Weekly Updates #8

Posted on 29 September 2012 by Keith Barrington

Oei JL, Kingsbury A, Dhawan A, Burns L, Feller JM, Clews S, Falconer J, Abdel-Latif ME: Amphetamines, the pregnant woman and her children: a review. J Perinatol 2012, 32(10):737-747.  This review article notes the limited evidence about the perinatal effects of amphetamines, showing for example that there is probably an increase in placental abruption; but this finding may be due to the drug, or may be associated with poorer prenatal care. Similarly for the increased incidence of low birth weight, and we know almost nothing about long term outcomes. With the dramatic increases in amphetamine abuse in many countries, better studies are very much needed.

Morton J, Wong RJ, Hall JY, Pang WW, Lai CT, Lui J, Hartmann PE, Rhine WD: Combining hand techniques with electric pumping increases the caloric content of milk in mothers of preterm infants. J Perinatol 2012, 32(10):791-796. This observational study examined the milk composition of mothers who were combining pump expression of their milk with hand expression. Mothers who hand expressed more than 5 times a day in addition to pumping 8 times a day had more volume of milk, but also a higher calorie concentration. This is not necessarily how things normally happen, as a general rule mothers who produce more volume of milk for their term babies tend to produce milk with a higher water content, and thus lower calorie and protein concentration. In the very abnormal situation of expressing milk for preterm babies this may not always be true, and this study suggests that those women who are capable of following this demanding regime produced milk with more calories (and similar protein). I often tell my residents and fellows that we are fortunate that in nature it is the mothers who provide milk for their babies, if men had to pump their breasts 8 times a day, and then had express themselves in between, there would be a lot more formula fed preterm babies!!! The website of the Lucille Packard Children’s hospital at Stanford, which is the source of this study, have a number of resources for supporting breast feeding of mothers of preterm babies.

Porat S, Amsalem H, Shah PS, Murphy KE: Transabdominal amnioinfusion for preterm premature rupture of membranes: a systematic review and metaanalysis of randomized and observational studies. Am J Obstet Gynecol 2012(0). This systematic review of both RCTs and observational studies suggests that there is quite possibly a major benefit of routine regular amnioinfusion after preterm premature rupture of membranes, and that we should do a definitive large RCT to show for sure whether or not this is true.

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More sweetness, some light?

Posted on 27 September 2012 by Keith Barrington

The latest NEJM has an article addressing an issue that I recently posted about, glucose control in the critically ill. This study was in 980 children less than 3 years of age who had undergone cardiac surgery in 2 centers in the US. They were randomized either to tight glucose control, aiming for 4.4 to 6.1 mmol/l, or standard care. Agus MS, Steil GM, Wypij D, Costello JM, Laussen PC, Langer M, Alexander JL, Scoppettuolo LA, Pigula FA, Charpie JR et al: Tight glycemic control versus standard care after pediatric cardiac surgery. N Engl J Med 2012, 367(13):1208-1219.

Standard care meant according to whatever the attending intensivist thought was a good idea, and only 9 of the controls received insulin. Now one feature of this study is that there were not that many controls who were very hyperglycaemic, about 2/3 of each group were above 6.1 at admission to the cardiac ICU, but most controls gradually came down to normal levels pretty quickly even without insulin. Which meant that the groups received the same total glucose infusion, and the same calories. The article is accompanied by an editorial from Brian Kavanagh, Kavanagh BP: Glucose in the icu — evidence, guidelines, and outcomes. New England Journal of Medicine 2012, 367(13):1259-1260. who points out the hazards of writing guidelines, which sometimes turn out to be based on information later shown to be incorrect, as well as reviewing the current status of glucose control in the critically ill child or adult.

So what does this mean for the preterm? It is important to recognize that the mechanisms of hyperglycemia in the preterm are quite different. There is a relative insulin deficiency due to immature processing of proinsulin by the beta cells, and in addition there is a relative insulin resistance, shown by a failure to suppress glucose production during insulin infusion, this insulin resistance is probably due to an immaturity of the GLUT-4 insulin responsive glucose transporter. There is a good short review by Delphine Mitanchez which describes much of the physiology, and another more extensive (in French) by the same author here.

These factors lead to a much higher incidence of hyperglycemia in the extremely preterm, at much lower levels of glucose intake, which lasts much longer. So, as usual, you can’t extrapolate the results from older patients (even though 20% of the patients were less than 30 days old) to small preterm babies.

