed by cerebrospinal fluid sampling. Zagociguat induced up to 6.1 mmHg reduction in mean systolic and up to 7.5 mmHg reduction in mean diastolic blood pressure. No consistent pharmacodynamic (PD) effects on neurocognitive function were observed. Zagociguat was well‐tolerated, CNS‐penetrant, and demonstrated PD activity consistent with other sGC stimulators. The results of this study support further development of zagociguat.
Phoronida—A small clade with a big role in understanding the evolution of lophophorates
Authors: Gąsiorowski Ludwik
Published: April 2023

Phoronids, together with brachiopods and bryozoans, form the animal clade Lophophorata. Modern lophophorates are quite diverse—some can biomineralize while others are soft‐bodied, they could be either solitary or colonial, and they develop through various eccentric larval stages that undergo different types of metamorphoses. The diversity of this clade is further enriched by numerous extinct fossil lineages with their own distinct body plans and life histories. In this review, I discuss how data on phoronid development, genetics, and morphology can inform our understanding of lophophorate evolution. The actinotrocha larvae of phoronids is a well documented example of intercalation of the new larval body plan, which can be used to study how new life stages emerge in animals with biphasic life cycle. The genomic and embryonic data from phoronids, in concert with studies of the fossil lophophorates, allow the more precise reconstruction of the evolution of lophophorate biomineralization. Finally, the regenerative and asexual abilities of phoronids can shed new light on the evolution of coloniality in lophophorates. As evident from those examples, Phoronida occupies a central role in the discussion of the evolution of lophophorate body plans and life histories.
Cholinergic‐related pupil activity reflects level of emotionality during motor performance
Authors: Vidal Marc , Onderdijk Kelsey E. , Aguilera Ana M. , Six Joren , Maes Pieter‐Jan , Fritz Thomas Hans , Leman Marc
Published: April 2023

Pupil size covaries with the diffusion rate of the cholinergic and noradrenergic neurons throughout the brain, which are essential to arousal. Recent findings suggest that slow pupil fluctuations during locomotion are an index of sustained activity in cholinergic axons, whereas phasic dilations are related to the activity of noradrenergic axons. Here, we investigated movement induced arousal (i.e., by singing and swaying to music), hypothesising that actively engaging in musical behaviour will provoke stronger emotional engagement in participants and lead to different qualitative patterns of tonic and phasic pupil activity. A challenge in the analysis of pupil data is the turbulent behaviour of pupil diameter due to exogenous ocular activity commonly encountered during motor tasks and the high variability typically found between individuals. To address this, we developed an algorithm that adaptively estimates and removes pupil responses to ocular events, as well as a functional data methodology, derived from Pfaffs' generalised arousal, that provides a new statistical dimension on how pupil data can be interpreted according to putative neuromodulatory signalling. We found that actively engaging in singing enhanced slow cholinergic‐related pupil dilations and having the opportunity to move your body while performing amplified the effect of singing on pupil activity. Phasic pupil oscillations during motor execution attenuated in time, which is often interpreted as a measure of sense of agency over movement.
Septohippocampal cholinergic system at the intersection of stress and cognition: Current trends and translational implications
Authors: Kniffin Alyssa , Bangasser Debra A. , Parikh Vinay
Published: April 2023

Deficits in hippocampus‐dependent memory processes are common across psychiatric and neurodegenerative disorders such as depression, anxiety and Alzheimer's disease. Moreover, stress is a major environmental risk factor for these pathologies and it exerts detrimental effects on hippocampal functioning via the activation of hypothalamic–pituitary–adrenal (HPA) axis. The medial septum cholinergic neurons extensively innervate the hippocampus. Although, the cholinergic septohippocampal pathway (SHP) has long been implicated in learning and memory, its involvement in mediating the adaptive and maladaptive impact of stress on mnemonic processes remains less clear. Here, we discuss current research highlighting the contributions of cholinergic SHP in modulating memory encoding, consolidation and retrieval. Then, we present evidence supporting the view that neurobiological interactions between HPA axis stress response and cholinergic signalling impact hippocampal computations. Finally, we critically discuss potential challenges and opportunities to target cholinergic SHP as a therapeutic strategy to improve cognitive impairments in stress‐related disorders. We argue that such efforts should consider recent conceptualisations on the dynamic nature of cholinergic signalling in modulating distinct subcomponents of memory and its interactions with cellular substrates that regulate the adaptive stress response.
Studying the function of ecosystem in preventing aeolian dust emission in the dryland areas of China
Authors: Wang Xuesong , Ferreira Carla Sofia Santos
Published: April 2023

Aeolian dust emissions can cause many environmental hazards, like accelerating land degradation and desertification, polluting air, harming human health, and so on. The dryland areas of China (DAC) are hot spots of aeolian dust emissions. To date, many efforts have been paid to researching dust emissions processes and effects, but research studies on ecosystems' function in preventing dust emissions are still very limited. In this study, we investigated the function of DAC ecosystems in preventing dust emissions, and the corresponding driving factors through integrated wind erosion modelling system (IWEMS) modelling. The main results indicate that: (1) from 2001 to 2020, the ecosystems of DAC prevented the emission of dust ~40,554 Tg, approximately 15 times as much as the total actual dust emission (~2776 Tg); (2) the function of DAC ecosystems in preventing dust emissions was relatively strong in spring and winter; (3) grassland ecosystems had the strongest function in preventing dust emissions among all the land cover types, avoiding the emission of dust ~20,857 Tg over 2001–2020; (4) dust emission prevention function provided by the DAC ecosystems benefits almost every region of China, which provides a theoretical basis for formulating ecological compensation policies; and (5) the changes in dust emissions were dominated by wind speed in most areas of DAC.
Femininity work: The gendered politics of women managing violence in bar work
Authors: Coffey Julia , Farrugia David , Gill Rosalind , Threadgold Steven , Sharp Megan , Adkins Lisa
Published: April 2023

