The 2022 monkeypox outbreak: A UK military perspective.

With the emergence of SARS-CoV-2 and now monkeypox, the UK Defence Medical Services have been required to provide rapid advice in the management of patients with airborne high consequence infectious diseases (A-HCID). The Defence Public Health Network (DPHN) cadre, consisting of closely aligned uniformed and civilian public health specialists have worked at pace to provide evidence-based recommendations on the clinical management, public health response and policy for monkeypox, with military medicine and pathology clinicians (primarily infectious disease physicians and medical microbiologists). Military environments can be complicated and nuanced requiring specialist input and advice to non-specialists as well as unit commanders both in the UK and overseas. DPHN and military infection clinicians have close links with the UK National Health Service (NHS) and the UK Health Security Agency (UKHSA), allowing for a dynamic two-way relationship that encompasses patient management, public health response, research and development of both UK military and national guidelines. This is further demonstrated with the Royal Air Force (RAF) Air Transport Isolator (ATI) capability, provided by Defence to support the UK Government and UKHSA. Military infectious disease clinicians are also embedded within NHS A-HCID units. In this manuscript we provide examples of the close interdisciplinary working of the DPHN and Defence clinicians in managing military monkeypox patients, co-ordinating the public health response, advising the Command and developing monkeypox policy for Defence through cross-government partnership. We also highlight the co-operation between civilian and military medical authorities in managing the current outbreak.

A prospective cohort study on the safety of checkpoint inhibitors in older cancer patients - the ELDERS study.

OBJECTIVE: Older cancer patients are underrepresented in the pivotal trials of checkpoint inhibitors (CPIs). This study aimed to investigate the impact of an ageing immune system on CPI-related toxicity and provide evidence for the role of geriatric assessments with CPI. METHODS: The ELDERS study is a prospective observational study with two cohorts: older (70+ years of age) and younger (<70 years of age). Patients with advanced/metastatic non-small-cell lung cancer or melanoma starting single-agent CPI were eligible. The older cohort was assessed for frailty with Geriatric-8 (G8) screening, which when positive (<15 points) was followed by a holistic set of geriatric assessments. Primary endpoint was the incidence of grade 3-5 immune-related adverse events (irAEs). RESULTS: One hundred and forty patients were enrolled with 43% being pretreated and pembrolizumab represented 92% of treatments on study. The older cohort had a significantly higher comorbidity burden (P < 0.001) and polypharmacy (P = 0.004). While 50% of older patients had a positive G8 screening, 60% on this frail subgroup had a performance status score of 0 or 1. There was no significant difference in the incidence of irAEs grade 3-5 between older and younger cohorts (18.6% versus 12.9%; odds ratio 1.55, confidence interval 95% 0.61-3.89; P = 0.353). Exposure to systemic steroids due to irAEs was numerically longer for older patients (22 versus 8 weeks; P = 0.208). A positive G8 screening predicted hospital admissions (P = 0.031) and risk of death (P = 0.01). CONCLUSIONS: The use of CPI in older patients was not associated with more high-grade toxicity. The G8 screening identified a subgroup with higher risk of AEs and its implementation should be considered in the context of CPI.

Molecular basis of a new ovine model for human 3M syndrome-2.

BACKGROUND: Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595-9940 ) is a previously reported recessively inherited disorder in Australian Poll Merino/Merino sheep. Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2. Here we report the identification of a likely disease-causing variant and propose an ovine model for human 3M syndrome-2. RESULTS: Eight positional candidate genes were identified among the 39 genes in the approximately 1 Mb interval to which the disease was mapped previously. Obscurin like cytoskeletal adaptor 1 (OBSL1) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220472248delC within OBSL1. Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant. A genotyping assay was developed to genotype 583 animals from the original flock, giving an estimated allele frequency of 5%. CONCLUSIONS: The identification of a likely disease-causing variant resulting in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein has enabled improved breeding management of the implicated flock. The opportunity for an ovine model for human 3M syndrome and ensuing therapeutic research is promising given the availability of carrier ram semen for BCRHS.

An ABCA12 missense variant in a Shorthorn calf with ichthyosis fetalis.

