Roux-en-Y gastric bypass for morbid obesity: what are the preoperative predictors of weight loss?

Obesity has become an increasingly important health problem over the past 30 years. Presently around a quarter of the UK adult population are obese and this figure is set to increase further in the coming decades. The health consequences of obesity on multiple body systems have been well established as has the financial cost of the condition to both the individuals affected as well as to society as a whole. Bariatric surgery has been shown to be the only long term effective solution in terms of sustained weight loss and comorbidity resolution. The commonest bariatric procedure in the UK is the Roux-en-y gastric bypass which consistently results in the loss of 70%-80% of excess bodyweight. Results however are variable and in order to optimise resource allocation and avoid exposing patients unlikely to benefit from surgery to its inherent risks, much research has been done to try to identify those patients most likely to obtain a good result. The only factor which has been subjected to meta-analysis is that of preoperative weight loss which shows a positive association with postoperative weight loss following bypass surgery. Although the remaining data are not based on level 1 evidence those other preoperatively identifiable factors which are associated with an improved outcome include Caucasian or Hispanic ethnicity, higher educational status, non-shift-work working patterns, female gender and divorced or single marital status. Similarly increased levels of preoperative physical activity and an absence of binge eating behaviour are consistent with a favourable result whereas increased age, smoking and other socioeconomic factors have not been shown to have a significant impact. Conversely diabetes mellitus seems to have a slight negative correlation with postoperative weight loss; however, a history of sexual abuse or psychiatric illness has not been shown to have a lasting influence.


Source: Source: PMJ. BMJ






Restless legs syndrome: pathophysiology and modern management.

Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is characterised by an irresistible urge to move the legs that significantly affects the quality of life of the patient. Prevalence in the general population is 5-25% and it is twice as prevalent in women as in men. RLS is the most common movement disorder in pregnancy with a fourfold increased risk of developing this disorder later in life. The pathophysiology of RLS is centred on dopaminergic dysfunction, reduced central nervous system iron, genetic linkages, or alteration in neurotransmitters such as hypocretins, endorphins levels and immune dysfunction and inflammatory mechanisms. With the emergence of new evidence, there are changes to the previous treatment recommendations for RLS. There is sufficient evidence to conclude that dopamine agonists such as rotigotine transdermal patch, pramipexole, ropinirole, gabapentin enacarbil, pregabalin and gabapentin are effective in the short-term treatment of RLS and rotigotine, followed by gabapentin enacarbil, ropinirole, pramipexole and gabapentin for long-term treatment. Based on expert consensus, the recommendation for daily RLS is dopamine agonists or gabapentin or low-potency opioids. Levodopa is less preferred for treating daily RLS due to its high risk of augmentation. For intermittent RLS, it is levodopa or dopamine agonists or low-potency opioids or benzodiazepines. For refractory RLS, the choice is to change to gabapentin or a different dopamine agonist, addition of a second agent like gabapentin or benzodiazepine to the existing drug or changing to a high-potency opioid or tramadol. Medications with safety record in pregnancy include opioids and antiepileptics such as carbamazepine and gabapentin. There are concerns that patients with RLS are at risk for metabolic deregulation, autonomic dysfunction and cardiovascular morbidity. However, a recent study concluded that RLS is not associated with increased risk of cardiovascular complications.

Source: Source: PMJ. BMJ


The development and validation of an internet-based training package for the management of perineal trauma following childbirth:MaternityPEARLS.


Background Birth-related perineal trauma has a major impact on women’s health. Appropriate management of perineal injuries requires clinical knowledge and skill. At present, there is no agreement as to what constitutes an effective clinical training programme, despite the presence of sufficient evidence to support standardised perineal repair techniques. To address this deficiency, we developed and validated an interactive distance learning multi-professional training package called MaternityPEARLS.

Method MaternityPEARLS was developed as a comprehensive e-learning package in 2010. The main aim of the MaternityPEARLS project was to develop, refine and validate this multi-professional e-learning tool. The effect of MaternityPEARLS in improving clinical skills and knowledge was compared with two other training models; traditional training (lectures + model-based hands on training) and offline computer lab-based training. Midwives and obstetricians were recruited for each training modality from three maternity units. An analysis of covariance was done to assess the effects of clinical profession and years of experience on scoring within each group. Feedback on MaternityPEARLS was also collected from participants. The project started in January 2010 and was completed in December 2010.