This paper explores how women bar workers manage violence at work. Women bar workers in our study described that the capacity to recognize, intervene, and defuse potentially violent situations was a pragmatic response to the problem of men's violence in the night‐time economy. We analyze the gendered norms and expectations at play in how violence in bar work is managed by staff and locate this as a form of “femininity work” extending from the modes of attentive, emotionally‐attuned femininity that labor feminist labor studies theorists have described. In a context where hospitality labor already makes complex and often unexamined demands on young workers, the positioning of women bar staff as being more adept at managing violent situations suggests a particularly important demand made of women bar workers, central for understanding the enduring gendered power relations in contemporary interactive service labor.
Preparation of MgAl2O4 solar thermal storage ceramics from different magnesium sources
Authors: Wu Jianfeng , Hao Shuai , Xu Xiaohong , Ma Sitong , Li Peixian , Shi Xinxin
Published: April 2023

In order to study the performance and feasibility of magnesia‐alumina spinel (MgAl2O4) ceramics for thermal storage in solar thermal power generation, MgAl2O4 was prepared by theoretical composition using α‐Al2O3 as aluminium source, fused magnesia, magnesite, and light burned magnesia as different magnesium sources and kaolin as additive. The effects of magnesium source and the additive on sintering properties, thermal shock resistance and thermal properties of MgAl2O4 ceramics were researched. The results shown sample A1 (with fused magnesia) sintered at 1670°C possessed the optimum comprehensive properties, the bending strength increased by 7.71% after 30 thermal shock times (room temperature‐1000°C, air cooling), the specific heat capacity was 1.05 J/ (g·K). Therefore, the MgAl2O4 ceramics exhibited great potential in high‐temperature thermal storage material.
Would you like to become a union leader? Analysing leadership intentions through a generational lens
Authors: Smith Christopher Gordon , Zhang Tingting , Frangi Lorenzo , Duxbury Linda
Published: April 2023

Identifying the next generation of leaders is fundamental for union renewal. Taking a sequential mixed methods approach using interview (n = 25) and survey (n = 4765) data, our study seeks to identify roadblocks members may face on the path to union leadership. Specifically, we explore the impact of union efficacy, perceived role ambiguity and perceived work role overload on union members' intentions to pursue a leadership role. We found perceptions of union efficacy positively influenced leadership intentions, while perceived work role ambiguity and overload had a negative impact. Generational cohort (Boomer, Gen X, Millennial) moderated the relationship between perceived work role overload and leadership intentions, but not the other relationships in the model. Findings from this study help unions develop strategies to motivate members to take on leadership roles.
RETRACTED: Risk factors for postoperative surgical site wound problems after metastatic and primary spine tumour surgery: A meta‐analysis
Authors: Zhu Jiwen , Si Mengdi , Huang Zongqiang
Published: April 2023

A meta‐analysis study was conducted to assess the risk factors (RFs) for postoperative surgical site wound problems (POSSWPs) after metastatic and primary spine tumour surgery (STS). A comprehensive literature examination until February 2023 was implemented, and 1786 linked studies were appraised. The 18 picked studies contained 18 580 subjects with surgery in the studies' baseline with and without different RFs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of RFs for POSSWPs after metastatic and primary STS using the dichotomous and continuous styles and a fixed or random model. Subjects with surgical instrumentation in their surgery had a significantly higher rate of POSSWPs in STS (OR, 2.28; 95% CI, 1.49–3.49, P < 0.001) compared with those without surgical instrumentation. Subjects with preoperative chemotherapy had a significantly higher rate of POSSWPs in STS (OR, 1.81; 95% CI, 1.09–3.00, P = 0.02) compared with those without preoperative chemotherapy. Subjects with preoperative radiotherapy had a significantly higher rate of POSSWPs in STS (OR, 1.93; 95% CI, 1.12–3.34, P = 0.02) compared with those without preoperative radiotherapy. Subjects with corticosteroid intake had a significantly higher rate of POSSWPs in STS (OR, 2.89; 95% CI, 1.73–4.82, P < 0.001) compared with those without corticosteroid intake. No significant difference was found between males and females in the rate of POSSWPs in STS (OR, 0.95; 95% CI, 0.66–1.37, P = 0.78). Surgical instrumentation, preoperative chemotherapy, preoperative radiotherapy and corticosteroid are RFs for the higher rate of POSSWPs in STS; however, gender was not shown to be a risk factor. Though precautions should be taken when commerce with the consequences since some of the studies picked for this meta‐analysis had low sample sizes.
COMPARISON OF CLARITHROMYCIN SUSPENSION AND AMOXYCILLIN SYRUP FOR THE TREATMENT OF CHILDREN WITH PHARYNGITIS AND/OR TONSILLITIS
Authors: Kearsley NL , Campbell A , Sanderson AAF , Weir RD , Kamdar MK , Coles SJ
Published: April 2023