Two clinical forms of ichthyosis in cattle have been reported, ichthyosis fetalis and congenital ichthyosis. Ichthyosis poses animal welfare and economic issues and the more severe form, ichthyosis fetalis, is lethal. A Shorthorn calf with ichthyosis fetalis was investigated and a likely causal missense variant on chromosome 2 in the ABCA12 gene (NM_001191294.2:c.6776T>C) was identified by whole genome sequencing. Mutations in the ABCA12 gene are known to cause ichthyosis fetalis in cattle and Harlequin ichthyosis in humans. Sanger sequencing of the affected calf and the dam confirmed the variant was homozygous in the affected calf and heterozygous in the dam. Further genotyping of 130 Shorthorn animals from the same property revealed an estimated allele frequency of 3.8%. The presented findings enable genetic testing for breeding and diagnostics.

Hepatitis B in a vaccinated soldier: a case report.

Assessing for an adequate immunological response to a pre-exposure course of hepatitis B vaccine is not routinely recommended in all vaccinated individuals. Current UK guidelines advise checking hepatitis B surface antibody titres only in those considered at high occupational risk such as healthcare and laboratory workers. We present a case of an infantry soldier who developed acute hepatitis B despite having a complete course of hepatitis B vaccinations. This case emphasises that hepatitis B is still an important differential diagnosis for all returning military personnel who present with compatible symptoms despite being vaccinated.

Simultaneously occurring Zenker's diverticulum and Killian-Jamieson diverticulum: case report and literature review.

BACKGROUND: Pharyngoesophageal diverticula have many subtypes, with Zenker's diverticulum being the most common. First described in 1983, a Killian-Jamieson diverticulum is an outpouching in the anterolateral wall at the pharyngoesophageal junction. This is located inferiorly to the cricopharyngeus muscle, unlike Zenker's diverticula which occur superiorly. Killian-Jamieson diverticula are rare and are commonly misdiagnosed as Zenker's diverticula. Less than 30 reports of Killian-Jamieson diverticula have been described in the literature. CASE REPORT: A 69-year-old man presented with a 2-year symptomatic history, and was found to have simultaneous Zenker's diverticulum and Killian-Jamieson diverticulum. He was treated successfully with open surgical excision of both pouches. CONCLUSION: Zenker's diverticulum and Killian-Jamieson diverticulum are diagnosed using radiological studies and endoscopy. Their differentiation is important, as surgical management differs. This paper reviews the literature on Killian-Jamieson diverticula and the management options available.

Variability in action: Contributions of a songbird cortical-basal ganglia circuit to vocal motor learning and control.

Many motor behaviors, from walking to speaking, are acquired through experience, in particular, through trial-and-error learning. The acquisition and maintenance of such motor behaviors in a wide range of species, including humans, appear to depend on cortical-basal ganglia circuits. In this review, we discuss recent studies in songbirds that have been pivotal in informing our current understanding of motor learning and cortical-basal ganglia function. Songbirds are important ethological model systems for the study of motor learning because young songbirds naturally develop and refine their songs through trial-and-error learning. In addition, reinforcement mechanisms are hypothesized to be important for the maintenance and plasticity of structured adult song. Computational and experimental studies highlight the importance of vocal motor variability as the substrate upon which reinforcement mechanisms could operate to shape developing song and to maintain adult song. Recent studies in songbirds indicate that this vocal motor variability is actively generated and modulated by a highly specialized cortical-basal ganglia circuit evolved for a single behavior, song. We argue that these and other recent findings illustrate how the tight association between a specialized neural circuit and a natural behavior make songbirds a unique and powerful model in which to investigate the neural substrates of motor learning and plasticity.

An audit of the cost effectiveness of protocol-driven versus surgeon-directed pre-operative assessment of NHS patients referred to a General Surgeon.

