Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study.


Summary

Background

Although trastuzumab plus chemotherapy is the standard of care for first-line treatment of HER2-positive advanced gastric cancer, there is no established therapy in the second-line setting. In GATSBY, we examined the efficacy and tolerability of trastuzumab emtansine in patients previously treated for HER2-positive advanced gastric cancer (unresectable, locally advanced, or metastatic gastric cancer, including adenocarcinoma of the gastro-oesophageal junction).

Methods

This is the final analysis from GATSBY, a randomised, open-label, adaptive, phase 2/3 study, done at 107 centres (28 countries worldwide). Eligible patients had HER2-positive advanced gastric cancer and progressed during or after first-line therapy. In stage one of the trial, patients were randomly assigned to treatment groups (2:2:1) to receive intravenous trastuzumab emtansine (3·6 mg/kg every 3 weeks or 2·4 mg/kg weekly) or physician’s choice of a taxane (intravenous docetaxel 75 mg/m2every 3 weeks or intravenous paclitaxel 80 mg/m2 weekly). In stage two, patients were randomly assigned to treatment groups (2:1) to receive the independent data monitoring committee (IDMC)-selected dose of trastuzumab emtansine (2·4 mg/kg weekly) or a taxane (same regimen as above). We used permuted block randomisation, stratified by world region, previous HER2-targeted therapy, and previous gastrectomy. The primary endpoint (overall survival) was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01641939.

Findings

Between Sept 3, 2012, and Oct 14, 2013, 70 patients were assigned to receive trastuzumab emtansine 3·6 mg/kg every 3 weeks, 75 to receive trastuzumab emtansine 2·4 mg/kg weekly, and 37 to receive a taxane in the stage 1 part of the trial. At the pre-planned interim analysis (Oct 14, 2013), the IDMC selected trastuzumab emtansine 2·4 mg/kg weekly as the dose to proceed to stage 2. By Feb 9, 2015, a further 153 patients had been randomly assigned to receive trastuzumab emtansine 2·4 mg/kg weekly and a further 80 to receive a taxane. At data cutoff, median follow-up was 17·5 months (IQR 12·1–23·0) for the trastuzumab emtansine 2·4 mg/kg weekly group and 15·4 months (9·2–18·1) in the taxane group. Median overall survival was 7·9 months (95% CI 6·7–9·5) with trastuzumab emtansine 2·4 mg/kg weekly and 8·6 months (7·1–11·2) with taxane treatment (hazard ratio 1·15, 95% CI 0·87–1·51, one-sided p=0·86). The trastuzumab emtansine 2·4 mg/kg group had lower incidences of grade 3 or more adverse events (134 [60%] of 224 patients treated with trastuzumab emtansine vs 78 [70%] of 111 patients treated with a taxane), and similar incidences of adverse events leading to death (eight [4%] vs four [4%]), serious adverse events (65 [29%] vs 31 [28%]), and adverse events leading to treatment discontinuation (31 [14%] vs 15 [14%]) than did taxane treatment. The most common grade 3 or more adverse events in the trastuzumab emtansine 2·4 mg/kg weekly group were anaemia (59 [26%]) and thrombocytopenia (25 [11%]) compared with neutropenia (43 [39%]), and anaemia (20 [18%]), in the taxane group. The most common serious adverse events were anaemia (eight [4%]), upper gastrointestinal haemorrhage (eight [4%]), pneumonia (seven [3%]), gastric haemorrhage (six [3%]), and gastrointestinal haemorrhage (five [2%]) in the trastuzumab emtansine 2·4 mg/kg weekly group compared with pneumonia (four [4%]), febrile neutropenia (four [4%]), anaemia (three [3%]), and neutropenia (three [3%]) in the taxane group.

Interpretation

Trastuzumab emtansine was not superior to taxane in patients with previously treated, HER2-positive advanced gastric cancer. There is still an unmet need in this patient group and therapeutic options remain limited.

Source:http://www.thelancet.com

Living and looking for lavatories – why researching relief is so relevant


Toilets are a source of interaction, social structures, organisation, norms and values. So why aren’t sociologists discussing them more?

Toilets are a private side of life that is rarely discussed, or if we do disclose our habits we do so with hesitation, euphemisms or a nervous giggle. But toilets are a very public issue.
Toilets are a private side of life that is rarely discussed, or if we do disclose our habits we do so with hesitation, euphemisms or a nervous giggle. But toilets are a very public issue. 

It may be a turn of the stomach, a nervous flutter, a morning coffee or a sudden, unpredictable rush. You may look for a sign, if you are lucky enough to live in a society where they are readily available. There may or may not be a queue, often depending on the room of your gender. You may look for disabled access, whether you are in a wheelchair or have an invisible illness. You may select a space based on who is there, or your perception of its cleanliness. For some, it is an unwritten rule that one cannot go next to another person relieving themselves. What are you looking for?

A lavatory.

Also known as a toilet, bog, ladies, gents, pisspot, restroom, dunny, convenience, powder room, and the WC, to name a few alternatives.

Toilets are mundane, an everyday space, a common fixture in the home and the workplace, a thing that we all use, in diverse ways. Toilets have historically been(and continue to be) shaped by our cultures, gender, social class and ethnicity with clear boundaries, distinctions and divisions imposed. This, in turn, shapes our social identities.

Toilets are a personal thing; a private side of life that is rarely discussed. If we do disclose our habits or toilet trips we do so with hesitation, euphemisms or a nervous giggle. However, toilets are a very public issue. They are in department stores, coffee shops, pubs, restaurants and on trains. There is a declining number of public toilets, now often vandalised and abandoned, perceived as unhygienic, or a place of illegal activity and other “hazards”.

Toilets are a source of interaction, of social structures, organisation, norms and values. So why aren’t sociologists discussing them more?

I have a bowel problem. I live with an unpredictable bowel, one that changes every day, with symptoms ranging from abdominal pain to bloating and urgency to find a toilet. Bowel conditions are not socially accepted and discussed conditions: a disclosure is often regarded as “too much information”. The anxiety of the symptoms and the urgent need to use toilets led me to toilet mapping: making mental notes of the nearest toilets, and the quickest way to get to them. Toilets became not just a functional space, but also a place of safety and relief, in more than one sense.

I am not alone. There are a variety of conditions for which knowledge of toilet locations are crucial for managing symptoms – conditions such as bladder incontinence, Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS), for example. My PhD research is focusing on the common condition of IBS. According to NHS Choices, 20% of the UK population lives with IBS – arguably more, given the concealment of the condition. Despite this, bowel conditions and the symptoms of constipation, diarrhoea, flatulence, (in)continence and other activities that take place in the “private” realm of the toilets remain heavily taboo topics in contemporary western society.

My research explores the lived experience of managing symptoms of IBS, particularly in the spaces where symptoms are mostly managed: the bathroom.

My research examines how places such as toilets can be reflective of our practices of privacy and containment of our bodily excretions. We may divide ourselves and our relations to each other in such a way that makes life with conditions such as IBS incredibly isolating. This means that the coping strategies and challenges faced in the day-to-day life of people who live with these conditions are underappreciated, hidden and, crucially, misunderstood.

Some would argue that bathrooms and toilets are the backstage of social life. However, there are many performances still going on within the toilet cubicle: the holding on until another person has left the toilet; waiting until the hand dryer goes on; blaming the time spent in the toilet on a fictional queue. Whilst this may seem an obvious behaviour of privacy and dignity, the strategies of toilet mapping and negotiating toilet spaces to keep one’s IBS identity private question the boundaries of society, the public and the private, the clean and the dirty, self and other.

