A Review of the Economic Evidence of Typhoid Fever and Typhoid Vaccines.

Typhoid places a substantial economic burden on low- and middle-income countries. We performed a literature review and critical overview of typhoid-related economic issues to inform vaccine introduction. We searched 4 literature databases, covering 2000-2017, to identify typhoid-related cost-of-illness (COI) studies, cost-of-delivery studies, cost-effectiveness analyses (CEAs), and demand forecast studies. Manual bibliographic searches of reviews revealed studies in the gray literature. Planned studies were identified in conference proceedings and through partner organization outreach. We identified 29 published, unpublished, and planned studies. Published COI studies revealed a substantial burden in Asia, with hospitalization costs alone ranging from $159 to $636 (in 2016 US$) in India, but there was less evidence for the burden in Africa. Cost-of-delivery studies are largely unpublished, but 1 study found that $671 000 in government investments would avert $60 000 in public treatment costs. CEA evidence was limited, but generally found targeted vaccination programs to be cost-effective. This review revealed insufficient economic evidence for vaccine introduction. Countries considering vaccine introduction should have access to relevant economic evidence to aid in decision-making and planning. Planned studies will fill many of the existing gaps in the literature.

Nutritional status, exclusive breastfeeding and management of acute respiratory illness and diarrhea in the first 6 months of life in infants from two regions of Indonesia.

BACKGROUND: Infant morbidity and mortality rates remain high in Indonesia, with acute respiratory illnesses (ARI) and diarrhea the leading two health problems in children under 5 years. We aimed to describe the nutritional status, feeding practice and case management of ARI and diarrhea of infants from two regions of Indonesia during the first 6 months of life. METHODS: This study was an observational study conducted in parallel to an immunogenicity and efficacy trial of an oral rotavirus vaccine (RV3-BB) in the Klaten and Yogyakarta regions, Indonesia. Mothers were interviewed at 3 time points: within the first 6 days of their infant's life, and at 8-10 and 22-24 weeks of age. Questions asked included pregnancy history, infant nutritional status, feeding status and health of infants within up to 2 weeks prior to the assessment. RESULTS: Between February 2013 and January 2014, 233 mother-infant pairs were recruited. 60% (136/223) of infants were exclusively breastfed (EBF) until 6 months of age with the strongest support for EBF reported by mothers themselves 70% (101/223) and 25% (36/223) from their partners. At 6 months, 6% (14/223) of infants were underweight and severely underweight; 4% (8/ 223) wasted and severely wasted; and 12% (28/223) were stunted and severely stunted. Non-recommended medication use was high, with 54% (21/39) of infants with reported cough within 2 weeks of an assessment receiving cough medication, 70% (27 /39) an antihistamine, 26% (10/39) a mucolytic and 15% (6 /39) an oral bronchodilator. At age 22-24 week, infants with reported diarrhea within 2 weeks of an assessment had low use of oral rehydration solutions (ORS) (3/21;14%) and zinc therapy (2/ 21;10%). CONCLUSION: In this unique observational study, breastfeeding rates of 60% at 6 months were below the Indonesian national target of >75%. Adherence to WHO guidelines for management of ARI and diarrhea was poor, with high use of non-recommended cough medications and oral bronchodilators in the first 6 months of life and low use of ORS and zinc therapy. Ongoing education of primary health care workers and parents regarding management of common illness is needed in Indonesia.

Manual perineal support at the time of childbirth: a systematic review and meta-analysis.

BACKGROUND: Genital tract trauma is common with vaginal births and is associated with significant morbidity, particularly with obstetric anal sphincter injuries (OASIS). Debate continues regarding the effectiveness of perineal support during childbirth in reducing the risk of trauma. OBJECTIVES: This review aimed to assess the effect of routine 'hands on'/manual perineal support (MPS) during childbirth, versus ad hoc/no perineal support ('hands off/poised'), on the risk and degree of perineal trauma. SEARCH STRATEGY: This review is registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007058). We searched the CENTRAL, Embase, Medline, CINAHL, and OVIDs midwifery and infant care databases (from inception to December 2014). SELECTION CRITERIA: Published randomised controlled trials (RCTs) and non-randomised studies (NRSs) evaluating any 'hands on' perineal support technique during childbirth. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion, data extraction, and methodological quality. Discrepancies were resolved by discussion with a third reviewer. MAIN RESULTS: We included five RCTs and seven NRSs in the review. Meta-analysis of RCTs did not demonstrate a statistically significant protective effect of MPS on the risk of OASIS (three studies, 6647 women; relative risk, RR 1.03; 95% confidence interval, 95% CI 0.32-3.36; statistical test for heterogeneity I(2) = 71%). Meta-analysis of NRSs showed a significant reduction in the risk of OASIS with MPS (three studies, 74,744 women; RR 0.45; 95% CI 0.40-0.50; I(2) = 32%). CONCLUSION: Current evidence is insufficient to drive change in practice. An adequately powered randomised trial with an efficient design to evaluate the complex interventions adopted as part of MPS policies, ensuring controlled childbirth, is urgently needed.

