Quality Improvement: The Next Frontier in Neonatology

Quality Improvement: The Next Frontier in Neonatology

The giant leaps in Neonatology may for the most part be over.  So many outstanding research trials have brought us to where we are today.  The major innovations of surfactant replacement, the discovery of nitric oxide and its later use to treat pulmonary hypertension, caffeine for apnea have all changed our field for the better.  Cooling for HIE has certainly changed my practice in that I now truly have no idea what to tell parents after even some of the worst cases of asphyxia as our team has witnessed “miracles”after cooling.  What will come next?  My bet is that we are about to enter the era of Quality Improvement more and more.  Think about the last study you read that had a major change in your practice or better yet made a substantial change in survival or neurodevelopmental outcome.

Tweaking care is where its at.

I like to think of it as fine tuning.  fine-tuningAs the era of the major leaps in care seems to be passing us by what I see more and more are studies looking at how to make further improvements on what we already know.  In some cases such as using higher doses of caffeine may reduce the incidence of apnea further compared to standard dosing while cooling for 96 hours instead of 72 and at lower temperatures after asphyxia may not be such a good idea after all.  There will be some studies that suggest a modification of practice and then others that suggest we should look elsewhere for further improvements.  With all of this evidence coming out in hundreds if not thousands of journals every week it is difficult to keep up and it may be that our focus is in need of a change in direction or at least devoting members of the team to look at something different.

That Focus Is On Quality Improvement (QI)

Before I go on I don’t want to insinuate that I am something that I am not.  I do not have any formal training in QI and consider myself an amateur but I do understand enough to undertake a PDSA cycle and see where it takes me.  pdsaTo me QI is about finding ways to actually make your best practices the best they can be.  Take for example our units goal to minimize needle pokes by carefully examining the usefulness of common tests that we perform.  Add to this the recent implementation of non invasive technology such as transcutaneous bilirubin metres which our evidence suggests can reliably replace a serum sample to screen for those in need of phototherapy.  While I commonly like to praise our team for its ability to critically think about needed bloodwork it was only through the collection of data using audit tools that we discovered we had a problem.  The problem was that the rate of CBC samples that were clotting were unacceptably high at over 30%.  This was compared to another NICU in the same city that had a rate of less than 1/3 that.  The initial reaction since it was trained lab personnel collecting at the low clotting site vs nursing at the high rate site was that the solution was simple.  Just change back to lab personnel (as it used to be) at the high rate site!  Ah but that would create another problem.  Other evidence used to build a care plan for our preterm infants suggested that clustering of care was better for them than poking them at the usual run time of the lab techs so we had a conflict.  How did we solve it?  We resisted our urge for the quick fix and entered into a formal QI project.

How did we do it and what were the results?

It took us four rounds of PDSA cycles but in the end we found a solution that has lasted.  As I write this I learned that one of our two units that had the high rates set a record low this past month of a 4.9% clotting rate even lower than the comparative site that began with a low clotting rate.  It took work and was by no means easy but the dedication of our nurse educator to the task made all the difference.  Fortunately, for those who don’t know where to begin an incredible resource is available from BMJ Quality Improvement who provide a step by step process to carry out your project.  Moreover after using their template for publishing such work, we were able to publish our work which we hope may be of help for other centres that find themselves in a similar situation.  Perhaps the solution might be the same or at least similar enough to try one of our interventions?  The full paper can be found at the end of the post but the trend over time is so impressive that I felt obliged to show you the results.Clotting PDSA Graph Median_Trendline

Why should you care?

Teams spend so much time rolling out new evidence based initiatives.  All the evidence in world won’t help if the intervention isn’t achieving the results you expect.  How will you know unless you audit your results?  You may be surprised to find that what you expected in terms of benefit you aren’t seeing.  By applying the principals of QI you may find you don’t need to look for another treatment or device but rather you simply need to change your current practice.  9780060545789_custom-b5f01806d4ecf9181bfa5dca982f2b0fd22dca4d-s400-c85A little education and direction may be all that is needed.  You may also find to your surprise that what you thought everyone was doing is not what they are doing at all.
Resist the quick solution and put in the time to find the right solution.  As Carl Honore suggests slowing things down may be the best thing for all of us and more importantly the patients we care for.

