MPH Master pieces

Cystic fibrosis - screening couples

Verona offers mutation testing for cystic fibrosis only to affected families; Padua offers it to anyone who asks. This difference has set up a natural experiment into the effects on couples of knowing their carrier status. The result is reported in this paper in JAMA. It's worth a careful read, especially the discussion section. Natural experiments are by definition observational and confounders abound. But this analysis sheds interesting light on reproductive choices by ordinary people.

Preventing adolescent drug use

The past decade has started to see success in efforts to prevent adolescents from doing what comes naturally to them - being delinquent and taking drugs. Here is a trial of 'Communities that care'. The concept was interesting - not a standardised package but a framework for allowing each community to do its own local survey and then set its own priorities. They are however required to choose their interventions from an evidence based menu. All looks good, but note that these are small communities - about 15 000 population, with some barely 2 000.

Next up (but maybe not for another decade or two)  - how to stop teenagers from having sex.

League tables

Now here's an impressive pice of research. What's impressive is that anyone thought to research it, and that the hospitals agreed to participate. The topic is public reporting of performance data, which in the hands of newspapers rapidly turns into hospital league tables.

The trial is based on a belief that public reporting will lead to improvements - a mild version of naming and shaming. Randomised design; the outcome is a 'composite indicator' which is always slightly problematical because different elements may change in different places, but let nothing detract from the excellent effort involved in setting up and running this trial.

In the UK feedback is thought most effective if confidential - a graph of results from all hospitals with a private annotation of "You are here >>". I can't remember any evidence for this practice; I'm certain there has been no RCT.

The most famous and long-running experience of public reporting (for cardiac surgery) is in New York State, where it prompted some low volume surgeons to stop, and some other hospitals to identify and fix problems.

Clean water in California

Even in advanced societies, drinking water may be a hazard - at least to older people. Here is a randomised controlled trial from California. Water filters were installed in homes which had - at least by standard tests - water which was safe to drink.  The study was 'triple' blind and the authors are honest enough to admit that this led to a mix-up.

What we need now is some economics - is this worth doing, given the expense involved?

Event rates in trials

You have to be pretty well informed to spot this kind of problem in a trial. In what looked like a good trial, subjects had a suspiciously low rate of myocardial infarct. So maybe the triallists failed to capture a lot of data. I guess we'd notice pretty quickly if a paper on smoking reported a prevalence of 3% (or 80%), but it's much more difficult in clinical trials. We have to rely on commentaries or correspondence columns.

 Moral - read the correspondence! If you read electronically, most journals now have a link to commentaries / readers' responses / commentaries. You should certainly be wary of journals with none of these features.

Sudden infant death

I haven't seen much written about sudden infant death recently but here is a good paper from Bristol. A nice simple case-control design and a clear message.

There was a huge drop in postneonatal death from about 1985 - see this graph. Further reductions, but less dramatic, followed the 1991 'Back to sleep' campaign. Case control studies had shown a problem with babies being placed on their tummies. Cases of sudden infant death were far more likely than controls to have been laid to sleep prone. Hence the 'Back to sleep' campaign. 

You may wonder why anyone would put a baby to sleep on its tummy. The answer is that in the 1960s had shown that very premature babies do badly when placed on their backs. This finding, from intensive care units, was unwsiely - indeed fatally - generalised to all babies as general advice to parents. I guess we'd need a historian to document fully quite how this happened. But for now the moral is clear: when you interpret research, be very careful about the situation to which the research does, and does not, apply.

Autism

Autism in on the increase. Or is it? The diagnostic criteria are pretty vague, and they keep changing. And to ignite this explosive mix, a diagnosis of autism now secures a hefty range of services and benefits.

This paper from California is quite tricky to follow. The basic idea is simple, which is to count how many individuals had a diagnosis of autism added to an existing diagnosis of mental retardation. This is called 'accretion' of an extra diagnosis. Autism and mental retardation (MR) are related because two key features of autism - poor social skills and little speech - would of course also be features of learning disability. Hence in young children they are difficult to tell apart. In California, most people receiving services for autism or MR are tested each year; so the database used has individual information plus individual test scores for the period 1992 to 2005.