Coin-cidence? Have cashless payments reduced the incidence of upper aerodigestive foreign body insertion? A study of UK Hospital Episode Statistics.

OBJECTIVES: Insertions of nasal and oral foreign bodies (FB) are common presentations in the emergency department, with coins frequently implicated among paediatric populations. Contactless payments were first introduced in the UK in 2007, and cash payments significantly declined from 2012. This study aims to explore the potential implications of increasing contactless payments on FB ingestion. METHODS: UK Hospital Episode Statistics (HES) were reviewed between 2000 and 2022. All FB retrieval procedures involving the alimentary tract, respiratory tract and nasal cavity were included. Regression analysis was performed to assess trends in the incidence of FB ingestion before and following the transition to cashless payments in 2012. RESULTS: Following the decline in cash payments in 2012, the frequency of alimentary tract FB removal procedures decreased significantly by 27.78 procedures per year (p < 0.001). Similarly, respiratory FB removal procedure decreased by 4.83 per year (p = 0.009) and nasal cavity FB removal procedures decreased by 52.82 per year (p < 0.001). CONCLUSIONS: This study suggests a statistically significant decline in the number of procedures for removal of FB performed in the UK from 2012. Although this relationship is multifactorial, our data suggest an association between the introduction of contactless payments and a reduction in the number of FB retrieval procedures from the of upper aerodigestive tract.

Balance testing: does it make a difference?

OBJECTIVE: This study aimed to analyse whether referral for specialist balance testing influences diagnosis and management of patients with dizziness. METHOD: This was a retrospective study examining patients referred for vestibular function testing between 1 January 2018 and 30 June 2018. RESULTS: A total of 101 patients were referred, with 69 patients (68.3 per cent) receiving a preliminary 'pre-vestibular function testing balance diagnosis', which included benign paroxysmal positional vertigo (32.7 per cent), Ménière's disease (13.8 per cent) and migraine (14.9 per cent). Following vestibular function testing, revised diagnoses were achieved for 54 patients (53.5 per cent), including benign paroxysmal positional vertigo (14.9 per cent), Ménière's disease (3.0 per cent) and migraine (10.9 per cent). Pre-vestibular function testing balance diagnoses were confirmed for 32.4 per cent of patients. If no pre-vestibular function testing suspected diagnosis was provided, vestibular function testing was significantly more likely to be inconclusive. Following vestibular function testing, 38.6 per cent were discharged, 21.7 per cent were referred to another specialty and treatment was commenced for 17.8 per cent of patients. CONCLUSION: Referral for vestibular function testing has a role when attempting to answer a clear clinical question. Diagnosing the underlying aetiology of complex imbalance is challenging, but diagnosis can be assisted by judicious use of vestibular function testing.

Sinus, middle-ear and mastoid radiological findings of severe acute respiratory syndrome coronavirus-2.

OBJECTIVE: To assess the incidence of radiological inflammation within the paranasal sinuses, middle ear and mastoid in patients with confirmed severe acute respiratory syndrome coronavirus-2. METHODS: A retrospective cohort study was conducted to examine consecutive adults (aged over 18 years) with coronavirus disease 2019 (confirmed on polymerase chain reaction within 7 days of imaging) who underwent computed tomography of the head between 1 March 2020 and 24 June 2020. Lund-Mackay and mastoid and middle-ear opacification scores were used to categorise the extent of sinus and mastoid opacification on axial and coronal computed tomography images. RESULTS: Of 147 patients originally identified, only 83 met the inclusion criteria. Sinus opacification was present in 51.8 per cent of patients (n = 43), and middle-ear or mastoid opacification was observed in 24.1 per cent (n = 20). There was no statistically significant difference in sinus or middle-ear and mastoid opacification between patients after stratification based on 30-day all-cause mortality. CONCLUSION: Radiological computed tomography findings suggest mild mucosal disease within the sinuses, middle ear and mastoid. There was no statistical correlation between such opacification and 30-day mortality.

