Prevalence of genotypic and phenotypic resistance to anti-retroviral drugs in a cohort of therapy-naïve HIV-1 infected US military personnel.

OBJECTIVE: While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy. DESIGN: Cross-sectional cohort study. METHODS: Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay. RESULTS: Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes. CONCLUSIONS: A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.

Dual-energy X-ray absorptiometry derived structural geometry for stress fracture prediction in male U.S. Marine Corps recruits.

A total of 626 U.S. male Marine Corps recruits underwent anthropometric measurements and dual-energy X-ray absorptiometry (DXA) scans of the femoral midshaft and the distal third of the tibia prior to a 12 week physical training program. Conventionally obtained frontal plane DXA scan data were used to measure the bone mineral density (BMD) as well as to derive the cross-sectional area, moment of inertia, section modulus, and bone width in the femur, tibia, and fibula. During training, 23 recruits (3.7%) presented with a total of 27 radiologically confirmed stress fractures in various locations in the lower extremity. After excluding 16 cases of shin splints, periostitis, and other stress reactions that did not meet fracture definition criteria, we compared anthropometric and bone structural geometry measurements between fracture cases and the remaining 587 normals. There was no significant difference in age (p = 0.8), femur length (p = 0.2), pelvic width (p = 0.08), and knee width at the femoral condyles (p = 0.06), but fracture cases were shorter (p = 0.01), lighter (p = 0.0006), and smaller in most anthropometric girth dimensions (p < 0.04). Fracture case bone cross-sectional areas (p < 0.001), moments of inertia (p < 0.001), section moduli (p < 0.001), and widths (p < 0.001) as well as BMD (p < 0.03) were significantly smaller in the tibia and femur. After correcting for body weight differences, the tibia cross-sectional area (p = 0.03), section modulus (p = 0.05), and width (p = 0.03) remained significantly smaller in fracture subjects. We conclude that both small body weight and small diaphyseal dimensions relative to body weight are factors predisposing to the development of stress fractures in this population. These results suggest that bone structural geometry measurements derived from DXA data may provide a simple noninvasive methodology for assessing the risk of stress fracture.

Use-dependent loss of active sympathetic neurogenic vasodilation after nitric oxide synthase inhibition in conscious rats. Evidence for the presence of preformed stores of nitric oxide-containing factors.

In this study, we examined whether air-jet stress-induced active sympathetic hindlimb vasodilation in conscious rats involves the release of preformed stores of nitric oxide-containing factors. We determined the effects of repeated episodes of air-jet stress (six episodes given 5 minutes apart) on mean arterial pressure and vascular resistances in the mesenteric bed and intact and sympathetically denervated hindlimb beds of conscious rats treated with saline or the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg IV). In saline-treated rats, air-jet stress produced alerting behavior, minor changes in blood pressure, pronounced mesenteric vaso-constriction, and immediate and marked vasodilation in the sympathetically intact hindlimb but a minor vasodilation in the sympathetically denervated hindlimb. Each air-jet stress produced virtually identical responses. In L-NAME-treated rats, the first air-jet stress produced vasodilator responses in the sympathetically intact and sympathetically denervated hindlimbs that were similar to those in the saline-treated rats. However, each subsequent air-jet stress produced progressively smaller vasodilator responses in the sympathetically intact but not the sympathetically denervated hindlimb. There was no loss of air-jet stress-induced alerting behavior or mesenteric vasoconstriction, suggesting that L-NAME did not interfere with the central processing of the air-jet or the resultant changes in autonomic nerve activity. The progressive diminution of air-jet stress-induced vasodilation in the intact hindlimb of L-NAME-treated rats may be due to the use-dependent depletion of preformed stores of nitric oxide-containing factors that cannot be replenished in the absence of nitric oxide synthesis.

Contribution of the sympathetic nervous system to vascular resistance in conscious young and adult spontaneously hypertensive rats.