AIMS: Pre-operative assessment (POA) is now commonplace and follows established protocols. This audit compares the cost-effectiveness of surgeon-directed (SD) POA compared to the standard practice of protocol-driven (PD) POA. METHODS: One hundred and fifty-six NHS patients who were referred to a single surgeon during 2009 were allocated to one of three groups. Group 1: SDPOA required no investigations, whereas the PDPOA would have mandated only Methycillin-Resistant Staphylococcus aureus (MRSA) screening and urinalysis; Group 2: SDPOA required no pre-operative investigations, whereas the PDPOA would have required investigations to be performed; Group 3: SDPOA recommended selective investigations, PDPOA required additional tests. For each group the investigations requested and performed, their cost and whether the results affected patient care were recorded. There is no individual PDPOA group, but the cost of the extra tests was calculated where the PDPOA protocols were followed and therefore the cost differed between the SDPOA and PDPOA. RESULTS: The total cost for all investigations for the 156 patients was pound 43,985. A potential cost saving of pound 9,694 (group 2) and pound 8,898 (group 3) was demonstrated. The total potential saving identified for all 3 groups was pound 18,592, which was 42% of the total cost of all the investigations. Patient care was not affected by these additional investigations. CONCLUSIONS: There were no observed peri-operative complications during the study, implying that the additional pre-operative investigations were clinically unnecessary and identifying an additional cost saving of pound 18,592.

Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include slowing disease progression, nutrition, and respiratory management for patients with ALS. RESULTS: The authors identified 8 Class I studies, 5 Class II studies, and 43 Class III studies in ALS. Important treatments are available for patients with ALS that are underutilized. Noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), and riluzole are particularly important and have the best evidence. More studies are needed to examine the best tests of respiratory function in ALS, as well as the optimal time for starting PEG, the impact of PEG on quality of life and survival, and the effect of vitamins and supplements on ALS. RECOMMENDATIONS: Riluzole should be offered to slow disease progression (Level A). PEG should be considered to stabilize weight and to prolong survival in patients with ALS (Level B). NIV should be considered to treat respiratory insufficiency in order to lengthen survival (Level B) and to slow the decline of forced vital capacity (Level B). NIV may be considered to improve quality of life (Level C) [corrected].Early initiation of NIV may increase compliance (Level C), and insufflation/exsufflation may be considered to help clear secretions (Level C).

Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include breaking the news, multidisciplinary clinics, symptom management, cognitive and behavioral impairment, communication, and palliative care for patients with ALS. RESULTS: The authors identified 2 Class I studies, 8 Class II studies, and 30 Class III studies in ALS, but many important areas have been little studied. More high-quality, controlled studies of symptomatic therapies and palliative care are needed to guide management and assess outcomes in patients with ALS. RECOMMENDATIONS: Multidisciplinary clinic referral should be considered for managing patients with ALS to optimize health care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C). For the treatment of refractory sialorrhea, botulinum toxin B should be considered (Level B) and low-dose radiation therapy to the salivary glands may be considered (Level C). For treatment of pseudobulbar affect, dextromethorphan and quinidine should be considered if approved by the US Food and Drug Administration (Level B). For patients who develop fatigue while taking riluzole, withholding the drug may be considered (Level C). Because many patients with ALS demonstrate cognitive impairment, which in some cases meets criteria for dementia, screening for cognitive and behavioral impairment should be considered in patients with ALS (Level B). Other management strategies all lack strong evidence.

Paediatric conscious sedation: views and experience of specialists in paediatric dentistry.

OBJECTIVES: The objectives were three-fold: to investigate the level of conscious sedation training received prior to and during specialist training in paediatric dentistry; to establish the use of conscious sedation during and following specialisation; and to determine the attitudes of specialists in paediatric dentistry to conscious sedation. SUBJECTS AND METHODS: A self-administered postal questionnaire was sent to all specialists in paediatric dentistry registered with the General Dental Council in January 2008. Non-responders were contacted again after a four-week period. RESULTS: A response rate of 60% was achieved. Of the 122 respondents, 67 (55%) had received sedation training as an undergraduate; 89 (75%) had been trained during specialisation. All respondents performed dental treatment under sedation as a trainee and the majority used nitrous oxide inhalation sedation (NOIS). Over 90% of respondents felt that NOIS should be available to all children, both in appropriate primary care settings and in hospitals. One hundred and twenty-one (99%) respondents thought that all trainees in paediatric dentistry should have sedation training. CONCLUSIONS: The most popular form of sedation amongst specialists in paediatric dentistry was NOIS. However, some of the respondents felt that children should have access to other forms of sedation in both the primary care and hospital settings. Additional research on other forms of sedation is required to evaluate their effectiveness and safety.