What the NEJM study also showed was a very low incidence of hypoglycemia in the intervention group, 3%, showing that you can achieve tight control relatively safely, in this study the intervention group had a continuous glucose monitor, but all the insulin dose decisions were based on a bedside glucose meter the results of which were “entered into a proportional–integral–derivative insulin-dosing algorithm on a Microsoft Excel spreadsheet displayed on a dedicated laptop computer at the patient’s bedside.” I have no idea what that means but it sounds high tech; so I am sure that Proportional Integrative Derivative is what we need!

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Outcomes of Prematurity… Pregnancy!

Posted on 26 September 2012 by Keith Barrington

One very long term outcome study of premature infants has just been published by my colleagues from Sainte Justine: Boivin A, Luo Z-C, Audibert F, Mâsse B, Lefebvre F, Tessier R, Nuyt AM: Pregnancy complications among women born preterm. Canadian Medical Association Journal 2012. Using a linked data base approach, the authors examined what pregnancy complications were recorded among women who themselves had been born prematurely. They found that the more preterm the woman was born the higher the risk of pregnancy complications when she was pregnant herself. The complications examined were pre-eclampsia, gestational hypertension and gestational diabetes. and the risk of having at least one of these increased from 9.6% among women born at term to 17% among the very prematurely (before 32 weeks) born women during their first pregnancy. There are multiple possible explanations for this finding: it could be that there is a genetic component to these complications, and that the mothers of the included women had the same complications, which increased their chances of delivering prematurely. It could be that being born prematurely changes you cardiovascular development, or your insulin resistance profile (see Barker hypothesis).

Anne-Monique Nuyt and her co-workers also found that being Small for Gestational Age increased the same risks, and did so in an additive fashion across the groups of women, term, premature, and very premature.

This very interesting study has much stronger data than other previous attempts to investigate this issue, and includes over 7400 women who were born preterm and then delivered a baby (and 2 controls for each former preterm woman). I don’t think we should include this in our prenatal counselling guidelines! (Even though total disclosure of everything is the expected norm) but I do think it warrants some more thought and more investigation.

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Weekly updates #7

Posted on 25 September 2012 by Keith Barrington

Jain A, Deshpande P, Shah P: Peripherally inserted central catheter tip position and risk of associated complications in neonates. J Perinatol 2012. This retrospective cohort study showed more complications when catheters were mid-clavicular, in terms of infiltration, breakage and leaking, compared to brachiocephalic or SVC or IVC positions.

Sgro M, Campbell DM, Kandasamy S, Shah V: Incidence of chronic bilirubin encephalopathy in canada, 2007–2008. Pediatrics 2012. Even though it is rare, chronic after effects of kernicterus still occur in Canada,  with about 10 cases per year. Unfortunately this study was started 6 months after we published the guidelines for which  I was the primary author that recommended routine screening with structured follow up. Doesn’t seem to have worked! At least not yet.

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Sweet!

Posted on 24 September 2012 by Keith Barrington

Very immature babies often become hyperglycemic during the first few days of life. How to respond (or prevent) this has been uncertain.

One problem in deciding on the best course of action is the multiple possible approaches that need to be compared:

One could: ignore the problem and do nothing directly to the blood sugar; reduce glucose intake; switch the calorie intake to another form; start insulin to prevent the most severe hyperglycemia, with various possible thresholds; or start insulin and aim for a normal blood sugar.

There is no standard approach, but I think that ignoring it isn’t an option, some babies become very severely hyperglycemic and as a result severely hyperosmolar, they occasionally develop osmotic diuresis. However, at what threshold you need to address the issue is quite unclear. Many of us start to react when the blood sugar is significantly elevated, in order to avoid either reducing the calorie intake too much or the risks of hypoglycemia if we start insulin.

Is this the right approach? We really don’t have a good answer in the preterm newborn. Even in adults where there are a number of important studies, the response is not exactly clear. A series of controlled studies from Leuven seemed to show a survival advantage of adults treated aggressively to achieve normoglycemia. This was followed by a pivotal multi-center trial (using a somewhat different protocol) that showed a survival disadvantage to aggressive maintenance of normoglycemia Nearly a 3% excess in mortality in the intervention group. And a few other trials also showing either no effect or a survival disadvantage.

