Hip bone geometry in HIV/HCV-co-infected men and healthy controls.

UNLABELLED: People with both HIV and hepatitis C are more likely than those with HIV alone to have wrist, hip, and spine fractures. We compared hip strength between HIV/HCV-co-infected men and healthy men and found that HIV/HCV-co-infected men had decreased hip strength due to lower lean body mass. INTRODUCTION: Hepatitis C co-infection is a risk factor for fragility fracture among HIV-infected populations. Whether bone strength is compromised in HIV/HCV-co-infected patients is unknown. METHODS: We compared dual-energy x-ray absorptiometry (DXA)-derived hip geometry, a measure of bone strength, in 88 HIV/HCV-co-infected men from the Johns Hopkins HIV Clinic to 289 men of similar age and race and without HIV or HCV from the Boston Area Community Health Survey/Bone Survey. Hip geometry was assessed at the narrow neck, intertrochanter, and shaft using hip structural analysis. Lean body mass (LBM), total fat mass (FM), and fat mass ratio (FMR) were measured by whole-body DXA. Linear regression was used to identify body composition parameters that accounted for differences in bone strength between cohorts. RESULTS: HIV/HCV-co-infected men had lower BMI, LBM, and FM and higher FMR compared to controls (all p < 0.05). At the narrow neck, significant differences were observed between HIV/HCV-co-infected men and controls in bone mineral density, cross-sectional area, section modulus, buckling ratio, and centroid position. After adjustment for race, age, smoking status, height, and weight, only buckling ratio and centroid position remained significantly different between cohorts (all p < 0.05). Substituting LBM, FM, and FMR for weight in the multivariate model revealed that differences in LBM, but not FM or FMR, accounted for differences in all narrow neck parameters between cohorts, except buckling ratio and centroid position. CONCLUSION: HIV/HCV-co-infected men have compromised hip strength at the narrow neck compared to uninfected controls, which is attributable in large part to lower lean body mass.

Comparison of oral and maxillofacial trauma during the first and third lockdown of the COVID-19 pandemic in the United Kingdom.

The incidence and management of maxillofacial trauma was compared between the first and third lockdowns in the United Kingdom due to the COVID-19 pandemic. From 6 January, 2021 to 8 March 2021, the units that had participated in the collection of data during the first lockdown were asked to update their information into the same database for the third. Nine units participated with 929 entries. Compared to the first lockdown, the number of patients whose treatment had been changed due to the pandemic reduced from 7.6% to 0.4% in the third lockdown. In the UK during the third lockdown there were higher numbers infected with COVID-19 and admitted to hospital than in the first lockdown. Despite this OMFS units that participated in the second study were able to continue the management of maxillofacial trauma without the pandemic affecting care.

Accounting for racial/ethnic variation in bone mineral content and density: the competing influences of socioeconomic factors, body composition, health and lifestyle, and circulating androgens and estrogens.

UNLABELLED: The relative importance of various contributors to racial/ethnic variation in BMC/BMD is not established. Using population-based data, we determined that body composition differences (specifically skeletal muscle and fat mass) are among the strongest contributors to these variations. INTRODUCTION: Racial/ethnic variation in fracture risk is well documented, but the mechanisms by which such heterogeneity arises are poorly understood. We analyzed data from black, Hispanic, and white men enrolled in the Boston Area Community Health/Bone (BACH/Bone) Survey to determine the contributions of risk factors to racial/ethnic differences in bone mineral content (BMC) and density (BMD). METHODS: In a population-based study, BMC, BMD, and body composition were ascertained by DXA. Socioeconomic status, health history, and dietary intake were obtained via interview. Hormones and markers of bone turnover were obtained from non-fasting blood samples. Multivariate analyses measured percentage reductions in estimated racial/ethnic differences in BMC/BMD, accompanying the successive removal of covariates from linear regression models. RESULTS: Black men demonstrated greater BMC than their Hispanic and white counterparts. At the femoral neck, adjustment for covariables was sufficient to reduce these differences by 46% and 35%, respectively. While absolute differences in BMC were smaller at the distal radius than femoral neck, the proportionate reductions in racial/ethnic differences after covariable adjustment were comparable or greater. Multivariate models provided evidence that lean and fat mass, serum 25(OH)D, osteocalcin, estradiol, and aspects of socioeconomic status influence the magnitude of racial/ethnic differences in BMC, with lean and fat mass providing the strongest effects. Results for BMD were similar, but typically of lesser magnitude and statistical significance. CONCLUSIONS: These cross-sectional analyses demonstrate that much of the racial/ethnic heterogeneity in measures of bone mass and density can be accounted for through variation in body composition, diet, and socio-demographic factors.