Link to the full article:

Reducing CBC Clotting Rates in the Neonatal Patient Care Areas

References

  1.  Mohammed S et al. High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial. Eur J Pediatr 2015 Jul;174(7):949-56.
  2. Shankaran S et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial.JAMA 2014 Dec 24-31;312(24):2629-39

 

Can Parental Administered Physiotherapy Lead to Better Outcome in Preemies?

Can Parental Administered Physiotherapy Lead to Better Outcome in Preemies?

I don’t know about your place of work but our centre is busy and by busy I mean our resources and staff are almost always working at full capacity.  There is a shift afoot though in modern Neonatal care to shift some of the responsibility for care to the parents.  You might say it always should have been this way but as with any speciality we grow, learn and evolve over time.

The most recent stage of evolution is the development of the FiCare philosophy.  This is not the first time (and likely not the last) that I will reference this strategy.  For more information on what it is and what it takes to practice this concept you can click on the FiCare website from Mt. Sinai Hospital in Toronto here.  The gist of it though is that with education and support from nursing in particular some of the traditional functions that are carried out by health care staff can be transferred to the parents.  Something as basic as identifying their baby can be a start with progression to providing part of the daily report, participating in handling of their infant during times of stress and performing skin to skin care for many hours a day.  The parents are asked to commit to a significant number of hours per day to make this work and the benefits of having close contact are obvious as well.

Can Physiotherapy Be Taught To Parents?

As someone who has been involved in the FiCare project I took particular interest in an article this past month which in essence is related to the teachings of FiCare.  T. Ustad from Norway and colleagues published the following Early Parent-Administered Physical Therapy for Preterm Infants: A Randomized Controlled Trial.  As someone who values the contribution of our physiotherapists I was curious as to what could be transferred given the demands on an individual PT’s time.  Add to this that during surges when many babies under 29 weeks are born and the number of patients they need to see may become overwhelming.  What if parents though could take over some of this workload?  Well that is what they did in three centres in Norway in a RCT single blinded intervention.

What did they do?

All babies were born < 32 weeks and underwent the intervention between 34 – 36 weeks with final evaluation at 37 week.  Parents were taught to perform 10 minutes of manipulation with the goal of improving postural control, head control, and midline orientation.  Teaching was done through videos, photos, booklets and direct teaching by the PT on day 1 and then on day 2 return demonstration with correction by the PT occurred.

It was single blinded in that the parent and the PT who did the teaching knew of course which baby received what treatment but the PT doing the standardized evaluation after the two week period was over was blind to treatment assignment.  The authors used the TIMP scoring system for spontaneous movements which as it can take up to 30 minutes in some cases may stress the infants so for those a scoring system consisting of half the items was developed called the TIMPSI.  This has beee shown previously to correlate well with the larger more involved test.

Sample size calculations were based on finding a difference at 2 years of 0.5 SD between groups which meant they needed 63 infants to show such a difference. They enrolled 153 but after some withdrew the groups were 63 in the intervention and 76 in conventional care.

On to the results

Just so we are clear, this was only designed to be a two week intervention but it was meant to be twice daily for ten minutes at a time.  Graphically, using the z-scores for the TIMP scores we have the following graph.  Clicking on the highlighted link will tell you more about z-scores but it measures simply how many standard deviations above or below a population mean a score is.

F2.large

So in this case the absolute difference after the two week period with evaluation one week later is 0.42.  This falls short of the 0.5 at two years the sample size calculation was looking for.  As with many differences in outcome the results tend to improve with time.  Think about the CAP study as an example in which those babies who received caffeine initially had better developmental outcome measures than those who did not but by school age there was no longer a differenced. If the difference is less then one needs many more patients to show a difference than the original sample size would allow.  In the end one also needs to think about whether the difference in scores is of statistical interest or if it has true clinical impact.

Some things to consider though

The parents in the intervention group did keep a journal and what they actually did was not what was designed in the study. The average number of sessions per day was only 1.3 with a length of 9 minutes per session.  The goals again were 2 for 10 minutes each.  The second thing to think about is that by looking at the difference in results from this short intervention it is an exciting mental exercise to think about a couple things.  The first is what might the differences look like if the families had been able to do two sessions each per day instead of being closer to 1.  The extra minute may not have made such a difference but the extra session might have.