So we come to one of the publications that have triggered this posting, a secondary analysis of that pivotal study, showing that hypoglycemia is a major risk factor for mortality . The NICE-SUGAR Study Investigators. Hypoglycemia and Risk of Death in Critically Ill Patients. New England Journal of Medicine 2012, 367(12):1108-1118. (Risk factor meaning, as usual, a characteristic which is significantly associated with the adverse outcome, not necessarily the cause of the adverse outcome.) This analysis showed that the increased risk of death with hypoglycemia occurred in both groups in the study (in fact the hazard ratio for death was greater in the controls than the insulin group). There is a nice review article accompanying the publication.

One of the other publications that interested me recently was the publication of a standard protocol for insulin therapy in pediatric patients (Chima RS, Schoettker PJ, Varadarajan KR, Kloppenborg E, Hutson TK, Brilli RJ, Repaske DR, Seid M: Reduction in hypoglycemic events in critically ill patients on continuous insulin following implementation of a treatment guideline. Quality management in health care 2012, 21(1):20-28). This before and after study showed much less hypoglycemia when a standard pre-printed protocol was introduced than in the historical controls. (3% compared to 36%).

The final recent paper that this post will refer to is the very well done small trial (n=88) by Jane Alsweiler and Colleagues in Auckland, New Zealand Alsweiler JM, Harding JE, Bloomfield FH: Tight Glycemic Control With Insulin in Hyperglycemic Preterm Babies: A Randomized Controlled Trial. Pediatrics 2012. They randomized very preterm infants of less than 1500 grams birth weight who became hyperglycemic (2 blood sugars more than 8.5 (that’s in modern units: millimoles per litre, for the americans)) to a target blood sugar of 4 to 6 or a target of 8 to 10, the ‘control group’ who were only treated with insulin if they met all of the following criteria: sugar > 10 mmol/L or persistent glycosuria >2+; tolerating <100 kcal/kg per day; >72 hours.    64% of the controls received insulin. So this is really an RCT comparing early to late insulin, and in the control group the authors were trying to get up to 100 kcal despite hyperglycemia, using insulin if they couldn’t get up to 100 kcal and have a blood sugar less than 10. The results showed more hypoglycemic episodes in the tight control group (more than 1/2 had at least one sugar below 2.6) than the controls (but 1/4 the controls still had hypoglycemia), the other differences between the groups were a greater growth in weight and head circumference in the tight control group, and a greater linear growth in the controls.

If I try to put this in the context of other literature (which is one big reason I write this blog) there are several other trials that have looked at blood sugar management in the preterm. The unsinkable Jack Sinclair (who is supposed to be retired, but you wouldn’t know it from his production of Cochrane Reviews) has co-authored 2 systematic reviews, one of prevention of hyperglycemia, the other of treatment. As for prevention of hypoglycemia, the only studies of insulin therapy appear to be the 2 trials of low dose routine insulin infusion accompanied by 20% glucose by Kathryn Beardsall (the first being a small pilot trial, the 2nd including nearly 200 babies per group). In neither of those studies was there a clinical benefit found, and there was much more hypoglycemia in the intervention group. The other studies are not very informative for clinically important outcomes.

As for the trials investigating how to treat hyperglycemia, Collins and co-workers compared giving insulin to not doing so, and Meetze compared giving insulin to reducing the glucose intake. Both small trials showed short term advantages of giving insulin, in terms of energy balance, growth, and in one trial reduced infections. Overall survival advantages or other clinically important outcomes are not available from these small studies.

So what makes most sense, given a lack of good evidence about clinically important outcomes? It doesn’t seem that ignoring the sugars is appropriate, infants with very high sugars will be hyperosmolar which opens the blood brain barrier to bilirubin and is a reported risk factor for intra-ventricular haemorrhage. In addition they lose many of their precious calories in the urine. We can reduce the chances of hyperglycemia a little by giving less sugar, but very preterm babies will still become hyperglycemic, and in addition will be less well nourished. If we give more lipid, starting earlier in life we can probably reduce the adverse effects of giving too little calories, but exceeding the basic metabolic requirements (between 70 to 80 kcal/kg/day) as fast as possible is appropriate and an aim to reach 100 calories/kg/day needed for growth is also reasonable. As we do this many very preterm infants will become hyperglycemic, over 6, and many will become very hyperglycemic, over 10. However, trying to prevent this with routine insulin therapy is risky and has not been shown to improve any outcomes.

