Obesity is a common health problem that requires a long-term care approach. We systematically reviewed long-term (> or =2 y) studies investigating dietary/lifestyle, pharmacologic, and surgical ...weight loss methods to assess (1) weight loss efficacy, defined by absolute weight loss and the proportion of subjects with > or =5% weight loss, (2) effects of weight loss on cardiovascular risk factors, and (3) applicability of findings from studies to everyday clinical practice.
The MEDLINE, HealthSTAR, and the Cochrane Controlled Trials databases were searched for studies investigating the long-term efficacy of weight loss methods in overweight and obese adults. Data were extracted for (i) weight loss after 1 y (pharmacologic studies only), 2 y, 3 y, and 4 y, (ii) proportion of subjects with > or =5% weight loss at the end of follow-up, and (iii) changes (end-of follow-up minus baseline values) in blood lipids, fasting blood glucose, and systolic and diastolic blood pressure.
Dietary/lifestyle therapy provides <5 kg weight loss after 2-4 y, pharmacologic therapy provides 5-10 kg weight loss after 1-2 y, and surgical therapy provides 25-75 kg weight loss after 2-4 y. Weight loss of > or =5% baseline weight is not consistently associated with improvements in cardiovascular risk factors and these benefits appear to be intervention specific and occur mainly in people with concomitant cardiovascular risk factors. Weight loss studies have methodologic limitations that restrict the applicability of findings to unselected obese people assessed in everyday clinical practice. These limitations include an inadequate study duration, large proportions of subjects lost to follow-up, a lack of an appropriate usual care group, and a lack of reporting of outcomes in high-risk subgroups.
Dietary/lifestyle and pharmacologic weight loss interventions provide modest weight loss, and may improve markers of cardiovascular risk factors although these benefits occur mainly in patients with cardiovascular risks. Studies investigating weight loss have methodologic limitations that restrict the applicability of findings to obese patients assessed in clinical practice.
To estimate per-person and aggregate direct medical costs of overweight and obesity and to examine the effect of study design factors. PubMed (1968-2009), EconLit (1969-2009) and Business Source ...Premier (1995-2009) were searched for original studies. Results were standardized to compute the incremental cost per overweight person and per obese person, and to compute the national aggregate cost. A total of 33 US studies met review criteria. Among the four highest-quality studies, the 2008 per-person direct medical cost of overweight was $266 and of obesity was $1723. The aggregate national cost of overweight and obesity combined was $113.9 billion. Study design factors that affected cost estimates included use of national samples vs. more selected populations, age groups examined, inclusion of all medical costs vs. obesity-related costs only, and body mass index cut-offs for defining overweight and obesity. Depending on the source of total national healthcare expenditures used, the direct medical cost of overweight and obesity combined is approximately 5.0% to 10% of US healthcare spending. Future studies should include nationally representative samples, evaluate adults of all ages, report all medical costs and use standard body mass index cut-offs.
BACKGROUND: Little is known about childhood factors and adult obesity. A previous study found a strong association between childhood neglect and obesity in young adults. OBJECTIVE: To estimate ...associations between self-reported abuse in childhood (sexual, verbal, fear of physical abuse and physical) adult body weight, and risk of obesity. DESIGN: Retrospective cohort study with surveys during 1995-1997. PATIENTS: A total of 13 177 members of California health maintenance organization aged 19-92 y. MEASUREMENTS: Body weight measured during clinical examination, followed by mailed survey to recall experiences during first 18 y of life. Estimates adjusted for adult demographic factors and health practices, and characteristics of the childhood household. RESULTS: Some 66% of participants reported one or more type of abuse. Physical abuse and verbal abuse were most strongly associated with body weight and obesity. Compared with no physical abuse (55%), being 'often hit and injured' (2.5%) had a 4.0 kg (95% confidence interval: 2.4-5.6 kg) higher weight and a 1.4 (1.2-1.6) relative risk (RR) of body mass index (BMI)30. Compared with no verbal abuse (53%), being 'often verbally abused' (9.5%) had an RR of 1.9 (1.3-2.7) for BMI40. The abuse associations were not mutually independent, however, because the abuse types strongly co-occurred. Obesity risk increased with number and severity of each type of abuse. The population attributable fraction for 'any mention' of abuse (67%) was 8% (3.4-12.3%) for BMI30 and 17.3% (-1.0-32.4%) for BMI40. CONCLUSIONS: Abuse in childhood is associated with adult obesity. If causal, preventing child abuse may modestly decrease adult obesity. Treatment of obese adults abused as children may benefit from identification of mechanisms that lead to maintenance of adult obesity.
The indications for transfusing fresh‐frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of ...transmitting infection are similar to those of other blood components unless a pathogen‐reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion‐related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near‐patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non‐UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.
Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized ...OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.