Twenty‐three general practices in the UK randomised 229 paediatric patients (aged 1‐12 years, body weight >8 kg) with clinical evidence suggestive of streptococcal tonsillitis and/or pharyngitis in this physician‐blind study. Patients received either clarithromycin suspension (7.5 mg/kg twice daily) or amoxycillin syrup (125 mg/kg three times daily body weight <25 kg, or 250 mg/kg three times daily body weight 25 kg) for 7 days and were followed up 3‐8 days post treatment and 21‐28 days later. Clinical and microbiological assessments were made at each visit. A total of 189 patients (98 on clarithromycin and 91 on amoxycillin) were clinically evaluable. At the post‐treatment visit, clinical success rates were high and comparable: 98% on clarithromycin and 97% on amoxycillin. Streptococcus pyogenes was eradicated in 88% of clarithromycin patients and 86% of amoxycillin patients. Both treatments were well tolerated. In conclusion, clarithromycin suspension was as safe and at least as effective as amoxycillin syrup for the treatment of pharyngitis and/or tonsillitis in children, and would be a suitable alternative therapy.
EASE OF HANDLING AND CLINICAL EFFICACY OF FLUTICASONE PROPIONATE ACCUHALER/DISKUS™ INHALER COMPARED WITH THE TURBOHALER™ INHALER IN PAEDIATRIC PATIENTS
Authors: Williams J , Richards KA ,   UK Study Group
Published: April 2023

A total of 323 children aged 4‐11 years who were receiving, or had symptoms indicating a clinical requirement for, inhaled corticosteroid at a daily dose of 400 μg budesonide (BUD) or beclomethasone dipropionate (BDP), or 200 μg fluticasone propionate (FP), were randomised into this multicentre, open‐label, parallel group study. Patients received either FP 100 μg b.d. administered via the Accuhaler/Diskus inhaler (n=159) or BUD 200 μg b.d. administered via a Turbohaler inhaler (n=164) for four weeks and recorded daily their morning and evening peak expiratory flow (PEF), asthma symptoms and use of relief medication. Device handling was assessed by a questionnaire, with responses recorded on three‐ or five‐point ordinal scales. The primary efficacy parameter was mean percent predicted morning PEF. The device handling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use, ease of telling how many doses were left, ease of knowing whether a dose had been inhaled and overall liking of the device. More patients in the Accuhaler/Diskus group (85%) than in the Turbohaler group (58%) said they would be happy to receive the same device again, while 8% and 25% respectively said they would not be happy to be given it again. In addition, the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group, indicating that FP 200 μg daily via Accuhaler/Diskus inhaler is at least as clinically effective as BUD 400 μg daily via the Turbohaler inhaler.
NEW LONG‐STAY PATIENTS ON ACUTE PSYCHIATRIC UNITS: DOES AUDIT CHANGE PRACTICE?
Authors: Rowlands P
Published: April 2023

Patients who have prolonged stays on acute psychiatric wards are a feature of many modern community psychiatric services. The present study aimed to determine if the care delivered to these patients could be improved by reflecting back to practitioners easily auditable components of the patients' care. The subjects comprised patients resident on the acute psychiatric units in Sheffield for more than six months. These patients were surveyed in April 1995 and again in February 1996. After the first survey, clinicians received a presentation and feedback regarding aspects of their patients' care. The results demonstrated there had been little change in the percentage of acute bed capacity occupied by patients with inpatient stays in excess of six months, despite improvement in many of the audit standards. The main reason for prolonged inpatient treatment was continued mental state or behavioural disturbance. The mean length of stay of patients in this category actually increased. The results suggest that a simple audit exercise can improve the quality of care delivered to this group of patients, but that they will continue to occupy a substantial proportion of acute bed capacity in the absence of suitable alternative treatment settings.
BEHAVIOURAL AND PSYCHIATRIC ASPECTS OF SILENT CEREBRAL INFARCTION
Authors: Nagaratnam N , Pathma‐Nathan N
Published: April 2023

A number of psychiatric and behavioural symptoms have been described in relation to silent cerebral infarction. At least four symptom clusters were identified, namely, affective, paranoid delusional, confusional state and changes in mood with behavioural disturbances. The mechanisms involved are unclear. Biochemical changes involving neurotransmitter mechanisms, vascular compromise or structural damage to the anatomical pathways may be contributory if not causal. It is clear that in patients presenting with behavioural or psychiatric manifestations without any previous history of mental illness and without any focal or lateralising neurological signs, cerebrovascular disease should be a diagnostic consideration.
RESEARCH AND THE PROBLEMS OF LITTER AND MEDICAL WASTES ON THE UK COASTLINE
Authors: Philipp R , Pond K , Rees G
Published: April 2023