In discussing my research, I often face a reception of pure horror, a nervous laugh or a joke, but very rarely an open, honest, discussion of our own bowel habits and toilet behaviours. The awkwardness around the topic creates greater challenges for those living with bowel conditions, and reinforces stigma. Some may laugh at the fact I talk about poo and toilets in my academic life. There may be banter about bowels, a joke that I need a colon in my future research papers or conference presentations. But is the difficulty of living with an unpredictable bowel in an unaccommodating society really that funny? It’s time to talk shit.

Source:/www.theguardian.com

Irish Study Finds Those Eating More Dairy Are Skinnier and Don’t Have Higher Cholesterol


But is it too good to be true?

 

A new study brings good news to those who love dairy – the results found those who ate more dairy on average (even high fat dairy products) had lower body fat percentages, and lower BMIs.

The research is counter-intuitive to what we all learn – higher fat dairy products such as butter, cheese, and cream are high in saturated fats and should be eaten as ‘sometimes foods‘ if you want to be healthy.

Plus, having too much LDL cholesterol in your blood increases the risk of heart disease and heart attacks – around 10,000 Irish people die from those diseases every year and the rates are similar around the world.

But this new research, undertaken by the University of Dublin, Ireland, shows that cheese and other high fat dairy products might not be the culprit.

“What we saw was that in the high consumers [of cheese] they had a significantly higher intake of saturated fat than the non-consumers and the low consumers and yet there was no difference in their LDL Cholesterol levels,” said Emma Feeney, the lead researcher on the paper.

The study looked at 1,500 people in Ireland between 18 and 90-years-old over a four-day period.

The researchers looked at their level of dairy intake on those days, what type of dairy they were consuming, and whether it was low fat or full fat options.

“‘High’ consumers of total dairy, after adjustment for energy intake, gender, age, social class and smoking, had significantly lower BMI and percentage body fat, a lower waist circumference, and a higher insulin sensitivity score compared with ‘low’ consumers,” the researchers write in their paper.

Source:http://www.sciencealert.com

The researchers also found that although those who consumed the most yogurt had the lowest body fat, the highest consumers of cheese didn’t have any differences in markers for metabolic health.

But as the cherry on the cake the researchers found that total cholesterol was “lower in the ‘Whole milk’ and ‘Butter and cream’ clusters than in the ‘Reduced milk and yogurt’ cluster”.

That means that those consuming the lower fat versions of their favourite dairy products had higher cholesterol.

So what the hell is going on here? Is it just the luck of the Irish, or should we all start sculling full cream milk and cheese for our health?

Well, probably not – but the truth is it’s really damn complicated.

Correlation doesn’t equal causation – so we might find that those eating lower-fat foods might also be eating something else that causes them to have higher cholesterol.

Plus the researchers had the participants keep food diaries, meaning that there was no real way to tell if foods could have been missed or excluded – and food diaries tend to make people change their eating habits.

And finally food science is incredibly complex – scientists are still not sure if fasting is the way to go, or if gluten free food increases your risk of diabetes.

“We have to consider not just the nutrients themselves but also the matrix in which we are eating them in and what the overall dietary pattern is, so not just about the food then, but the pattern of other foods we eat with them as well,” said Feeney.

So right now the jury is out. Scientists will need more studies over longer time frames and with more diverse groups to be able to get a better picture of exactly what is happening when we enjoy cheddar or some butter on our toast.

But for the moment, lets savour this, and enjoy a wedge of brie or gouda without feeling too guilty.

World’s First Clinical Trial Finds Diet Works for Depression.


Pioneering research from the Land Down Under shows you how to get out from under your depression!

Felice Jacka PhD is a trailblazing researcher at Deakin University in Australia who is calling the world’s attention to the powerful impact of food on mood. On January 30, 2017, the journal BMC Medicine published her new randomized controlled study called The SMILES Trial. This groundbreaking research demonstrates for the first time that people with moderate to severe depression can improve their mood by eating a healthier diet.

You may be surprised to hear that this kind of study has never been done before, probably because you have read headlines in the past proclaiming that healthier diets decrease risk for depression. We have Professor Jacka and her team to thank for many of those hopeful headlines. Over the past seven years, she published numerous epidemiological (survey-based) studies suggesting that people who report eating an unhealthy diet are more likely to be depressed. However, since these studies were based on questionnaires and weren’t actual diet experiments, they didn’t have the power to PROVE that unhealthy diets CAUSE depression, and couldn’t prove that healthy diets could TREAT depression. These were simply educated guesses that hadn’t been tested in the real world yet. Until now.

Professor Jacka boldly went where no one has gone before: she tested her theories on actual people with clinical depression…and emerged victorious.

The Study

Professor Jacka’s team recruited 67 men and women with moderate to severe depression who reported eating a relatively unhealthy diet. Most were taking antidepressants and/or were in regular psychotherapy.

They put half of these depressed people on a modified Mediterranean diet (aka the “ModiMed” diet—more details below) and required them to attend dietary support sessions with a nutritionist.

The other half continued eating their usual unhealthy diet, but were required to attend social support “befriending” sessions.

Before and after the 12-week study, everyone’s depression symptoms were graded using several different tests. The test this research group chose to focus on was the MADRS scale (Montgomery–Åsberg Depression Rating Scale), which rates mood on a scale of 0 to 60, with 60 being the most severely depressed.

Adapted from Jacka FN et al 2017.
Source: Adapted from Jacka FN et al 2017.

After 12 weeks, people in the ModiMed diet group saw their MADRS scores improve on average by about 11 points. Thirty-two percent (10 out of 31 completers) had MADRS scores so low that they no longer met criteria for depression—remission!

People in the unhealthy diet group improved by only about 4 points on the MADRS test and only 8% (2 of 25 completers) achieved remission.

More happy details:

Calories were not restricted and body weight stayed about the same for everyone in the study, so people didn’t have to lose weight to feel better.

Surprisingly, the ModiMed diet cost about 19% less than the standard unhealthy diet.

The diet plan was apparently easier to stick to than the social support plan, since more people in the diet group (31 out of 33) made it all the way to the end of the study, compared to only 25 out of 34 people in the support group.

What is the ModiMed diet?

Suzi Smith, used with permission
Source: Suzi Smith, used with permission

Encouraged foods: whole grains, fruits, vegetables, legumes, low-fat/ unsweetened dairy, raw unsalted nuts, lean red meat, chicken, fish, eggs, and olive oil

Discouraged foods: sweets, refined cereals, fried food, fast food, processed meat.

Beverages: maximum two sugar-sweetened beverages per week and maximum two alcoholic drinks per day, preferably red wine.

So, what is so special about the ModiMed diet?

Well, THAT is the $64,000 question, and the answer is? We don’t know.

It could be that this diet was higher in some potentially magical ingredient like olive oil or nuts.

It could be that this diet was lower in some potentially evil ingredient like processed meat or refined carbohydrates.

It could be both.