A pilot study of the use and perceived utility of a scale to assess clinical dental teaching within a UK dental school restorative department.

INTRODUCTION: Feedback on individual teaching performance gives an important contribution and support to the reflective practices of educators. Unfortunately, feedback is an infrequent exercise provided to dental teachers about their teaching practices. The Effective Clinical Dental Teaching (ECDT) scale has been used previously to assess clinical teachers, but has not been used within the UK. METHODS: This study looks at the use of the ECDT scale in the setting of a UK dental school, as a method of feedback collection and delivery in seven domains of clinical teaching. The ECDT was used to evaluate the teaching of 16 clinical teachers by dental undergraduates, and to investigate the opinions of these clinical teachers and clinical dental students about the utility of this scale. RESULTS: The study identified that there was a disparity between self and student perception of teaching. The total ECDT scores ranged from a minimum of 55% 66.6/125 to a maximum of 90% 113.8/125, with a mean group score of 73% 91.6/125. Most clinicians evaluated by students scored above 3/5 for all teaching domains, although there appeared to be significant differences between the four teacher groups. The majority of staff and students were in favour of the use of such a scale to support the progression and development of teaching styles. CONCLUSION: The ECDT scale is a useful tool for highlighting the areas of strength and deficiency within clinical dental teaching. Its use may complement peer review for individual teachers and identify future topics for staff development sessions. Further research is recommended to identify the individual strengths and weaknesses that different types of teacher may bring to curriculum teaching.

An audit of referrals to a secondary care sedation unit.

AIMS AND OBJECTIVES: This audit was carried out to assess referrals received by a clinic treating anxious patients within a dental hospital setting. The audit aimed to provide a baseline measurement prior to the publication of a referral protocol. Referral frequencies were examined to explore the concept of serial referrers. METHODS: A retrospective design was used. The referrals of all patients given assessment appointments for treatment within the Sedation Suite between 1 January and 31 December 2006 were examined. In addition, a random sample of 100 cases was examined for the referral request. RESULTS: Three hundred and six referrals were sent assessment appointments by the Sedation Suite in 2006. The majority of referrals received (76.1%, n = 233) were from practitioners working in the general dental services. On average 1.68 referrals were received per clinician, with a maximum of 18 referrals from one clinician. The majority of patients were female and had an average age of 33.5. One hundred and eighty-seven patients attended for assessment. One hundred and forty-three (46.7%) were treatment planned to receive treatment with pharmacological help. Twenty-two (7.2%) were planned to receive treatment without pharmacological help, though none of the referrals received had considered requesting behavioural management. CONCLUSION: This audit confirmed results from previous audits. The standards set for referral were not met. Despite the efficacy of psychological treatments, referring clinicians do not seem to consider their use for anxious patients. Referral patterns seemed to support the idea that a minority of practitioners refer significantly higher numbers of patients than their peers.

Adult cystic hygroma: successful use of OK-432 (Picibanil).

OBJECTIVE: We report an adult case of cystic lymphangioma treated with OK-432 (Picibanil). METHOD: A case report and review of the literature concerning the use of OK-432 to treat cystic lymphangioma is presented. RESULTS: A 31-year-old woman developed a cystic lymphangioma four weeks post-partum. This was treated initially by aspiration, for diagnostic purposes. Investigation suggested that surgery would be challenging. A review of the literature demonstrated success with OK-432 in the treatment of this condition, although primarily in the paediatric population. This patient was successfully treated thus, and at the time of writing remained symptom free. A suggested management plan is outlined. CONCLUSION: Treatment with OK-432 is useful in the management of cystic lymphangiomas in adults and should be considered as first line treatment.

Complete recovery of an isolated left vocal fold palsy associated with a benign mediastinal thymic cyst.