Although evidence exists for exaggerated sympathetic nervous system activity in spontaneously hypertensive rats (SHR), there are no studies in conscious animals that directly demonstrate that this increased activity is functionally involved in the elevated vascular resistance of these animals. In our present study, 8-week-old and 13-week-old SHR and Wistar Kyoto controls (WKY) were chronically instrumented with arterial and venous catheters and miniaturized pulsed Doppler flow probes on the renal and mesenteric arteries and lower abdominal aorta. While the rats were conscious and unrestrained, hexamethonium was administered intravenously to block sympathetic nervous system transmission. Prior to hexamethonium, the mean arterial pressure of young SHR and WKY averaged 123 plus or minus 5 and 109 plus or minus 4 mm Hg respectively (p smaller than 0.05), while adult SHR and WKY averaged 159 plus or minus 7 and 128 plus or minus 3 mm Hg respectively (p smaller than 0.05). Hexamethonium produced an equivalent fall in arterial pressure of young SHR (-32%) and WKY (-30%) and adult SHR (-39%) and WKY (-41%). Vascular resistance was reduced by hexamethonium in the kidney, gut, and hindquarters, but the percent changes were not significant between SHR and WKY. These data suggest that, in both young and adult SHR, vascular resistance and arterial pressure are sustained at elevated levels by some other mechanism than neurally-derived vasoconstrictor tone.

State-of-the-art-lecture: Obesity-induced hypertension: new concepts from the emerging biology of obesity.

offsity is associated with an increased risk of hypertension. In the past 5 years there have been dramatic advances into the genetic and neurobiological mechanisms of obesity with the discovery of leptin and novel neuropeptide pathways regulating appetite and metabolism. In this brief review, we argue that these mounting advances into the neurobiology of obesity have and will continue to provide new insights into the regulation of arterial pressure in obesity. We focus our comments on the sympathetic, vascular, and renal mechanisms of leptin and melanocortin receptor agonists and on the regulation of arterial pressure in rodent models of genetic obesity. We suggest 3 concepts. First, the effect of obesity on blood pressure may depend critically on the genetic-neurobiological mechanisms underlying the obesity. Second, obesity is not consistently associated with increased blood pressure, at least in rodent models. Third, the blood pressure response to obesity may be critically influenced by modifying alleles in the genetic background.

Stress fracture in military recruits: gender differences in muscle and bone susceptibility factors.

A total of 693 female U.S. Marine Corps recruits were studied with anthropometry and dual-energy X-ray absorptiometry (DXA) scans of the midthigh and distal third of the lower leg prior to a 12 week physical training program. In this group, 37 incident stress fracture cases were radiologically confirmed. Female data were compared with male data from an earlier study of 626 Marine recruits extended with additional cases for a total of 38 stress fracture cases. Using DXA data, bone structural geometry and cortical dimensions were derived at scan locations and muscle cross-sectional area was computed at the midthigh. Measurements were compared within gender between pooled fracture cases and controls after excluding subjects diagnosed with shin splints. In both genders, fracture cases were less physically fit, and had smaller thigh muscles compared with controls. After correction for height and weight, section moduli (Z) and bone strength indices (Z/bone length) of the femur and tibia were significantly smaller in fracture cases of both genders, but patterns differed. Female cases had thinner cortices and lower areal bone mineral density (BMD), whereas male cases had externally narrower bones but similar cortical thicknesses and areal BMDs compared with controls. In both genders, differences in fitness, muscle, and bone parameters suggest poor skeletal adaptation in fracture cases due to inadequate physical conditioning prior to training. To determine whether bone and muscle strength parameters differed between genders, all data were pooled and adjusted for height and weight. In both the tibia and femur, men had significantly larger section moduli and bone strength indices than women, although women had higher tibia but lower femur areal BMDs. Female bones, on average, were narrower and had thinner cortices (not significant in the femur, p = 0.07). Unlike the bone geometry differences, thigh muscle cross-sectional areas were virtually identical to those of the men, suggesting that the muscles of the women were not relatively weaker.

Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice.

