Behavioural weight management interventions consistently produce 8–10% reductions in body weight, yet most participants regain weight after treatment ends. One strategy for extending the effects of ...behavioural interventions has been the provision of extended care. The current study is a systematic review and meta‐analysis of the literature on the effect of extended care on maintenance of weight loss. Through database searches (using PubMED, PsychInfo and Cochrane Reviews) and manual searches through reference lists of related publications, 463 studies were identified. Of these, 11 were included in the meta‐analysis and an additional two were retained for qualitative analysis. The average effect of extended care on weight loss maintenance was g = 0.385 (95% confidence interval: 0.281, 0.489; P < 0.0001). This effect would lead to the maintenance of an additional 3.2 kg weight loss over 17.6 months post‐intervention in participants provided extended care compared with control. There was no significant heterogeneity between studies, Q = 5.63, P = 0.845, and there was minimal evidence for publication bias. These findings suggest that extended care is a viable and efficacious solution to addressing long‐term maintenance of lost weight. Given the chronic disease nature of obesity, extended care may be necessary for long‐term health benefits.
Few investigations of successful long-term weight loss beyond two years have been conducted, and none has examined weight changes in medically underserved rural populations of older adults. The ...purpose of this study was to assess long-term weight loss maintenance 3.5 years after the completion of an initial six-month lifestyle intervention for obesity among women aged 50-75 years residing in rural communities.
One hundred and ten obese women with a mean (± standard deviation) age of 60.08 ± 6.17 years and mean body mass index of 36.76 ± 5.10 kg/m(2) completed an in-person assessment during which their weight and adherence to behavioral weight management strategies were evaluated.
Participants showed a mean weight reduction of 10.17% ± 5.0% during the initial six- month intervention and regained 6.95% ± 9.44% from the completion of treatment to follow-up assessment 3.5 years later. A substantial proportion of participants (41.80%) were able to maintain weight reductions of 5% or greater from baseline to follow-up. "Successful" participants (those who maintained losses of 5% or greater at follow-up) reported weighing themselves, self-monitoring their intake and calories, planning meals in advance, and choosing lower calorie foods with greater frequency than "unsuccessful" participants (those who lost less than 5%).
Collectively, these findings indicate that a large proportion of participants were able to maintain clinically significant weight losses for multiple years after treatment, and that self-monitoring was a key component of successful long-term weight management.
A recent hypothesis to explain the recurrence of bluetongue disease after winter seasonal absences of the vector has suggested a role for persistent infection of sheep. This report presents combined ...independent work from two laboratories investigating the possible recovery of Bluetongue virus (BTV) over a protracted period after infection of both sheep and cattle. Prior to infection with either cell-culture-adapted or non-culture-adapted BTV, sheep were subjected to a preliminary exposure to Culicoides sp. insects, which reportedly facilitates recovery of virus from infected sheep several months post-infection (p.i.). A series of skin biopsies at different intervals p.i. was used to establish skin fibroblast (SF) cultures from which attempts were made to detect virus by isolation and by molecular and immunological methods. Also examined was the effect on virus recovery of additional exposure to Culicoides sp. prior to skin biopsy during the post-inoculation period. A herd of cattle sentinels for surveillance of natural BTV infection in northern Australia was monitored prospectively for seroconversion. Evidence of infection initiated attempted virus recovery by establishing SF cultures. It was found that in both cattle and sheep there was not a protracted period over which BTV could be recovered from SF cultures. The data do not support a general hypothesis that BTV persists in either sheep or cattle.
Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may ...improve pregnancy outcomes in women who have bleeding in early pregnancy.
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data.
A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval CI, 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups.
Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).
Objectives
To assess the cost‐effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding.
Design
Economic evaluation alongside a ...large multi‐centre randomised placebo‐controlled trial.
Setting
Forty‐eight UK NHS early pregnancy units.
Population
Four thousand one hundred and fifty‐three women aged 16–39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac.
Methods
An incremental cost‐effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages.
Main outcome measures
Cost per additional live birth at ≥34 weeks of gestation.
Results
Progesterone intervention led to an effect difference of 0.022 (95% CI −0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI −£559 to £711) more than the mean cost in the placebo group. The incremental cost‐effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014–0.096) and this was associated with a cost saving of £322 (95% CI −£1318 to £673).
Conclusions
The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost‐effective intervention, particularly for women with previous miscarriage(s).
Tweetable
Progesterone treatment is likely to be cost‐effective in women with early pregnancy bleeding and a history of miscarriage.
Tweetable
Progesterone treatment is likely to be cost‐effective in women with early pregnancy bleeding and a history of miscarriage.
To assess the accuracy of physical examination, ultrasonography, and mammography in predicting residual size of breast tumors following neoadjuvant chemotherapy.
Neoadjuvant chemotherapy is an ...accepted part of the management of stage II and III breast cancer. Accurate prediction of residual pathologic tumor size after neoadjuvant chemotherapy is critical in guiding surgical therapy. Although physical examination, ultrasonography, and mammography have all been used to predict residual tumor size, there have been conflicting reports about the accuracy of these methods in the neoadjuvant setting.
We reviewed the records of 189 patients who participated in 1 of 2 protocols using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by physical examination, ultrasonography, and/or mammography no more than 60 days before their surgical resection. Size correlations were performed using Spearman rho analysis. Clinical and pathologic measurements were also compared categorically using the weighted kappa statistic.
Size estimates by physical examination, ultrasonography, and mammography were only moderately correlated with residual pathologic tumor size after neoadjuvant chemotherapy (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy of +/-1 cm in 66% of patients by physical examination, 75% by ultrasonography, and 70% by mammography. Kappa values (0.24-0.35) indicated poor agreement between clinical and pathologic measurements.
Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy.
ITM (defined as intralymphatic local, satellite, and regional cutaneous/subcutaneous metastases) is associated with significant morbidity; optimal therapy is poorly defined. T-VEC is an oncolytic ...immunotherapy approved for melanoma treatment based on results from the phase III OPTiM trial. This retrospective analysis of OPTiM assessed T-VEC in pts with unresectable AJCC 7 stage IIIB/C melanoma who had LR disease, including ITM, as the site of first recurrence following primary surgery.
In OPTiM, pts were randomised to intralesional T-VEC or subcutaneous recombinant GM-CSF. All pts were treated for ≥6 months, after which treatment was continued until clinically relevant disease progression, intolerability, consent withdrawal, complete response (CR), lack of response by 1yr, or disappearance of injectable lesions (T-VEC arm only).
109 patients (T-VEC n=79; GM-CSF n=30) had LR disease as the site of first recurrence (including ITM, local surgical scar, and regional lymph nodes). Most pts (63%) had ITM. Median time from primary melanoma diagnosis to first LR recurrence was 10.4 months. Time from first recurrence to randomisation into OPTiM was 6.6 months. At primary diagnosis, 45% of 109 pts had melanoma in the lower limbs, 25% in the head/neck, 15% on the trunk, and 11% upper limbs. At baseline, median age was 65 yrs, 94% had LDH ≤ULN, 76% had ECOG PS 0 and 35% had nodular melanoma. T-VEC vs GM-CSF led to objective response rates of 56% vs 1%, CR rates of 24% vs 0%, and durable response rates of 34% vs 0% (all p<0.002 vs GM-CSF). Median OS was not reached with T-VEC vs 25 months with GM-CSF (HR, 0.48; 95% CI, 0.28–0.84; p=0.0088). The LR subpopulation experienced higher T-VEC efficacy vs the entire study population (Table).Table1342PTableOutcomeOPTiM locoregional subpopulation, incl. ITM*OPTiM overall study population (ITT; stage IIIB-IVM1c melanoma)T-VEC (n=79)GM-CSF (n=30)Difference (p value or 95% CI)T-VEC (n=295)GM-CSF (n=141)Difference (p value or 95% CI)Objective response rate, % (n)56 (44)3 (1)52.4 (p<0.0001)26 (78)6 (8)20.8 (p<0.01)Complete response, % (n)24 (19)0 (0)24.1 (p<0.0015)11 (32)<1 (1)10.1 (p<0.0001)Durable response rate (response for ≥6 consecutive months), % (n)34 (27)0 (0)34.2 (p<0.0001)16 (48)2 (3)14.1 (p<0.001)Deaths, % (n)42 (33)67 (20)HR: 0.48 (p=0.0088)64 (189)72 (101)HR: 0.79(0=0.051)OS probability at landmark times (KM estimate), % 1 year 2 years 3 years 4 years92 75 62 5280 50 40 3012.4 (-3.1, 27.9) 24.7 (4.4, 45.0) 21.9 (1.3, 42.4) 22.8 (-0.6, 46.2)74 50 39 3369 40 30 214.6 (-4.7, 13.8) 9.5 (-0.5, 19.6) 8.5 (-1.2, 18.1) 11.3 (1.0, 21.5)HR, hazard ratio; ITT, intent-to-treat; KM, Kaplan-Meier; NR, not reported; OS, overall survival.*Grouped term including in-transit/satellitosis (ITM), local surgical scar, and regional lymph nodes (LNs). 59 pts had ITM only as the site of 1st recurrence, 17 had regional LNs only, 20 had surgical scar only, 2 had ITM AND regional LNs, 3 had surgical scar AND regional LNs, 5 had ITM AND surgical scar, and 3 pts had ITM, regional LNs AND surgical scar as the sites of 1st recurrence.
This analysis suggests that T-VEC may be of particular benefit in melanoma pts with LR recurrence, including ITM.
NCT00769704.
Ryan Woodrow, PhD, CMPP of Aspire Scientific (Bollington, UK), funded by Amgen (Europe) GmbH (Rotkreuz, Switzerland).
Amgen Inc.
Amgen Inc.
M.R. Middleton: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex. K. Harrington: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD. M. Ross: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck ; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen. K. Ohrling: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. H. Radcliffe: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck.
We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker ...Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.
Escalating doses of OXi4503 were given ...intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors.
Doses were escalated in single-patient cohorts from 0.06 to 1.92 mg/m(2), then expanded cohorts to 15.4 mg/m(2) in 43 patients. Common adverse drug reactions were hypertension, tumor pain, anemia, lymphopenia, and easily controllable nausea/vomiting and fatigue. Five patients experienced different drug-related dose-limiting toxicities, atrial fibrillation, increased troponin, blurred vision, diplopia, and tumor lysis. Prophylactic amlodipine failed to prevent adverse events. Pharmacokinetics showed dose-dependent linear increases in peak plasma concentrations and area under the curve value of OXi4503. One partial response was seen in a heavily pretreated patient with ovarian cancer. Dynamic contrast-enhanced MRI confirmed a dose effect and showed significant antivascular effects in 10 of 13 patients treated at doses of 11 mg/m(2) or higher.
The maximum tolerated dose was 8.5 mg/m(2) but escalation to 14 mg/m(2) was possible with only temporary reversible cerebrovascular toxicity by excluding hypertensive patients. As a tumor response was seen at 14 mg/m(2) and maximum tumor perfusion reductions were seen at doses of 11 mg/m(2) or higher, the recommended phase II dose is from 11 to 14 mg/m(2).
PDF