My opinion, based on everything I know about food and the brain, is that this diet is better than the average diet because:

  1. It is extremely low in refined carbohydrates (sugar, flour, refined cereals, etc). These non-foods put your blood sugar, insulin, hormones, and neurotransmitters on a dangerous invisible roller coaster. This destabilizes mood and increases risk for insulin resistance, which causes brain damage over time.
  2. It contains plenty of natural fat and cholesterol, which the brain needs to function properly [in my opinion the ModiMed diet unnecessarily limits saturated animal fats].
  3. It is low in processed oils from seeds such as cottonseed, safflower and corn. These industrially-refined oils are very high in omega-6 fatty acids, which tilt the brain towards inflammation and away from healing.
  4. It contains animal sources of protein, which are rich in key brain nutrients such as iron, zinc, and vitamin B 12, and free of anti-nutrients, which interfere with protein and mineral absorption.
  5. It is based primarily on whole foods, which humans are well-adapted to eating.

Real Hope for the Real World

I LOVE this study, because it proves that the human brain cares deeply about what we eat. I wish ALL of all of my patients would try a healthy diet before trying a prescription medication. Don’t get me wrong—I prescribe medications every day and I have seen them work wonders. But clearly the most powerful way to fundamentally change your brain chemistry is through food, because that’s where the brain chemicals come from in the first place! I believe a healthy diet can in many cases reduce or eliminate the need for prescription medications.

With the exception of crisis situations and special barriers to dietary change, why not start by improving the quality of your diet? What do you have to lose? Healthy diets have no co-pays, no side effects, and are good for the whole body, not just the brain.

The bottom line is this: the ModiMed diet is clearly superior to a junky standard diet loaded with fast food, processed foods, and refined carbohydrates. It is also affordable and manageable in the real world!

Take a Bite Out of Your Depression!

For those of you who eat a low-fat, vegan, vegetarian, low-carb, or Paleo diet, this study cannot tell you whether or not the ModiMed diet is better for depression than your diet. Until we have studies that compare these diets to each other, the only way for you to know which diet works best for your mood is to compare them yourself.

For those of you who have tried a Mediterranean diet without success, there is still tremendous hope. There are other healthy changes worth trying—my two favorite recommendations being:

  1. Lowering overall carbohydrate intake, especially if you have insulin resistance.
  2. Removing grains and legumes, which interfere with the absorption of key nutrients the brain needs to work properly, such as iron and zinc.

For those of you who don’t care to try the ModiMed diet, there are MOUNDS of evidence incriminating the refined carbohydrates and industrially-produced foods that form the basis of our American diet. So, regardless of what is IN your favorite diet, make sure you get the junk OUT.

Your brain, your metabolism, and your whole body will be happier and healthier.

ECSPECT prospective multicentre registry for single-port laparoscopic colorectal procedures


Abstract

Background

The international multicentre registry ECSPECT (European Consensus of Single Port Expertise in Colorectal Treatment) was established to evaluate the general feasibility and safety of single-port colorectal surgery with regard to preoperative risk assessment.

Methods

Consecutive patients undergoing single-port colorectal surgery were enrolled from 11 European centres between March 2010 and March 2014. Data were analysed to assess patient-, technique- and procedure-dependent parameters. A validated sex-adjusted risk chart was developed for prediction of single-port colorectal surgery-related conversion and complications.

Results

Some 1769 patients were enrolled, 937 with benign and 832 with malignant conditions. Procedures were completed without additional trocars in 1628 patients (92·0 per cent). Conversion to open surgery was required in 75 patients (4·2 per cent) and was related to male sex and ASA fitness grade exceeding I. Conversions were more frequent in pelvic procedures involving the rectum compared with abdominal procedures (8·1 versus 3·2 per cent; odds ratio 2·69, P < 0·001). Postoperative complications were observed in a total of 224 patients (12·7 per cent). Independent predictors of complications included male sex (P < 0·001), higher ASA grade (P = 0·006) and rectal procedures (P =0·002). The overall 30-day mortality rate was 0·5 per cent (8 of 1769 patients); three deaths (0·2 per cent; 1 blood loss, 2 leaks) were attributable to surgical causes.

Conclusion

The feasibility and safety, conversion and complication profile demonstrated here provides guidance for patient selection.

Introduction

Laparoscopic colorectal surgery is well established as an alternative to conventional open resection, and has been shown to be associated with short-term benefits, including earlier postoperative recovery, decreased postoperative pain, reduced impairment of pulmonary function and shorter hospital stay[1, 2]. Minimally invasive laparoscopic colorectal surgery is conventionally performed using several trocar sites and a separate incision for specimen extraction (multiport laparoscopic colorectal surgery). However, each incision has the potential for bleeding, haematoma, infection and incisional hernia. Single-port colorectal surgery has been used in recent years for both benign and malignant colorectal surgery[3-5]. Nevertheless, despite the potential advantages of single-port colorectal surgery, any innovative technique requires evaluation of its feasibility and safety before gaining wider acceptance[6]. To date, the literature on single-port colorectal surgery is limited to small case series and comparative studies. Furthermore, indications and preoperative selection criteria for the single-port colorectal surgery technique remain unclear, and risk factors for conversions and complications have not been established. Therefore, a multi-institutional European study group (ECSPECT) was established to assess the risk and safety of single-port colorectal surgery.

Methods

The objective of this study was to evaluate the safety and feasibility of single-port colorectal surgery. Thus, particular efforts were made to assess risk and complications, with the further objective of developing a complication risk chart. All surgical procedures were performed primarily using single-port access with only one abdominal incision. Use of any additional trocar was registered but not considered a complication itself. Intraoperative complications were defined as unintentional events that required deviation from the standard technique.

Procedures were classified as proximal or distal abdominal surgery, with the proximal category including right and left colonic resections, and distal incorporating all those with pelvic dissection for rectal resection, abdominoperineal resection (APR) and restorative proctocolectomy.

Postoperative complications were graded according to the Dindo–Demartines–Clavien classification[7]. An anastomotic leak was defined by: radiological demonstration of contrast extravasation; diffuse peritonitis with the presence of faecal fluid at reoperation; presence of a local abscess in the vicinity of the anastomosis; or faecal discharge from the drain or wound[8]. Operative mortality was defined as death from any cause during or after surgery within 30 days if the patient was discharged from hospital, or within any interval if the patient was not discharged.

Data collection

The local institutional review board for clinical trials approved the study and all patients gave informed consent. The clinical effectiveness committees of the participating centres considered this technique to be a formal laparoscopic method. To limit bias owing to heterogeneous learning curves, one surgeon responsible for the colorectal programme in each centre had performed more than 100 single-port colorectal surgery procedures before enrolment. Procedure numbers varied in relation to the preferences for the single-port approach in each centre. Five centres predominantly included patients with left-sided colectomies, whereas two centres mainly performed right colonic resections. Lower single-port procedures such as restorative proctocolectomy, rectal resections and APR were performed in seven of the 11 centres. The hospital data and records included medical notes and operating reports for all hospital admissions, and included patient-, technique- and procedure-dependent variables. All data were blinded and monitored by independent investigators. Data were then entered into the ECSPECT registry system, based on Microsoft Access® (Microsoft, Redmond, Washington, USA), by local study assistants who were unaware of patient identities. Patients were seen at an outpatient clinic 1 month after surgery, or had telephone interviews with study assistants. As such, the 30-day follow-up was 100 per cent complete.

Statistical analysis

In this prospective observational study, potential risk factors were investigated by means of univariable analyses; Fisher’s exact test and χ2 test were used for categorical variables, and the Wilcoxon rank-sum test or Kruskal–Wallis test for continuous variables. A univariable logistic regression analysis was also performed. Multivariable logistic regression models were fitted for conversion and complication as dependent variables. A risk score based on the estimated conversion and complication probabilities was devised: low risk corresponded to an estimated probability below the median for the patient group considered; moderate risk was scored between the median and the 90 per cent quantile and high risk above the 90 per cent quantile. Statistical analyses were carried out using R software version 3.0.3 (http://www.r-project.org). All statistical assessments were two-sided and a significance level of 0·050 was used.