Treating infants who have become very hyperglycemic with insulin rather than reducing their calorie intake seems to be generally well tolerated, and has growth benefits. Trying to reduce the glucose to normal with insulin is risky in terms of hypoglycemia, and doesn’t seem to do much good, compared to leaving the glucose a little high, say 8 to 10, which might be a better idea. Pre-printed standardised insulin protocols help older children to avoid hypoglycemia, and should be developed for the preterm infant, and trialed to see if we can safely reduce hypoglycemia, and control hyperglycemia.

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CRPs; are they CRaP?

Posted on 19 September 2012 by Keith Barrington

I was taught before asking for a test to always ask myself 2 questions.

What will I do if the result is negative?

What will I do if the result is positive?

The counsel was that if the 2 answers are the same: don’t do the test!

In neonatology we have for many years been trying to find accurate predictive tests for sepsis. In a child with possible clinical signs for sepsis, or a clinical situation that puts them at high risk, then an accurate test that could reduce antibiotic use, might be helpful. At present about 0.8% of cultures taken to rule out early onset sepsis, and 10% for late onset sepsis, are positive. So 99.2% and 90% of antibiotic courses do not help the infant, but select out resistant organisms. What we really need is a test which is rapidly positive, and specific for sepsis. A test which becomes positive the day after the antibiotics are already started, and which is sensitive but not specific is not much use to us.

It seems to be not much use in older children either. A publication in BMC Pediatrics reviewed the use of CRPs in neonates and older children in an acute care hospital. They showed that most of the tests did not have any impact on clinical management, and they cost a great deal of money.

They did not mention the blood loss, but in tiny preterm babies this can be a significant issue for any test we do. A blood test needing 0.6 mL of blood for example (such as the CRP requirement for the lab in our hospital) will often lead to the baby having substantially more than 0.6 mL taken, say 1 mL. And if repeated 10 times during a hospitalisation, lead to a substantial blood loss.

The Health Technology Assessment program in the UK is amazingly productive in many different areas of medicine. They have just published a systematic review of predictive tests for serious infections in children. Unfortunately for my purposes they excluded neonatal studies and patients under 1 month of age. But I am convinced they would find the same thing that they note in their discussion. ‘Both CRP and PCT offer similar diagnostic performance and are superior to WBCs. However, neither CRP nor PCT has sufficient diagnostic value to either confirm or exclude a serious infection, and thus their results must be interpreted in the light of clinical findings’.

Very often when CRP is requested, the answer to the 2 questions posed above will be ‘I will  start antibiotics and wait until the cultures are negative before stopping them’. If that is the case, save the money and reduce the blood loss!

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Homeopathy: not good medicine, not medicine at all!

Posted on 19 September 2012 by Keith Barrington

You might be a little interested in a rapid response I wrote to an article in the BMJ from a family doctor in Glasgow. In that article the author had been touting the benefits of homeopathy as an intervention for patients who had nothing wrong with them! He also made some ridiculous negative comments about actual effective medicine, quoting distorted information from quacks.

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Weekly updates #6

Posted on 19 September 2012 by Keith Barrington

van der Ham DP, van der Heyden JL, Opmeer BC, Mulder AL, Moonen RM, van Beek JH, Franssen MT, Bloemenkamp KW, Sikkema JM, de Groot CJ et al: Management of late-preterm premature rupture of membranes: the PPROMEXIL-2 trial. Am J Obstet Gynecol 2012(0). This is a follow-on to the trial I mentioned a few weeks ago, another  cohort of 200 women were randomized using the same protocol as PPROMEXIL, that is they were eligible if they had ruptured membranes, they were between 34 and 37 weeks and did not go into labour within 24 hours of membrane rupture (so some 17% of them ruptured before 34 weeks then were randomized when they passed 33 6/7. The were either induced or allocated to expectant management. They confirmed no differences in any outcome between groups. The expectant managament group only gained about 3.5 days of pregnancy on average. The authors also updated a meta-analysis of all similar trials in the discussion section (a practice that should be encouraged) which confirms no differences in neonatal sepsis or other outcomes.