The next thing to consider is how short a time period this really was.  What if the plan had been rather than only two weeks, providing the intervention till discharge which for some born at 24 weeks might have been a corrected age at 40 – 44 weeks when they finally went home.  Would a much longer exposure have made a bigger difference?

It is always fun to speculate and while I cautioned that the difference seen at two years may narrow further I wonder what the impact on the families will be after the intervention and post discharge.  They were taught a new set of techniques to support motor development.  Would they simply revert back to the control group afterwards or informally continue on which is what I suspect to some degree they would.  The log book doesn’t count the impact of these “extra sessions”.  The authors plan an interim analysis along the way so that will be interesting to see.

What the study does show though and what I think is exciting is that it is not just nursing that can transfer some functions to parents.  Clearly the parents in this study learned something about handling of patients from the perspective of a PT.  I would hope that this study might inspire PTs and other disciplines as the FiCARE approach widens to consider equipping parents with some of their skills sets that are traditionally owned by those specialties alone.  What we are discovering with time is that parents are capable of doing more than we have had them do in the past.  To make it family centred care truly make them part of the team!

 

 

The Art of Doing Nothing

The Art of Doing Nothing

There may be nothing that is harder in medicine.  We are trained to respond to changes in patients condition with a response that more often than not suggests a new treatment or change in management.  Sometimes the best thing for the patient is in fact to do nothing or at least resist a dramatic response to the issue in front of you.  This may be the most common issue facing the new trainee who is undoubtedly biased towards doing something.  Take for instance the situation in which the trainee who is new to the service finding out that their 26 week infant has a PDA.  Their mind races as they digest this information from morning signover.  There is less than 2 hours until they come face to face with their attending who no doubt will ask them the dreaded question.  “What are you going to do about it?”.  When having to choose a path, if they state “I want to sit tight and watch” they fear the thought of the attending thinking they don’t know what to do. Conversely they could stick their neck out and choose to treat with a variety of approaches but then might they be seen as too aggressive?!  The likely path is suggesting treatment but in fact the more I think about it the option of benign neglect may be the best approach or at least one in which if you treat and it doesn’t work the first time you just shrug your shoulders and say “I’ll deal with it till it closes on it’s own”.

This post really is a follow-up to a previous one entitled The Pesky PDA.  A Puzzle After All These Years.  What triggered this writing was another before and after comparison of two periods in which the management of PDAs for a unit took a 180 degree turn.

Know When to Hold Em And No When to Fold Emgambler

This is the essence of the issue for one unit.  Sung SI et al published a paper this month entitled Mandatory Closure Versus Nonintervention for Patent Ductus Arteriosus in Very Preterm Infants.  They describe a before and after comparison of 81 infants from 2009-11 and 97 infants from 2012-14.  All babies were born between 23-26 weeks gestational age.  In the first time period their unit had a mandatory PDA closure policy.  That is they gave one course of indomethacin and if possible a second course followed by surgical ligation.  A significant PDA was defined as one that had a left to right shunt and was at least 2 mm in diameter and the patient had to be ventilated.  Any patient who had been extubated regardless of need for CPAP did not have to have their PDA closed.  In the second time period the group attempted to avoid indomethacin and ligation at all costs and in fact in this cohort none received either.

So What Happened?

In the first time period 52 (64%) received indomethacin but only 29% responded and a full 37/52 (71%) went on to receive surgical ligation.  Of the 29 that did not receive indomethacin due to contraindications they underwent primary ligation for a total of 82% receiving surgical ligation.  The average day of closure for period 1 was 12.9 days.

In period 2 a number of interesting findings occurred. The average day of closure was at 44.2 days.  Five infants were discharged with a PDA with 3 experiencing spontaneous closure after discharge and the remaining infants undergoing transcatheter occlusion.  In period 2 there were more diuretics and fluid restriction employed.  Comparing the two periods for a number of other outcomes reveals some other intriguing findings.

Table 3

Even with such differing approaches there is no difference in mortality, severe IVH, ROP, PVL, NEC or sepsis.  What is different though is the diagnosis of BPD yet there is no difference in total ventilation. In period 2 there is a shift towards more of this ventilation being HFOV less CPAP use at the same time.

What Might It All Mean?