Results

The ECSPECT registry includes data on 2032 consecutive patients who underwent single-port colorectal surgery between March 2010 and March 2014 at 11 centres in Austria, Denmark, Germany, Italy, the Netherlands, Spain, Switzerland and the UK. The surgical procedures (single-port colorectal surgery as a proportion of the total number of colorectal procedures) were performed in Leverkusen (638 of 1070), Salzburg (360 of 613), Turin (263 of 490), Varese (173 of 265), Bristol (145 of 310), St Gallen (142 of 451), Seville (109 of 210), Vienna (81 of 132), Amsterdam (49 of 130), Copenhagen (39 of 765) and Bremerhaven (33 of 114). Reasons for non-eligibility for single-port colorectal surgery were: cT4 tumours, bulky lymph nodules attached to vital pedicles (such as superior mesenteric vein in right colectomies), emergency procedure, or non-availability of the surgeon experienced in single-port colorectal surgery. The complete data were registered in a central database. A random group of 263 patients was excluded before any analysis and used as internal validation for the risk charts, leaving 1769 complete data sets as the study group for review and analyses.

Demographic characteristics according to the single-port procedures performed are shown in Table 1. As expected, sex differences were found between proximal procedure types without rectal involvement (right and left colectomies) and distal abdominal procedures (restorative proctocolectomy, APR and rectal resections). Younger patients were more likely to undergo restorative proctocolectomy or left colonic resections (Fig. S1a, supporting information), probably a result of the higher rates of inflammatory bowel disease in this cohort. There were no differences in distribution of ASA grades for proximal versus distal procedures: 25·5 versus 22·5 per cent ASA I, 54·3 versus 59·7 per cent ASA II, 18·7 versus 16·5 per cent ASA III, and 0·4 versus 0·5 per cent ASA IV, respectively (P = 0·297). However, among patients with ASA III and IV the single-port approach was used more often for right colonic resections than for all other procedures (Fig. S1b, supporting information). In contrast to left colectomies and restorative proctocolectomies, right colectomies, rectal resections and APR were performed significantly more often for malignancies. The histopathological staging of the malignant disease is shown in Table 2.

Table 1. Demographic data for patients who underwent single-incision laparoscopic surgery, in total and according to surgical procedure
Total Right colectomy Left colectomy Rectal resection Abdominoperineal resection Restorative proctocolectomy
(n = 1769) (n = 519) (n = 868) (n = 214) (n = 48) (n = 120) P
  • Values in parentheses are percentages unless indicated otherwise;
  • *values are mean(s.d.) (range).
  • χ2 test, except
  • Kruskal–Wallis test.
Age (years)* 61·1(14·4) 64·5(15·5) 60·2(12·2) 62·7(12·9) 65·9(13·3) 48·6(18·5) < 0·001
(13–93) (13–92) (21–89) (22–93) (23–88) (17–90)
Sex ratio (F : M) 913 : 856 275 : 244 465 : 403 100 : 114 16 : 32 57 : 63 0·026
BMI (kg/m2)* 26·0(4·6) 25·9(4·8) 26·4(4·6) 25·7(4·5) 25·2(4·0) 25·4(5·1) 0·020
(15–52) (16–52) (15–47) (17–48) (16–36) (16–45)
ASA fitness grade
I 439 (24·8) 132 (25·4) 221 (25·5) 62 (29·0) 3 (6) 21 (17·5) 0·005
II 981 (55·5) 242 (46·6) 511 (58·9) 112 (52·3) 38 (79) 78 (65·0) < 0·001
III 323 (18·3) 133 (25·6) 127 (14·6) 36 (16·8) 7 (15) 20 (16·7) < 0·001
IV 8 (0·5) 6 (1·2) 0 (0) 2 (0·9) 0 (0) 0 (0) 0·011
Not assessed 18 (1·0) 6 (1·2) 9 (1·0) 2 (0·9) 0 (0) 1 (0·8)
Disease type < 0·001
Benign 937 (53·0) 170 (32·8) 644 (74·2) 29 (13·6) 2 (4) 92 (76·7)
Malignant 832 (47·0) 349 (67·2) 224 (25·8) 185 (86·4) 46 (96) 28 (23·3)
Table 2. Tumour staging in patients with malignancy
Total Right colectomy Left colectomy Rectal resection Abdominoperineal resection Restorative proctocolectomy
(n = 832) (n = 349) (n = 224) (n = 185) (n = 46) (n = 28) P
  • Values in parentheses are percentages followed by standardized residuals unless indicated otherwise;
  • *values are mean(s.d).
  • χ2 test, except
  • Kruskal–Wallis test.
Tumour category < 0·001
ypT0/pTis 54 (6·5) 34 (9·7) 6 (2·7) 8 (4·3) 2 (4) 4 (14)
(3·24) (–2·71) (–1·36) (–0·61) (1·70)
pT1 125 (15·0) 34 (9·7) 49 (21·9) 24 (13·0) 5 (11) 13 (46)
(–3·62) (3·36) (–0·89) (–0·81) (4·73)
pT2 194 (23·3) 74 (21·2) 40 (17·9) 53 (28·6) 22 (48) 5 (18)
(–1·23) (–2·26) (1·94) (4·04) (–0·70)
pT3 451 (54·2) 203 (58·2) 128 (57·1) 98 (53·0) 17 (37) 5 (18)
(1·95) (1·03) (–0·38) (–2·42) (–3·93)
pT4 8 (1·0) 4 (1·1) 1 (0·4) 2 (1·1) 0 (0) 1 (4)
(0·46) (–0·92) (0·19) (–0·69) (1·44)
Node category 0·031
pN0 409 (49·2) 172 (49·3) 129 (57·6) 71 (38·4) 20 (43) 17 (61)
(0·06) (2·95) (–3·33) (–0·79) (1·24)
pN1 160 (19·2) 68 (19·5) 45 (20·1) 30 (16·2) 13 (28) 4 (14)
(0·16) (0·38) (–1·18) (1·60) (–0·68)
pN2 83 (10·0) 43 (12·3) 17 (7·6) 22 (11·9) 1 (2) 0 (0)
(1·92) (–1·39) (0·99) (–1·82) (–1·79)
Not assessed 180 (21·6) 66 (18·9) 33 (14·7) 62 (33·5) 12 (26) 7 (25)
(–1·62) (–2·93) (4·45) (0·75) (0·44)
No. of nodes retrieved* 18·00(8·55) 16·53(9·64) 16·74(9·61) 17·58(7·34) 15·07(6·17) 8·37(15·60) 0·133
Metastasis category < 0·001
pM0 614 (73·8) 266 (76·2) 181 (80·8) 136 (73·5) 23 (50) 8 (29)
(1·35) (2·79) (–0·10) (–3·78) (–5·54)
pM1 100 (12·0) 28 (8·0) 29 (12·9) 25 (13·5) 12 (26) 6 (21)
(–3·01) (0·50) (0·71) (3·02) (1·56)
Not assessed 118 (14·2) 55 (15·8) 14 (6·3) 24 (13·0) 11 (24) 14 (50)
(1·11) (–3·98) (–0·53) (1·95) (5·53)

