Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank.

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.

Management of Gustilo-Anderson IIIB open tibial fractures in adults-a systematic review.

INTRODUCTION: Open tibial fractures are the most common open long bone fracture, despite this, the management of these complex injuries still remains a topic of discussion amongst orthopaedic surgeons. SOURCES OF DATA: We searched the EMBASE, MEDLINE and Google Scholar and a systematic review of 7500 articles, leaving 23 after exclusion criteria were applied, in order to analyse the management of open tibial fractures. AREAS OF AGREEMENT AND CONTROVERSY: Infection was noted to be the most significant concern amongst authors, with definitive external fixation having a high rate of superficial pin-site infection and internal fixation having a high deep infection rate. GROWING POINTS: It is essential to have a combined ortho-plastic approach to the management of these fractures as muscle flaps were the most common form of soft tissue coverage. AREAS TIMELY FOR DEVELOPING RESEARCH: A national pragmatic trial into the management of open tibial fractures is required looking at fixation methods and soft tissue coverage, with at least a 2-year follow-up in order to ascertain the most appropriate management of these fractures and patient-related outcomes.

Developing a novel risk prediction model for severe malarial anemia.

As a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002-2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as a Plasmodium falciparum infection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1ß provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.77 (95% CI 0.70-0.84), whereas a pragmatic model based on sex, gravidity, transmission season at delivery, and bed net possession yielded a more modest C-index of 0.63 (95% CI 0.54-0.71). Although additional studies, ideally incorporating larger sample sizes and higher event per predictor ratios, are needed to externally validate these prediction models, the findings provide proof of concept that risk score-based screening programs could be developed to avert severe malaria cases in early childhood.

Return to sport following stress fractures of the great toe sesamoids: a systematic review.

Introduction: This review aims to provide information on return rates and times to sport following stress fractures of the great toe sesamoids (SFGTSs). Sources of data: A systematic search of CINAHAL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Scopus, SPORTDiscus and Web of Science was performed using the keywords 'stress', 'fractures', 'great', 'toe', 'sesamoid', 'athletes', 'sports', 'non-operative', 'conservative', 'operative' and 'return to sport'. Areas of agreement: Fourteen studies were included: three studies reported on the outcome of conservatively-managed SFGTSs; thirteen studies reported on the outcome of surgically-managed SFGTSs. The management principles were to attempt conservative management for 2-6 months using activity modification, analgesia, orthotics and physiotherapy; if symptoms persisted following this, surgical management was to be recommended, either with internal fixation or sesamoidectomy. Areas of controversy: The optimal treatment modalities for SFGTSs remain to be defined. Growing points: Internal fixation shows the best return to full-level sport rates with low rates of complications. Areas timely for developing research: Future prospective studies should aim to establish the optimal treatment modalities for SFGTSs.

CrossFitter's knee: patellofemoral chondral injury following high-intensity functional training.

We present a case series of patients with patellofemoral joint (PFJ) chondral injuries presenting as anterior knee pain secondary to participation in high-intensity functional training programmes. We aim to highlight PFJ chondral injuries as a potential complication of military servicemen engaging in high-intensity functional training programmes. This may allow medical staff to identify the injuries early, and highlight this possible injury mechanism to Physical Training staff to help educate participants and mitigate the risk of injury.

Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study.

Nicotine replacement therapy (NRT) is a common first-line treatment to prevent nicotine withdrawal in smokers. However, available literature reports conflicting results regarding its efficacy and safety in critically ill patients. The objective of this study was to evaluate the relationship between NRT in smokers in the intensive care unit (ICU) and outcomes. This case-control study was conducted in a university-affiliated tertiary hospital ICU. Over a period of five years, 126 active smokers who received transdermal NRT were matched to 126 active smokers who did not receive NRT. The groups were case-matched for sex, age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary outcome was administration of antipsychotic medication. Secondary outcomes included use of physical restraints, 30-day mortality, and ventilation requirements. Antipsychotic medication was prescribed in 43 (34.1%) patients who received NRT compared to 14 (11.1%) in controls (P <0.01). Physical restraints were used in 37 (29.4%) patients who received NRT, compared to 12 (9.5%) of controls (P <0.01). The 30-day mortality and number of patients intubated was not statistically different between groups. Average length of intubation time was greater in the NRT group (2.56 days; standard deviation 4.16) compared to the control group (1.44 days; standard deviation 2.68) (P=0.012). The use of NRT to prevent nicotine withdrawal in ICU patients is associated with increased use of antipsychotic medication and physical restraint, and with prolonged mechanical ventilation.