CONTEXT Suicide is a leading cause of death in the United States, but identifying
persons at risk is difficult. Thus, the US surgeon general has made suicide
prevention a national priority. An ...expanding body of research suggests that
childhood trauma and adverse experiences can lead to a variety of negative
health outcomes, including attempted suicide among adolescents and adults. OBJECTIVE To examine the relationship between the risk of suicide attempts and
adverse childhood experiences and the number of such experiences (adverse
childhood experiences ACE score). DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 17 337 adult health maintenance
organization members (54% female; mean SD age, 57 15.3 years) who attended
a primary care clinic in San Diego, Calif, within a 3-year period (1995-1997)
and completed a survey about childhood abuse and household dysfunction, suicide
attempts (including age at first attempt), and multiple other health-related
issues. MAIN OUTCOME MEASURE Self-reported suicide attempts, compared by number of adverse childhood
experiences, including emotional, physical, and sexual abuse; household substance
abuse, mental illness, and incarceration; and parental domestic violence,
separation, or divorce. RESULTS The lifetime prevalence of having at least 1 suicide attempt was 3.8%.
Adverse childhood experiences in any category increased the risk of attempted
suicide 2- to 5-fold. The ACE score had a strong, graded relationship to attempted
suicide during childhood/adolescence and adulthood (P<.001).
Compared with persons with no such experiences (prevalence of attempted suicide,
1.1%), the adjusted odds ratio of ever attempting suicide among persons with
7 or more experiences (35.2%) was 31.1 (95% confidence interval, 20.6-47.1).
Adjustment for illicit drug use, depressed affect, and self-reported alcoholism
reduced the strength of the relationship between the ACE score and suicide
attempts, suggesting partial mediation of the adverse childhood experience–suicide
attempt relationship by these factors. The population-attributable risk fractions
for 1 or more experiences were 67%, 64%, and 80% for lifetime, adult, and
childhood/adolescent suicide attempts, respectively. CONCLUSIONS A powerful graded relationship exists between adverse childhood experiences
and risk of attempted suicide throughout the life span. Alcoholism, depressed
affect, and illicit drug use, which are strongly associated with such experiences,
appear to partially mediate this relationship. Because estimates of the attributable
risk fraction caused by these experiences were large, prevention of these
experiences and the treatment of persons affected by them may lead to progress
in suicide prevention.
Summary Background Handwashing to prevent transmission of respiratory tract infections (RTIs) has been widely advocated, especially during the H1N1 pandemic. However, the role of handwashing is ...debated, and no good randomised evidence exists among adults in non-deprived settings. We aimed to assess whether an internet-delivered intervention to modify handwashing would reduce the number of RTIs among adults and their household members. Methods We recruited individuals sharing a household by mailed invitation through general practices in England. After consent, participants were randomised online by an automated computer-generated random number programme to receive either no access or access to a bespoke automated web-based intervention that maximised handwashing intention, monitored handwashing behaviour, provided tailored feedback, reinforced helpful attitudes and norms, and addressed negative beliefs. We enrolled participants into an additional cohort (randomised to receive intervention or no intervention) to assess whether the baseline questionnaire on handwashing would affect handwashing behaviour. Participants were not masked to intervention allocation, but statistical analysis commands were constructed masked to group. The primary outcome was number of episodes of RTIs in index participants in a modified intention-to-treat population of randomly assigned participants who completed follow-up at 16 weeks. This trial is registered with the ISRCTN registry, number ISRCTN75058295. Findings Across three winters between Jan 17, 2011, and March 31, 2013, we enrolled 20 066 participants and randomly assigned them to receive intervention (n=10 040) or no intervention (n=10 026). 16 908 (84%) participants were followed up with the 16 week questionnaire (8241 index participants in intervention group and 8667 in control group). After 16 weeks, 4242 individuals (51%) in the intervention group reported one or more episodes of RTI compared with 5135 (59%) in the control group (multivariate risk ratio 0·86, 95% CI 0·83–0·89; p<0·0001). The intervention reduced transmission of RTIs (reported within 1 week of another household member) both to and from the index person. We noted a slight increase in minor self-reported skin irritation (231 4% of 5429 in intervention group vs 79 1% of 6087 in control group) and no reported serious adverse events. Interpretation In non-pandemic years, an effective internet intervention designed to increase handwashing could have an important effect in reduction of infection transmission. In view of the heightened concern during a pandemic and the likely role of the internet in access to advice, the intervention also has potential for effective implementation during a pandemic. Funding Medical Research Council.