OBJECTIVE: Recent advances in understanding the neuroendocrine pathways regulating appetite, metabolism and body weight afford an opportunity to explore further the mechanisms by which obesity influences arterial pressure. ob/ob(Lep(ob)/Lep(ob)) mice have a mutation in the ob gene and are leptin-deficient. Leptin possesses pressor actions and has been shown to increase arterial pressure when infused chronically or over-expressed transgenically. In contrast, agouti yellow obese(Ay) mice have overexpression of an agouti peptide that blocks melanocortin receptors. Stimulation of melanocortin receptors by alpha-melanocyte-stimulating hormone decreases arterial pressure. DESIGN AND METHODS: This study measured arterial pressure in leptin-deficient ob/ob mice, agouti yellow obese mice and their lean controls to test the hypothesis that the effects of obesity on arterial pressure are importantly influenced by the genetic and neuroendocrine mechanisms causing the obesity. We measured arterial pressure directly in conscious ob/ob mice (n = 14), agouti yellow obese mice (n = 6) and the same number of lean littermates. RESULTS: Body weight was nearly twice as high in ob/ob mice as in their lean controls, but mean arterial pressure was significantly lower in ob/ob mice (92+/-3 mmHg) compared with their lean controls (106+/-2 mmHg; P = 0.00017). In contrast, mean arterial pressure was significantly higher in agouti yellow obese mice (124+/-3 mmHg) than in their lean controls (99+/-1 mmHg; P = 0.000002) despite the fact that the agouti mice had milder obesity. CONCLUSIONS: This study prompts three conclusions: (1) leptin-deficient ob/ob mice and agouti yellow obese mice have contrasting blood pressure responses to obesity, (2) obesity does not invariably increase arterial pressure in mice, and (3) the arterial pressure response to obesity may depend critically on the underlying genetic and neuroendocrine mechanisms.

Stimulation of lumbar sympathetic nerves may produce hindlimb vasodilation via the release of pre-formed stores of nitrosyl factors.

The physiological activation of lumbar sympathetic nerves by air-jet stress produces a hindlimb vasodilation in conscious rats. Although the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester markedly reduces the duration of this air-jet stress-induced vasodilation, it does not prevent the initial fall in resistance. These data suggest that the vasodilation is initiated by the release of an as yet unidentified factor, whereas the vasodilation is sustained by the release of nitric oxide or newly synthesized nitrosyl factors such as S-nitrosothiols. At present, the possibility that neurogenic vasodilation may be initiated by the release of pre-formed pools of nitrosyl factors from storage sites within the hindlimb vasculature has not been addressed. We reasoned that if nitrosyl factors do exist in storage pools, then we should be able to demonstrate a "use-dependent" loss of vasodilation after nitric oxide synthesis inhibition which would be the result of a gradual depletion of the releasable pools of these nitrosyl factors. In the present study, we examined the effects of repeated episodes of direct electrical stimulation of the lumbar sympathetic chain on ipsilateral hindlimb vascular resistance in pentobarbital-anesthetized rats prior to and following administration of the nitric oxide synthesis inhibitors N(G)-nitro-L-arginine methyl ester (10, 25 or 100 mumol/kg i.v.) or N(G)-nitro-L-arginine (50 mumol/kg i.v.). Three episodes of electrical stimulation of 3.2 +/- 0.4 V (20 Hz, 5 ms duration, 5 ms delay for 10 s given 5 min apart) produced pronounced and reproducible reductions in hindlimb vascular resistance in the ipsilateral hindlimb (-56 +/- 5%, -55 +/- 5% and -53 +/- 6%, respectively), but no changes in mean arterial pressure. Three episodes of electrical stimulation at 4.8 +/- 0.4 V also caused reproducible decreases in hindlimb resistance (-59 +/- 7%, -61 +/- 9% and -64 +/- 12%) and minor but reproducible decreases in blood pressure. The vasodilation produced by the first electrical stimulation at 3.2 +/- 0.4 V was completely abolished by a 25 mumol/kg dose of N(G)-nitro-L-arginine methyl ester (-11 +/- 9%). The initial episode of electrical stimulation at 4.8 +/- 0.4 V produced a pronounced fall in ipsilateral hindlimb resistance in the N(G)-nitro-L-arginine methyl ester-treated animals whereas the second and third stimulations produced progressively smaller vasodilations (-55 +/- 4%, -34 +/- 3% and -19 +/- 2%, respectively). The 10 mumol/kg dose of N(G)-nitro-L-arginine methyl ester was not effective whereas the 100 mumol/kg dose produced similar effects as the 25 mumol/kg dose. The 50 mumol/kg dose of N(G)-nitro-L-arginine produced similar effects as the higher doses of N(G)-nitro-L-arginine methyl ester. Those results suggest that lower intensity electrical stimulation of the lumbar sympathetic nerves produces vasodilation via the release of nitric oxide or newly synthesized nitrosyl factors such as S-nitrosothiols. In contrast, the vasodilation produced by higher intensity electrical stimulation may involve the mobilization and release of pre-formed pools of nitrosyl factors which undergo a "use-dependent" depletion in the absence of nitric oxide synthesis. These pre-formed pools of nitrosyl factors may exist within the sympathetic nerves themselves. In addition, they may be stored within the vascular endothelium and released by neurogenically-derived neurotransmitters/neuromodulators.