Recent research has shown that recreational water and bathing beach quality are associated with injury, infection and personal well‐being. Continued surveillance is essential to audit the environmental and associated health trends. In the Coastwatch UK project and since 1989, annual surveys each autumn have been undertaken during a two‐week study period, into the extent of littering of the UK coastline. The Public Health Laboratory Service also collects data on the use of hepatitis B immunoglobulin. In these studies it is now possible to examine time trends. The findings are not reassuring. They help to justify present concern about the health effects of discarded litter and medical waste and fears that environmental degradation could lead to loss of income from tourism. In response, some health and local authorities have started public education programmes, supplying litter bins on or near bathing beaches, emptying them regularly and undertaking beach cleansing during the summer months. The UK government is also introducing new legislation that will require 6 mm fine mesh wire screens on all shore‐based sewage outlets around the UK coastline. Continued monitoring is needed to assess the effectiveness of these interventions. The need for greater personal responsibility is particularly identified.
REACTIVE ARTHRITIS: IS IT A USEFUL CONCEPT?
Authors: Beutler AM , Schumacher HR
Published: April 2023

Reactive arthritis (ReA) is one of the most common arthritides affecting young adults. In most cases it follows urogenital or enteric bacterial infection, but its pathogenesis is not fully understood. It is generally considered a sterile arthritis which appears to involve immune response to bacterial organisms and genetic host susceptibility associated with the presence of HLA‐B27 antigen. New findings suggest that in some ReA cases, viable bacteria are present inside the joints, and these organisms may cause the disease and trigger the inflammatory response. ReA manifests clinically as a rheumatoid factor negative oligoarthritis associated with enthesopathy and certain mucosal and skin lesions. Laboratory findings in ReA are non‐specific. Although concepts of its pathogenesis are still evolving, so‐called ReA remains an important condition to be distinguished from rheumatoid arthritis. Prognosis is generally better. Treatments with known effects in some cases include non‐steroidal antiinflammatory drugs, intra‐articular corticosteroids, oral tetracyclines and sulphasalazine. The occasional chronic and severe ReA may be very difficult to treat.
PLACENTAL CHORIOANGIOMA: A CASE REPORT AND LITERATURE REVIEW
Authors: Esen UI , Orife SU , Pollard K
Published: April 2023

We report on a large asymptomatic placental chorioangioma, identified as an area of reduced echogenicity on ultrasound at 36 weeks' gestation. Despite the large size, it was not associated with the usual maternal or fetal complications expected with a chorioangioma of that size, possibly because of thrombosis and tumour degeneration.
SCHISTOSOMIASIS OF THE APPENDIX IN THE UK
Authors: Jones HJS , Ibrahim AEK , Deroda JK
Published: April 2023

Schistosomiasis is endemic in many parts of the world but is rare in the UK. It usually affects the bladder or intestine, resulting in bleeding and fibrosis. However, schistosomal eggs are frequently found in the appendix and these can be symptomatic. The present case describes appendiceal infestation accompanied by acute appendicitis.
TUMOUR PRESENTING AS A RETROSTERNAL ABSCESS FOLLOWING MEDIAN STERNOTOMY
Authors: Martin IR , Jowett NI
Published: April 2023

A 73‐year‐old lady, who underwent coronary artery bypass grafting eight months previously, presented with rigors and chest pain. The upper sternum was tender, swollen and erythematous, suggesting a retrosternal abscess. Radiological investigation supported the clinical diagnosis. Local infections following median sternotomy are uncommon, most being early and superficial. Late infections are very uncommon, and should suggest alternative pathology. Following open surgical drainage, histology showed the mass to be a poorly differentiated adenocarcinoma. The primary tumour was never found.
CEREBRAL VENOUS THROMBOSIS OCCURRING DURING AN ECTOPIC PREGNANCY AND COMPLICATED BY INTRACRANIAL HYPERTENSION
Authors: McDonnell GV , Patterson VH , Mckinstry S
Published: April 2023

Thrombosis of the cerebral dural sinuses and veins has been described since the early 19th century.1,2 Clinically the process is characterised by diverse symptomatology and physical findings and in spite of advances in diagnostic radiological techniques it remains an under‐recognised condition. It has been most commonly associated with sepsis, trauma, pregnancy, the puerperium and many other hypercoagulable states. We describe an apparently unique case of sagittal sinus thrombosis occurring during an ectopic pregnancy. This was subsequently complicated by intracranial hypertension in spite of clinical improvement and magnetic resonance imaging (MRI) evidence suggesting a return of venous patency. The clinical presentation, radiological features and management is discussed.
SELF‐EXPANDABLE OESOPHAGEAL STENTS IN THE MANAGEMENT OF BENIGN PEPTIC OESOPHAGEAL STRICTURES IN THE ELDERLY
Authors: Foster
Published: April 2023

Self‐expandable oesophageal stents are being increasingly used in the management of malignant oesophageal strictures. Most benign peptic oesophageal strictures can be successfully managed using endoscopic oesophageal dilatation combined with long‐term Proton pump inhibition therapy. Although endoscopic oesophageal dilatation can be performed on an outpatient basis, it often requires repeated hospital visits. There is a small risk of oesophageal perforation, while cardiorespiratory complications may be encountered during the use of intravenous sedation in an elderly population. The use of self‐expandable Strecker stents in three elderly patients with benign peptic oesophageal strictures is described.
LONG‐TERM POTASSIUM SUPPLEMENTATION LOWERS BLOOD PRESSURE IN ELDERLY HYPERTENSIVE SUBJECTS
Authors: Fotherby MD , Potter JF
Published: April 2023