Surgical techniques

Disposable ports used for single-port laparoscopic procedures included: SILS-Port™ 56·5 per cent (Covidien-Medtronic, Dublin, Ireland); GelPort® 23·4 per cent (Applied Medical, Rancho Santa Margarita, California, USA); OctoPort™ 6·0 per cent (DalimSurgNET, Seoul, Korea); TriPort™ 2·2 per cent and QuadPort™ 0·1 per cent (Advanced Surgical Concepts, Wicklow, Ireland); and S.P.I.D.E.R. 0·1 per cent (TransEnterix®, Research Triangle Park, North Carolina, USA). Alternatively, reusable trocars were employed, namely: Storz X-Cone™ 7·9 per cent (Karl Storz, Tuttlingen, Germany); multiple trocars 3·6 per cent; homemade glove trocar 0·2 per cent; or KeyPort™ 0·1 per cent (Richard Wolf, Knittlingen, Germany). The incision was made routinely at the umbilical groove, except when a protective ileostomy was planned after rectal resection. Three patients (0·2 per cent) had a suprapubic incision via pre-existing scars. Fascial and skin closure was according to the preference of the surgeon. Pre-existing hernias were closed directly without the use of prophylactic mesh. In all procedures extra-long optical devices were used. Surgeons predominantly used straight working instruments (62·2 per cent) followed by curved instruments (37·8 per cent). Suspension devices were used in 160 patients (9·0 per cent) to improve exposure of the surgical field, including sutures in 143 (8·1 per cent), lifting devices in 14 (0·8 per cent) and magnets in three (0·2 per cent). The main indication for use of a suspension device was to place tension on the ileocolic segment in right hemicolectomy (19·1 per cent) or to elevate the uterus or bladder in APR (25·0 per cent) or rectal resection (6·1 per cent). No additional suspension was considered necessary in other procedures (1609, 91·0 per cent). Anastomoses were performed intracorporeally (1304, 73·7 per cent) and extracorporeally (390, 22·0 per cent); 75 patients (4·2 per cent) required no anastomosis. Extracorporeal stapling was the method of choice in right colectomy (73·0 per cent). All other procedures favoured either intracorporeal stapling (left colectomy 98·3 per cent, rectal resection 93·5 per cent, restorative proctocolectomy 92·5 per cent) or no anastomosis (note that 1 anastomosis in the APR group was performed elsewhere in the colon).

Technical results

A total of 1628 procedures (92·0 per cent) were completed without any additional trocar. One, two and three supplementary trocars were used in 121 (6·8 per cent), 17 (1·0 per cent) and three (0·2 per cent) procedures respectively. There was a trend towards use of more trocars in distal procedures with rectal resection (Fig. 1a) and in patients with higher BMI (Fig. 1b). Operating times differed significantly for right colectomy (mean(s.d.) 124(48) min), left colectomy (157(58) min), rectal resection (183(90) min), APR (305(76) min) and restorative proctocolectomy (197(108) min) (P < 0·001) (Fig. S2, supporting information). The duration of operation was prolonged in transrectal retrieval compared with that in the centre-matched cohort of patients undergoing rectal resections via an abdominal retrieval site (239·0(103·7) versus185·1(73·4) min; P = 0·014). In centres performing both types of anastomosis, operating times for right-sided colectomies with intracorporeal and extracorporeal anastomoses were not significantly different (123·0(47·4) versus 133·0(49·7) min; P = 0·057). Specimen retrieval was performed using a wound protector, a retrieval bag, or both, in all patients. Most specimens were removed via the primary incision, including APR (via the perineal incision) (Table 3). In left-sided colectomy and rectal resection, neither operating times nor complications were different between transvaginal and/or transrectal specimen retrieval routes. Predictors for prolonged operation were BMI (P = 0·005, univariable analysis), and ASA grade exceeding I, male sex, distal procedure, conversion, use of non-curved instruments, use of additional trocars and transrectal retrieval site (P < 0·001, multivariable regression analysis).

Correspondence analysis showing procedures (PC, restorative proctocolectomy; APR, abdominoperineal resection; rectal, rectal resection; left, left colectomy; right, right colectomy) in relation to need for additional trocars. b Box plots showing BMI in relation to need for additional trocars. Median value (bold line), interquartile range (box), and range (error bars) excluding outliers (symbols) are shown. P = 0·005 (Kruskal–Wallis test)
Table 3. Specimen retrieval site for single-incision laparoscopic colorectal procedures
Total Right colectomy Left colectomy Rectal resection Abdominoperineal excision Restorative proctocolectomy
(n = 1769) (n = 519) (n = 868) (n = 214) (n = 48) (n = 120)
  1. Values in parentheses are percentages.
Primary incision 1624 (91·8) 515 (99·2) 800 (92·2) 189 (88·3) 0 (0) 120 (100)
Transvaginal 44 (2·5) 3 (0·6) 39 (4·5) 2 (0·9) 0 (0) 0 (0)
Transrectal 41 (2·3) 0 (0) 28 (3·2) 13 (6·1) 0 (0) 0 (0)
Transperineal 48 (2·7) 0 (0) 0 (0) 0 (0) 48 (100) 0 (0)

Conversion

Some 1694 single-port colorectal surgery procedures (95·8 per cent) were completed without conversion. The reasons for conversion were anticipated operative difficulty (pre-emptive, strategic conversions: 68, 91 per cent) or intraoperative complications and technical problems after more than 15 min (reactive conversions: 7, 9 per cent). Conversion rates and independent predictors for conversion are shown in Table 4. BMI differed significantly among patients undergoing procedures with and without conversion (mean(s.d.) 26·0(4·6) versus 28·0(4·9) kg/m2; P < 0·001).

Table 4. Converted procedures and results of multivariable logistic regression analysis to identify independent predictors of conversion
No. of conversions Odds ratio P
  1. Values in parentheses are percentages.
Procedure
Right colectomy 17 (3·3)
Left colectomy 27 (3·1)
Rectal resection 19 (8·9)
Abdominoperineal resection 4 (8)
Restorative proctocolectomy 8 (6·7)
Procedure location
Proximal 44 (3·2) 1·00 (reference)
Distal 31 (8·1) 2·69 < 0·001
Sex
F 23 (2·5) 1·00 (reference)
M 52 (6·1) 2·50 < 0·001
ASA grade
I 5 (1·1) 1·00 (reference)
> I 70 (5·3) 4·89 < 0·001

Complications

Intraoperative complications were observed in 29 patients (1·6 per cent), and included bleeding (13), injury to the urinary tract (7), enterotomy (5) and splenectomy (owing to laceration, 1). In seven of these patients the operation was converted to open surgery. More patients with malignancies had intraoperative complications than those with benign underlying disease (20 versus 9 patients; odds ratio 2·53, P = 0·023). Most of the intraoperative complications were seen in right colonic resections (16 of 29). The use of additional trocars was different in patients with and without intraoperative complications (28 versus 7·6 per cent; odds ratio 4·60, P = 0·001). Interestingly, extracorporeal anastomosis was performed in nearly all patients with complicated right colonic resections (15 of 16 patients).

Postoperative complications were observed in 224 patients (12·7 per cent) (Table 5) and were unrelated to conversion to laparotomy.