Management of oral and maxillofacial trauma during the first wave of the COVID-19 pandemic in the United Kingdom.

We assess the effect of coronavirus disease 2019 (COVID-19) on UK oral and maxillofacial (OMF) trauma services and patient treatment during the first wave of the pandemic. From 1 April 2020 until 31 July 2020, OMF surgery units in the UK were invited to prospectively record all patients presenting with OMF trauma. Information included clinical presentation, mechanism of injury, how it was managed, and whether or not treatment included surgery. Participants were also asked to compare the patient's care with the treatment that would normally have been given before the crisis. Twenty-nine units across the UK contributed with 2,229 entries. The most common aetiology was mechanical fall (39%). The most common injuries were soft tissue wounds (52%) and, for hard tissues, mandibular fractures (13%). Of 876 facial fractures, 79 patients' treatment differed from what would have been normal pre-COVID, and 33 had their treatment deferred. Therefore the care of 112 (14%) patients was at variance with normal practice because of COVID restrictions. The pattern of OMFS injuries changed during the first COVID-19 lockdown. For the majority, best practice and delivery of quality trauma care continued despite the on-going operational challenges, and only a small proportion of patients had changes to their treatment. The lessons learnt from the first wave, combined with adequate resources and preoperative testing of patients, should allow those facial injuries in the second wave to receive best-practice care.

Management of odontogenic cervicofacial infections presenting to oral and maxillofacial units during the first wave of the COVID-19 pandemic in the United Kingdom.

On 25 March 2020, the Chief Dental Officer issued national guidance restricting the provision of all routine, non-urgent dental services in response to the spread of COVID-19. We analysed odontogenic cervicofacial infections (CFI) presenting to oral and maxillofacial surgery (OMFS) departments during the first wave of COVID-19 in the United Kingdom. From 1 April 2020 until 31 July 2020 a database was used to prospectively collect records for all patients with CFI who presented to oral and maxillofacial teams. Information gathered included clinical presentation, location/origin of infection, and how this was managed. The OMFS units were asked to compare the patient's care with the treatment that would usually have been given prior to the crisis. A total of 32 OMFS units recorded 1381 cases of CFI in the UK. Most of the infections were referred via the emergency department (74%). Lower first or second molars were the most common origin, contributing 40% of CFI. Collaborators reported that patients' treatments were modified as a response to COVID in 20% of cases, the most frequently cited reason being the application of COVID-19 hospital policy (85%). The impact of the first wave of COVID modified the management of a significant number of patients presenting with CFI, and there was a proactive move to avoid general anaesthetics where possible. Some patients who presented to secondary care were given no treatment, suggesting they could have been managed in primary dental care if this had been available. We recommend that OMFS units and urgent dental care centres (UDCCs) build strong communication links not only to provide the best possible patient care, but to minimise COVID exposure and the strain on emergency departments during the pandemic.

Situational awareness in driving, and lessons for surgeons.

It is often said that medicine could learn a lot from aviation. Human and system errors affect all complex organisations including healthcare, and there is increasing awareness of the role of non-technical skills in the safe practice of surgery. Comparisons are often drawn between the way in which the aviation industry learns from errors and the paucity of learning from errors in situational judgement in medical practice. Although many of us travel on planes, very few of us fly them, but most surgeons drive regularly. We review a series of motoring incidents that demonstrate poor situational awareness and judgement, and discuss the incidents, predisposing causes, and their relevance to medical practice. These errors are transferrable to medical practice, and perhaps we can learn from them.

