My Views on Drug Repurposing Conference

So, the last 3 posts have reported what I heard at the conference, and I thought it appropriate to reflect on this and record my views on what I heard.

Hidden Costs

I think that the most powerful thing was the "hidden costs of rare diseases" from Matt Hammond:

• Psychological

• Time (travelling, seeing professionals etc.)

• Finance (travelling)

• Missing out (on other activities and events)

• Form filling (it seems there a lot of forms in some cases)

• Loneliness (being the only one in your situation)

• The need to plan everything (because of the effects of the disease) 

Matts story was very powerful, and you could feel everyone in the room being affected by the emotional roller-coaster he described. It made me realise the benefits of having a quick and certain diagnosis, and I'm quite pleased I dont have all that uncertainty and delay in getting one.

Drug Repurposing

In terms of drug repurposing, I understand the process that is gone through. I hadn't realised quite the extent of drug re-purposing, and this is done because repurposing is cheaper, quicker and less risky. Although, there doesn't appear to be quite the same incentive to do this as there is for developing a new drug. The main thing to take away is the need to collaborate, most of the papers described that collaboration was needed between the different people involved in the chain. There are several steps:

1) Identify a need.

Firstly, it is necessary to define a need for a new drug. This is where the collaboration between patients, patient groups and clinicians is important. There needs to be sufficient interest in an issue for researchers to look at it, and this is where patient groups can come in very useful by keeping on top of research activities and knowing about patients with condition to (potentially) have a sample of real-world patients who are interested in taking part in research trials.

2) Look for solutions.

With a need in mind it becomes necessary for researchers/clinicians to look for solutions to the need. Several different approaches were described. At one end of the scale the knowledge of the clinician about the need can be used to look through existing information to identify candidates. At the other end of the scale computers are used to search through database libraries of molecules/drugs for candidates. It is a positive that the drug companies/pharma are getting involved with sharing their libraries of molecules/drugs with researchers. 

3) Gathering evidence.

The candidate drugs/molecules then have to be examined to ensure that they are safe and if so, tests and investigations can be made to identify the ones with the greatest potential. If the evidence does not demonstrate improvements in patients then it is necessary to set up a trial.

4) Trials.

Often a trial is needed in order to provide evidence that the drug is safe to use and gives results. Sometimes there will need to be a balance struck between improvements gained and negative side effects. Depending on funding and other constraints the trial may be large or small. Once successful trials are reported, this informs the medical community and the treatment can spread. Issues with trials revolve around getting the right population of patients to take part and their distance from the research centre. Sometimes it is a combination of therapies which gives good results.

Data Sources

I was interested to hear about the different work on data sources, with different tools extracting information from papers in order to allow them to be searched in a database. Two different examples were given, and I particularly like the healx one: https://rareomics.healx.io/disease/spastic-paraplegia-hereditary .

Sharing Results

One thing which came up a few times in presentations was about how it is generally only successful trials which are published/publicised. In terms of drug repurposing it is perhaps useful to see unsuccessful trial results to allow the safety/function of drugs to be evaluated for other purposes.

Funding

Naturally, researchers need to be paid to work, and there is the issue of funding for such work. There is not the same commercial drivers for funding as there are for new drug discoveries, and that is another aspect where collaboration is needed. Often, the patient groups raise money and provide funding, and often deals can be done with the drug manufacturers to get the drugs needed and information about them for trials at a reasonable price (or free). Various research organisations and drug companies are joining forces to be able to run/organise/fund research projects.

Student Essay Competition

One other thing which I felt was really good was the student essay competition. At the conference the awards were presented. You can see about this, and download the essays on the findacure website. http://www.findacure.org.uk/category/news/page/2/ As I write this is on page 2 of their news, but I suspect that will soon enough drop to a later page. Interesting stuff!

Summary

In conclusion I found the day really useful, and thanks to the UK HSP support group for paying for my ticket! There were also lots of interesting people to talk to in the coffee breaks and it was good to find out more about what happens. Many of the companies present at the event were based in Cambridge, which is my home town! I think that the role of patient groups in understanding what research is being done and sharing that information with their members is important, as is feeding back real world experience/problems to the researchers so they can potentially capture some of this in their research design. Social media seems to be a very important resource for promoting and sharing information, and I'm pleased to report what I heard and saw in order to share this information with you.

Drug Repurposing Conference, Part 3, London - 29th Feb 2016

On 29th Feb I had the pleasure of going to the Findacure Drug Repurposing for Rare Diseases conference which was held at the Royal Institution in London.  My notes on this conference will take up a few posts. This is part 3 of 3. Part 1 is here. Part 2 is here.

Dr Jack Scannel of Innogen Institute at the University of Edinburgh talked about the case for user led innovation. Scientists have survivor bias - they over-estimate the performance and nobody hears about the 9 out of 10 failures to get to the success. Nobody knows which drugs will sell well, and nobody knows what new drugs will be used for.