It is retrospective and therefore we cannot be certain that there are not other variables that are not affecting the results that would have had a better chance of being evened out in an RCT.  Having said that it is intriguing that having a PDA has been associated with BPD in the past but in this study having a PDA for a longer time is associated with a reduction in BPD.  We know that longer periods of invasive mechanical ventilation increase the risk of developing BPD so it is intriguing that that there is no difference in mechanical ventilation yet there is more BPD when you are aggressive with the PDA.  You might postulate that the need for surgery leads to greater need for ventilatory support and therefore damages the lungs but the needs for HFOV was higher in the second phase which at least hints that in terms of aggressiveness, Period 2 infants had a tougher go.

The culprit may be the heart.  In period 1 there was a significantly increased rate of myocardial dysfunction and need for inotropes following ligation.  It could well be that left ventricular dysfunction led to pulmonary edema such that in the 24-28 hours after the surgery ventilator requirements were increased and damaged the lung.  The lack of a difference in overall ventilation days supports this possibility.  Looking at the other common risk factors for BPD such as chorioamnionitis and lack of antenatal steroids these are no different between groups.  Although not statistically significant there are more male infants in period 2 which would usually tip the scales towards worse outcome as well.  It does need to be stressed as well that the rate of surgical ligation is higher than any study I have come across so the contribution of the surgery itself to the disparate outcome needs to be seriously considered.

What would I do?

Despite this study and some others that have preceded it I am not at the point of saying we shouldn’t treat at all.  Our own approach is to give prophylactic indomethacin to such babies and then for the most part if a PDA remains treat one more time but at all costs try and avoid ligation.  An RCT sounds like it is in the works though comparing the two approaches so that will certainly be interesting to see.  It is tough to say what the future holds but to any young trainees who are reading this, the next time you are asked what to do about a PDA you are well within your rights to suggest “Maybe we should do nothing”!

 

Is there a magic number for hematocrit prior to surgery?

Is there a magic number for hematocrit prior to surgery?

A 28 week preterm infant now two weeks of age develops bilious emesis and abdominal distension.  An x-ray reveals an intestinal perforation and surgery is consulted. Arrangements are made to go to the operating room for a laparotomy and due to apnea and hypotension the baby is both intubated and placed on dopamine.  The resident on service ensures that blood is available in the operating room and an hour after presentation the baby is found to have a HgB of 102 g/L with a HcT of 35%.

I don’t know about you but if I am then asked whether we should give blood now or in the OR I might say at that level with the degree of illness to give blood or I might say wait till the baby gets to the OR if perhaps they were fairly stable on the support.  article-1321698-0BAA9B22000005DC-712_468x484You the reader might be more convinced of your actions but if I manipulate the numbers a little bit to say 105 g/l and HcT of 37% might you feel different?  What about 110 g/L and 39%?  You get the picture.  Where is that magic cutoff where we say prior to an OR that a baby needs blood or can wait?  In our heads of course we conjure up the equation for delivery of O2 to tissues Cardiac output X (1.39 X HgB X Sat +0.003*pO2) and realize that the delivery of oxygen is critically dependent on HgB level but how much is enough?  The truth is I don’t think we really know but we do a good job of coming up with some markers such as lactate or more recently near infrared spectroscopy to give us an idea of how much O2 the tissues are seeing.

How much HgB does a baby need before surgery?

Although this may seem like something that is well known, the truth is we don’t really know.  We may have an inkling though based on a recent paper entitled Association of Preoperative Anemia With Postoperative Mortality in Neonates by S. Goobie et al. They performed a retrospective review of a US surgical quality database to examine mortality after operations and identified 2764 neonates out of 114395 children who underwent surgery.  Similar to previous studies the neonatal postoperative mortality rate was higher at 3.4% than the rest of childhood at 0.6%.  When examining the effect of low hematocrit prior to surgery they further identified a cutoff of 40% below which the risk of mortality increased.  Of the neonatal group that survived 31% had a preop hematocrit of 40% or more while of those who died 72% had a hematocrit < 40%.

Hematocrit was not the only factor predicting mortality though as ASA class 3 – 5 (an anesthesiology risk score where these scores indicate severe systemic disease or emergencies), weight < 2 kg, preoperative ventilation and inotropic support.  Put simply, sicker small patients have worse outcomes which I suppose should not surprise anyone.

So how do we interpret this data?