Following a randomised cross‐over trial of the effect of a four‐week 60 mmol/day potassium supplement versus placebo on blood pressure (BP), eight of the original 18 hypertensive subjects continued with a 48 mmol daily potassium supplement for four months. For these eight subjects 24‐h potassium excretion during placebo, one month of 60 mmol and four months of 48 mmol daily potassium supplementation phases was 56 ± 23, 102 ± 28 and 90 ± 35 mmol/24 hours, respectively, and mean 24‐h BP following each phase was 160 ± 16/89 + 11, 147 ± 13/83 ± 12 and 145 ± 14/81 ± 9 mmHg respectively, a significant fall in mean 24‐h SBP between four months of potassium supplement and placebo period of 15 ± 13 mmHg (95% CI: 4, 26 mmHg, p=0.02), although the fall in 24‐h DBP was not significant (8 ± 11 mmHg, 95% CI: 0, 17 mmHg, p=0.08). Modest increases in dietary potassium intake could have significant effects on lowering BP in the large proportion of elderly subjects with hypertension.
IMMUNE MODULATION AND SEPSIS
Authors: Karzai W , Reinhart K
Published: April 2023

The pathogenesis of sepsis involves not only microbial toxins but also activated host inflammatory mediators. Therefore, besides conventional antibiotic or surgical treatment of infection and supportive intensive therapy, modulating host inflammatory mediators as a conjunctive therapeutic option has been explored in the past decade. Although successful in animal models of sepsis, inhibiting host inflammatory response in human sepsis has failed to improve survival or otherwise show efficacy. Studies are needed which better describe the circumstances under which these therapies may ultimately prove successful.
CONTROVERSY AND CONSENSUS IN THE MANAGEMENT OF UPPER GASTROINTESTINAL DISEASE IN PRIMARY CARE
Authors: Whitaker MJ , Brun J , Carelli F ,   International Gastro Primary Care Group
Published: April 2023

Approximately 5% of all primary care consultations in the UK are for upper gastrointestinal (GI) diseases, the most common of which is dyspepsia, with a prevalence of between 25 and 50% in the western world. The exact definition of dyspepsia is elusive, which has resulted in confusion about diagnosis and treatment, highlighting the need for management guidelines. The International Gastro Primary Care Groups (IGPCG) has developed, by consensus, practical guidelines to help GPs manage patients with upper GI symptoms. After a detailed history is taken, alarm symptoms identified and organic disease excluded, the predominant symptom should be identified. This strategy, as outlined in the IGPCG upper GI disease management plan, can help the GP in the selection of the most appropriate treatment for each patient. This plan is flexible enough to be used in a wide variety of healthcare systems and will evolve as new evidence becomes available.
KOCH'S OR CROHN'S?
Authors: Kapoor VK
Published: April 2023

Abdominal tuberculosis is not uncommon in the UK, especially in Asian immigrants. It resembles Crohn's disease clinically and radiologically, and it may be difficult to differentiate between them, even at laparotomy or histology. The distinction is important, however, for proper management of the two conditions. Every effort must be made to exclude abdominal tuberculosis before the patient is diagnosed as having Crohn's disease and is treated with steroids.
SPONTANEOUS REGRESSION OF CANCER OR MISDIAGNOSIS? FOUR CASE REPORTS
Authors: Charlton RC
Published: April 2023

Four case reports regarding possible spontaneous regression of cancer are given. This is a rare but previously documented occurrence, with the literature suggesting possible causal factors for cancer regression or an indefinite period of dormancy. These include genetic, hormonal, immunological and psychological factors. However, the literature makes no reference to potential misdiagnosis, either clinically or histologically. The effect of being diagnosed as having terminal cancer is profound and even after regression or resolution of the disease, there are inevitable psychological sequelae.
SUBDURAL EFFUSION IN CHRONIC CRYPTOCOCCAL MENINGITIS IN A CIRRHOTIC PATIENT
Authors: Lee YT , Leung NWY , Kay R , Ng HK
Published: April 2023

A case of subdural effusion developing in chronic cryptococcal meningitis in a cirrhotic patient is described ‐ an association not previously reported.
RUPTURED HEPATOMA PRESENTING WITH PERITONITIS AND ACUTE LACTIC ACIDOSIS
Authors: Kelly J , Al‐Fallouji M
Published: April 2023

A case is reported in which a large hepatoma presented with rupture and acute severe lactic acidosis. Spontaneous rupture is a rare but recognised mode of presentation of hepatoma. Malignancy has also occasionally been associated with acute lactic acidosis, though the association with hepatoma has not previously been reported.
NEW PATIENTS PRESENTING TO THEIR GP WITH DYSPEPSIA: DOES HELICOBACTER PYLORI ERADICATION MINIMISE THE COST OF MANAGING THESE PATIENTS?
Authors: McIntyre A‐M , Macgregor S , Malek M , Dunbar JA , Hamley JG , Cromarty JA
Published: April 2023