Medeiros LF, Souza ACd, Souza Ad, Cioato SG, Scarabelot VL, Caumo W, Fernandes LC, Torres ILS: Fentanyl administration in infant rats produces long-term behavioral responses. International Journal of Developmental Neuroscience 2012, 30(1):25-30.
This is a bit concerning. 1 dose of fentanyl or ketamine to rats on day 14 of life led to behavioural changes that persisted into adulthood. Don’t know what that means for our babies, but we need to continue collecting data.

The latest issue of the Australian pediatric journal Paediatrics and Child Health has a number of interesting and well written pieces. (I am glad the Aussies know how to spell, unfortunately I keep forgetting, too long in North America I guess…must remember…oedema… haemoglobin…paediatrics….)  Nick Evans’ review of the therapy of PDA, Peter Dargaville and David Tingay’s review of lung protective ventilation, and Colm O’Donnel (who has outdone himself with the title of his review of neonatal resuscitation, I don’t know any other quotes of David Bowie songs in the neonatal literature)  Turn and face the strange – ch..Ch..Ch..Changes to neonatal resuscitation guidelines in the past decade are all to be particularly recommended.

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Analgesia and co-bedding or kangaroo care

Posted on 11 September 2012 by Keith Barrington

Campbell-Yeo ML, Johnston CC, Joseph KS, Feeley N, Chambers CT, Barrington KJ: Cobedding and Recovery Time After Heel Lance in Preterm Twins: Results of a Randomized Trial. Pediatrics 2012. If I might be permitted a little self-promotion… this new study (which was certainly not my idea, and was accomplished as a result of the efforts of Marsha Campell-Yeo, certainly not mine) is, I think, of very high quality.

There is a lot of talk about Co-bedding of twins, but little reliable data about the effects, benefits or risks. This study was designed to see if co-bedding is analgesic. Now that may seem a strange objective, but we know that kangaroo care is analgesic, whether done by mothers or fathers (another study by Celeste Johnston, Marsha, and Francoise Filion). I thought that just the physical closeness of the other twin could have an effect, by the same mechanisms as kangaroo care, whatever they might be. So we randomized twins to be co-bedded or not, and then examined their responses to  a heel prick that they needed for their medical care.

The primary outcome was not different between study groups, those co-bedded or not. We noted that the pain scores after heel stick were rather low, because all of the babies got sucrose, automated lancets, etc. So although both groups still had a small pain response to the heelstick, we were unable to show any effect of the co-bedding. The main secondary outcome, that is how quickly the babies settled back down to baseline after the intervention, was, in contrast, different between groups, the co-bedded babies recovered significantly more quickly.

The nice thing about this study was that the pain scores (PIPP the premature infant pain profile) increased to  maximum that was quite low (average of about 7) suggesting only mild pain. So in a controlled situation, with the use of good technique and sucrose, pain can be reduced even when doing invasive procedures.

Similarly low scores were reported in another study now available on-line (also from Celeste Johnston and her collaborators) which showed that kangaroo care by mothers is slightly more analgesic than kangaroo care by non-related other women. As you might imagine they had a relatively low rate of consent from the mothers to do the study, I don’t know if they had any trouble getting the volunteers to be the alternate “kangaroos” but I don’t think the nurses in my unit would be too happy giving kangaroo care to the babies during their blood sampling! But maybe I’m wrong.

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A life worth living: myelomeningocele.

Posted on 10 September 2012 by Keith Barrington

Do handicapped persons’ lives have value?

Even asking that question is offensive, at least to me, and I just asked it!

It seems to me that much of the focus of programs of antenatal diagnosis is based on the premise that being ‘handicapped’ is worse than being dead. So we search for anomalies and terminate many pregnancies based on the information that we then give to the parents; information which is strongly influenced by our own prejudices. I am convinced, and there is some supportive evidence, that the prejudices of physicians influence the choices that parents make. We know that most women terminate pregnancy after a diagnosis of trisomy 13 or 18, for example; but when couples are told that the disorder is lethal, and that the rare short term survivor is a ‘vegetable’, is it surprising that so many abort?

Our prejudices as health care providers are not shared by the rest of the population, in particular they are not shared by impaired members of the population. Quality of life studies in children with various impairments have uniformly shown much higher quality of life scores when children are asked themselves about their own life, compared to what health care providers estimate.