He described a paper by DeMonaco from 2006: The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies http://web.mit.edu/iandeseminar/Papers/Spring2006/Demonaco.pdf. This paper describes a study into new uses identified over 5 years for drugs introduced in 1998.

29 new drugs were introduced in 1998, and of these new uses were found for 22 of them. In total 143 new applications for those drugs were identified, 82 of these were field based discoveries based on looking at the reporting of the studies, and 57 were led by the laboratory. The paper looks at the field discoveries and reported that 60% of the applications were as a result of a clinician understanding the mechanism of the drug, some 11% were serendipitous discoveries, with the remaining 29% found some other way.

Drug repurposing can be for both common and rare diseases. Even with trials for common diseases clinical trials often don't tell enough about the real world populations who might use the drugs. The issue is how to sort out a trial for diseases with a small patient population.

Jacks key points were that:

• User-led innovation should be incentivised
• The would maximise the amount of safe chemicals available
•  The process reduces timescales
• The process reduces the demands for phase 3 clinical trials
• This should improve the ability to track and manage information. 

He observed that often the 2nd, 3rd or 4th use for drugs can be better than the original use.

People can find out about clinical trials at https://clinicaltrials.gov/ct2/home

The last paper of the day was by Dr Victoria Parker at Addenbrookes Hospital, Cambridge.  She talked about repurposing sirolimus for rare mosaic overgrowth disorders. The elephant man has mosaic overgrowth. There is a protein which is working too much, and the objective is to find a drug to turn off the protein.

The drug sirolimus was one example of a potential drug which was shown to work at low concentrations. They set up an open label, uncontrolled, non-randomised pilot trial with 10 patients from the UK. It took over a year to get the trial set up. Victoria described some of the challenges.

As mosaic overgrowth is a rare disease there is a limited overview, and not enough data to statistically justify a randomised controlled trial. The patients were scattered across the UK, so collaboration was needed in the trial design. NHS trusts have no capacity to undertake blood tests, and GPs need approvals to do so. Therefore the trial had to be designed to minimise the study interventions (blood tests), and private sector involvement was needed. 

Funding was the next challenge. The list of costs included: Staff time, a database for the results, the drug itself (and any placebos), shipping costs for the drug, imaging and blood test costs, insurance and pharmacy fees. Pfizer agreed to provide the drug free of charge, the determined that the database could simply be a spreadsheet, and it was cheaper for them to get insurance for 3 separate trials in single locations than a single policy for a multi-centre trial. Overall, the costs were reduced from an initial estimate of £150k down to £60-70k.

Victorias last points were about a revision to the EU Clinical Trials Directive around "low intervention trials" which have minimal additional risk, and therefore "less stringent rules". These come into play from 2018.

LIGHTNING TALKS

There was also a set of lightning talks - each for 5 miutes.

Ravi Jandhyala (Evidence for Access) described that research into treeatments for rare diseases is difficult. Studies have to trade between; Small number of subjects, requirements of randomised controlled trials, high attrition rates and long study durations. Judgement is needed in trial design, and should make use of real world experience, which involves looking at the evidence in the population, the characteristics of the patients and the identification of the patients. Focus on the patient is key.

Dr Julia Ambler (Sparks) outlined their expertise in awarding and managing grants for childrens medical research. They have the greatest chance of making an effort, researchers know where they money comes from, donors know where their money has gone and progress news is shared. Overall they aim to avoid duplication, save time/money and invest in quality research. They also support fundraising activites. http://www.sparks.org.uk/

Dr Alan Rothaul (Re-Pharm) described how it is possible to use a computer model to hunt for rare disease treatment candidates - computer aided chemistry. For any target that is identified it is necessary to understand the biology, and then to look through the database for candidate. They look at the 2D and 3D shapes and the field point representation of the drug and compare it with the target. With a match, a proof of concept is obtained which is the optimised and taken forward for development. He described a case where out of 2500 molecules they had 25 close hits, which resulted in 6 trials, identifying one lead compound, which they are tring to move forwards.

Heather Band (Batten Disease Family Association) described Batten disease and how research into drug repurposing is using zebra fish. She observed that family groups are often the starting point for patient groups.

Jane Reed (Linguamatics) described a text mining tool that uses natural language processing to extract chemical, gene and action information from text. However, she notes that the language used in medical texts if no common and it is difficult to get information out. http://www.linguamatics.com/products-services/about-i2e

Richard Smith (Healx) described an on-line tool which allows people to track rare disease research. There are around 1 million papers published per year, and around 100 thousand mention a rare/orphan disease. The tool aims to understand the hierarchy of the papers, and presents a summary of medical information and allows data to be filtered.  https://rareomics.healx.io/

PANEL DISCUSSION

These are my key points from the panel discussion:

The difference between off-label and approved drugs for the patient is often about reimbursement,

Routes to off label drugs in the UK is either through GP or hospital, but varies throughout the UK.

Randomised Controlled Trials are often not representative of the typical population.

Patient groups are often good at making sure that trials are valid/representative. 