Table 5. Complications and results of multivariable logistic regression analysis to identify independent predictors of complications
Postoperative complication SSI Anastomotic leak Odds ratio P
  • Values in parentheses are percentages.
  • *Dindo–Demartines–Clavien classification. SSI, surgical-site infection.
Complication grade*
I 66 (29·5)
II 40 (17·9)
III 73 (32·6)
IV 37 (16·5)
V 8 (3·6)
Procedure 0·008
Right colectomy 68 (13·1) 38 (7·3) 29 (5·6)
Left colectomy 89 (10·3) 5 (0·6) 28 (3·2)
Rectal resection 35 (16·4) 1 (0·5) 5 (2·3)
Abdominoperineal resection 9 (19) 0 (0)
Restorative proctocolectomy 23 (19·2) 2 (1·7) 1 (0·8)
Procedure location
Proximal 157 (11·3) 1·00 (reference)
Distal 67 (17·5) 1·67 0·002
Sex
F 91 (10·0) 1·00 (reference)
M 133 (15·5) 1·66 < 0·001
ASA grade
I–II 167 (11·8) 1·00 (reference)
III–IV 57 (17·2) 1·56 0·006
Disease type
Benign 104 (11·1) 1·00 (reference)
Malignant 120 (14·4) 1·35 0·038

Sex-adjusted risk charts for preoperative prediction of conversion and complication

Based on univariable risk analyses and logistic multivariable regression modelling to determine predicted probabilities for given patients’ profiles (scores), risk charts were developed for the prediction of conversion (Fig. 2) and complication. According to the median and 90 per cent quartile of the predicted probabilities for conversion, patients’ profiles were classified into low, moderate and high risk. Neither age nor malignancy had significant influence on the conversion rate. Thus, the conversion risk chart (Table S1, supporting information) allows preoperative assessment of any possible conversion according to BMI, sex, procedural involvement of the rectum (distal procedures) and ASA grade. Similarly, risk scores were established to classify patients as low, moderate or high complication risk according to a cluster analysis. In particular, male sex, ASA grade III–IV and distal procedures were found independently to result in a higher risk of complications. The complication risk chart (Table S2, supporting information) allows preoperative risk assessment of any possible intraoperative and/or postoperative complication based on the adjusted classification. These scores were validated by enrolment of an additional group of 263 patients who had single-port colorectal surgery.

Violin plots showing conversion risk in relation to a sex, b ASA grade and c procedure location. Median value (symbol), interquartile range (bold line), range (error bars) and kernel density estimate (shaded area) are shown. d Predicted probability of conversion during the single-incision laparoscopic procedure as a function of BMI

Mortality

The overall 30-day mortality rate was 0·5 per cent (8 of 1769), comprising three deaths each following right colectomy and left colectomy, and one death each following rectal resection and restorative proctocolectomy. There were no deaths among patients undergoing APR. The cause of death was surgical in three patients (bleeding 1; multiple organ failure following anastomotic leak in 2 patients on postoperative days 11 and 25 respectively) and medical in five (myocardial infarction 3, pulmonary embolism 1, stroke 1).

Hospital stay

The mean(s.d.) length of hospital stay was 7·8(8·9) days for right colectomy, 8·6(5·4) days for left colectomy, 8·7(6·6) days for rectal resection, 19·0(19·6) days for APR and 10·0(6·7) days for restorative proctocolectomy. Only 54 patients were discharged within 24 h.

Discussion

The broad feasibility and safety profile of the single-port colorectal surgery technique endorses its general applicability. Sex-specific, validated conversion and complication risk charts were compiled to guide patient selection, and to inform decision-making and consent.

Natural-orifice transluminal endoscopic surgery (NOTES) was developed to avoid external incisions and scars altogether, but lacks overall acceptance and experience with colorectal procedures is still sparse[8-10]. Techniques providing natural-orifice specimen extraction via transvaginal or transrectal routes remain valid options[11]. Unlike NOTES, single-port colorectal surgery is a simple modification of conventional laparoscopic surgery that does not require novel instruments or specific new operative strategies, but can be performed by surgeons who are experienced with laparoscopic techniques. Since the first colorectal applications of the single-port colorectal surgery technique were introduced in 2008[4, 5], many clinical series have been published on benign and malignant indications[3, 12-19]. Studies comparing single-port with multiport surgical techniques have demonstrated similar results in terms of complications, blood loss, number of lymph nodes harvested, tumour resection margins, complications and hospital stay[20-23]. Although single-port colorectal surgery is considered more technically demanding, only four early studies[24-27] reported longer operating times for single-port colorectal surgery compared with multiport laparoscopic colorectal procedures. Given that the registry analysis was not designed as a randomized case–control study, the mean(s.d.) operating time of 158(73) min, which includes even the most complex procedures and an array of indications, falls within the mean times reported for single-port and multiport surgery (130–175 min)[22].

Although it was reported that operations can be performed with straight instruments and without the need for special additional equipment[17, 18], interestingly, the use of curved instruments was associated with a significant decrease in operating time in the present study. Possibly the more convenient triangulation led to fewer collisions and allowed a better operative view, thus avoiding repetition of ineffective retraction and dissection. All surgeons used a variety of ports and the present data do not suggest any preference. As expected, longer operating times were associated with higher BMI, use of additional trocars and postoperative complications. The low 30-day mortality rate here is similar to published data (0·5 per cent), demonstrating that mortality after single-port colorectal surgery is mostly related to medical conditions and complications associated with the underlying disease[20-23]. Postoperative complications (in 12·7 per cent of patients) were unrelated to conversion to laparotomy and, unsurprisingly, more frequent in procedures that included pelvic dissection than right or left colectomies. The incidence of anastomotic leakage of 3·7 per cent is comparable to rates of 0·9–6·7 per cent for single-port colorectal surgery reported in smaller series[18, 26, 28]. Although the overall incidence of anastomotic leakage was very low, leakage was associated with death in two patients.

In right colectomies, intracorporeal anastomoses and extracorporeal stapling were associated with similar operating times, but the former resulted in fewer intraoperative complications (in particular bleeding). This might be explained by more traction on the bowel, and more technical difficulty in exteriorizing the specimen through the umbilicus, especially in overweight patients[29]. Buchs and colleagues[30] reported an incidence of 3·6 per cent for anastomotic leakage, and identified rectal location, higher ASA score and prolonged operating times as predictors. However, the low incidence of anastomotic dehiscence for rectal procedures (compared with right or left colonic resections) in the present study could be due to selection bias (patients and/or surgeons). Hirabayashi and co-workers[31] emphasized the importance of surgeon experience in 258 consecutive colorectal cancer procedures.

The rate of wound complications was low (2·5 per cent during short-term follow-up), which is identical to previous data for single-port colorectal surgery[20, 32]. The data are further supported by reports of substantial benefits in wound complication rates in single-port colorectal surgery compared with multiport laparoscopic colorectal procedures in patients undergoing surgery for colorectal cancer (4·3 versus 13 per cent)[28], diverticular disease[33] or complex colorectal surgery[34]. In single-port colorectal surgery the transumbilical access does not necessitate muscle transection, thus reducing the risk of bleeding and subsequent haematoma. This, combined with the wound protection offered by the device itself, may be responsible for the low rate of wound complications in the present series. Data from Japan suggest a 19 per cent lower cost for single-port colorectal surgery in comparison to multiport laparoscopic colorectal surgery using commercial single ports[32]. It is possible that the reduced length of hospital stay[17] and reduction in instrument costs for single-port colorectal surgery may potentially lead to an economic advantage, but this was not addressed in the present investigation. This registry study is limited by its non-randomized design and short follow-up period of 30 days after surgery. The assessment of late complications and overall (oncological) outcomes was not an objective of this study.