Summary Background Data from trials suggest that antibiotics reduce the risk of complications of sore throat by at least 50%, but few trials for complications have been done in modern settings, and ...datasets of delayed antibiotic prescription are underpowered. Observational evidence is important in view of poor compliance with antibiotic treatment outside trials, but no prospective observational cohort studies have been done to date. Methods We generated a large prospective cohort from the DESCARTE study, and the PRISM component of DESCARTE, of 12 829 adults presenting with sore throat (≤2 weeks duration) in primary care. Our follow-up of the cohort was based on a detailed and structured review of routine medical records, and analysis of the comparison of three antibiotic prescription strategies (no antibiotic prescription, immediate antibiotic prescription, and delayed antibiotic prescription) to control for the propensity to prescribe antibiotics. Information about antibiotic prescription was recorded in 12 677 individuals (4805 prescribed no antibiotics, 6088 prescribed antibiotics immediately, and 1784 prescribed delayed antibiotics). We documented by review of patients' notes (n=11 950) the development of suppurative complications (eg, quinsy, impetigo and cellulitis, otitis media, and sinusitis) or reconsultation with new or non-resolving symptoms). We used multivariate analysis to control for variables significantly related to the propensity to prescribe antibiotics and for clustering by general practitioner. Findings 164 (1·4%) of the 11 950 patients with information available developed complications; otitis media and sinusitis were the most common complications (101 patients 62%). Compared with no antibiotic prescription, immediate antibiotic prescription was associated with fewer complications (adjusted risk ratio RR 0·62, 95% CI 0·43–0·91, estimated number needed to treat NNT 193) as was delayed prescription of antibiotics (0·58, 0·34–0·98; NNT 174). 1787 of the 11 950 patients (15%) reconsulted with new or non-resolving symptoms; the risk of reconsultation was also reduced by immediate (0·83, 0·73–0·94; NNT 40) or delayed antibiotics (0·61, 0·50–0·74; NNT 18). Interpretation Suppurative complications are not common in primary care and most are not serious. The risks of suppurative complications or reconsultation in adults are reduced by antibiotics, but not as much as the trial evidence suggests. In most cases, no antibiotic is needed, but a delayed prescription strategy is likely to provide similar benefits to an immediate antibiotic prescription. Funding UK Medical Research Council.
Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data ...provided by whole genome and transcriptome sequencing and analysis (WGTA) presents an opportunity to align a much larger proportion of patients to therapies.
Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number, and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected.
Clinically actionable targets were identified for 83% of patients, 37% of whom received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, PARP inhibitors, and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%), and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies.
Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.
NCT02155621
•A prospective study of 570 patients used whole genome and transcriptome analysis (WGTA) for real-time treatment options•Of 248 WGTA-informed treatments, 46% resulted in clinical benefit to the patient•RNA expression information was as valuable as DNA-based information for selecting treatments with clinical benefit•Integrated data informs selection of standard-of-care therapies, clinical trial enrollment and off-label use•This study supports the use of whole genome and transcriptome analysis in clinical cancer care
CONTEXT In recent years, smoking among adolescents has increased and the decline
of adult smoking has slowed to nearly a halt; new insights into tobacco dependency
are needed to correct this ...situation. Long-term use of nicotine has been linked
with self-medicating efforts to cope with negative emotional, neurobiological,
and social effects of adverse childhood experiences. OBJECTIVE To assess the relationship between adverse childhood experiences and
5 smoking behaviors. DESIGN The ACE Study, a retrospective cohort survey including smoking and exposure
to 8 categories of adverse childhood experiences (emotional, physical, and
sexual abuse; a battered mother; parental separation or divorce; and growing
up with a substance-abusing, mentally ill, or incarcerated household member),
conducted from August to November 1995 and January to March 1996. SETTING A primary care clinic for adult members of a large health maintenance
organization in San Diego, Calif. PARTICIPANTS A total of 9215 adults (4958 women and 4257 men with mean SD ages
of 55.3 15.7 and 58.1 14.5 years, respectively) who responded to a survey
questionnaire, which was mailed to all patients 1 week after a clinic visit. MAIN OUTCOME MEASURES Smoking initiation by age 14 years or after age 18 years, and status
as ever, current, or heavy smoker. RESULTS At least 1 of 8 categories of adverse childhood experiences was reported
by 63% of respondents. After adjusting for age, sex, race, and education,
each category showed an increased risk for each smoking behavior, and these
risks were comparable for each category of adverse childhood experiences.
Compared with those reporting no adverse childhood experiences, persons reporting
5 or more categories had substantially higher risks of early smoking initiation
(odds ratio OR, 5.4; 95% confidence interval CI, 4.1-7.1), ever smoking
(OR, 3.1; 95% CI, 2.6-3.8), current smoking (OR, 2.1; 95% CI, 1.6-2.7), and
heavy smoking (OR, 2.8; 95% CI, 1.9-4.2). Each relationship between smoking
behavior and the number of adverse childhood experiences was strong and graded
(P<.001). For any given number of adverse childhood
experiences, recent problems with depressed affect were more common among
smokers than among nonsmokers. CONCLUSIONS Smoking was strongly associated with adverse childhood experiences.
Primary prevention of adverse childhood experiences and improved treatment
of exposed children could reduce smoking among both adolescents and adults.
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