Return to sport following clavicle fractures: a systematic review.

INTRODUCTION: This review aims to provide information on the return rates and return times to sport following clavicle fractures. SOURCES OF DATA: A systematic search of Medline, EMBASE, CINAHAL, Cochrane, Web of Science, PEDro, SPORTDiscus, Scopus and Google Scholar was performed using the keywords 'clavicle', 'clavicular', 'fractures', 'athletes', 'sports', 'non-operative', 'conservative', 'operative', 'return to sport'. AREAS OF AGREEMENT: Twenty-three studies were included: 10 reported on mid-shaft fractures, 14 on lateral fractures. The management principles for athletic patients were to attempt non-operative management for undisplaced fractures to undertake operative intervention for displaced lateral fractures and to recommend operative intervention for displaced mid-shaft fractures. AREAS OF CONTROVERSY: The optimal surgical modality for mid-shaft and lateral clavicle fractures. GROWING POINTS: Operative management of displaced mid-shaft fractures offers improved return rates and times to sport compared to non-operative management. Suture fixation and non-acromio-clavicular joint (ACJ)-spanning plate fixation of displaced lateral fractures show promising results. AREAS TIMELY FOR DEVELOPING RESEARCH: Future prospective studies should aim to establish the optimal treatment modalities for clavicle fractures.

British Military freezing cold injuries: a 13-year review.

INTRODUCTION: Cold injuries have been a recurrent feature of warfare for millennia and continue to present during British Military operations today. Those affecting the peripheries are divided into freezing cold injury (FCI) and non-FCI. FCI occurs when tissue fluids freeze at around -0.5°C and is commonly referred to as frostnip or frostbite. METHOD: All FMED7 notes held at the Institute of Naval Medicine's Cold Weather Injury Clinic (CIC) from 2002 to 2014 were searched for the terms 'frostbite' and 'frostnip' and then analysed to identify common themes. RESULTS: In total 245 results were found and from these, 149 patients with a positive FCI diagnosis were identified and formed the cohort of this study. Royal Marines (RM) represented over 50% of patients and Arctic training in Norway accounted for over two thirds of the total cases. The extremities were almost always those areas which were affected by FCI. Further analysis of the RM cases showed the majority of those injured were of the most junior rank (Marine/Private or Lance Corporal). CONCLUSIONS: A lack of supporting climatic and activity data meant that it was difficult to draw additional conclusions from the data collected. In future, a greater emphasis should be placed on collection of climatic and additional data when FCIs are diagnosed. These data should be collated at the end of each deployment and published as was regularly done historically. It is hoped that these data could then be used as the starting point for an annual climatic study day, where issues related to FCIs could be discussed in a Tri-Service environment and lessons learned disseminated around all British Forces personnel.

Previous caesarean delivery and the risk of unexplained stillbirth: retrospective cohort study and meta-analysis.

OBJECTIVE: To determine whether caesarean delivery in the first pregnancy is a risk factor for unexplained antepartum stillbirth in a second pregnancy. DESIGN: A population-based retrospective cohort study and meta-analysis. SETTING: All maternity units in Scotland. PARTICIPANTS: A cohort of 128 585 second births, 1999-2008. METHODS: Time-to-event analysis and random-effects meta-analysis. MAIN OUTCOME MEASURE: Risk of unexplained antepartum stillbirth in a second pregnancy. RESULTS: There were 88 stillbirths among 23 688 women with a previous caesarean delivery (2.34 per 10 000 women per week) and 288 stillbirths in 104 897 women who had previously delivered vaginally (1.67 per 10 000 women per week, P = 0.002). When analysed by cause, women with a previous caesarean delivery had an increased risk of unexplained stillbirth (hazard ratio, HR 1.47; 95% confidence interval, 95% CI 1.12-1.94; P = 0.006) and, as previously observed, the excess risk was apparent from 34 weeks of gestation onwards. The risk did not differ in relation to the indication of the caesarean delivery, and was independent of maternal characteristics and previous obstetric complications. We identified three other comparable studies (two in North America and one in Europe), and meta-analysis of these studies showed a statistically significant association between previous caesarean delivery and the risk of antepartum stillbirth in the second pregnancy (pooled HR 1.40; 95% CI 1.10-1.77; P = 0.006). CONCLUSIONS: Women who have had a previous caesarean delivery are at increased risk of unexplained stillbirth in the second pregnancy. TWEETABLE ABSTRACT: Caesarean first delivery is associated with an increased risk of unexplained stillbirth in the next pregnancy.