BAOMS QOMS: findings from the pilot phase and lessons learned in the feasibility evaluation of a national quality improvement initiative.

The BAOMS QOMS pilot was developed and run in six England OMFS units between December 2019 - April 2020. The aims of this pilot project were: to evaluate feasibility of the questionnaires developed for the audit and how effective they were with regards to quality improvement, to test the processes associated with the data collection system and finally, to provide baseline data to support patient data collection without the requirement of prospective consent. The pilot included a series of six audits (oral and dentoalveolar [ODA], oncology, orthognathic, reconstruction, trauma, and skin). Data entry was clinician-led in five OMFS units and in one unit (EKHU), it was additionally supported by members of the clinical coding team. One hundred and twenty-eight REDCap account user details were issued and of these, 45 (35%) completed registration and 22 (17%) were active users who participated in the pilot data entry. Disproportionate focus on individual audits within QOMS was seen, though not all units offered the full range of service audited. Users suggest the skin and ODA audits were sufficiently clear, but improvement is required in the oncology and reconstruction questionnaire particularly. The pilot was successful in aiding the project team identify areas of weaknesses and strength in the design of the REDCap registry and implementation of the next phase of the initiative. The information and experience gained has to date enabled a successful application for section 251 approval from the HRA and progress for the next phase of national data collection.

Current perspectives on the surgical management of mandibular third molars in the United Kingdom: the need for further research.

This survey of expert opinion regarding the management of mandibular third molar (M3M) impaction and its clinical sequelae was circulated to all members of the British Association of Oral and Maxillofacial Surgeons (BAOMS). It was completed by 289 clinicians who reported treating 60003 patients annually. Respondents included 199 (69%) specialists and 58 (20%) primary care clinicians. Most (99%) of the clinicians treated at least one M3M with complete surgical removal (CSR) annually. Only 69% performed one or more coronectomies (COR). Advocates of coronectomy reported lower rates of inferior alveolar nerve (IAN) injury, but IAN, lingual nerve, and adjacent second molar damage were rare, occurring in less than 0.5% of cases, with small differences between the COR and CSR groups. Although these differences are not statistically significant, they are likely to be clinically important. Also, the COR group would have comprised mainly high-risk teeth, while the CSR group would include many teeth at low risk of complications. This might have skewed the results. Those clinicians performing no coronectomies cited three main reasons for being low adopters of COR: the lack of irrefutable evidence to support its benefit, the increased need for a second operation, and more non-IAN complications. Although COR may prevent permanent IAN damage in high-risk cases, this paper highlights clinicians' views that there is a gap in evidence and knowledge to support COR. As a result, 47% of the clinicians surveyed recommended, and were prepared to participate in, further studies to determine the effectiveness and safety of COR.

Relative contributions of multiple determinants to bone mineral density in men.

SUMMARY: Focus on individual risk factors for osteoporosis could allocate disproportionate attention to trivial relationships. We tested many recognized risk factors of osteoporosis for their association with bone mineral density (BMD) in multivariate models among men. Lean mass accounted for the most variance, with substantially less accounted for by demographic, strength, and health factors. INTRODUCTION: Osteoporosis in men has gained recognition as a public health problem, generating an interest in the search for risk factors. Isolation of individual risk factors could allocate disproportionate attention to relationships that may be of limited consequence. METHODS: The Boston Area Community Health/Bone (BACH/Bone) Survey is a population-based study of randomly selected community-dwelling men (age, 30-79 years). BMD and lean mass were measured by dual X-ray absorptiometry. Socioeconomic status, health history, and lifestyle factors were obtained via interview. Hormone levels and markers of bone turnover were obtained from non-fasting blood samples. Multivariate analyses measured relative contributions of covariates to femoral neck (hip), one-third distal radius (wrist), and lumbar spine BMD. RESULTS: Factors positively associated with BMD in multivariate models at the three sites were black race and appendicular lean mass. Asthma was consistently negatively associated. Various other risk factors also contributed significantly to each of the individual sites. R (2) values for the hip, wrist, and spine were 41%, 30%, and 24%, respectively. Lean mass accounted for the most explained variance at all three sites. CONCLUSIONS: These data emphasize the limitation of focusing on individual risk factors and highlight the importance of potentially modifiable lean mass in predicting BMD.