Fifty‐seven patients newly presenting to their GP with dyspepsia agreed to take part in a pharmacist‐led clinic which tested and treated for Helicobacter pylori. Of these patients, 63% (36/57) tested positive and received eradication therapy. For 78% (28/36), eradication was successful with the first course of treatment, 89% (25/28) remaining symptom‐free over the six‐month follow‐up. Eradication was successful for a further 17% (6/36) after a second attempt; again, these patients remained free of symptoms over the follow‐up period. Thus, of the initial patients, 54% (31/57) were successfully treated, with no further symptoms. Such results had significant consequences on the expected direct cost of management per patient from a GP viewpoint. Using decision analysis it was found that H. pylori eradication for patients presenting with dyspepsia for the first time could result in considerable cost savings per patient in the long term.
EFFECT OF DOXAZOSIN ON THE SYMPTOMS OF BENIGN PROSTATIC HYPERPLASIA: RESULTS FROM THREE DOUBLE‐BLIND PLACEBO‐CONTROLLED STUDIES
Authors: Mobley DF , Kaplan S , Ice K , Gaffney M , Dias N
Published: April 2023

The urinary symptoms characteristic of benign prostatic hyperplasia (BPH) can have a considerable impact on patients' quality of life. Symptom score assessment is now used in BPH, although a number of different instruments are available. Controlled clinical trials with selective α1 adrenoceptor antagonists such as doxazosin, prazosin and terazosin have shown these agents to be effective in the treatment of BPH. The effects of doxazosin on the severity and bothersomeness of BPH symptoms were determined in three multicentre, double‐blind, placebo‐controlled clinical studies, involving a total of 609 normotensive and hypertensive patients. Doxazosin was initiated at a dosage of 0.5 or 1 mg once daily, with a final dose range of up to 12 mg once daily. The duration of active treatment was 12 to 14 weeks. Significant improvements were seen in symptom severity and bothersomeness with doxazosin compared with placebo, in both patient populations. The onset of symptomatic improvement was rapid, occurring within two weeks of treatment initiation, and efficacy was sustained throughout the treatment period. A long‐term, open label extension of these studies has demonstrated sustained efficacy during 48 months of follow‐up. Since symptom relief is the primary goal of therapy in BPH, and since doxazosin's effects are rapid in onset and sustained in duration, it appears that doxazosin is an effective agent for the treatment of symptomatic BPH in both normotensive and hypertensive men.
SELECTIVE ENDOSCOPY IN MANAGEMENT OF INGESTED FOREIGN BODIES OF THE UPPER GASTROINTESTINAL TRACT: IS IT SAFE?
Authors: O'Sullivan ST , McGreal GT , Reardon CM , Hehir DJ , Kirwan WO , Brady MP
Published: April 2023

During a four‐year period, 308 patients presented following ingestion of foreign bodies. Ingestion was accidental in 272 cases (88.3%) and deliberate in the remainder. Symptoms at presentation included dysphagia, odynophagia, nausea and vomiting, chest pain and pharyngeal discomfort. Sixty‐eight patients were asymptomatic. A policy of expectant management and selective endoscopy was employed. Following initial assessment 202 patients (65.6%) were discharged without treatment, 30 (9.7%) of whom were later reviewed as outpatients and did not require admission. Forty‐nine patients (16%) were admitted for treatment; 27 had oesophagoscopy, five bronchoscopy and two had foreign body extraction with direct laryngoscopy. In nine patients who were endoscoped, no foreign body was identified. Twenty‐seven others were referred to the otorhinolaryngology service in another hospital. There were no deaths in the group and morbidity was 1.2%. We conclude that a policy of selective endoscopy is safe and effective in the management of patients following ingestion of foreign bodies.
AN INVESTIGATION OF INTERFACE PRESSURES IN LOW AIR LOSS BEDS
Authors: Ryan DW , Allen V , Murray A
Published: April 2023

Prospective randomised trials indicate that the low air loss bed is a successful method of treatment for pressure sores. To study the properties of these beds interface pressures were measured in two different low air loss beds. Ten healthy volunteers had eight readings at six different body sites taken supine and sitting. Occipital and heel pressures for both products exceeded 4.7 kPa, the accepted capillary closing pressure, while pressures at other sites were below this. These findings suggest that pressure relief alone is not the sole reason for the clinical acceptance of low air loss beds in the treatment of pressure sores.
DIFFICULTIES AND DILEMMAS IN THE MANAGEMENT OF CONGENITAL ANOMALIES IN TWIN PREGNANCY
Authors: Edozien LC , Mayers FN , Gowland
Published: April 2023

Both the incidence of twin pregnancy and the demand for prenatal diagnosis are increasing. Unfortunately, biochemical screening and ultrasound scanning are less reliable for prenatal diagnosis in twin pregnancies than in singletons. Amniocentesis and chorionic villous biopsy are usually diagnostic in singleton pregnancies but may be marred by sampling errors in twin gestations. Where a congenital anomaly has been diagnosed in a twin pregnancy, difficult decisions may have to be made, especially if one twin is unaffected. In these cases, special skills are required to ensure that adequate information, psychological support and optimal medical care are provided.
THE MEDICAL TREATMENT OF PATIENTS PRESENTING WITH INTERMITTENT CLAUDICATION SECONDARY TO ATHEROSCLEROSIS
Authors: Sandison AJP , Taylor PR
Published: April 2023

Peripheral vascular disease affects a large number of elderly people but is symptomatic in only a few cases. Most of these will not be considered for surgical or radiological revascularisation procedures unless their disease affects the suprainguinal vessels. The traditional advice to stop smoking and keep walking is important but, in addition, thought should be given to the secondary prevention of cardiovascular disease in these patients. Thorough assessment and modification of their risk factors, including their lipid status, should be performed and aspirin should be prescribed to all patients who can tolerate it.
INTRACORONARY NITRATES MAY AVOID UNNECESSARY ANGIOPLASTY
Authors: Lloyd G , Cooke R , Jackson G
Published: April 2023