Let’s take the example of meningomyelocele. A very thoughtful review article just published in Pediatrics describes how attitudes have changed and continue to change (and need to change further) Pruitt LJ: Living With Spina Bifida: A Historical Perspective. Pediatrics 2012. I am sure that around the world different programs are at different stages of that process. In certain hospitals parents are erroneously told that ‘the quality of life is miserable if they survive’ (a direct quote from a medical dossier) ; whereas in others active treatment is never even considered to be optional except for the rarest, most severe cases. Unfortunately we often see pregnant women referred to our hospital who have already received extremely prejudicial misinformation. Who have been mis-informed about the intellectual disability of children with meningomyelocele, and who have been mis-informed of the discomfort, pain and repeated surgeries that the children need if they are actively treated. Not surprisingly many choose to terminate the pregnancy.

Lets put this straight.

Intellectual ability: infants in the control group of the MoMs study had a mean Bayley 2 MDI of about 87. This is a group of infants who had a fetal diagnosis of meningomyelocele with an upper level between T1 and S1 (almost all were lumbar) who also had hind-brain herniation, they were therefore among the group most severely affected. It is already well known that children with meningomyelocele often have multiple disorders of cerebral development. As well as the abnormality of closure of the neural tube, which is the primary problem, they have ‘abnormalities’ in other parts of brain development. If you do an MRI you will find other disorders of migration, and of cerebral structure. However. Even though the brains are structurally demonstrably different to infants who do not have a neural tube defect, they actually function quite well. So even if you select a group of children with an anomaly which is severe enough to be considered for antenatal surgery, the overall intellectual outcome is quite acceptable, and the large majority of the infants are close to the average of the general population. There are specific difficulties that the children face, but profound intellectual impairment is very rare.

Quality of Life: the health related quality of life of children (and adults) with meningomyelocele is reduced, but not disastrously lower, compared to those without the disorder. Subscales which are most affected by physical limitations are the most severely affected, which is hardly surprising. Other scales much less so. Interestingly there is not much difference between the QoL scores of children who are ambulant and those who are not. A recent Scandinavian study (Bartonek Å, Saraste H, Danielsson A: Health-related quality of life and ambulation in children with myelomeningocele in a swedish population. Acta Paediatrica 2012:no-no) asked parents to complete a QoL questionnaire for their 6 to 17 year old children. This study showed health related QoL scores which were lower than the scores from studies which asked the children themselves; such as the one mentioned below.  Other data note that quality of life of adolescents with spina bifida is much more related to their social interactions, such as by how many good friends they have, than it is by their impairments. (Muller-Godeffroy E, Michael T, Poster M, Seidel U, Schwarke D, Thyen U: Self-reported health-related quality of life in children and adolescents with myelomeningocele. Dev Med Child Neurol 2008, 50(6):456-461) which is probably the same as adolescents everywhere! The scores obtained from this study, which questioned the adolescents themselves, were somewhat lower than a healthy reference group, but not very much lower, and some scores were not statistically significantly different from the reference group.  

Pain: Both pre-op and post-op, children with spina bifida have very little pain. ( Ottenhoff MJ, Dammers R, Kompanje EJO, Tibboel D, de Jong THR: Discomfort and Pain in Newborns With Myelomeningocele: A Prospective Evaluation. Pediatrics 2012.) As the disorder interrupts some or all neural transmission below the level of the lesion, there is little discomfort associated with the actual abnormality.

When this diagnosis is made parents deserve accurate information. They deserve support and help. They deserve to hear the positives and not just the negatives. Annie Janvier hasn’t yet got round to doing her internet survey with parents of children with myelomeningocele (I don’t know if she will, she has about 20 projects on the go at present), but I would bet the responses after early antenatal diagnosis would not be much different to what she found with trisomy 13 and 18. I would wager that most parents who have an antenatal diagnosis before 20 weeks are repeatedly offered termination, and that those who decide against termination feel that they are judged by the medical community.

In contrast, I think that in most centers, once the child is born, active treatment options are usually offered with a positive attitude, and that multidisciplinary support is readily available in most developed countries. In this situation, at least, I think attitudes have changed somewhat. Sixty years ago, babies were often left to die, and parents were told that the infants would never have a life of quality. As the story told by that link proves, such predictions were often wrong. Fortunately, many parents chose not to believe them.

(In response to a comment from a reader, which you can see below, I edited this post on the 20th of September to replace some uses of the term ‘handicap’ with the term ‘impairment’- I however left the term in the introductory part as many physicians use that term, and I wanted the first paragraph or so to catch their attention.)
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