Successful management of an unstable paediatric laryngeal injury in a low-resource setting.

Laryngeal injury is rare but has a very high mortality rate. Compared to adults, laryngeal injury in children is more uncommon due to both behavioural and anatomical reasons. Severe laryngeal injury may require surgical repair, intensive care support and tracheostomy care, all of which are difficult to achieve in a low resource setting. We report a case of successful management of laryngeal trauma in a child involving an emergency tracheostomy insertion, open repair of thyroid cartilage fracture, tracheal stenting and successful decannulation after 8 weeks post-injury with full recovery.

Cryopreservation of Greenshell™ mussel (Perna canaliculus) trochophore larvae.

The Greenshell™ mussel (Perna canaliculus) is the main shellfish species farmed in New Zealand. The aim of this study was to evaluate the effects of cryoprotectant concentration, loading and unloading strategy as well as freezing and thawing method in order to develop a protocol for cryopreservation of trochophore larvae (16-20 h old). Toxicity tests showed that levels of 10-15% ethylene glycol (EG) were not toxic to larvae and could be loaded and unloaded in a single step. Through cryopreservation experiments, we designed a cryopreservation protocol that enabled 40-60% of trochophores to develop to D-larvae when normalized to controls. The protocol involved: holding at 0 °C for 5 min, then cooling at 1 °C min⁻¹ to -10 °C, holding for a further 5 min, then cooling at 0.5 °C min⁻¹ to -35 °C followed by a 5 min hold and then plunging into liquid nitrogen. A final larval rearing experiment of 18 days was conducted to assess the ability of these frozen larvae to develop further. Results showed that only 2.8% of the frozen trochophores were able to develop to competent pediveligers.

Local anaesthetic techniques in endoscopic sinonasal surgery: a contemporaneous review.

OBJECTIVE: Endoscopic endonasal surgery is a minimally invasive technique that has revolutionised the management of complex neurosurgical, otolaryngological, skull-base and craniofacial lesions. Traditionally performed under general anaesthetic, this study explores the growing role of local anaesthetic techniques. METHOD: A contemporaneous review of modified dental techniques and intraoral anatomy provides a supportive guide for performing endoscopic sinus surgery under local anaesthetic. RESULTS: The practical procedures for four midfacial nerve blocks are described with relevance to endoscopic surgery under local anaesthetic. Anatomy, surgical technique and potential complications are discussed for the incisive foramen block, sphenopalatine ganglion block (via endonasal approach), maxillary nerve block (via the greater palatine foramen and the transoral lateral pterygoid plate approach) and transcutaneous approach to the pterygomaxillary fissure. CONCLUSION: Ultimately, such techniques may extend the safety and efficacy of endoscopic sinus surgery, limit surgical risk and increase satisfaction for patients, surgeons and healthcare managers alike.

Rapeseed meal processing and dietary enzymes modulate excreta inositol phosphate profile, nutrient availability, and production performance of broiler chickens.

This study aimed to assess the effect of rapeseed meal (RSM) processing method, where solvent extraction occurred under standard industry conditions (ST) or cold-pressed hexane extraction was employed (MT), and exogenous enzyme supplementation (phytase [PHY] and xylanase [XYL]) alone or in combination on key nutritional factors of broiler chickens. A randomized control experiment was performed using 144 male Ross 308 broilers in a 2 × 2 × 3 factorial arrangement. Three diets including a nutritionally complete wheat-based basal diet (BD), a diet containing 200 g/kg of RSM extracted under ST and another diet containing 200 g/kg of RSM extracted under MT were produced. Each diet was then split into 4 parts and was fed as is, or supplemented with PHY at 1,500 FTU/kg or XYL at 16,000 BXU/kg, alone or in combination, resulting in 12 diets in total. Response criteria: feed intake (FI), weight gain (WG), and feed conversion ratio (FCR), from 7 to 21 d age, AMEn, retention coefficients for dry matter (DMR), nitrogen (NR), fat (FR), and the profile of inositol phosphate esters (IP2-6) and myo-inositol (MI) in excreta. Diets containing MT had higher AMEn compared to ST diets (P < 0.05). There was RSM by PHY interaction for FI, as only birds fed MT diet responded to PHY supplementation with reduced FI and FCR (P < 0.001). Feeding XYL reduced overall FI and FCR (P < 0.05). Feeding PHY reduced IP6 and increased MI in excreta (P < 0.001). Feeding XYL and PHY in combination reduced MI in excreta compared to PHY only (P = 0.05). Compared to BD, birds fed RSM diets had an increased IP6 (P < 0.05) and MI concentration in excreta (P < 0.01). This may be due to IP ester differences in RSM and BD.