Epidemiological patterns of musculoskeletal injuries and physical training.

PURPOSE: The purpose of this study was to identify rates of diagnosis-specific musculoskeletal injuries in U.S. Marine Corps recruits and to examine the association between patterns of physical training and these injuries. METHODS: Subjects were 1,296 randomly selected male Marine recruits, ages 17 to 28 yr, who reported to Marine Corps Recruit Depot San Diego for boot camp training between January 12 and September 14, 1993. Recruits were followed prospectively through 12 wk of training for injury outcomes. Injury patterns were examined in relation to weekly volumes and types of vigorous physical training. RESULTS: The overall injury rate was 39.6% (number of recruits injured/population at risk), with 82% of injuries occurring in the lower extremities. Overuse injuries accounted for 78% of the diagnoses. The most frequent site of injury was the ankle/foot region (34.3% of injuries), followed by the knee (28.1%). Ankle sprains (6.2%, N = 1,143), iliotibial band syndrome (5.3%, N = 1,143), and stress fractures (4.0%, N = 1,296) were the most common diagnoses. Injury rates were highest during the weeks with high total volumes of vigorous physical training and the most hours of running and marching. Weekly injury rates were significantly correlated with hours of vigorous physical training (overuse injuries r = 0.667, P = 0.018; acute injuries r = 0.633, P = 0.027). CONCLUSIONS: The results of this controlled epidemiological investigation indicate that volume of vigorous physical training may be an etiologic factor for exercise-related injuries. The findings also suggest that type of training, particularly running, and abrupt increases in training volume may further contribute to injury risk.

Running mileage, movement mileage, and fitness in male U.S. Navy recruits.

PURPOSE: The purpose of this study was to determine whether there is a relationship between overall fitness improvement and varying amounts of running and movement mileage. METHODS: Subjects were male U.S. Navy recruits (N = 1703, 25 divisions), ages 17-35 yr (mean age = 20.1 +/- 2.9 yr), who attended boot camp from April 1996 through August 1996. During the first week of training, recruits performed a 1.5-mile run to determine baseline fitness levels. The results from the initial run were compared with a final 1.5-mile run conducted 6 wk later. RESULTS: Based on an age-adjusted fitness scale for a 1.5-mile run time, about one third of the recruits began recruit training in "Excellent-Superior" condition (N = 558), one third began in "Good" condition (N = 582), and one third began in "Poor-Fair" condition (N = 563). Running mileage among divisions ranged from 11.5 to 43.5 miles for the entire 7-wk training period (mean = 22.7 +/- 7.2 miles; 8-22 run days, mean = 13 +/- 4 d). In addition to running, the divisions accumulated many movement miles (110-202 miles; mean = 145 +/- 26 miles) while marching in formation. Recruits who began training in Poor-Fair condition improved the most with an average decrease in run time of 1:55 +/- 1:06 min (15.6% improvement). The Good group improved by 47 +/- 37 s (7.3% improvement), and the Excellent-Superior group improved by 17 +/- 32 s (2.9% improvement). CONCLUSION: The magnitude of fitness improvement, as measured by run time improvement, was directly related to baseline fitness level but not related to movement mileage or high-intensity run mileage accrued during training.