Combination therapies (i.e. taking more than one treatment at once) can be effective.

Randomised Controlled Trials are not necessarily required for orphan drugs.

Drug Repurposing Conference, Part 2, London - 29th Feb 2016

On 29th Feb I had the pleasure of going to the Findacure Drug Repurposing for Rare Diseases conference which was held at the Royal Institution in London.  My notes on this conference will take up a few posts. This is part 2 of 3. Part 1 is here. Part 3 is here.

The next presentation was by Dr Julie Vallortigara from Ataxia UK. Ataxia UK is a patient led research charity. the charity supports patients with a helpline, magazinr and leaflets, it had a network of people in branches, and arranges patient conferences and workshops. The Ataxia specialist centres are in London, Sheffield and Newcastle. The group raises funds to support a number of projects, specifically;

• Improving diagnosis
• Pre-clinical studies
• Clinical trials
• Symptom alleviation

There is collaboration between patient groups. pharma companies, clinicians and specialists. The group organised a conference in 2015 which was attended by 43 people from 20 countries. The conference was aimed at sharing knowledge/information/care/treatment and was viewed as a success.

The group are involved with two different drug repurposing projects. Patients with Friedrich's Ataxia, the most common type, have a mutation in the FXN gene which decreases the production of the protein frataxin. The research is testing if the gene can be switched back on to produce more protein. 

The first is for Nicotinamide or Vitamin B3. This has a good safety profile, and a phase 1 trial of 10 people showed promising results, and was reported in the Lancet (http://www.ncbi.nlm.nih.gov/pubmed/24794816). the next stage is a larger trial and the group have been involved with giving the patient voice to the trial design. They are also providing some funding.

The second is for spinocerebellar ataxia type 3 (SCA3), and a range of drugs have been screened using animal models. There were two hits from the process, one of which was the anti-depressant citalopram, which was shown to improve motor function. The researchers are investigating a human trial with the groups help, and the group are also providing some funding,

The group also promotes; introductions to experts, advice on research, collaboration and funding, talks on ataxia and its impact, a patient registry, and recruitment to trials/studies.

Dr Michele Lufino of Oxford University the spoke next, providing an academic perspective on drug repurposing. He has been involved with the drug repurposing for Friedrich's Ataxia (FRDA). Friedrich's Ataxia gives rise to gait abnormalities, with age of onset 5-20. There are effects on vision, hearing and speech, There is no therapy at the moment and so the research is looking at stabilising the symptoms. They are looking at being able to increase the FXN gene in order to do this.

Dr Lufino reported a collaboration between Pfizer, who have a high quality library of small molecules, Oxford who have disease expertise and models, Imperial who are able to run a trial, UCL who have disease expertise and Ataxia UK who have the patients!

The collaboration between these means that there is a smooth and fast transition between identifying a candidate small molecule from the library to being able to run a trial. They are undertaking high quality science.

The speed is possible because  Friedrich's Ataxia is monogenic - it only affects one gene. Also the endpoint is known and there is knowledge on the cause of the disease.

Dr Lufino also mention the Oxford Rare Disease Initiative, ORDI: http://www.rarediseases.ox.ac.uk/home

Dr Nick Clarke of Pfizer spoke next with an industry perspective. Pfizer are looking to reposition themselves to have a greater involvement with rare diseases. They set up their own Rare Disease Research Unit (RDRU) in 2010, and they have 22 rare disease products on their books. However more recently they set up a Rare Disease Consortium in December 2013 which comprised Pfizer with leading universities, with the aim of making medicines. http://www.rarediseaseconsortium.co.uk/

They issue a call for projects and have one-to-one meetings with the applicants, this then leads to short expressions of interest, and then business plans.

Their first call was for neuromuscular diseases or haematology within certain disease classifications. This resulted in 400 applications. They were confident on 14 of these. which led to 10 plans, and funding for 5 projects.

Pfizer have around 3 million compounds in their library, and they are keen provide access to this to give compounds for research, and they are looking to collaborate with other companies to expand this number.

The process begins with the small molecule library. These are combined with biologics (genetically engineered proteins) and ideas (from the RDC) and converted into gene therapies (using genes to prevent/treat diseases), which can be turned into a product (medicine).

Some diseases have multiple mutations, and it is likely that products developed using the method would be for specific mutations.

Drug Repurposing Conference, Part 1, London - 29th Feb 2016

On 29th Feb I had the pleasure of going to the Findacure Drug Repurposing for Rare Diseases conference which was held at the Royal Institution in London.  My notes on this conference will take up a few posts. This is part 1 of 3. Part 2 is here. Part 3 is here.

The conference was opened by Dr Rick Thompson, one of the scientific officers at Findacure. He outlined some basic drug re-purposing and rare disease information:

• Rare diseases affect some 350 million people worldwide, around 5% of the population.
• Drug re-purposing is taking an existing drug and demonstrating that if effective for a different group of people

When you have an existing drug it has a known safety profile and known side effects. There is a history of human usage and the pathways of action are known. Once an idea for repurposing is identified these factors can reduce the requirements for clinical trials for the new group/population.