Results Thirty-eight participants were included in the study. Pretraining and post-training scores in each group showed considerable improvement in skill scores (p<0.001 in all groups). Mean changes were similar across all three groups for knowledge (3.24 (SD 5.38), 3.00 (SD 3.74), 3.30 (SD 3.73)) and skill (25.34 (SD 8.96), 22.82 (SD 9.24), 20.7 (SD 9.76)) in the traditional, offline computer lab-based and e-learning groups, respectively. There was no evidence of any effect of clinical experience and baseline knowledge on outcomes.

Conclusions MaternityPEARLS is the first validated perineal trauma management e-learning package. It provides a level of improvement in skill and knowledge comparable to traditional methods of training. However, as an e-learning system, it has the advantage of ensuring the delivery of a standardised, continuously updated curriculum that has global accessibility.

Source: PMJ. BMJ


High incidence of acute coronary occlusion in patients without protocol positive ST segment elevation referred to an open access primary angioplasty programme.


Background Primary percutaneous coronary intervention (PPCI) programmes vary in admission criteria from open referral to acceptance of electrocardiogram (ECG) protocol positive patients only. Rigid criteria may result in some patients with acutely occluded coronary arteries not receiving timely reperfusion therapy.

Objective To compare the prevalence of acute coronary occlusion and, in these cases, single time point biomarker estimates of myocardial infarct size between patients presenting with protocol positive ECG changes and those presenting with less diagnostic changes in the primary angioplasty cohort of an open access PPCI programme.

Methods We retrospectively performed a single centre cross sectional analysis of consecutive patients receiving PPCI between January and August 2008. Cases were categorised according to presenting ECG—group A: protocol positive (ST segment elevation/left bundle branch block/posterior ST elevation myocardial infarction), group B: ST segment depression or T-wave inversion, or group C: minor ECG changes. Clinical characteristics, coronary flow grades and 12 h postprocedure troponin-I levels were reviewed.

Results During the study period there were 513 activations of the PPCI service, of which 390 underwent immediate angiography and 308 underwent PPCI. Of those undergoing PPCI, 221 (72%) were in group A, 41 (13%) in group B and 46 (15%) in group C. Prevalence of coronary occlusion was 75% in group A compared with 73% in group B and 63% in group C. Median 12 h postintervention troponin-I (25th–75th percentile) for those with coronary occlusion was significantly higher in group A patients; 28.9 μg/l (13.2–58.5) versus 18.1 μg/l (6.7–32.4) for group B (p=0.03); and 15.5 μg/l (3.8–22.0) for group C (p<0.001), suggesting greater infarct size in group A.

Conclusions A number of patients referred to an open access PPCI programme have protocol negative ECGs but myocardial infarction and acute coronary artery occlusion amenable to angioplasty.

Source: PMJ. BMJ


Suboptimal access to primary healthcare among street-based sex workers in southwest Switzerland.


Objectives Street-based sex workers (SSWs) in Lausanne, Switzerland, are poorly characterised. We set out to quantify potential vulnerability factors in this population and to examine SSW healthcare use and unmet healthcare requirements.

Methods We conducted a cross-sectional questionnaire-based survey among SSWs working in Lausanne’s red light district between 1 February and 31 July 2010, examining SSW socio-demographic characteristics and factors related to their healthcare.

Results We interviewed 50 SSWs (76% of those approached). A fifth conducted their interviews in French, the official language in Lausanne. 48 participants (96%) were migrants, of whom 33/48 (69%) held no residence permit. 22/50 (44%) had been educated beyond obligatory schooling. 28/50 (56%) had no health insurance. 18/50 (36%) had been victims of physical violence. While 36/50 (72%) had seen a doctor during the preceding 12 months, only 15/50 (30%) were aware of a free clinic for individuals without health insurance. Those unaware of free services consulted emergency departments or doctors outside Switzerland. Gynaecology, primary healthcare and dental services were most often listed as needed. Two individuals (of 50, 4%) disclosed positive HIV status; of the others, 24/48 (50%) had never had an HIV test.

Conclusions This vulnerable population comprises SSWs who, whether through mobility, insufficient education or language barriers, are unaware of services they are entitled to. With half the participants reporting no HIV testing, there is a need to enhance awareness of available facilities as well as to increase provision and uptake of HIV testing.

Source: PMJ. BMJ

Desiccated thyroid extract a safe alternative to levothyroxine in hypothyroidism.

Desiccated thyroid extract could be a potential alternative treatment to standard therapy with levothyroxine in patients with hypothyroidism, Thanh D. Hoang, DO, staff endocrinologist of the Walter Reed National Military Medical Center in Bethesda, Md., told Endocrine Today here at ENDO 2013.