Gender differences in musculoskeletal injury rates: a function of symptom reporting?

PURPOSE: This study determined gender differences in voluntary reporting of lower extremity musculoskeletal injuries among U.S, Marine Corps (USMC) recruits, and it examined the association between these differences and the higher injury rates typically found among women trainees. METHODS: Subjects were 176 male and 241 female enlisted USMC recruits who were followed prospectively through 11 wk (men) and 12 wk (women) of boot camp training. Reported injuries were measured by medical record reviews. Unreported injuries were determined by a questionnaire and a medical examination administered at the completion of training. RESULTS: Among female recruits the most commonly reported injuries were patellofemoral syndrome (10.0% of subjects), ankle sprain (9.1%), and iliotibial band syndrome (5.8%); the most common unreported injuries were patellofemoral syndrome (2.1%), metatarsalgia (1.7%), and unspecified knee pain (1.7%). Among male recruits iliotibial band syndrome (4.0% of subjects), ankle sprain (2.8%), and Achilles tendinitis/bursitis (2.8%) were the most frequently reported injuries; shin splints (4.6%), iliotibial band syndrome (4.0%), and ankle sprain (2.8%) were the most common unreported diagnoses. Female recruits were more likely to have a reported injury than male recruits (44.0% vs 25.6%, relative risk (RR) = 1.72, 95% confidence interval (CI) 1.29-2.30), but they were less likely to have an unreported injury (11.6% vs 23.9%, RR = 0.49, 95% CI 0.31-0.75). When both reported and unreported injuries were measured, total injury rates were high for both sexes (53.5% women, 45.5% men, RR = 1.18, 95% CI 0.96-1.44), but the difference between the rates was not statistically significant. CONCLUSIONS: Our results indicate that the higher injury rates often found in female military trainees may be explained by gender differences in symptom reporting.

The effect of foot structure and range of motion on musculoskeletal overuse injuries.

The purpose of this prospective study was to determine whether an association exists between foot structure and the development of musculoskeletal overuse injuries. The study group was a well-defined cohort of 449 trainees at the Naval Special Warfare Training Center in Coronado, California. Before beginning training, measurements were made of ankle motion, subtalar motion, and the static (standing) and dynamic (walking) characteristics of the foot arch. The subjects were tracked prospectively for injuries throughout training. We identified risk factors that predispose people to lower extremity overuse injuries. These risk factors include dynamic pes planus, pes cavus, restricted ankle dorsiflexion, and increased hindfoot inversion, all of which are subject to intervention and possible correction.

Repairability of three resin-modified glass-ionomer restorative materials.

The purpose of this study was to evaluate the repair shear bond strengths of three resin-modified glass-ionomer restorative materials repaired at two different times. Thirty specimens of Fuji II LC, Vitremer, and Photac-Fil were prepared in cavities (2 mm x 7 mm) cut into acrylic resin cylinders. After the initial fill, half of the specimens were repaired 5 minutes later and half 1 week later. The specimens were stored in 37 degrees C distilled water when not being repaired or tested. Repairs were made without any surface preparation of the initial fill. Each specimen was mixed according to the manufacturer's directions, placed in the preparation in 1-mm increments and photocured for 40 seconds. The last increment was covered with a plastic strip and a glass slide before curing to create a smooth surface. Repairs were accomplished by drying the specimen for 10 seconds, then adding the new material to the unprepared surface using a 3-mm-thick polytetrafluoroethylene mold. The specimens were thermocycled 500 times, stored in 37 degrees C distilled water for 1 week, then loaded to failure in shear at a rate of 0.5 mm/min. Data were analyzed using a one-way ANOVA and Z-value multiple comparison test to determine significant differences at the 0.05 significance level. Vitremer showed no significant difference in shear bond strength for 5-minute and 1-week repair periods, while Fuji II LC and Photac-Fil did. Repair bond strength of Vitremer was significantly greater than Fuji II LC and Photac-Fil at both repair times. This study showed that time of repair significantly affected the bond strength of two of the materials tested.

Epidemiology of illness and injury among U.S. Navy and Marine Corps female training populations.