When drugs are repurposed there may be changes to the delivery of the drug, the dose of the drug or the formulation of the drug - although new safety data may be required.

Dr David Cavalla of Numedicus and Healx discussed what the opportunities for drug repurposing are.

In summary this process is quicker, cheaper and less risky. He outlined that with conventional drug development for every approved drug that is out there, there is another 23 drugs which have entered pre-clinical trials but not made it that far. The conventional drug development route takes some 4-9 years and costs 1.8 billion, but drug repurposing takes some 1-4 years and costs 0.3 billion.

Some 90% of drugs on the market already have secondary uses, which may be exploiting the same or different mechanisms, and this is an under-exploited area. Computer models can be used to explore if existing drugs have potential other uses.

David gave some well known examples of drug repurposing:

• Aspirin - 1899: Pain - 1970: Myocardial Infarction and Stroke - 2010: Cancer,
• Viagra - Originally: Erectile dysfunction - Now: Pulmonary arterial hypertension

The website http://www.drugrepurposing.info/ contains a database of compounds and lists some 94 examples of drug repurposing. The issue is that there is little commercial impetus to explore these avenues.

David described that Healx is working on drug repurposing with patient charities and big data. They are using big data to compare drug profiles with disease profiles to examine for potential matches. They know that some drugs can have some protective effects, and if these protective effects happen to be useful in a different disease there's a potential match.

Matt Hammond presented from a patient perspective. His daughter has congenital hyperinsulinism (CHI), and he told everyone about the emotional rollercoaster he and his family have been on since her birth. He described in detail the unknowns and the uncertainty around the whole journey, which you can read here: http://www.diseasespotlight.com/rare-disease-hyperinsulinism/. One of the conversations he had with a specialist led to the discussion of trialling a drug or removing her pancreas. This is an example of drug repurposing.

Matt gave a very useful list of the hidden costs of rare diseases:

• Psychological
• Time (travelling, seeing professionals etc.)
• Finance (travelling)
• Missing out (on other activities and events)
• Form filling (it seems there a lot of forms in some cases)
• Loneliness (being the only one in your situation)
• The need to plan everything (because of the effects of the disease) 

This was one of the most useful lists I've seen.

Symptoms Timeline

I'd been meaning for a while to get a page together with a symptoms timeline so that I (and anyone else) can monitor what is going on. I've got a spreadsheet which collates information on a monthly basis, which I then aggregate together on an annual basis. It will be another thing which I update annually.

I am tracking more than is shown in the table, but I'm keeping things simple with information which I perceive to be important first. If other information becomes important then I'll add it then.

You can access this here: http://hspjourney.blogspot.co.uk/p/symptoms-timeline.html

7th and 8th April: Minor update to data following me remembering that I'd not put any of my GP appointments in the data. I've also added a second table showing who my appointments have been with. Overall, there is some information on the timeline which I've not mentioned before:

GP Appointments: There are 3 GP appointments now included, although there may be the odd one or two others which I need to track down.

The first GP appointment was in 2008 to get a referral for the genetic testing. I dont remember when I did this, but I have a record of a telephone discussion with the genetics people in Jan 2009 which must put the appointment with the GP towards the tail end of 2008. I've also put in the last part of my first 'phase', the appointment with the neurologist in Bristol, Dr Hardie, who pointed me in the general direction of Pilates.

My other GP appointments are already noted, to get the referral to the National and for the stress/depression clinic, and then the follow up which got me the bladder medication and onto Physio, Orthotics and the bowel people.

The other "new" information is being a bit more explicit in my recollection of my early symptoms, with headline descriptions for the early decades of my life. I've previously mentioned having difficulties sitting cross legged as a child, but it also occurred to me that as a Scout I also found sitting in a canoe uncomfortable for long periods of time.

The observation for the 2000's came from my wife, who I first met right at the beginning of the decade. She observed that when we first went skiing, 2003, I found it easy to be comfortable in the ski boots whereas she (who normally stands with her knees straight) found it quite uncomfortable. So, another subtle observation to go along with my own observation of tripping on flat surfaces - which I had noted walking up and down Epsom High Street in the late 1990's.

All the other observations are described elsewhere in this blog!

Symptoms update

I realise that I did a symptoms update the other month, but I think that I might be at a corner in terms of symptoms.

General caveat: I've had a few really busy weeks at work, which has meant a few really late nights, so there may be an element of fatigue and/or missing out on some stretches coming into play.

My legs are starting to feel heavier, which means that they are more difficult to move about and perhaps requiring a moment or two more concentration to make each step. Some activities are becoming fractionally more difficult, especially when tired. I also spot that I'm walking more lazily at home with my feet dragging on the floor. I also notice the difference between wearing my orthotics and not doing so (I don't wear shoes at all at home.)