The complication arises because in earlier years an IQ test would be done and MR diagnosed, with the extra diagnosis of autism following later; in later years children were more likely given a diagnosis of autism and then not tested for IQ. So a statistical model is needed to estimate how much accretion would have happened if people weren't in later years jumping straight to a diagnosis of autism without any IQ testing.

Another paper, from Australia , is simpler - no modelling involved! The key graph shows prevalence each year from 1983 to 1999 and marks on the graph which years saw the major changes in diagnostic criteria. Note that this paper focusses on autism spectrum disorder - a wider category than the Californian study.

Elsewhere in the same issue of IJE is a paper from Nottingham looking at trends in schizophrenia and other psychotic disorders, based on evidence from three big studies which happen to have been done there around 1978, 1993 and 1997. The incidence of schizophrenia seems to have gone down but other psychoses - especially drug related - have gone up. Overall the proportion of of people using illicit drugs hasn't changed much in this time (up from 22% to 33% in young men from 1994 to 1998) so the authors speculate that illict drugs are stronger than they used to be, or used more heavily.

Surgical mortality

We have known for over 50 years that surgery is safer in some hospitals than others. But we are still plumbing the reasons. Here is a worthy addition to the literature.

A very large database was used, covering 84 730 patients with a wide range of clinical information available to allow for risk adjustment. As expected there was variation in death rates after surgery, from 3.5% in the best quintile to 6.9% in the worst. But interestingly the complication rate was about the same across the quintiles. So the difference is that in the good hospitals, when you get a complication they deal with it. The largest differences were for stroke, deep wound infection and septic shock.

Flu masks

Ontario got hit by SARS so you can assume people there are interested in face masks.

This trial compared the simple surgical masks with the fitted N95. In theory the surgical mask might let a cough or sneeze in through the side, whereas the fitted mask should not. In practice however (always do the trial) there was no difference.

The trial used laboratory confirmed influenza as the outcome. Nurses were randomised to use either the surgical mask or the N95 when caring for patients with acute respiratory symptoms. In both groups about 23% of the nurses caught flu. As the authors say this implies that droplet transmission is not a major route of infection. (It's also a frightening high infection rate once you start to think about a pandemic.)

The trial is called a 'non-inferiority' trial. Don't worry too much about this - it's still a randomised trial with an outcome in two group. The 'non-inferiority' bit affects how the study power is calculated since what you are interested in is the lower confidence interval: we need to be confident that the intervention is no worse (or 'not more than 9% worse') than the control group.

Halfway through the trial H1N1 flu reached Ontario and the health ministry ordered everyone onto the N95. Sometimes politics trumps evidence.

Avoiding CT scans

The temptation to order a CT scan is great indeed when faced with a child, a history of head injury, and frightened parents (with or without their lawyers in attendance). But CT scan carries a heavy radiation dose, and radiation induces cancer. For every 1000 to 5000 paediatric CT of the brain, you get one extra brain cancer, and every year about 150 000 children in the USA have a CT for head injury. All of this info comes from a paper which describes the development and validation of a rule intended to allow a doctors safely and accurately to say that a head injury does not warrant a CT.

This is a model of how to develop and validate a classification: hige database, separate derivation and validation samples etc.

The rule had a negative predictive value of 100% and sensitivity of 100% in children under 2 years old (1176/1176 with no clinically important injury and 25/25 with an injury correctly classified). The equivalent figures for a different rules in patients over two were 3798/3800 and 61/63. Of course even in under 2s the performance is not necessarily perfect, with lower confidence intervals on the 100%s being 99.7% and 86% respectively. So there is room for absolutists to argue that you still need a CT to be absolutely certain.

Hopefully this definitive paper will stop lawyers suing when doctors don't take a CT. (But knowing how lawyers behave in the US, we probably need a lawyer to sue a doctor who did order a CT when the child goes on to develop a brain cancer.)