Guidance of magnetic resonance imaging and placement of skin-marker localization devices.

AIM: A variety of magnetic resonance imaging (MRI)-compatible skin-marker localization devices are available on the market. MRI protocols call for the liberal use of the skin markers over the specific site of symptoms or over any palpable mass. This study investigates the usefulness of patient-assisted placement of 1 000-mg fish oil capsules as skin markers over the area of maximum localized pain, signs, or symptoms and correlates this placement with any potential underlying neuropathology or potential pain generator. METHODS: One-hundred symptomatic patients undergoing MRI were assessed for focal or localized signs or symptoms. Under the direction of a physician and with guidance from the patient, the MRI technician placed a 1 000-mg fish-oil capsule over the area of maximum pain or signs and symptoms. Patients with poorly localized, diffuse symptoms or an area of maximal signs and symptoms outside the field of view of the MRI were not included in this study. All MRI exams were reviewed by clinical physicians and radiologists or neuroimaging physicians. RESULTS: In all 100 cases, the images show clearly visible MRI-compatible skin-surface markers that correlate with potential underlying neuropathology. CONCLUSION: Our results show that 1 000-mg fish-oil capsules can be used as MRI localization devices as a cost-effective alternative to more expensive commercially available devices.

Carbynes: carriers of primordial noble gases in meteorites.

Five carbynes (triply bonded allotropes of carbon) have been found by electron diffraction in the Allende and Murchison carbonaceous chondrites: carbon VI, VIII, X, XI, and (tentatively) XII. From the isotopic composition of the associated noble-gas components, it appears that the carbynes in Allende (C3V chondrite) are local condensates from the solar nebula, whereas at least two carbynes in Murchison (C2 chondrite) are of exotic, presolar origin. They may be dust grains that condensed in stellar envelopes and trapped isotopically anomalous matter from stellar nucleosynthesis.

The effect of host movement on viral transmission dynamics in a vector-borne disease system.

Many vector-borne pathogens whose primary vectors are generalists, such as Ixodid ticks, can infect a wide range of host species and are often zoonotic. Understanding their transmission dynamics is important for the development of disease management programmes. Models exist to describe the transmission dynamics of such diseases, but are necessarily simplistic and generally limited by knowledge of vector population dynamics. They are typically deterministic SIR-type models, which predict disease dynamics in a single, non-spatial, closed patch. Here we explore the limitations of such a model of louping-ill virus dynamics by challenging it with novel field data. The model was only partially successful in predicting Ixodes ricinus density and louping-ill virus prevalence at 6 Scottish sites. We extend the existing multi-host model by forming a two-patch model, incorporating the impact of roaming hosts. This demonstrates that host movement may account for some of the discrepancies between the original model and empirical data. We conclude that insights into the dynamics of multi-host vector-borne pathogens can be gained by using a simple two-patch model. Potential improvements to the model, incorporating aspects of spatial and temporal heterogeneity, are outlined.

Community nurses' practices in managing perianal abscesses.

A survey of community nurses identified that a wide range of dressings, and in some cases unethical practices, are being used for this simple postoperative condition. Communication between hospital, community staff and patients was poor.

Post-stapedectomy granuloma: a devastating complication.

OBJECTIVES: This paper reports three cases of severe post-stapedectomy granuloma, emphasising the variable presentation of this devastating complication and the challenges of its management. METHODS: A retrospective review was conducted of three cases of post-stapedectomy granuloma requiring surgical debulking between 2010 and 2015. Clinical symptoms, serial imaging, histopathology and post-operative outcomes were considered. RESULTS: Intra-operatively, extensive granulation tissue with erosion of the otic capsule was found. There was spread along the VIIth and VIIIth cranial nerves to the cochlear nucleus in one patient. Post-operative clinical improvement was demonstrable, corroborated by diminution of contrast enhancement on serial magnetic resonance imaging. Facial nerve function recovered, tinnitus amelioration was variable and some otalgia persisted. Post-operative complications included grade IV facial weakness and late Pseudomonas aeruginosa meningitis, which all resolved. CONCLUSION: To the authors' knowledge, this paper reports the only case of post-stapedectomy granuloma tracking to the brainstem. Otalgia was present in all our cases, and may be deemed a red flag symptom of progressive bony destruction and otic capsule involvement. Although granuloma remains rare, it should be considered in any patient with worsening otological symptoms following stapes surgery.