At my physio appointment she asked if I had considered baclofen  (or one of the other similar drugs). We were testing how my walking deteriorates when I am in a rush/tired/stressed etc. Effectively, I might be getting to the point where I need a little more help. Perhaps time for another appointment at the national hospital for neurosurgery.

On this theme, in April i've got a review with both my physio and orthotist to talk about if it is also time for me to get ankle foot orthoses  (AFOs).

On a related theme, i'm also finding that i'm losing pressure with some urinations, so that might be another thing to review at the national.

Quick note whilst I remember (8th April) - back at Christmas I was at a work Christmas do along with some colleagues from the office I used to work in (96-03). As I was walking down the street with one of them he asked if I'd developed a limp. Obviously it means that my gait must be changing a bit.

New research report tool

Quick post:

I've recently found a new tool which may be of use who like reading research papers. I was introduced to this at the rare disease conference I went to on rare disease day. (More on that in another post).

The tool is a website which references the pubmed database, and allows you to search for papers on any (rare disease) topic. HSP is included:

https://rareomics.healx.io/disease/spastic-paraplegia-hereditary

This then gives you the most recent research papers, from 2000, and these are indexed. There are 2 powerful tools included, the ability to search within the results by other search terms, and a set of trends/graphs.


(update 5th April:)

The trends and statistics part shows graphs of;

• The number of papers per year for HSP for the last 10 years - which shows a peak in 2014, following a similar peak in 2009.
• The top 5 genes mentioned in papers in the last 10 years, which shows that the five most common genes are SPG7, HSP90B2P, SPAST, SPG11 and ATL1. There is no particular trend in these, all following lines that are roughly horizontal.
• The top 5 authors of papers in the last 10 years, who are Stevanin G, Santorelli FM, Blackstone C, Durr A, Brice A. Similarly to the genes, this shows roughly horizontal lines indicating that there are no particular trends.

I draw from this that the HSP research is reasonably well established, and that the dominant topics and authors are well established. This data looks similar to my own data analysis, which shouldn't be too surprising as it uses the same data source! It is interesting to note that this tool draws 927 papers from 2000, whereas I have only a few more than this with papers going back over the second half of the 1900's.

The news feed tab can be used to look up specifics, so you could, for example look up papers about "treatments" which it returns 114 papers (today, out of 927 papers) which include the term "theraputics". These can then be filtered using the summaries on the left, for example on "muscle spasticity" which gives 7 papers. Alternatively you can look up particular treatments - baclofen (8 papers), pain (10 papers), depression (3 papers), Botulinum Toxins (5 papers), dalfampridine (1 paper). This works OK, but you have to get the right term - for example "botox" returns zero papers.

Another feature is that you can list the results by "impact", so you can see which papers are regarded as having the greatest impact by looking at the number of times a paper has been referenced by other papers and the impact of the journal in which the paper is published. 

This seems really well put together.

Note to self, I really need to update and re-present my analysis of this data!

2015 Survey Results

It is rare disease day again, and this year on the leap day, 29th February.

I am pleased to publish the results of my third HSP survey which I launched in September 2015. Many thanks are due to the 109 people who gave their time and completed the survey - this wouldn't have been possible without you.

Here is a short version of the results. The full version goes into more detail on modifications made, and I hope that readers can use the information given to help themselves adapt to life with HSP. The full analysis can be found here: 

https://drive.google.com/file/d/0BzEoTkR5HCWhRjMtejZhSGpHSG8/view?usp=sharing&resourcekey=0-pcbblZR9Vb7hu6OrJk7iOA

This post reports a short version of the findings of an on-line survey undertaken between September 2015 and January 2016. 109 respondents with Hereditary Spastic Paraplegia (HSP) completed the survey, predominantly from the USA and the UK. The survey covered modifications at home, depression and quality of life. Respondents also answered questions about their mobility allowing trends to be spotted with level of mobility. Around a quarter of respondents had completed one or both of my previous surveys.

The full version includes further detail on the mobility and change in mobility of respondents, more observations on modifications made around the home, greater detail on depression and quality of life and a set of data looking at the spastic paraplegia rating scale.

  

Mobility Analysis

All 109 respondents gave answers to this question. From the results it is possible to see which mobility aids are the most regularly used. Around two fifths of respondents use walking sticks/poles/crutches/canes, and similarly, around two fifths of respondents use a wheelchair or mobility scooter. FES is the mobility aid used by the least number of people, with a take-up of around 5%.

In the remainder of this paper, whenever “sticks” are referred to as a mobility aid, this term includes poles, crutches and canes. Whenever “frames” are referred to this includes both walking frames and rollators. Whenever “chairs” are referred to this includes both wheelchairs and mobility scooters. Whenever AFO is mentioned it refers to Orthotics and/or AFO.