The large number of surgeons and participating institutions emphasizes the value of this registry study in representing a real-life scenario and reducing selection bias. Increasing patient numbers and long follow-up are current objectives of the ECSPECT registry to provide continued robust evaluation of single-port colorectal surgery. Finally, only well conducted randomized trials will allow a definite conclusion regarding the technical superiority of single-port colorectal surgery over conventional laparoscopy.

Evaluating industry’s role in vaccine access – The Lancet


On March 6, 2017, the Access to Medicine Foundation released its first Access to Vaccines Index, a baseline analysis of industry activities to improve access to vaccines worldwide. Two targets for the Sustainable Development Goals (SDG 3.8 and SDG 3.B) explicitly mention vaccines. Yet, despite the global consensus on the centrality of vaccines to modern health systems, access is highly variable, and in 2016 there were 19 million unvaccinated and under-vaccinated children in the world.

Large image of Figure.

Challenges to universal and sustainable access to vaccines include development of new vaccines, financing, affordability, supply, and implementation. Recognising the vital role of the pharmaceutical industry—as innovators, manufacturers, and suppliers—the index examines the behaviour of eight companies across 69 diseases, 107 countries, and three areas: research and development (R&D), pricing and registration, and manufacture and supply. Although most companies were found to make some consideration of affordability when setting vaccine prices, a more systematic approach is required, particularly for middle-income countries. For the most part, current R&D activities are linked to commercial incentives, with vaccines for seasonal influenza, pneumococcal disease, and human papillomavirus receiving the most attention. Although a third of R&D projects targeted a disease for which no vaccine exists, the report also identified 32 important diseases with no current R&D projects, including yaws, cytomegalovirus, and schistosomiasis. While detailing recent successes in the development of new vaccines for diseases of global health importance (specifically, dengue and malaria), the report highlights the ongoing need to improve vaccines once they reach the market to ensure they address usage needs in resource-limited settings.

Overall, the index paints a mixed picture of industry efforts. But in setting clear benchmarks it shows a path forward for industry to take a conscious and leading role in ensuring that every person, regardless of geography or income, has access to effective and affordable vaccines.

ECSPECT single‐port laparoscopic colorectal procedures.


Laparoscopic colorectal surgery is well established as an alternative to conventional open resection, leading to earlier postoperative recovery, decreased postoperative pain and a shorter hospital stay. Conventionally, invasive laparoscopic colorectal surgery is performed as a multiport surgery, using several trocar sites and a separate incision for specimen extraction; but this has the disadvantage of each incision being a potential site of bleeding, hematoma, infection and incisional hernia, explain the authors of the present pan-European study. Single-port colorectal surgery would offer significant advantages in this respect, but the data on this approach is still insufficient. The multi-institutional European study group (ECSPECT) was established to assess the general feasibility and safety of single-port colorectal surgery, and to provide guidance for patient selection. The study included 1,769 patients (937 with benign conditions, 832 with malignant conditions).

4.2 % of patients required conversion to open surgery; conversions were more than twice as frequent in pelvic procedures involving the rectum than in abdominal procedures (8.1 versus 3.2 %; odds ratio 2.69, P < 0.001). Postoperative complications occurred in 12.7 % of patients, and independent predictors of complications included male sex (P < 0.001), higher ASA grade (P = 0.006) and rectal procedures (P = 0.002). The overall 30-day mortality rate was 0.5 %.

This study shows the broad feasibility and safety profile of the single-port colorectal surgery technique and therefore endorses its general applicability, conclude the authors. Patient selection should be guided by the sex of the patient and his or her risks for conversion and complication.

Multivitamin-Cancer Study Details Tell Different Story


Multivitamin-Cancer Study Details Tell Different Story

Multivitamin-Cancer Study Details Tell Different Story

Contradicting recent studies that showed multivitamin use had little effect upon chronic disease, Harvard researchers have found that multivitamin use over a long period reduces the incidence of many cancers along with mortality.

The researchers conducted a study of male doctors called the Physicians’ Health Study II Randomized Controlled Trial. The study began in 1997 and included 14,641 physicians from the United States. They were 50 years or older at the beginning of the study, and the average age was 64 years old. The study group also included 1,312 men who had previously contracted cancer. The study continued through June 1, 2011. The study was randomized, double-blinded, and placebo-controlled.

While the study found that multivitamin use decreased all types of cancer by 12%, and decreased deaths from all cancers by 12%, these statistics do not tell the entire story. The details by cancer type tell of an even more compelling result of taking multivitamins.

 The all-cancer statistics were significantly skewed by the fact that multivitamin use only reduced the risk of prostate cancer by 2%, while prostate cancer accounted for approximately half of all the cancer cases among the men. There were about 18 cases of cancer for every 1,000 men, and about 9 cases of prostate cancer for every 1,000 men. This means that the reduction in other types of cancer were significantly higher when prostate cancer is removed from the equation.

This is also evidenced that among individual cancers, bladder cancers were reduced by 28% among the multivitamin users, and lung cancer was reduced by 16% among the multivitamin group. By the process of deduction, other cancer reductions would also certainly have been in the 15-25% range. These statistics were not well publicized by the mass media covering the study, some of which indicated that multivitamins reduced cancer incidence by as little as 8%.

Another fact not well publicized is that cancer incidence among men who had a previous history of cancer was 27% lower among those who took multivitamins.

Even the researchers largely dismissed the fact that multivitamin use reduced mortality (death) among the group by 6%. This result was considered “insignificant.”

Obviously, these statements, along with their echoes through the mass media, indicate a bias among researchers and conventional medical publications regarding natural approaches towards cancer prevention – ignoring the fact that the best cure for cancer is prevention.

It is also significant that this study reverses two previous studies that showed no evidence of benefit for chronic diseases in those who use multivitamins consistently. This prompted the following statement with the 2010 Dietary Guidelines for Americans: “For the general, healthy population, there is no evidence to support a recommendation for the use of multivitamin/mineral supplements in the primary prevention of chronic disease.”

Many natural health advocates cried foul to such an announcement, claiming that not only were the study protocols flawed amongst these studies, but the research was seemingly funded by “big pharma.” These claims have thus far remained unproven.

Now we find that multivitamins not only reduce the incidence of the type of chronic disease that strikes the most Americans outside of heart disease (and multivitamins also reduce heart disease risk), but that multivitamins reduce the incidence of death.

And the fact that this study was carried out over such a long period with very strict protocol indicates that the benefits of multivitamin usage are on solid ground.

These results confirm other studies that have found that increasing the intake of fruits and vegetables decreases cancer incidence. However, these studies only showed moderate reductions of some 2-5% in all cancers. But their increased dosages of fruits and vegetables only accounted for 100-200 grams per day.

This is the equivalent to one to two servings a day, while even the most conservative recommendations suggest 5-6 servings a day of fruit and vegetables. A 2007 study by the Centers of Disease Control found that less than a third of American adults eat fruits and vegetables two or three times a day or more – well below the 5-6 servings conservatively recommended.

In other words, adding one or two servings of fruits and vegetables a day is not that likely to make a significant impact upon the nutrient intake of an adult – especially when considering the reduced nutrient levels of most conventional (chemically-fertilized and force ripened) produce. This multivitamin study confirms this reality, along with other studies that have shown decreasing nutrient content among conventional produce during the twentieth century.

As for prostate cancer, reductions in this form of cancer has been linked to other types of phytonutrients, as well as sun exposure.

