A preoperative package of care for osteoarthritis, consisting of weight loss, orthotics, rehabilitation, and topical and oral analgesia (OPPORTUNITY): a two-centre, open-label, randomised controlled feasibility trial.

BACKGROUND: Osteoarthritis of the knee is a major cause of disability worldwide. Non-operative treatments can reduce the morbidity but adherence is poor. We hypothesised that adherence could be optimised if behavioural change was established in the preoperative period. Therefore, we aimed to assess feasibility, acceptability, and recruitment and retention rates of a preoperative package of non-operative care in patients awaiting knee replacement surgery. METHODS: We did an open-label, randomised controlled, feasibility trial in two secondary care centres in the UK. Eligible participants were aged 15-85 years, on the waiting list for a knee arthroplasty for osteoarthritis, and met at least one of the thresholds for one of the four components of the preoperative package of non-operative care intervention (ie, weight loss, exercise therapy, use of insoles, and analgesia adjustment). Participants were randomly assigned (2:1) to either the intervention group or the standard of care (ie, control) group. All four aspects of the intervention were delivered weekly over 12 weeks. Participants in the intervention group were reviewed regularly to assess adherence. The primary outcome was acceptability and feasibility of delivering the intervention, as measured by recruitment rate, retention rate at follow-up review after planned surgery, health-related quality of life, joint-specific scores, and adherence (weight change and qualitative interviews). This study is registered with ISRCTN, ISRCTN96684272. FINDINGS: Between Sept 3 2018, and Aug 30, 2019, we screened 233 patients, of whom 163 (73%) were excluded and 60 (27%) were randomly assigned to either the intervention group (n=40) or the control group (n=20). 34 (57%) of 60 participants were women, 26 (43%) were men, and the mean age was 66·8 years (SD 8·6). Uptake of the specific intervention components varied: 31 (78%) of 40 had exercise therapy, 28 (70%) weight loss, 22 (55%) analgesia adjustment, and insoles (18 [45%]). Overall median adherence was 94% (IQR 79·5-100). At the final review, the intervention group lost a mean of 11·2 kg (SD 5·6) compared with 1·3 kg (3·8) in the control group (estimated difference -9·8 kg [95% CI -13·4 to -6·3]). A clinically significant improvement in health-related quality o life (mean change 0·078 [SD 0·195]) were reported, and joint-specific scores showed greater improvement in the intervention group than in the control group. No adverse events attributable to the intervention occurred. INTERPRETATION: Participants adhered well to the non-operative interventions and their health-related quality of life improved. Participant and health professional feedback were extremely positive. These findings support progression to a full-scale effectiveness trial. FUNDING: Versus Arthritis.

Improvements in Sperm Motility Following Low- or High-Intensity Dietary Interventions in Men With Obesity.

INTRODUCTION: Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that a low-energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted. METHODS: Men with obesity (18-60 years) with normal sperm concentration (normal count) (n = 24) or oligozoospermia (n = 43) were randomized 1:1 to either 800 kcal/day LED for 16 weeks or control, brief dietary intervention (BDI) with 16 weeks' observation. Semen parameters were compared at baseline and 16 weeks. RESULTS: Mean age of men with normal count was 39.4 ± 6.4 in BDI and 40.2 ± 9.6 years in the LED group. Mean age of men with oligozoospermia was 39.5 ± 7.5 in BDI and 37.7 ± 6.6 years in the LED group. LED caused more weight loss than BDI in men with normal count (14.4 vs 6.3 kg; P < .001) and men with oligozoospermia (17.6 vs 1.8 kg; P < .001). Compared with baseline, in men with normal count total motility (TM) increased 48 ± 17% to 60 ± 10% (P < .05) after LED, and 52 ± 8% to 61 ± 6% (P < .0001) after BDI; progressive motility (PM) increased 41 ± 16% to 53 ± 10% (P < .05) after LED, and 45 ± 8% to 54 ± 65% (P < .001) after BDI. In men with oligozoospermia compared with baseline, TM increased 35% [26] to 52% [16] (P < .05) after LED, and 43% [28] to 50% [23] (P = .0587) after BDI; PM increased 29% [23] to 46% [18] (P < .05) after LED, and 33% [25] to 44% [25] (P < .05) after BDI. No differences in postintervention TM or PM were observed between LED and BDI groups in men with normal count or oligozoospermia. CONCLUSION: LED or BDI may be sufficient to improve sperm motility in men with obesity. The effects of paternal dietary intervention on fertility outcomes requires investigation.

Correction to: Osteoarthritis Preoperative Package for care of Orthotics, Rehabilitation, Topical and oral agent Usage and Nutrition to Improve ouTcomes at a Year (OPPORTUNITY); a feasibility study protocol for a randomised controlled trial.