Folding of insulin receptor monomers is facilitated by the molecular chaperones calnexin and calreticulin and impaired by rapid dimerization.

Many complex membrane proteins undergo subunit folding and assembly in the ER before transport to the cell surface. Receptors for insulin and insulin-like growth factor I, both integral membrane proteins and members of the family of receptor tyrosine kinases (RTKs), are unusual in that they require homodimerization before export from the ER. To better understand chaperone mechanisms in endogenous membrane protein assembly in living cells, we have examined the folding, assembly, and transport of the human insulin receptor (HIR), a dimeric RTK. Using pulse-chase labeling and nonreducing SDS-PAGE analysis, we have explored the molecular basis of several sequential maturation steps during receptor biosynthesis. Under normal growth conditions, newly synthesized receptor monomers undergo disulfide bond formation while associated with the homologous chaperones calnexin (Cnx) and calreticulin (Crt). An inhibitor of glucose trimming, castanospermine (CST), abolished binding to Cnx/Crt but also unexpectedly accelerated receptor homodimerization resulting in misfolded oligomeric proreceptors whose processing was delayed and cell surface expression was also decreased by approximately 30%. Prematurely-dimerized receptors were retained in the ER and more avidly associated with the heat shock protein of 70 kD homologue binding protein. In CST-treated cells, receptor misfolding followed disordered oligomerization. Together, these studies demonstrate a chaperone function for Cnx/Crt in HIR folding in vivo and also provide evidence that folding efficiency and homodimerization are counterbalanced.

The efficiency and quality of the care pathway for adult patients being referred to the East Lancashire and Blackburn with Darwen Oral Surgery Services.

Objective: To evaluate the quality of the care pathway for adult patients being referred to the East Lancashire Blackburn with Darwen Oral Surgery Service using the referral management system between 2013 and 2014. Results: In the 2013­14 financial year, of the 5,285 referrals that were made to the Oral Surgery Service, 1,962 (37%) were directed to a primary care location for management. After being referred to a primary care location, 92% of patients had been seen within eight weeks. In total, £232,320 was paid to the providers for their service. Conclusion: The East Lancashire Blackburn with Darwen Oral Surgery Services delivered in primary care was found to be effective, with a good standard of quality care. There is ease of access in the community, and reduced waiting times for treatment. It is cost effective with a decreased spend to secondary care. However, there were no cost savings to the commissioners, as overall secondary care activity has not reduced.

Has the primary care oral surgery service reduced the activity in secondary care oral and maxillofacial units?

To find out if the devolution of some dentoalveolar services into primary care in 2007 was having an effect on the workload of oral and maxillofacial units, I reviewed the workload of two units in 2011-13.

Should patients take vitamin D before mandibular operations?

Vitamin D deficiency is endemic in the United Kingdom (UK), particularly in high-risk groups. We report the outcomes of patients with low concentrations of the vitamin who had complications after reduction of mandibular fractures or osteotomy, and those who were screened preoperatively. A deficiency can be diagnosed with a simple and inexpensive blood test, and in the UK the cost of a vitamin D tablet is about £0.04/tablet/day. Patients at risk of a deficiency should be screened before mandibular operations, and those listed for orthognathic surgery or replacement of the temporomandibular joint should be asked to take a supplement before operation.

Sister chromatid exchange frequency in asbestos workers.