CLINICAL MESSAGE Nitrates in unstable angina may identify coronary artery spasm and obviate the need for angioplasty.
CHEMISTRY SET POISONING
Authors: Mucklow ES
Published: April 2023

A prospective survey of chemistry set poisoning (CSP) was undertaken using the monthly postal enquiry report system of the British Paediatric Surveillance Unit (BPSU). Fourteen cases were reported, with one fatality and uneventful full recovery in the other 13. The packaging of the chemicals was unsatisfactory in all cases: it was not child resistant and had no proper closures. Risk factors were lack of supervision 64.3%, emotional factors 28.6%, genuine accident 7% and unidentified 7%. An additional retrospective survey of CSP reported to the National Poisons Information Service centres over the same period added a further 19 cases of CSP, making a total of 33 cases, 14 (42%) being due to copper sulphate and four (12%) to cobalt chloride, respectively. This survey showed CSP to be a significant problem, with an incidence of 0.3 cases per 100,000 children. Six recommendations were made concerning child‐resistant containers, toxic hazard warnings, size and content of the lettering, health education programmes targeted at the most vulnerable groups, and lastly, a legal restriction on the chemicals that can be included in these sets, so that the most toxic are excluded.
LOCALLY APPLIED TRANSDERMAL NITRATE PATCHES FOR THE TREATMENT OF ISCHAEMIC REST PAIN
Authors: Fletcher S , Wright M , Wilkinson A , Farr M , Sellars L
Published: April 2023

Patients with severe peripheral vascular disease may suffer considerable pain which can be difficult to control with conventional analgesics. We sought to assess the analgesic effect of transdermal nitrate patches in such patients. A prospective trial was performed in 15 patients with ischaemic rest pain due to atherosclerotic peripheral vascular disease. Pain control and oral analgesic requirement were assessed. Fourteen of the 15 had a good or moderate response to the nitrate patches with a subsequent reduction in oral analgesic requirement. The patients with primarily small vessel disease had the greatest improvement in pain control. We conclude that topical nitrates may be used to provide rapid and safe analgesia for patients with ischaemic rest pain.
ACUTE PSEUDO‐OBSTRUCTION OF THE COLON FOLLOWING LEFT‐SIDED TOTAL HIP REPLACEMENT: AN ANALYSIS OF FIVE PATIENTS
Authors: Breusch SJ , Lavender CP
Published: April 2023

We report five cases of acute large bowel pseudo‐obstruction following left‐sided total hip replacement. All five cases presented with a similar sequence of clinical symptoms and physical signs. Acetabular trauma and heat generation from bone cement may lead to an imbalance of the autonomic nervous supply of the colon. We discuss a possible explanation for this phenomenon. We conclude that this condition is probably more common after total hip replacement than is currently diagnosed.
LATE PRESENTATION OF SOLITARY JEJUNAL METASTASIS FROM RENAL CELL CARCINOMA
Authors: Hession PR , Campbell RSD
Published: April 2023

Haematogenous metastases to the small bowel are a rare occurrence, usually from malignant melanoma or bronchogenic carcinoma. There are occasional reports of other primary tumours presenting with small bowel involvement as the first evidence of metastases. We describe a case of intraluminal jejunal metastasis from a renal cell carcinoma, occurring 10 years after the original nephrectomy.
CENTRAL RETINAL VEIN OCCLUSION ASSOCIATED WITH THE POLYCYSTIC OVARIAN SYNDROME
Authors: Salzmann J , Jagger J
Published: April 2023

We report a case of central retinal vein occlusion (CRVO) in a young woman with polycystic ovarian syndrome (PCOS). CRVO in young patients is a rare condition, frequently associated with a severe underlying systemic disorder. This is the first report of CRVO associated with documented PCOS. We discuss the therapeutic dilemma.
SURGICAL NUTRITIONAL TEAM AND ITS IMPACT ON TOTAL PARENTERAL NUTRITION IN THE NATIONAL UNIVERSITY HOSPITAL, SINGAPORE
Authors: Png DJC , Ong CL , Chan S
Published: April 2023

The Surgical Nutrition Advisory Team (SNAT) of our hospital, formed in October 1992, decided to study the impact of such a team on the six months before and after its formation on catheter care and nutritional support in total parenteral nutrition. Our study showed that with a dedicated nutritional team, catheter sepsis was reduced from 35.1% to 15.4%. The median lifespan of central catheters was increased from 7 to 11 days. Mechanical complications were reduced from 11% to zero. Better patient selection resulted in more severely malnourished patients receiving preoperative nutrition and fewer postoperative patients being started on total parenteral nutrition. Better monitoring of nutritional requirements, electrolyte and metabolite levels and consequently faster correction of abnormal blood levels, were also obtained.
ANTIDEPRESSANTS IN THE ELDERLY
Authors: Chiu HFK
Published: April 2023