After publication of our article [1] we have been notified that two of the author names have been mistakenly removed from the authorship list: Colin R. Howie and Nicholas D. Clement.

Osteoarthritis Preoperative Package for care of Orthotics, Rehabilitation, Topical and oral agent Usage and Nutrition to Improve ouTcomes at a Year (OPPORTUNITY); a feasibility study protocol for a randomised controlled trial.

BACKGROUND: Patients' pre-operative health and physical function is known to influence their post-operative outcomes. In patients with knee osteoarthritis, pharmacological and non-pharmacological options are often not optimised prior to joint replacement. This results in some patients undergoing surgery when they are not as fit as they could be. The aim of this study is to assess the feasibility and acceptability of a pre-operative package of non-operative care versus standard care prior to joint replacement. METHODS/DESIGN: This is a multicentre, randomised controlled feasibility trial of patients undergoing primary total knee replacement for osteoarthritis. Sixty patients will be recruited and randomised (2:1) to intervention or standard care arms. Data will be collected at baseline (before the start of the intervention), around the end of the intervention period and a minimum of 90 days after the planned date of surgery. Adherence will be reviewed each week during the intervention period (by telephone or in person). Participants will be randomised to a pre-operative package of non-operative care or standard care. The non-operative care will consist of (1) a weight-loss programme, (2) a set of exercises, (3) provision of advice on analgesia use and (4) provision of insoles. The intervention will be started as soon as possible after patients have been added to the waiting list for joint replacement surgery to take advantage of the incentive for behavioural change that this will create. The primary outcomes of this study are feasibility outcomes which will indicate whether the intervention and study protocol is feasible and acceptable and whether a full-scale effectiveness trial is warranted. The following will be measured and used to inform study feasibility: rate of recruitment, rate of retention at 90-day follow-up review after planned surgery date, and adherence to the intervention estimated through review questionnaires and weight change (for those receiving the weight-loss aspect of intervention). In addition the following information will be assessed qualitatively: analysis of qualitative interviews exploring acceptability, feasibility, adherence and possible barriers to implementing the intervention, and acceptability of the different outcome measures. DISCUSSION: The aims of the study specifically relate to testing the feasibility and acceptability of the proposed effectiveness trial intervention and the feasibility of the trial methods. This study forms the important first step in developing and assessing whether the intervention has the potential to be assessed in a future fully powered effectiveness trial. The findings will also be used to refine the design of the effectiveness trial. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN96684272. Registered on 18 April 2018.

Low-energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin: a randomized trial.

OBJECTIVES: The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT. RESEARCH DESIGN AND METHODS: In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL). RESULTS: Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference -4.3 kg, 95% CI -6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (-18.6 units, 95% CI -29.2 to -7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01). CONCLUSIONS: Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success. TRIAL REGISTRATION NUMBER: ISRCTN21335883.

Long-term weight-loss maintenance in obese patients with knee osteoarthritis: a randomized trial.

Background: A formula low-energy diet (LED) reduces weight effectively in obese patients with knee osteoarthritis, but the role of LED in long-term weight-loss maintenance is unclear.Objective: We aimed to determine the effect of intermittent LED compared with daily meal replacements on weight-loss maintenance and number of knee replacements over 3 y.Design: The design was a randomized trial with participants aged >50 y who had knee osteoarthritis and a body mass index [BMI (in kg/m2)] ≥30. Participants were recruited from the osteoarthritis outpatient clinic at Copenhagen University Hospital in Frederiksberg, Denmark; they had previously completed a 68-wk lifestyle intervention trial and achieved an average weight loss of 10.5 kg (10% of initial body weight). Participants were randomly assigned to either the intermittent treatment (IN) group with LED for 5 wk every 4 mo for 3 y or to daily meal replacements of 1-2 meals for 3 y [regular (RE) group]. Attention by dietitians and the amount of formula products were similar. Primary outcomes were changes in body weight and proportion of participants receiving knee replacements. Outcomes were analyzed on the intention-to-treat-population with the use of baseline-carried-forward imputation for missing data.Results: A total of 153 participants (means ± SDs: BMI: 33.3 ± 4.6; age: 63.8 ± 6.3 y; 83% women) were recruited between June and December 2009 and randomly assigned to the IN (n = 76) or RE (n = 77) group. A total of 53 and 56 participants, respectively, completed the trial. Weight increased by 0.68 and 1.75 kg in the IN and RE groups, respectively (mean difference: -1.06 kg; 95% CI: -2.75, 0.63 kg; P = 0.22). Alloplasty rates were low and did not differ (IN group: 8 of 76 participants; RE group: 12 of 77 participants; P = 0.35).Conclusions: After a mean 10% weight-loss and 1-y maintenance, additional use of daily meal replacements or intermittent LED resulted in weight-loss maintenance for 3 y. These results challenge the commonly held assumption that weight regain in the long term is inevitable. This trial was registered at clinicaltrials.gov as NCT00938808.

Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial.

OBJECTIVE: To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or "no attention" (C; control group). METHODS: We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. RESULTS: Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). CONCLUSION: A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.

Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial.

OBJECTIVE: To evaluate 1-year symptomatic improvement in obese patients with knee osteoarthritis (OA) on an intensive low-energy diet (LED) maintained by frequent consultations with a dietician compared to minimal attention. METHODS: The LED programme consisted of group therapy with dietary consultations and two periods of a low-calorie diet of 810 kcal/day during weeks 0-8 and weeks 32-36. The control group only received dietary instruction and attention for 2 h at baseline, and at weeks 8, 32, 36 and 52. The primary end point (total Western Ontario and McMaster Universities (WOMAC) index) was assessed as the mean group difference during and after 1 year. RESULTS: The study population consisted of 89 patients, 89% women, average age 63 years. After 1 year, mean weight loss in the LED group was -10.9 kg (11%) versus -3.6 kg (4%) in the control group (p<0.0001). There was no difference between the groups in total WOMAC index (p=0.11), although both groups improved. However, the LED intervention resulted in less WOMAC pain (7.7 mm), with a group mean difference of 7.2 mm (95% CI 1.0 to 13.4, p=0.022). After one year 14 (32.8%) responded to LED versus 7 (15.6%) to control, with an absolute benefit of 16.3% (-1.1& to 33.6%, p=0.066). CONCLUSION: Continuous reinforcement of a weight loss programme can be successful over a year in obese knee OA patients. Weight loss was statistically reflected only by a reduction in pain. However, the overall clinical benefits of the intervention on health should lead to a strong recommendation of weight loss in this group of patients.

The effect of dietary glycemic index on weight maintenance in overweight subjects: a pilot study.

Evidence suggests that a low-glycemic index (LGI) diet has a satiating effect and thus may enhance weight maintenance following weight loss. This study was conducted at Hammersmith Hospital, London, UK, and assessed the effect of altering diet GI on weight-loss maintenance. It consisted of a weight-loss phase and a 4-month randomized weight maintenance phase. Subjects were seen monthly to assess dietary compliance and anthropometrics. Appetite was assessed bimonthly by visual analogue scales while meal challenge postprandial insulin and glucose concentrations were assessed before and after the intervention. Following a median weight loss of 6.1 (interquartile range: 5.2-7.1) % body weight, subjects were randomized to a high-glycemic index (HGI) (n = 19) or LGI (n = 23) diet. Dietary composition differed only in GI (HGI group: 63.7 +/- 9.4; LGI group: 49.7 +/- 5.7, P < 0.001) and glycemic load (HGI group: 136.8 +/- 56.3; LGI group: 89.7 +/- 27.5, P < 0.001). Groups did not differ in body weight (weight change over 4 months, HGI group: 0.3 +/- 1.9 kg; LGI group: -0.7 +/- 2.9 kg, P = 0.3) or other anthropometric measurements. This pilot study suggests that in the setting of healthy eating, changing the diet GI does not appear to significantly affect weight maintenance.

Increased dietary cholesterol does not increase plasma low density lipoprotein when accompanied by an energy-restricted diet and weight loss.

BACKGROUND: Diets enriched with dietary cholesterol, frequently from eggs, have been shown to produce a small but variable increase in plasma low density lipoprotein (LDL) cholesterol. There is evidence to suggest that energy-restricted diets, that may contain a relatively high proportion of fat and cholesterol, can attenuate the cholesterol-raising effect of dietary cholesterol on plasma LDL. AIM OF THE STUDY: To determine the combined effects of increased dietary cholesterol and weight loss produced by energy restriction on plasma LDL cholesterol and lipoproteins. METHODS: A randomized, controlled, parallel study was performed in two groups of free-living volunteers on an energy-restricted diet for 12 weeks, one group was instructed to consume two eggs a day (n = 24), the other, to exclude eggs (n = 21). Dietary advice on energy restriction was based on the British Heart Foundation guidelines on how to lose weight for men and women. RESULTS: Energy intake fell by 25 and 29% in the egg-fed and non-egg-fed groups, resulting in a moderate weight loss of 3.4 kg (P < 0.05) and 4.4 kg (P < 0.05), respectively. The daily intake of dietary cholesterol increased significantly in the egg-fed group from 278 to 582 mg after 6 weeks. The concentration of plasma LDL cholesterol decreased in the non-egg-fed groups after 6 weeks (P < 0.01) and in the egg-fed and non-egg-fed at 12 weeks relative to baseline. There were no other significant changes in plasma lipoproteins or LDL particle size. CONCLUSIONS: An increased intake of dietary cholesterol from two eggs a day, does not increase total plasma or LDL cholesterol when accompanied by moderate weight loss. These findings suggest that cholesterol-rich foods should not be excluded from dietary advice to lose weight on account of an unfavorable influence on plasma LDL cholesterol.