Return to sports after stress fractures of the tibial diaphysis: a systematic review.

INTRODUCTION: This review aims to provide information on the time taken to resume sport following tibial diaphyseal stress fractures (TDSFs). SOURCES OF DATA: A systematic search of Medline, EMBASE, CINHAL, Cochrane, Web of Science, PEDro, Sports Discus, Scopus and Google Scholar was performed using the keywords 'tibial', 'tibia', 'stress', 'fractures', 'athletes', 'sports', 'non-operative', 'conservative', 'operative' and 'return to sport'. AREAS OF AGREEMENT: Twenty-seven studies were included: 16 reported specifically on anterior TDSFs and 5 on posterior TDSFs. The general principles were to primarily attempt non-operative management for all TDSFs and to consider operative intervention for anterior TDSFs that remained symptomatic after 3-6 months. Anterior TDSFs showed a prolonged return to sport. AREAS OF CONTROVERSY: The best time to return to sport and the optimal management modalities for TDSFs remain undefined. GROWING POINTS: Management of TDSFs should include a full assessment of training methods, equipment and diet to modify pre-disposing factors. AREAS TIMELY FOR DEVELOPING RESEARCH: Future prospective studies should aim to establish the optimal treatment modalities for TDSFs.

Previous miscarriage and the subsequent risk of preterm birth in Scotland, 1980-2008: a historical cohort study.

OBJECTIVE: To determine whether the relationship between previous miscarriage and risk of preterm birth changed over the period 1980-2008, and to determine whether the pattern varied according to the cause of the preterm birth. DESIGN: Linked birth databases. SETTING: All Scottish NHS hospitals. POPULATION: A total of 732 719 nulliparous women with a first live birth between 1980 and 2008. METHODS: Risk was estimated using logistic regression. MAIN OUTCOME MEASURES: Preterm birth, subdivided by cause (spontaneous, induced with a diagnosis of pre-eclampsia, or induced without a diagnosis of pre-eclampsia) and severity [extreme (24-28 weeks of gestation), moderate (29-32 weeks of gestation), and mild (33-36 weeks of gestation)]. RESULTS: Consistent with previous studies, previous miscarriage was associated with an increased risk of all-cause preterm birth (adjusted odds ratio, aOR 1.26; 95% confidence interval, 95% CI 1.22-1.29). This arose from associations with all subtypes. The strongest association was found with extreme preterm birth (aOR 1.73; 95% CI 1.57-1.90). Risk increased with the number of miscarriages. Women with three or more miscarriages had the greatest risk of all-cause preterm birth (aOR 2.14; 95% CI 1.93-2.38), and the strongest association was with extreme preterm birth (aOR 3.87; 95% CI 2.85-5.26). The strength of the association between miscarriage and preterm birth decreased from 1980 to 2008. This was because of weakening associations with spontaneous preterm birth and induced preterm birth without a diagnosis of pre-eclampsia. CONCLUSIONS: The association between a prior history of miscarriage and the risk of preterm birth declined in Scotland over the period 1980-2008. We speculate that changes in the methods of managing incomplete termination of pregnancy might explain the trend, through reduced cervical damage.

Lower limb stress fractures in military training.

This article describes stress fractures that are seen in military training, and reviews the relevant literature. The information is vital for medical personnel who work with the United Kingdom (UK) Armed Forces, particularly those working in training establishments. The author suggests areas for further research and discusses some of the issues in current UK Armed Forces training.

Infection control hazards associated with the use of forced-air warming in operating theatres.

A review is presented of the published experimental and clinical research into the infection control hazards of using forced air-warming (FAW) in operating theatres to prevent inadvertent hypothermia. This evidence has been reviewed with emphasis on the use of ultra-clean ventilation, any interaction it has with different types of patient warming (and FAW in particular), and any related increased risk of surgical site infection (SSI). We conclude that FAW does contaminate ultra-clean air ventilation; however, there appears to be no definite link to an increased risk of SSI based on current research. Nevertheless, whereas this remains unproven, we recommend that surgeons should at least consider alternative patient-warming systems in areas where contamination of the operative field may be critical. Although this is not a systematic review of acceptable randomized controlled clinical trials, which do not exist, it does identify that there is a need for definitive research in this field.

A single strain of Tetratrichomonas gallinarum causes fatal typhlohepatitis in red-legged partridges (Alectoris rufa) to be distinguished from histomonosis.