Antidepressants are effective in the treatment of depression but their use in the elderly merits special attention. In general, the tertiary amine tricyclic antidepressants (TCAs) tend to produce significant side‐effects in the elderly. In contrast, nortriptyline, desipramine and lofepramine are better tolerated than other TCAs. The newer antidepressants including the selective serotonin reuptake inhibitors are useful alternatives in the treatment of depression in the elderly. As pharmacokinetic studies show that higher steady‐state plasma levels of tertiary amine antidepressants may be found in the elderly than in the younger population, a lower dosage is recommended. However, the need for a lower dose in the elderly is less certain for the secondary amine TCAs. The optimum duration of continuation and maintenance antidepressant therapy requires further study. For delusional depression, there is evidence to support the superiority of ECT and combination antipsychotic/antidepressant treatment over antidepressant alone. The ultimate choice of antidepressant will be a balance of efficacy, safety, acceptability and cost.
THE CHANGING INDICATIONS FOR CAROTID ENDARTERECTOMY IN THE UK
Authors: Panayiotopoulos YP , Padayachee S , Colchester ACE , Taylor PR
Published: April 2023

In early series the majority of carotid endarterectomies were performed in patients with amaurosis fugax (AFx) or transient ischaemic attacks (TIAs) who were thought to have atheromatous ulcers of the carotid bifurcation or the internal carotid artery (ICA). The degree of stenosis was considered to be of secondary importance. We compared our own data with two British series undertaken in the early and late 80s/early 90s. This reflects the broadening of indications and the change of practice for carotid endarterectomy over the years, on the one hand towards including patients who are at greater risk of perioperative stroke (previous CVAs vs TIAs, crescendo TIAs and stroke in evolution), and on the other towards patients who have had no symptoms attributable to the carotid lesion (asymptomatic cases, combined carotid and cardiac procedures).
DIAGNOSIS AND MANAGEMENT OF HYPERLIPIDAEMIA
Authors: Wierzbicki AS
Published: April 2023

Hyperlipidaemia is acknowledged as the major risk factor for coronary heart disease and atheroma progression. This review considers the strategies that should be followed to reduce overall cardiovascular risk in patients with hyperlipidaemia and deals with the identification and management of treating both polygenic and monogenic lipid disorders in the presence or absence of overt cardiovascular disease.
INFORMATION DELIVERY: THE PROVISION OF WRITTEN INFORMATION FOR PATIENTS FOLLOWING CORONARY ANGIOGRAPHY AND POST‐DISCHARGE MANAGEMENT
Authors: Lloyd G , Cooper A , Jackson G
Published: April 2023

To improve management of risk factors in patients diagnosed with significant coronary artery disease after day case angiography, we gave patients a discharge information sheet emphasising the importance of prognostic therapy, risk factors and follow‐up. The sheet was evaluated in 40 patients. A nurse talked through the information sheet with the patients after their angiogram and helped to complete relevant sections. One group of patients was given a copy of the sheet to take home, while the second group remained a ‘verbal information only’ group. Providing written information resulted in improvements in follow‐up regarding blood pressure and drug therapy checks, but there was no significant difference between the groups in the follow‐up management of cholesterol or in patient awareness of their cholesterol level. Patients were not likely to remember the sheet, even though a nurse had talked them through it, unless it was backed up with a written copy which could be taken away. It became apparent that the vast majority of patients remembered a pictorial representation of the extent of their disease (routinely provided) in contrast to the relatively disappointing numbers (43%) who remembered the information sheet. To evaluate further the importance of content and style in effective information delivery, we are evaluating the combination of written information with a visual representation of the heart.
SURGERY FOR LUNG CANCER: AGE ALONE IS NOT A CONTRAINDICATION
Authors: Jack CIA , Lye M , Lesley F , Wilson G , Donnelly RJ , Hind CRK
Published: April 2023

A retrospective analysis of the clinical features, operative procedures, postoperative complications and subsequent survival of 70 (50 male) elderly patients undergoing surgery for lung cancer compared with 74 (53 male) younger patients treated at the same hospital during the same period was performed, to determine if elderly people with lung cancer are less likely to benefit from and/or tolerate surgery. The elderly group had to wait longer for operation (p=0.001) and were more likely to have pre‐existing disease (p=0.019). In contrast, they had fewer recognised postoperative complications (p=0.032) and there was no difference between the two groups in perioperative mortality and subsequent survival. Surgical treatment of localised lung cancer represents the best chance for cure and this study suggests that age should not be a consideration in the decision to operate or not. The patient's general state of health should be assessed and management decisions based on individual status rather than on age.
ANTICOAGULANT CONTROL IN THE FIRST THREE MONTHS AFTER MECHANICAL HEART VALVE REPLACEMENT
Authors: Hsin M , Speight J , Cooper GJ
Published: April 2023

To establish the precision of anticoagulant control in the first three months after mechanical heart valve replacement, 53 patients from a consecutive series of 91 were telephoned and asked to read out their anticoagulation record. The levels of international normalised ratio (INR) were analysed by Rosendaal's method. Twenty‐nine per cent of patient days were spent with an INR in the recommended range of 3.0‐4.5. Warfarin dosage was increased at a median INR of 2.1 (interquartile range 1.7‐2.3), unchanged at 2.7 (interquartile range 2.3‐3.1) and decreased at 4.3 (interquartile range 3.6‐5.1). Anticoagulant control is poor in the first three months after mechanical heart valve replacement. Data on the INR at which warfarin dosage is changed suggest either that recommended guidelines are not being followed or a reluctance to increase the dosage in patients receiving inadequate anticoagulation.