The effect of high and low glycemic index diets on urinary chromium in healthy individuals: a cross-over study.

BACKGROUND: Insufficient dietary intake of chromium as an essential nutrient leads to signs and symptoms that are similar to those observed for diabetes and cardiovascular diseases. We postulate that in healthy individuals, urinary chromium excretion following a high glycemic index diet is higher than after a low glycemic index diet. METHODS: A sequential randomized controlled cross-over study was carried out at the Metabolic Unit of Nutrition Department of King's College London. Sixteen healthy individuals aged 18 - 60 years were recruited from 26 volunteers. A low or high glycemic index diet (as the main meals/day) was given to the volunteers over six days. Fasting blood glucose and insulin changes were determined and 24-hr urine samples were collected to measure chromium excretion before intervention and every second day within each treatment with a one wash-out period using Dynamic Reaction Cell Inductively Coupled Plasma Mass Spectrometer. RESULTS: During the six-day diet study, there were no significant differences in 24-hr urinary chromium losses between the two groups following the low glycemic index (0.58+/-0.08 microg/24 hr) and high glycemic index diets (0.48+/-0.06 microg/24 hr). However, during day six there was a trend towards greater loss of chromium after the high glycemic index diet (0.73+/-0.1 microg/24 hr) in comparison with the low glycemic index diet (0.54+/-0.07 microg/24 hr). CONCLUSION: Evidence that urinary chromium loses following the high glycemic index diets have not been clearly demonstrated in normal subjects. These results suggest that chromium excretion may need to be observed for longer than six days to address this question.

Effects of oral administration of androstenedione on plasma androgens in young women using hormonal contraception.

Androstenedione as a dietary supplement has been targeted at the sporting community, but there are limited data regarding its effects on plasma androgens in young women. A double-blind, cross-over study was undertaken involving 10 women (20-32 yr) using hormonal contraception. Because contamination of supplements has been reported, an in-house oral formulation was prepared containing purified androstenedione, the control being lactose only. After oral administration of a single dose of androstenedione (100 mg), blood was collected frequently up to 8 h and at 24 h. Maximum plasma androgen concentrations observed between volunteers were well above the upper limit of reference ranges for women, being 121-346 nmol/liter for androstenedione, 14-54 nmol/liter for testosterone (T), 11-32 nmol/liter for 5alpha-dihydrotestosterone, and 23-90 nmol/liter for 3alpha-androstanediol glucuronide. The free androgen index and T concentration changed in a similar manner. The mean change in area under the plasma concentration-time curve (0-24 h), compared with control data were: androstenedione approximately 7-fold, T approximately 16-fold, 5alpha-dihydrotestosterone approximately 9-fold, and 3alpha-androstanediol glucuronide approximately 5-fold; the mean conversion ratio of androstenedione to T was 12.5% (range 7.8-21.6%). Increases in T area under the plasma concentration-time curve were correlated with SHBG concentration (r = 0.80; P = 0.005). Formulation characteristics and SHBG levels appear to be important factors when considering plasma androgen increases after acute androstenedione administration.

Glycemic index and heart disease.

A diet high in carbohydrates with high glycemic indexes (GI) and glycemic load were linked to risk of coronary heart disease development in women in a large prospective study. Two cross-sectional studies showed that low-GI diets are associated with high HDL-cholesterol concentrations, especially in women. In a tightly controlled study of patients with type 2 diabetes, serum total cholesterol, LDL cholesterol, and apolipoprotein B concentrations fell more significantly after a low-GI diet than after a high-GI diet. In the same study, plasminogen activator inhibitor-1 concentrations were reduced by 58% after the low-GI diet. Insulin-stimulated glucose uptake by adipocytes was significantly higher in patients undergoing coronary artery bypass graft surgery after 4 wk of consuming a low-GI diet than after consuming a high-GI diet. The effects of low-GI diets may be mediated by changes in postprandial fatty acid concentrations or by hormonal signals from adipocytes, but a possible association of low-GI diets with some other dietary factor such as chromium must not be excluded. Proof of the clinical value of low-GI diets awaits prospective trials, which should include short-term observations covering periods of metabolic stress induced by surgery as well as long-term trials with clinical endpoints.