One important point that this article does not control for is the specific type of condition that the patient had.  Clearly all conditions of the newborn are not the same as for example an umbilical flap closure of gastroschisis compared to fulminant necrotizing enterocolitis.  The authors do try and control somewhat for this by demonstrating that the ASA categories demonstrate if you have severe systemic disease you are worse off but where does this leave the hematocrit?  The other possible explanation is that the anemia is simply a reflection of the critical nature of the patient.  Sicker patients are more likely to be anemic and also patients who present later are as well.  A baby needing a colostomy for a bowel obstruction diagnosed after birth is likely to have low risk of mortality and also have a normal HgB.  Contrast this with the baby who develops NEC at 3 weeks of age who is likely anemic or close to being so when they present and in the presence of shock and DIC becomes even more so.    Is the low HcT just a proxy for severity of disease?

I suspect for the otherwise well infant who is electively intubated for surgery, having a hematocrit alone below 40% is not dangerous.  What do we do though with the baby who is on inotropes for example.  To truly answer this question we need a randomized controlled trial comparing transfusing patients with a hematocrit below 40% vs choosing a higher threshold of say 50% to say whether it makes a difference.  That doesn’t help us though in the here and now.  This gold standard for studies won’t tell me what to do for a few years but right now I have to decide what to do for a patient in front of me.

Not everyone may agree with me on this but I think in such circumstances I would transfuse based on this publications results.  To the naysayers out there I would suggest that whether I choose to give the blood or not before the operation, they will be getting it after they enter the OR.  Why not give them a boost before they undergo the knife?  It is not a question of whether they will be transfused or not it is a difference in time.

If I have the chance I will “top them up” but what will you do?

IV Intermittent Flushing or Continuous Infusions.  Which is better for longevity?

IV Intermittent Flushing or Continuous Infusions. Which is better for longevity?

As with many things in Neonatology, changes in practice come and go.  Such is the case with how best to manage an IV.  During my career I have seen advocates for both continuous infusions and intermittent flushing.  Sometimes with heparin and at other times none.  The issue at hand is how best to preserve the precious IV.  Based on opinion only I would have said that having a continuous flow through a plastic catheter should help avoid clot formation and prolong the life of an IV but what is the actual evidence to support one method or the other.

Why might flushing be better?

Clotting may not be the biggest issue to contend with.  When I think about the IVs that are “lost” I am more commonly approached by nurses with concerns that the site is looking “red” and ultimately becomes indurated as the catheter extravasates.  Far less common, is a concern that the catheter has simply obstructed or is reading high resistance these days.  While we flush IVs with isotonic saline, infusions of dextrose are both hypotonic and acidic which may lead to endothelial damage.  In theory then phlebitis should be lessened with intermittent flushes but could blockage due to clots still be an issue if there is no flow at the tip and lumen of the catheter?

What does the evidence show?

In 2012 Perez A et al looked at this in their paper Intermittent flushing improves cannula patency compared to continuous infusion for peripherally inserted venous catheters in newborns: results from a prospective observational study. As with the few recent papers out there on the subject, the study was small and performed over one year as an observational cohort. Out of 53 patients with 86 cannula insertions 25 had continuous dextrose infusions vs 28 who received at least one flush with NS per day.  The findings in this study were that the mean cannula patency was 62.1 hr in the continuous group vs 92.8 hrs in the flushing group.  Given the size of the study it might not be too surprising that practice did not change but that is where a more recent study may add some strength.

A more recent paper by Stok and Wieringa adds to this discussion by looking exclusively at the use for durations of antibiotics (Continuous infusion versus intermittent flushing: maintaining peripheral intravenous access in newborn infants).  As with the previous study this was an observational cohort in which a shift in practice occurred from use of continuous 5% dextrose infusions to flushing six times per day with NS through a 24 gauge IV.  The primary outcome was duration of catheter patency but several other important outcomes were followed as well in particular the time required by nursing to deal with IV issues.

A total of 115 newborns were recruited with 98 completing the analysis after excluding some patients.  Of these newborns 71 fell into the continuous infusion vs 62 cannulas in the flushing cohort.  Interestingly the main outcome was found to be no different between groups (55.42 hrs flushing vs 57.48 hrs continuous) regardless of placement site.  Also interesting is that the median number of cannula placements were no different as well.