The results also allow the distribution of respondents within a scale of mobility to be understood. I have devised an “HSP mobility score” which then allows me to cross-reference mobility against the other questions in the questionnaire. The definition of the HSP mobility score is;

0. No mobility effects
1. Can walk without aids but some effects
2. Orthotics/AFO/FES and/or Sticks/Poles/Crutches/Canes some of the time
3. Sticks/Poles/Crutches/Canes and Frame/Chair some of the time
4. Sticks/Poles/Crutches/Canes most of the time
5. Sticks/Poles/Crutches/Canes all of the time
6. Rollator/Walking frame most of the time
7. Rollator/Walking frame all of the time
8. Wheelchair/Mobility scooter most of the time
9. Wheelchair/Mobility scooter all of the time

  Overview of mobility aids used

Mobility Aids Used - Overview:	Respondents	Percentage	Mobility Score
Those without aids	23	21%	0-1
Those who use mobility aids some of the time	20	18%	2-3
Those who use sticks most/all of the time	27	25%	4-5
Those who use frames most/all of the time	22	20%	6-7
Those who use chairs most/all of the time	17	16%	8-9

Modifications Around The Home

Overall, there were 99 respondents who answered these questions. An overview of the data is presented below, noting that respondents may appear in more than one of these categories:

Table 9 – Overview of Modification Data

Situation	Mobility 0-1	Mobility 2-3	Mobility 4-5	Mobility 6-7	Mobility 8-9	Total Answers
Total number of respondents	20	18	24	21	16	99
Zero modifications made	10	6	8	6	1	31
Furniture moved within the property	3	0	2	1	0	6
Have moved to a single storey property	5	2	5	5	7	24
Live on one floor within their property	1	2	0	1	1	5
Plan: Change property in the future	2	2	3	4	2	13
Plan: Stay at current property	3	9	7	6	6	31
Plan: Stay as long as possible	4	1	4	5	1	15

There were 31 respondents who indicated that they had made no modifications to their properties. These fell into two general groups;

• those that had not made modifications yet, and
• those who didn’t need to make modifications because they had moved into an accessible property which meets their needs.

Respondents across all mobility bands have moved into properties which are either single storey or they are able to live on a single storey within their existing property.

Plans to move properties reflect a range of attitudes of people, with some people preferring to stay in their current home and make whatever modifications they need to, with others planning to move properties as the effects of HSP on their lives change. Different respondents gave answers suggesting that moving property would be something which they would expect to do in the near future whilst others were planning to move in the longer term.

The overall conclusion of this appears to be that as HSP progresses modifications will need to be made to properties, and many respondents indicate that living in a single storey dwelling makes life much easier. The requirement to move to a single storey dwelling will depend ultimately on personal situations and preferences and the progression of HSP, and there will be plenty of other factors in any decision to stay or to move house.

There were 22 different types of modifications which were mentioned by more than one respondent. As these questions were free-form answers I have had to make a few assumptions on what respondents have meant in some cases, and therefore there may be a small amount of variance in the data in this table.

Modifications by more than 5 people

Modification	Mobility 0-1	Mobility 2-3	Mobility 4-5	Mobility 6-7	Mobility 8-9	Total Answers
Total number of respondents	20	18	24	21	16	99
Grab rails (all data, in any location)	3	7	8	13	8	39
Ramps (external or internal)	1	2	5	4	5	17
Grab rails (within the shower or bath)	2	5	3	3	1	14
Accessible/raised toilet	2	2	2	2	4	12
Stair lift	0	3	0	3	5	11
Bath seat/shower seat/bath board	2	1	2	2	4	11
Conversion of bathroom to wetroom	2	1	0	3	4	10
Hospital/power/electric/adjustable bed	0	0	1	2	4	7
Making the level of the bed lower	2	0	1	2	1	6
Modifications to the kitchen*	1	0	1	3	1	6

.

I have presented a commentary on each of the most common modifications made, i.e. those with 10 or more respondents, and there is more detail in the full version. The parts of properties that are modified the most after the inclusion of grab rails are the bathroom/toilet with a range of different modifications made. Adjustments to beds are relatively common. Modifications in other parts of properties are made less frequently. This would appear to reflect the importance of different activities – using the toilet and keeping clean are important as is getting sleep.

Grab Rails

Grab rails are by far the most common modifications that are made around homes, and are present in some homes at all levels of mobility. The majority of grab rails are installed in bathrooms/toilets although respondents also included them by doors, in bedrooms, kitchens, hallways, garages and other rooms.

The reasons for installing grab rails fall generally into two groups, one group includes reasons around helping to keep balance and move around, and the other group includes reasons around helping to get up/down in/out off/on from things like showers/baths/chairs/beds and getting up/down stairs. Reasons for installing are often following similar incidents or being increasingly unable to do something.

Advice for others includes “Definitely help to keep you on your feet and preventing falls”, “it is a small step to take but it makes life so much easier”, “Safety is more important [than] decor or vanity”, “more confidence while showering”. Several respondents mention talking to occupational therapists about this.

Ramps

Ramps are also a common modification, again made by people at all levels of mobility. There are two general types of ramps mentioned, the larger scale purpose built external ramp used for access to the property, and smaller portable ramps which may be for use either outside or inside the property.