Evidence suggests that female military populations are at greater risk than their male counterparts for certain training- and combat-related illnesses and injuries. The objective of this prospective, multisite, epidemiological study was to define the patterns of illness and injury in military women during training. We developed a computer-based outpatient tracking system for prospective data collection of all outpatient encounters for use at (1) Officer Candidate School (OCS), Quantico; (2) Marine Corps Recruit Depot (MCRD), Parris Island; and (3) Recruit Training Command (RTC), Great Lakes. During the study period, 85.8% of OCS candidates (260 of 303), 72.4% of MCRD recruits (2,002 of 2,766), and 83.4% of RTC recruits (7,395 of 8,865) had at least one medical encounter during training. The most common category of medical encounters at all three sites was musculoskeletal injury, followed by respiratory and dermatological disorders. This study establishes high morbidity rates and identifies medical priorities for preventive interventions in Marine Corps and Navy female trainees.

Evaluation of a sexually transmitted disease/human immunodeficiency virus prevention train-the-trainer program.

In this study, a behavioral intervention known as the STD/HIV Intervention Program (SHIP) was implemented at the Navy preventive medicine technician (PMT) school as a "train-the-trainer" course. Course evaluation questionnaires were administered to PMT students immediately after the training. Follow-up interviews evaluating the SHIP course were conducted with PMTs (N = 73) 1 year after the training. PMT students were fairly satisfied with SHIP overall, as well as with specific components of the course. As hypothesized, the SHIP train-the-trainer course was considered useful by most PMTs in their first duty assignments after completing PMT school.

One-year follow-up evaluation of the sexually transmitted diseases/human immunodeficiency virus intervention program in a marine corps sample.

Although a substantial number of studies have been conducted to evaluate the impact of various human immunodeficiency virus (HIV) prevention programs, most of them have focused on civilian populations. There is a clear need to develop and evaluate sexually transmitted diseases (STD)/HIV prevention programs designed specifically for U.S. military populations. The objective of the present study was to determine whether a behavioral intervention known as the STD/HIV Intervention Program (SHIP) would have a sustained positive impact on the behavior of a sample of Marines. A 1-year follow-up telephone interview was administered to (1) Marines who participated in the SHIP course (intervention group), and (2) a quasi-control group of Marines who were not exposed to the SHIP course. The intervention and control groups differed significantly in the percentage of the time they had used condoms during the past year. The intervention participants reported using condoms a greater percentage of the time than the nonparticipants.

The association of blisters with musculoskeletal injuries in male marine recruits.

A prospective study examining the epidemiology of blisters and, in particular, the association of blisters with subsequent injuries was conducted involving 2,130 male US Marine Corps recruits participating in initial physical training at the Marine Corps Recruit Depot in San Diego, California. From January 1993 through September 1994, recruits experienced an incidence of 2.05 blisters per 100 recruit-months. Recruits with blisters were 50% more likely to experience an additional training-related injury. Blisters, in combination with other related injuries, resulted in 159 clinic visits, 103 days of assigned light duty, and 177 lost days of training. This loss of time cost a minimum of $29,529. Extrapolating to the annual population of recruits, this represents an approximate annual expense of $690,000. Aggressive blister prevention and management in this setting has the potential to greatly reduce morbidity and fiscal costs.

The risk of surgical site infection and re-admission in obese patients undergoing total joint replacement who lose weight before surgery and keep it off post-operatively.

This study evaluated whether obese patients who lost weight before their total joint replacement and kept it off post-operatively were at lower risk of surgical site infection (SSI) and re-admission compared with those who remained the same weight. We reviewed 444 patients who underwent a total hip replacement and 937 with a total knee replacement who lost weight pre-operatively and sustained their weight loss after surgery. After adjustments, patients who lost weight before a total hip replacement and kept it off post-operatively had a 3.77 (95% confidence interval (CI) 1.59 to 8.95) greater likelihood of deep SSIs and those who lost weight before a total knee replacement had a 1.63 (95% CI 1.16 to 2.28) greater likelihood of re-admission compared with the reference group. These findings raise questions about the safety of weight management before total replacement of the hip and knee joints.