Antibiotic Shows No Benefit in Asthma Exacerbation


AZALEA trial highlights overuse of antibiotics in asthma attacks

Adding the antibiotic azithromycin to standard treatment for asthma exacerbations in adults had no significant therapeutic benefit in the AZALEA randomized clinical trial.
Findings were consistently negative across different symptom and quality-of-life scores, and treatment with the antibiotic also had no measurable impact on lung function, including FEV1, wrote researcher Sebastian L. Johnston, PhD, of the Imperial College London, and colleagues in JAMA Internal Medicine, published online Sept. 19.

The negative findings contrast with the TELICAST study, also reported by Johnston and colleagues, which demonstrated a positive clinical benefit for another macrolide antibiotic — telithromycin — for asthma exacerbations. Severe adverse reactions — especially liver toxicity — limit the use of this drug to patients with life-threatening infections.
Treatment guidelines, included those recently published by the Global Initiative for Asthma (GINA), do not recommend routine antibiotic use for asthma exacerbations. Yet, in the current trial, the investigators had to exclude nearly half of those screened because they had recently received antibiotics.
The Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) study was conducted to examine the activity of the semisynthetic macrolide antibiotic azithromycin on asthma exacerbations.
“Macrolide antibiotics might benefit asthma exacerbations through antimicrobial activity and/or anti-inflammatory properties; and azithromycin, but not telithromycin, has been shown to have antiviral properties, augmenting production of interferons that are deficiency in patients with asthma,” the researchers wrote.
The study, conducted in the United Kingdom, included adults with a history of asthma for more than six months who were recruited within 48 hours of presenting at one of 31 treatment centers for an asthma exacerbation requiring a course of oral and/or systemic corticosteroids.

Of 4,582 patients screened, just 199 were eligible for randomization, barely half of the 380 the investigators had hoped to enroll. More than 2,000 were excluded because of antibiotic use within the previous 4 weeks.
In addition to usual treatment, for exacerbations, the patients were randomized 1:1 to receive azithromycin at 500 mg daily for three days, or a matched placebo.
Median time from presentation to drug administration was 22 hours (interquartile range 14-28 hours) and exacerbation characteristics were similar in the two treatment groups.
Among the main study findings:
Primary outcome asthma symptom scores averaged 4.14 (SD 1.38) at exacerbation and 2.09 (SD 1.71) at 10 days for the azithromycin group and 4.18 (SD 1.48) and 2.20 (SD 1.51) for the placebo group, respectively
Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference −0.166; 95% CI −0.670 to 0.337). No difference was seen on any day between exacerbation and day 10
No significant between-group differences were shown in quality-of-life questionnaire responses or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score
The researchers noted that recruitment was a major challenge, and that this might have influenced the findings.

“A remarkable finding of this study was the number of patients (n=2,044) excluded because they were already receiving antibiotic therapy for their asthma exacerbation despite treatment guidelines recommending that such therapy not be routinely given,” they wrote.
“This important finding has obvious and worrying implications regarding antibiotic stewardship; in addition, such high antibiotic use rates may also have directly influenced the study outcome because it is possible that patients who might potentially have benefitted from antibiotic therapy for their asthma exacerbations were excluded from the study through already having received them,” the researchers wrote.
In an editorial published with the study, Guy Brusselle, MD, PhD, and Eva Van Braeckel, MD, PhD, of Ghent University Hospital in Belgium, called the overuse of antibiotics in adult patients with acute asthma exacerbations a “striking finding,” given that treatment guidelines recommend against the practice and several Cochrane reviews, including one published last year, have been negative.
Strategies recommended by the authors to reduce antibiotic use in this population included:
Raising awareness among both prescribers and patients
Implementing asthma guideline recommendations against the routine use of antibiotics in asthma exacerbations
Performing studies in primary and secondary care to examine if a subset of patients with asthma exacerbations might benefit from antibiotics.
Validating known biomarkers such as C-reactive protein and procalcitonin; and developing novel biomarkers for guiding targeted antibiotic treatments
“Further study of azithromycin treatment in acute exacerbations of asthma in adults and children in settings of low rates of antibiotic use and stratifying on blood and/or sputum cell counts seems justified,” they concluded.

Smacked children more successful later in life, study finds


Children who are smacked by their parents may grow up to be happier and more successful than those spared physical discipline, research suggests.

 

Children should be provided with the same protection against physical assault as adults.

A study found that youngsters smacked up to the age of six did better at school and were more optimistic about their lives than those never hit by their parents.

They were also more likely to undertake voluntary work and keener to attend university, experts discovered.

The research, conducted in the United States, is likely to anger children’s rights campaigners who have unsuccessfully fought to ban smacking in Britain.

Currently, parents are allowed by law to mete out “reasonable chastisement” on their children, providing smacking does not leave a mark or bruise. These limits were clarified in the 2004 Children’s Act.

But children’s groups and MPs have argued that spanking is an outdated form of punishment that can cause long-term mental health problems.

“While anything more than a light tap is definitely wrong, parents should be allowed the freedom to discipline their children without the fear that they will be reported to police”
Margaret Morrissey

She said: “The claims made for not spanking children fail to hold up. They are not consistent with the data.

“I think of spanking as a dangerous tool, but there are times when there is a job big enough for a dangerous tool. You just don’t use it for all your jobs.”

The research questioned 179 teenagers about how often they were smacked as children and how old they were when they were last spanked.

Their answers were then compared with information they gave about their behaviour that could have been affected by smacking. This included negative effects such as anti-social behaviour, early sexual activity, violence and depression, as well as positives such as academic success and ambitions.

Those who had been smacked up to the age of six performed better in almost all the positive categories and no worse in the negatives than those never punished physically.

Teenagers who had been hit by their parents from age seven to 11 were also found to be more successful at school than those not smacked but fared less well on some negative measures, such as getting involved in more fights.

However, youngsters who claimed they were still being smacked scored worse than every other group across all the categories.

Prof Gunnoe found little difference in the results between sexes and different racial groups.

“If it’s done judiciously by a parent who is normally affectionate and sensitive to their child, our society should not be up in arms about that. Parents should be trusted to distinguish this from a punch in the face.”
Aric Sigman

The findings were rejected by the National Society for the Prevention of Cruelty to Children, which has fought to ban smacking.

A spokesman for the charity said: “The NSPCC believes that children should have the same legal protection from assault as adults do.

“Other research has shown that smacking young children affects their behaviour and mental development, and makes them more likely to be anti-social.”

However, Parents Outloud, the pressure group, welcomed the research, saying parents should not be criminalised for mild smacking.

Its spokeswoman, Margaret Morrissey, said: “It is very difficult to explain verbally to a young child why something they have done is wrong.

“A light tap is often the most effective way of teaching them not to do something that is dangerous or hurtful to other people – it is a preventive measure.

 

“While anything more than a light tap is definitely wrong, parents should be allowed the freedom to discipline their children without the fear that they will be reported to police.”

Aric Sigman, a psychologist and author of The Spoilt Generation: Why Restoring Authority will Make our Children and Society Happier, told the Sunday Times: “The idea that smacking and violence are on a continuum is a bizarre and fetishised view of what punishment or smacking is for most parents.

“If it’s done judiciously by a parent who is normally affectionate and sensitive to their child, our society should not be up in arms about that. Parents should be trusted to distinguish this from a punch in the face.”

Previous studies have suggested that smacking children can lead them to develop behavioural problems such as being more aggressive.