Typhlohepatitis was observed in a flock of 2500 red-legged partridges in Great Britain, characterized by the sudden deaths of 15 birds within 2 days. Necropsy of five dead birds revealed severe lesions in the caeca with thickened caecal walls, a reddened lining and bloody contents. The livers contained multiple miliary lesions and similar pathological changes were found in the spleens of some birds. Microscopic examination of intestinal contents showed the occurrence of coccidial oocysts in two partridges. Different methods for the detection of bacteria from liver and intestine samples were conducted without positive results. Histopathological examination revealed the presence of protozoan parasites in the caecum, liver and spleen of the affected birds. In situ hybridization (ISH) for the detection of trichomonads resulted in positive findings and polymerase chain reaction (PCR) confirmed the presence of Tetratrichomonas gallinarum in the lesions. Additionally, archived tissues of red-legged partridges from different flocks suffering from severe typhlohepatitis in Great Britain in 2008 and 2009 were re-investigated by ISH and PCR. Beside the sporadic occurrence of histomonosis, in most of the cases trichomonads were detected by ISH in the caecum and liver of affected birds. Furthermore, dissemination of the flagellate into the lung and bursa of Fabricius could be demonstrated. Analyses of T. gallinarum DNA obtained from the different cases resulted in homologous nucleotide sequences. Altogether, the results demonstrate the circulation of a virulent strain of T. gallinarum in reared red-legged partridges.

Changes in vitamin D and matrix metalloproteinase-9 in submariners during a submerged patrol.

OBJECTIVES: To quantify changes in vitamin D and matrix metalloproteinase-9 (MMP9) in submariners over a single long patrol and compare the data to a group of non-deploying servicemen from their base port. METHODS: A prospective time-series analysis was performed. Blood samples were taken from 49 submariners deploying on patrol and 43 shore-side controls from the base port (naval officers from base or non-deploying submariners), following a winter ashore at latitude 56° north. Samples were drawn immediately before the submarine sailed, in January, and again in the final week of patrol 85 days later. Paired pre-patrol and late samples from each individual were assayed together and changes in vitamin D and MMP9 were assessed. RESULTS: Mean pre-patrol vitamin D concentrations were 58 and 49 nmol/L for the controls and submariners, respectively. Mean vitamin D concentrations increased in controls as expected (mean increase 12.6 nmol/L), but not in the submariners (mean decrease 1.6 nmol/L). MMP9 levels were significantly higher in submariners pre-patrol, and increased significantly during the patrol. There was a significant inverse correlation between MMP9 and vitamin D levels (r=-0.41, p=0.01). CONCLUSIONS: This is the first study to quantify vitamin D and MMP levels in submariners. Circulating vitamin D concentrations on board were insufficient to prevent a rise in MMP. This has potential for adverse health effects and requires further study.

The management of the acutely swollen ankle.

Patients presenting with an acutely swollen ankle are common in both the military and civilian settings. Accurate diagnosis is vital, as there are various potentially serious causes. This article aims to review the common causes of an acutely swollen ankle, as well as the rarer causes, with their significant consequences.

Injuries and medical issues on the Zambezi "Great River".

We report the injuries and medical issues incurred during a rowing expedition conducted along the Zambezi River in May 2011. All injuries and illnesses requiring medical intervention were recorded during a 30-day expedition. There were 22 rowers and 8 support staff sustaining 32 injuries, an injury incidence of 36 per 1000 days. We discuss the medical issues regarding conducting an expedition along the Zambezi and the medical preparation and education required to successfully support wilderness expeditions.

Ten-year results of the Press Fit Condylar Sigma total knee replacement.

We report ten-year clinical and radiological follow-up data for the Sigma Press Fit Condylar total knee replacement system (Sigma PFC TKR). Between October 1998 and October 1999 a total of 235 consecutive PFC Sigma TKRs were carried out in 203 patients. Patients were seen at a specialist nurse-led clinic seven to ten days before admission and at six and 18 months, three, five and eight to ten years after surgery. Data were recorded prospectively at each clinic visit. Radiographs were obtained at the five- and eight- to ten-year follow-up appointments. Of the 203 patients, 147 (171 knees) were alive at ten years and 12 were lost to follow-up. A total of eight knees (3.4%) were revised, five for infection and three to change the polyethylene insert. The survival at ten years with an endpoint of revision for any reason was 95.9%, and with an endpoint of revision for aseptic failure was 98.7%. The mean American Knee Society Score (AKSS) was 79 (10 to 99) at eight to ten years, compared with 31 (2 to 62) pre-operatively. Of 109 knee with radiographs reviewed, 47 knees had radiolucent lines but none showed evidence of loosening.