During a poster session, Hoang said that desiccated thyroid extract could be a viable treatment option for patients with symptoms of hypothyroidism, despite normal TSH measurements while taking levothyroxine alone. Further, the desiccated thyroid extract yielded superior weight loss compared with levothyroxine, he said.

“The current gold standard right now is synthetic levothyroxine, so we wanted to do this randomized, double blind, crossover study to look at the efficacy of both drugs,” Hoang told Endocrine Today.

He and colleagues included 70 patients aged 18 to 65 years with primary hypothyroidism who were prescribed levothyroxine for 6 months. Patients were randomly assigned to either desiccated thyroid extract (DTE) or levothyroxine for 16 weeks.

According to data, patients assigned to DTE lost 3 lb, compared with those assigned levothyroxine (172.9 lb vs. 175.7 lb, P<.001).

“We didn’t find any differences in the neurocognitive measurements between the two therapies, but at the end of the study we did ask our patients which regimen they preferred,” Hoang said.

At the end of the 16-week study, 34 patients (48.6%) preferred DTE therapy, whereas 13 (18.6%) preferred levothyroxine; 23 (32.9%) did not specify a preference, he said. Further analysis confirmed those who preferred DTE lost even more weight over a 4-month period.

“We now know that once-daily desiccated thyroid extract is a safe alternative treatment for patients with hypothyroidism who are not satisfied with levothyroxine treatment. It’s an option for them to try, and also desiccated can cause modest weight loss in these patients as well,” Hoang said. –bySamantha Costa

Source: Endocrine today

Liraglutide-metformin combo superior to either treatment alone for weight loss in PCOS.

Short-term combination liraglutide and metformin yielded significant weight loss among obese women with polycystic ovary syndrome,Mojca Jensterle Sever, MD, PhD, of the University Medical Center in Ljubljana, Slovenia, told Endocrine Today here at ENDO 2013.

Obesity is a great problem in women with polycystic ovary syndrome (PCOS) and we do not have a conventional satisfactory treatment for it. The most widely used drug is metformin for women with PCOS and metabolic disturbances, but it’s somehow not successful enough to curb obesity. That’s why we tried to use our experience with diabetes to test long-acting GLP-1 agonists for any effect on the PCOS population,” Jenterle Sever said in an interview.

She and colleagues conducted a 12-week open, metformin-controlled trial by randomly assigning 36 obese women with PCOS aged 31.3 years (BMI 37.1 kg/m2) to one of the following treatment arms: metformin 1,000 mg twice daily (n=14), liraglutide (Victoza, Novo Nordisk) 1.2-mg administered daily subcutaneously (n=11) or combined therapy (n=11).

Jensterle Sever said that 38% of patients lost ≥5% body weight (22% in the combination group, 16% in the liraglutide group and zero in the metformin group). Patients assigned to combination therapy lost an average of 6.5 kg vs. 3.8 kg among those in the liraglutide group and 1.2 kg in the metformin group (P<.001), according to data.

Patients in the combination group also demonstrated a greater decrease in BMI and waist circumference compared with the other two treatment groups, according to data.

“We found that this combined arm was more successful in reducing weight, BMI and waist circumference as compared with liraglutide and metformin treatment arm alone.”

Adverse events included nausea during liraglutide treatment. However, this effect gradually declined over time and was not correlated with weight loss, Jensterle Sever said.

These findings suggest that short-term combined treatment of liraglutide and metformin led to statistically significant weight loss in obese women with PCOS. – by Samantha Costa

Source: Endocrine today

Low-dose BPA exposure increased prostate cancer risk in stem cells.

In vivo evidence shows that developmental exposure to bisphenol A significantly increases the carcinogenic susceptibility of the human prostate epithelium, according to data presented here at ENDO 2013.

“Our new findings provide the first direct in vivo evidence that early life exposure to BPA [bisphenol A] at levels found every day in humans increases cancer susceptibility in the human prostate epithelium,” Gail S. Prins, PhD,Michael Reese professor of urology in the departments of urology and physiology and biophysics at the University of Illinois at Chicago, said during a press conference here.

In a rodent study published in 2007, Prins and colleagues demonstrated that brief exposure to low doses of BPA early in life reprogrammed the prostate gland and enhanced the carcinogenic potential when exposed to elevated adult estrogen levels, as seen in aging men.

In the current study, Prins and colleagues tested the effects of BPA in an in vivo chimeric prostate model of human prostate epithelial stem-progenitor cells cultured from primary prostate epithelial cells of healthy donors.