In vitro cytogenetic studies of amosite, chrysotile, and crocidolite asbestos have shown that these fibers may induce chromosome abnormalities and an elevated sister chromatid exchange (SCE) rate in mammalian cells. Twenty-five asbestos insulators (6 with radiographic asbestosis) were compared to 14 controls frequency matched for age and were found to have a marginally increased SCE rate in circulating lymphocytes with increasing years of exposure (P= 0.057). There was a significant association between SCE rate and smoking (P=0.002) after controlling for years of asbestos exposure and age. Smoking asbestos insulators had the highest SCE rate. Sister chromatid exchanges in chromosomes of group A, i.e., the group with the longest chromosomes, were significantly associated with asbestos exposure and cigarette smoking, with an interaction between the two.

Selective protein interactions with phosphatidylserine containing liposomes alter the steric stabilization properties of poly(ethylene glycol).

Incorporation of 5 mol% poly(ethylene glycol)-conjugated lipids (PEG-lipids) has been shown to extend the circulation longevity of neutral liposomes due to steric repulsion of PEG at the membrane surface. The effects of PEG-lipids on protein interactions with biologically reactive membranes were examined using phosphatidylserine (PS) containing liposomes as the model. Incorporating 15 mol% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG 2000 into PS liposomes resulted in circulation lifetimes comparable to that obtained with neutral liposomes containing 5 mol% DSPE-PEG 2000. These results suggested that 15 mol% DSPE-PEG 2000 may be effective in protecting PS liposomes from the high affinity, PS-mediated binding of plasma proteins. This was determined by monitoring the effects of PEG-lipids on calcium-mediated blood coagulation protein interactions with PS liposomes. Prothrombin binding and procoagulant activity of PS liposomes could be inhibited >80% when 15 mol% DSPE-PEG 2000 was used. These results are consistent with PS on membrane surfaces forming transient nucleation sites for protein binding that may result in lateral exclusion of PEG-lipids incorporated at <10 mol%. These nucleation sites may be inaccessible when PEG-lipids are present at elevated levels where they adopt a highly compressed brush conformation. This suggests that liposomes with reactive groups and PEG-lipids may be appropriately designed to impart selectivity to protein interactions with membrane surfaces.

Preparing for a career in oral and maxillofacial surgery: a survey of dentists at medical schools.

A questionnaire was sent to the 112 dental graduates who were doing a second degree in medicine in the United Kingdom (UK) in the academic year 2002-2003. Seventy-four students replied. The most common time from graduating from dental school to returning to medical school was 36 months. Of the 74 respondents 50 (68%) wrote that they intended to return to oral and maxillofacial surgery.

Risk factors for hip fractures in men: a preliminary study.

Although hip fracture rates are higher in women than in men, for older men the lifetime risk of fractures of the femur is substantial. Very little is known about risk factors for hip fracture in men. A preliminary case control study was conducted comparing the medical charts of men with first hip fractures with two sets of age-matched controls. The major risk factors for hip fracture that emerged were preadmission ambulatory problems, confusion, heavy alcohol use, and low body mass. Although this study is limited to a medical chart review in a veteran population, these results confirm some of the known associations for hip fracture in women. Further studies in men are recommended.

Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate.

A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3-(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human alpha adrenoceptors as well as the rat L-type calcium channel. Within this compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73) and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the human prostate.

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 3. Approaches to eliminate opioid agonist metabolites by using substituted phenylpiperazine side chains.

Dihydropyrimidinones, such as 1, represent a novel class of alpha(1a) adrenoceptor antagonists with potential for the treatment of benign prostatic hyperplasia (BPH) (see part 1 of this series). Analysis of the metabolites of 1 revealed that 4-methoxycarbonyl-4-phenylpiperidine is formed as the major metabolite and is an agonist at the mu-opioid receptor. To circumvent any potential liability resulting from the metabolite, we decided to identify alternate templates devoid of agonist activity at the mu-opioid receptor to replace the 4-methoxycarbonyl-4-phenylpiperidine moiety. The present study describes the synthesis and SAR of dihydropyrimidinones linked to substituted 4-phenylpiperazine containing side chains. Compound (+)-38 was identified as a lead compound with a binding and functional profile comparable to that of 1. The putative metabolite 2-carboxamidophenylpiperazine has negligible affinity for the mu-opioid receptor.