Whilst many of the respondents include in their reasons for installing ramps that it gives them wheelchair access to parts of their property, other respondents indicated that they have ramps because of their issues getting over/up/down steps when walking. Most of the ramps are used by respondents who rely on mobility aids of one kind or another all or most of the time.

Advice for others includes looking on Amazon to purchase directly and purchasing second hand ramps. “Worth doing provided you can” and “Very good, not too expensive.”

Raised/Accessible Toilets

This modification includes toilets that were described either as raised or accessible and has been made across the full range of mobility. Generally this was described as making it easier to stand up/sit down from the toilet and was installed because people were finding it difficult to do so. Advice for others includes “Really makes a big difference” and “Make sure that the height of the [seat] suits you”.

A couple of respondents who had been having work done on their bathrooms had elected to install a taller toilet in preparation for expected future changes to their mobility.

Stair lift

The stair lift tends to have been installed by respondents who rely more frequently on mobility aids, although a few respondents have had one installed earlier.

Stair lifts are reported as giving access to otherwise inaccessible parts of the property or, installed because it makes access easier to parts of the property by people who have difficulties getting up or down stairs.

Advice for others includes “Best thing I did! I'm not the only one who uses it!”, “Do it- though ugly and expensive my back is better for it” and “It is beneficial if you struggle to get upstairs”. Of those with lower mobility scores, the reasons for installing are “Used a lot of energy and time”, “Assessment by Occupational Therapist” and “to make life easier and safer”.

Bath seat/shower seat/bath board

This modification covers several things. Some respondents describe having a seat, chair or stool in their bath or shower and others describe having a bath board – i.e. a board which spans the bath which you can sit on. This modification has been made by people across the range of mobility.

What is not clear from all of the descriptions is if these seats are fixed to wall/bath or if free standing seats have been added. From the descriptions some clearly are permanent. These are described as helping people keep from falling, prevention of dizziness, helping get in/out of the bath/shower, relieving fatigue. These are installed in showers generally when people are no longer able to stand, or after a fall. Advice for others includes “makes showering much more enjoyable” and “Just do it. It helps so much”

Conversion of bathroom to wetroom, or conversion of bath to shower.

The wetroom modification has been made by a number of respondents across the range of mobility. Some have specifically referred to this modification as a wetroom whereas others have described it as having a shower level with the floor. Where it is not clear if the shower is level with the floor or not I have grouped as “conversion of bath to shower”, and there is some uncertainty here.

The main reason for making this modification is enabling the respondent to shower because getting in/out of the bath has become difficult or impossible. Advice for others includes “It has made bathing so much easier.” “it helps so much”, “Strongly consider keeping a bath as laying in the bath reduces stiffness.” “Bathroom mods are expensive. Get professional advice and plan carefully if you need to modify an existing bathroom.” These comments show that the decision to make this modification may difficult for some.

Modifications Conclusions

There is a wide range of modifications that people have made around their properties and the approach depends heavily on personal preferences. Modifications tend to be made after a change in mobility/symptoms has been noticed, particularly after an incident/accident. Although, some people are planning for future changes in mobility. I asked respondents for the length of time that they have had these modifications, but there is sufficient information from the mobility scores to establish the general pattern.

Frequently the first modifications made are the installation of grab rails within the property, and these are often fitted in the bathroom first. Subsequent modifications are made depending on the rate of progression of HSP. The parts of properties which are modified the most after the inclusion of grab rails are the bathroom/toilet with a range of different modifications made. Adjustments to beds are relatively common. Modifications in other parts of properties are made less frequently.

Some people prefer to make modifications within their existing property whilst others prefer or have to move into accommodation which has been or can be set up to meet their needs. Some people are designing and building their own property to their own specification. Other key factors in modifications and moving home are practicality and affordability.

8) Depression

I included the two question Patient Health Questionnaire-2 (PHQ2 http://www.cqaimh.org/pdf/tool_phq2.pdf and http://www.apa.org/pi/about/publications/caregivers/practice-settings/assessment/tools/patient-health.aspx) in my survey, and followed the scoring given for these questions. 104 respondents completed this part of the survey, and the following table shows the results, by mobility score and by total score:

PHQ-2 Scores

Mobility score	Respondents	Score 0	Score 1 or 2	Score 3 or 4	Score 5 or 6	Percent 1 to 5	Percent 3 to 6	Percent 5 or 6
0 or 1	21	9	7	3	2	57%	24%	10%
2 or 3	19	9	8	0	2	53%	11%	11%
4 or 5	26	7	12	7	0	73%	27%	0%
6 or 7	21	8	4	6	3	62%	43%	14%
8 or 9	17	6	7	3	1	65%	24%	6%
Overall	104	39	38	19	8	63%	26%	8%

Overall this study shows 63% of respondents having some symptoms of depression and 37% without those symptoms. Additionally, it suggests that around one quarter of people with HSP may require further assessment for depression, particularly for those who are using walking frames all or most of the time to get around. Figure 1 shows the results in more detail, giving the split of assessment scores in each mobility band.