With respect to complications the results indicate that this is more of an issue with continuous infusions and is shown in the table below.  The differences in complication rates were significant between the two groups.  Consistent with endothelial damage being more common from dextrose infusions, the incidence of phlebitis and infiltration were both higher in the continuous group.  Arguably this was not a blinded study so the diagnosis of phlebitis could be subject to bias but infiltration should have been more objective.

The amount of time nursing spent addressing IV related activities was significantly shorter with 8.8 minutes per shift vs 5.5 minutes in the continuous vs flushing groups respectively.  Statistically significant but perhaps not that clinically relevant.  Then again the extra three minutes of aggravation might be quite significant!

Finally, it may be surprising that the length of IV patency was no different between the groups but the majority of the IVs were utilized for less than 48 hours so one can only speculate what would have happened if a different target population was looked at such as babies being treated with peripheral IVs for 7 days of antibiotics as an example.  Given the differing rates of complications I would think that with longer use a difference in mean durations of patency would in fact present itself.

What does the future hold?

This is hard to say.  Opinions run strong on this topic with most members of the medical team favouring continuous infusions as they “don’t want to lose the IV”.  I suspect the way to truly look at this will not be through a randomized trial but rather a quality project in which a formal PDSA cycle is utilized to first collect our own numbers and then implement a formal change to using flushing only for those who only have an IV for antibiotics.  Certainly something to discuss with our group and perhaps your own.  If you have already done such a project and wish to share the results I would love to hear from you though!

 

 

 

At the Edge of Viability Does Every Day Count?

At the Edge of Viability Does Every Day Count?

Preterm infants born between 22 to 25 weeks gestational age has been a topic covered in this blog before.

Winnipeg hospital now resuscitating all infants at 22 weeks! A media led case of broken telephone.

Is anything other than “perfect practice” acceptable for resuscitating infants from 22 – 25 weeks?

Winnipeg Hospital About to Start Resuscitating Infants at 23 weeks!

I think it is safe to say that this topic stirs up emotions on both sides of the argument of how aggressive to be when it comes to resuscitating some of these infants, particularly those at 22 and 23 weeks.  Where I work we have drawn a line at 23 weeks for active resuscitation but there are those that would point out the challenge of creating such a hard-line when the accuracy of dating a  pregnancy can be off by anywhere from 5 – 14 days.  Having said that, this is what we have decided after much deliberation and before entertaining anything further it is critical to determine how well these infants are doing not just in terms of survival but also in the long run.  In the next 6 months our first cohort should be coming up for their 18 month follow ups so this will be an informative time for sure.

Do Days Matter?

This is the subject of a short report out of Australia by Schindler T et al.  In this communication they looked at the survival alone for preterm infants in a larger study but broke them down into 3 and four-day periods from 23  to 25 weeks as shown below.

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The asterisk over the two bars means that the improvement in survival was statistically significant between being born in the last half of the preceding week and the first half of the next week. In this study in other words days make a difference.  A word of caution is needed here though.  When you look at the variation in survival in each category one sees that while the means are statistically different the error bars show some overlap with the previous half week.  At a population level we are able to say that for the average late 23 week infant survival is expected to be about 30% in this study and about 55% at 24 +0-3 days.  What do you say to the individual parent though?  I am not suggesting that this information is useless as it serves to provide us with an average estimate of outcome.  It also is important I believe in that it suggests that dating on average is fairly accurate.  Yes the dates may be off for an individual by 5 – 14 days but overall when you group everyone together when a pregnancy is dated it is reasonably accurate for the population.

Don’t become a slave to the number

The goal of this post is to remind everyone that while these numbers are important for looking at average outcomes they do not provide strict guidance for outcome at the individual level.  For an individual, the prenatal history including maternal nutrition, receipt of antenatal steroids, timing of pregnancy dating and weight of the fetus are just some of the factors that may lead us to be more or less optimistic about the chances for a fetus.  Any decisions to either pursue or forego treatment should be based on conversations with families taking into account all factors that are pertinent to the decision for that family.  Age is just a number as people say and I worry that a graph such as the one above that is certainly interesting may be used by some to sway families one way or another based on whether the clock has turned past 12 AM.  At 23 weeks 3 days and 23 hours do we really think that the patient is that much better off than at 24 weeks 4 days and 1 hour?