Management of massive acetabular bone defects in revision arthroplasty of the hip using a reconstruction cage and porous metal augment.

AIMS: It may not be possible to undertake revision total hip arthroplasty (THA) in the presence of massive loss of acetabular bone stock using standard cementless hemispherical acetabular components and metal augments, as satisfactory stability cannot always be achieved. We aimed to study the outcome using a reconstruction cage and a porous metal augment in these patients. PATIENTS AND METHODS: A total of 22 acetabular revisions in 19 patients were performed using a combination of a reconstruction cage and porous metal augments. The augments were used in place of structural allografts. The mean age of the patients at the time of surgery was 70 years (27 to 85) and the mean follow-up was 39 months (27 to 58). The mean number of previous THAs was 1.9 (1 to 3). All patients had segmental defects involving more than 50% of the acetabulum and seven hips had an associated pelvic discontinuity. RESULTS: Three failures were observed in two hips, both of which had undergone a previous resection of a tumour affecting the acetabulum. Other complications included a late arterial injury, a sciatic nerve palsy, a dislocation treated with a femoral revision, a deep infection treated with irrigation and debridement and a fracture of the greater trochanter treated conservatively. The mean Oxford Hip Score significantly increased from 13.9 (2 to 23) to 28.7 (13 to 38) (p < 0.00001). The mean vertical distance between the centre of rotation of the hip and its normal location decreased from 30 mm to 10 mm. CONCLUSIONS: Acceptable early survivorship can be achieved using this novel technique, but it may be unsuitable for use in patients who have previously undergone the resection of a tumour involving the acetabulum. Cite this article: Bone Joint J 2017;99-B:607-13.

Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism.

Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.

Colorectal cancer outcomes in patients aged over 85 years.

INTRODUCTION: The prevalence of colorectal cancer is increasing in the elderly. We examined the treatment and outcomes in our institution of patients aged over 85 years with proven colorectal adenocarcinoma. METHODS: One hundred and five patients were identified and stratified by treatment received: curative surgery (CS), other treatments (OT) or best supportive care (BSC). Data on demographics, staging, treatment and survival was collected and analysed. RESULTS: Forty two patients received CS, 36 OT and 27 BSC. While the treated groups (CS and OT) were similar in terms of age (p=0.35) and staging (p=0.16), BSC patients were significantly older and had higher stage disease (p<0.01). Survival was significantly poorer among BSC patients, at a mean of 9.7 months (95% confidence interval [CI] 4.7-14.7) versus 41.6 months (95% CI 32.5-50.7) and OT 27.3 months (95% CI 20.4-34.1) for the CS and OT groups (p<0.001). There was no significant survival difference between CS and OT groups within 2 years of treatment (p=0.12). Thereafter, OT patients had a very similar 5-year survival to that of the BSC group, at 13% versus 43% in CS patients (p<0.001). CONCLUSIONS: These data suggest that, up to 2 years following treatment, the risks of resectional surgery for colorectal cancer may neutralise any benefit. However, those that survive beyond this period show improvements. The challenge of improving patient selection is most acute in the growing ageing population, and highlights the current focus on presenting all treatment options to 'a reasonable patient'.

The role of cages in the management of severe acetabular bone defects at revision arthroplasty.

An uncemented hemispherical acetabular component is the mainstay of acetabular revision and gives excellent long-term results. Occasionally, the degree of acetabular bone loss means that a hemispherical component will be unstable when sited in the correct anatomical location or there is minimal bleeding host bone left for biological fixation. On these occasions an alternative method of reconstruction has to be used. A major column structural allograft has been shown to restore the deficient bone stock to some degree, but it needs to be off-loaded with a reconstruction cage to prevent collapse of the graft. The use of porous metal augments is a promising method of overcoming some of the problems associated with structural allograft. If the defect is large, the augment needs to be protected by a cage to allow ingrowth to occur. Cup-cage reconstruction is an effective method of treating chronic pelvic discontinuity and large contained or uncontained bone defects. This paper presents the indications, surgical techniques and outcomes of various methods which use acetabular reconstruction cages for revision total hip arthroplasty.