Looking at the highest scores, where people have “Little interest or pleasure in doing things” and/or “Feeling down, depressed or hopeless” nearly every day, it is my hypothesis that this seems to occur at the beginning of peoples’ journeys with HSP and at the point where people are beginning to lose the ability to walk. These highest scores are not seen in whose who have accepted the use of walking sticks and are not often in those who have accepted the use of a wheelchair, and perhaps the acceptance of these mobility aids relieves the depression. I repeat, this is just my hypothesis and I accept there is not much to back this up. Interestingly, the three respondents with the most rapid change in mobility in five years score 2, 2 and 3.

As a comparator, According to the World Health Organisation (http://www.who.int/mental_health/management/depression/who_paper_depression_wfmh_2012.pdf) 350million people in the world were affected by depression. The population in 2012, when that was published, was around 7 billion, giving a prevalence of around 5%. It is not clear what those people affected by depression would score using PHQ2.

There is also one paper which estimates the prevalence of depression in HSP in Estonia. The paper is: The prevalence of depression in hereditary spastic paraplegia, by L Vahter, M Braschinsky, S Haldre, K Gross-Paju, published in Clinical Rehabilitation in 2009 (PubMed ID 19561033, DOI 10.1177/0269215509337186). The abstract indicates that the Beck Depression Inventory was used and that, 44% (21/48) had mild, 13% (6/48) moderate and one person revealed severe depression. My interpretation of this study is that around 60% of people with HSP have some form of depression, which I estimate by summing the different percentages together: 44% (mild) + 13% (moderate) + 2% (severe – 1 out of 48) = 59%.

My conclusion is that the responses to this survey show that people with HSP appear to suffer from depression more than the general population. It is not possible to correlate scores between the PHQ2 used here and the Beck Depression Inventory, however, the Estonian study shows around 60% of people with HSP having some form of depression and my results shows that 63% having a score above zero. This may indicate a similar result.

Quality of Life

The next section of the questionnaire looked at respondents’ quality of life. Respondents were asked 3 questions about physical functioning and 2 questions about social functioning from the Patients Like Me Quality of Life survey (https://www.patientslikeme.com/ and  https://www.openresearchexchange.com/public/library/instruments/16/instructions ). In the full survey there are 11 physical functioning questions, 8 mental functioning questions and 5 social functioning questions. The questionnaire is used across many conditions and I selected a few general questions as a sample.

The questions on physical functioning were:

·         How much has your health limited you in accomplishing as much as you would like to?

·         How much has your health limited you in the type of work or other activities you can do?

·         How much has your health limited you in doing your work or other activities?

The questions on social functioning were:

·         Did your physical health interfere with your social activities with family, friends, neighbours or social groups?

·         Did your emotional problems interfere with your social activities with family, friends, neighbours or social groups?

Respondents selected from options which each have a score out of 4, which is multiplied by 25 to covert it to a percentage, and an average is taken. The average score is then ranked as follows:

·         85-100% - Best

·         50-85% - Good

·         15-50% - Bad

·         0-15% - Worst

In total 102 respondents answered this question, and the following results are shown:

The physical functioning results show that over 60% of respondents score good or best when using no mobility aids or when they are used some of the time (mobility score 0 to 3). There are no clear differences between these two mobility bands. Once mobility aids are used most or all of the time (mobility score 4 to 9) the physical functioning score lowers, with around 30% of respondents scoring good or best. Again, there are no clear differences between these three mobility bands. There may be an upturn in physical function for those most affected by HSP, perhaps as they have optimised their lives to their mobilties.

This sample analysis appears to show that a step change in quality of life occurs at the point when mobility aids are needed to be relied on more often.

The social functioning results show that before mobility aids are needed (mobility score 0 or 1) around 90% of respondents score good or best for social functioning. Once mobility aids need to be used (mobility score 2 to 9), the percentage of respondents scoring good or best drops to around 75%.

Within this, the proportion of respondents scoring best drops from 50% with no mobility aids to around 20% when some are needed. Once mobility aids are used the social functioning score does not change significantly, and this sample analysis appears to show that a step change in quality of life occurs at the point when mobility aids are needed.

The conclusion I draw from this is that HSP does affect quality of life and there appear to be two step changes, the first step change is a reduction in social functioning at the point when mobility aids are needed and a step change in physical functioning when mobility aids need to be relied on most or all of the time.

Like this? in other years:
Overview of all my surveys: http://hspjourney.blogspot.co.uk/p/my-on-line-resarch.html
2016: Fatigue, bladder, bowel & information: http://hspjourney.blogspot.co.uk/2017/02/2016-survey-results.html
2014: Medication, exercise & relaxation: http://hspjourney.blogspot.co.uk/2015/02/2014-survey-results.html
2013: Symptoms and misdiagnosis: http://hspjourney.blogspot.co.uk/2014/02/hsp-survey-results.html