OBJECTIVES: To present a case of benign mediastinal thymic cyst, and to review the published information on these cysts, including their incidence, presentation, diagnosis and management. METHODS: We report the case of a 55-year-old man who presented with a unilateral vocal fold palsy subsequently found to be due to the presence of a benign mediastinal thymic cyst. A literature search was undertaken to identify the incidence, key features and management of this rare condition. RESULTS: Benign mediastinal thymic cysts are a rare cause of mediastinal masses. Usually diagnosed incidentally, their management is usually surgical. Vocal fold palsy in isolation has not previously been reported in association with mediastinal thymic cysts. CONCLUSION: This report describes what we believe to be the first published case of a completely reversible vocal fold palsy presenting in association with a rare benign mediastinal thymic cyst.

Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients.

Atypical antipsychotics induce pre-diabetic symptoms in some but not all patients, characterized most notably by elevated weight. The side effect profiles of the various drugs in the class differ, however, raising the possibility of drug-specific mechanisms for similar side effects. We used physiogenomic analysis, an approach previously employed to study the genetics of drug and diet response, to discover and compare genetic associations with weight profiles observed in patients treated with olanzapine and risperidone as an approach to unraveling contrasting mechanistic features of both drugs. A total of 29 single nucleotide polymorphisms (SNPs) were selected from 13 candidate genes relevant to two potential pharmacological axes of psychotropic-related weight profiles, appetite peptides and peripheral lipid homeostasis. We applied physiogenomic analysis to a cross-section of 67 and 101 patients being treated with olanzapine and risperidone, respectively, and assessed genetic associations with the weight profiles. Weight profiles in patients treated with olanzapine were significantly associated with SNPs in the genes for apolipoprotein E, apolipoprotein A4 and scavenger receptor class B, member 1. Weight profiles in patients treated with risperidone were significantly associated with SNPs in the genes for leptin receptor, neuropeptide Y receptor Y5 and paraoxonase 1. These results are consistent with contrasting mechanisms for the weight profile of patients treated with these drugs. Genes associated with olanzapine weight profiles may be related to peripheral lipid homeostatic axes, whereas those associated with risperidone's may be related to brain appetite peptide regulation. Future physiogenomic studies will include neurotransmitter receptor SNPs and validation in independent samples.

ENT surgery, blood and Jehovah's Witnesses.

Surgical procedures in otolaryngology are often associated with the need for blood transfusions. Homologous blood transfusions carry risks and may be unacceptable to some patient groups. The Jehovah's Witness Society is known to many because of its stance on blood products. Refusal of potentially life-saving treatment creates ethical dilemmas for treating clinicians. Throughout the world, Jehovah's Witnesses have fought for the right to refuse blood products. This article examines the need for blood in otolaryngological procedures, surgical strategies to reduce blood loss, the beliefs of Jehovah's Witnesses regarding the acceptability of blood, and procedures and legal stances adopted when treating Jehovah's Witnesses.

Hypopharyngeal perforation following minor trauma: a case report and literature review.

Hypopharyngeal perforation is mainly reported in association with high velocity road traffic accidents, or with low velocity direct blows to the neck. We report a case of hypopharyngeal perforation following a low velocity motorcycle accident where neither of these mechanisms of injury was apparent. A 52 year old man was referred from the emergency department (ED) with a sore throat and dysphagia, following a low speed side impact accident. A gastrograffin swallow demonstrated a posterior pharyngeal wall tear. After 11 days of conservative hospital treatment, he recovered and was discharged. The presumed mechanism of injury in this case was cervical spine hyperextension without cervical compression.

Pharyngeal perforation: a late complication of cervical spine surgery.

Anterior cervical spine fusion and stabilization is a well-recognized procedure for a number of cervical spine disorders. Unfortunately, the complex anatomy of the cervical spine means that these procedures are not without complications. Pharyngo-oesophageal perforation is a rare but potentially life-threatening complication of cervical spine surgery and may present intra-operatively, in the immediate post-operative period or many years later. We present the case of a gentleman with ankylosing spondylitis who presented with a pharyngeal perforation and fistula five years after cervical spine surgery.