They exposed host mice to daily oral low doses of BPA (100 mcg/kg of body weight [BW], n=15; 250 mcg/kg of body weight [BW], n=27) or vehicle (n=34) during the first 2 weeks of tissue formation in vivo.

At day 7, serum BPA levels were 0.16 ng/mL free-BPA and 0.47 ng/mL free-BPA for the 100 mcg/kg BW and 250 mcg/kg BW groups, respectively.

One month after the graft, mice were administered testosterone plus estradiol (T+E) pellets and researchers monitored carcinogensis over a 4-month period.

Among controls with T+E alone, the incidence rate for high grade prostate intraepithelial neoplasia and prostate adenocarcinoma was 12%; 26% of grafts demonstrated normal histology.

During tissue development, treatment with either BPA dose significantly increased intraepithelial neoplasia and prostate adenocarcinoma, with an incidence of 33% (P<.05); the remainder had benign lesions with no grafts demonstrating normal histology.

An additional group (n=42) was given 200 nM BPA during prostasphere culture, followed by 250 mcg/kg BW in vivo during tissue formation to model continuous developmental exposure. Among this group, incidence of intraepithelial neoplasia and prostate adenocarcinoma increased to 45% (P<.01).

Source: Endocrine today

Testosterone reduced pain perception in hypogonadism.

During a press conference here at ENDO 2013,Shehzad S. Basaria, MDmedical director of the section of men’s health, aging and metabolism at Brigham and Women’s Hospital, Harvard Medical School, said testosterone therapy administered to men with opioid-induced androgen deficiency led to a decrease in pain perception on Quantitative Pain Testing (QST) in the pain laboratory.

Basaria and colleagues randomly assigned 65 men (mean age, 49 years; BMI: 33 kg/m2) with an androgen deficiency to 5 g transdermal testosterone gel (n=36) or placebo (n=29) for 14 weeks. Abstract data indicate baseline total testosterone (228 ng/dL) and free serum testosterone levels (44 pg/mL) increased significantly among those assigned to testosterone.

At 12 weeks, patients randomly assigned to testosterone displayed significant improvements to pressure pain thresholds (P<.031), mechanical pain intensity (P=.049) and cold pain after-sensations (P=.08), according to data.

Clinical pain perception, as measured by a validated questionnaire, was not different between the two groups, Basaria said.

“Previous data suggest that improvement in pain perception and tolerance on QST testing generally precedes improvement in clinical pain. A longer study might have shown improvement in clinical pain as well,” Basaria said.

These findings suggest that testosterone therapy administered to men with opioid-induced androgen deficiency led to a greater reduction in pain sensitivity compared with placebo. However, further trials examining the anti-nociceptive role of testosterone are warranted. In an interview with Endocrine Today, Basaria said that the most important message to clinicians would be not to initiate testosterone treatment solely for the treatment of pain. He and colleagues are currently looking at longer term studies that may examine improvements in clinical pain perception as well.

Clinicians should become more aware of this condition called opioid-induced androgen deficiency. Many clinicians do not appreciate that testosterone levels are reduced in a significant number of men who are on opioid analgesics. In some men, testosterone levels are suppressed in castrate range,” Basaria said. “It’s important for clinicians when they have patients in their clinic on opioids to pay attention to complaints of sexual dysfunction, fatigue or decreased energy. Testosterone levels should be checked as these men might benefit from testosterone therapy.” – by Samantha Costa

Source: Endocrine today

Comparative Effectiveness Research in Oncology.

Although randomized controlled trials represent the gold standard for comparative effective research (CER), a number of additional methods are available when randomized controlled trials are lacking or inconclusive because of the limitations of such trials. In addition to more relevant, efficient, and generalizable trials, there is a need for additional approaches utilizing rigorous methodology while fully recognizing their inherent limitations. CER is an important construct for defining and summarizing evidence on effectiveness and safety and comparing the value of competing strategies so that patients, providers, and policymakers can be offered appropriate recommendations for optimal patient care. Nevertheless, methodological as well as political and social challenges for CER remain. CER requires constant and sophisticated methodological oversight of study design and analysis similar to that required for randomized trials to reduce the potential for bias. At the same time, if appropriately conducted, CER offers an opportunity to identify the most effective and safe approach to patient care. Despite rising and unsustainable increases in health care costs, an even greater challenge to the implementation of CER arises from the social and political environment questioning the very motives and goals of CER. Oncologists and oncology professional societies are uniquely positioned to provide informed clinical and methodological expertise to steer the appropriate application of CER toward critical discussions related to health care costs, cost-effectiveness, and the comparative value of the available options for appropriate care of patients with cancer.

Source: the oncologist