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• Effect of multiple daily insulins versus
  continues subcutaneous insulin infusion in
  patient with diabetic patient systemic review
  and meta-analysis
• Prepared By Shimelis Engida
• ID No .GSR/6186/14
• Adviser- zelalem Tilahun (BSc .MSc. asst prof)

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Content

• Introduction
• Objective
• Method
• Result
• discussion
• Limitation
• Conclusion
• Reference

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Introduction

• Diabetes mellitus, is a collection of metabolic
  illnesses
• The diverse an aetiology includes abnormalities
  in insulin production, insulin action, or both.
• Characterized by the development of
  hyperglycaemia in the absence of therapy.
• Diabetes long-term consequences include
  retinopathy, nephropathy, and neuropathy.

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Conti..

• Diabetes also increases the risk of various
  illnesses such as cardiac, peripheral arterial,
  and cerebrovascular disease, cataracts,, and non
  alcoholic fatty liver disease
• Diabetes mellitus (DM) has become more prevalent
  worldwide.
• Diabetes affected roughly 463million persons aged
  20 to 79 worldwide in 2019, resulting in an
  estimated 1.5 million fatalities.

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Conti..

• By 2045, this figure is predicted to climb to 700
  million.it accounts for at least 727 billion in
  health-care costs, accounting for 12 of total
  adult spending.
• It is now well established that the serious
  microvascular complications of diabetes are
  linked to the duration and severity of high blood
  sugar
• The risk of developing complications of type 1
  diabetes (T1D) is related to glycaemic control
  and is reduced in patients by the use of
  intensive insulin treatment regimens

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Conti

• multiple daily injections (MDI) ( 4) and
  continuous subcutaneous insulin infusion (CSII).
• Despite a lack of evidence Despite a lack of
  evidence that the more expensive treatment with
  CSII is superior to MDI, both treatments are used
  widely within the NHS
• The term sliding scale' refers to increasing the
  premeal insulin dose dependent on blood sugar
  levels before the meal. For example, if a
  person's blood glucose level is between 140 mg/dL
  and 180 mg/dL, a short acting typical insulin
  dosage of 4 units insulin would be reasonable

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Conti..

• whereas a blood glucose level between 181 mg/dL
  and 220 mg/dL would require 6 units insulin.
• continuous subcutaneous insulin infusion
  (CSII)(insulin pump therapy) with an external
  pump are prominent ways of intensive insulin
  therapy (IIT)
• MDI therapy included the bolus injection of short
  or rapid-acting
• insulin at each meal, along with long-acting
  insulin once or twice a to its established
  efficacy, improved pump technology

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Conti..

• patient preference. Sometimes patients on CSII
  therapy discontinues it temporarily because of
  pump malfunction, skin problems or physical
  activity.
• During such periods, type 1 diabetic patients
  (T1DM) switching to MDI therapy could continue
• Insulin pumps are wearable medical devices that
  inject rapid-acting insulin in the subcutaneous
  tissue of the abdomen at the almost continuous
  time, by a cannula connected to a disposable
  reservoir of insulin in the pump

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Conti..

• Insulin pump therapy (or continuous subcutaneous
  insulin infusion CSII) in people with type 1
  diabetes (T1D) presents advantages over multiple
  daily insulin injection (MDI) regimens.
• These include improved glycaemic control and a
  reduced rate of hypoglycaemic episodes however,
  real-world data show that, despite using CSII
  with or without continuous monitoring devices,
  only 30 of adults with T1D achieve

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Conti

• These include improved glycaemic control and a
  reduced rate of hypoglycaemic episodes however,
  real-world data show that, despite using CSII
  with or without continuous monitoring devices,
  only 30 of adults with T1D achieve glycated
  haemoglobin (HbA1c) of lt53 mmol /mole (lt7.0)
• Despite this, many clinicians still use sliding
  scale insulin (SSI) regimens.

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Conti

• The medical literature supports the fact that
  sliding scale dosing of insulin is an ineffective
  means to control blood glucose concentrations.
• A better tool for controlling hyperglycaemia is
  clearly needed.
• Conventional sliding scales for insulin infusion
  have been shown to be associated with delay in
  reaching target and increased risk of
  hypoglycaemia and glycaemic variability

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Objective

• The aim of these systemic review and
  meta-analysis
• To compare glycaemic control during treatment
  with continues subcutaneous insulin infusion
  (CSII) versus multiple daily infusion MDI)
  (sliding scale )

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Methods

• This systematic review and meta-analysis were
  reported by Preferred Reporting Items for
  Systematic reviews and Meta-analysis (PRISMA)
  statement guideline for systematic reviews and
  meta-analysis
• guided by PRISMA checklists this review did not
  have a protocol and hence not registered.
• Data sources and searching strategies
• We searched candidate articles using PubMed, Web
  of Science, Cochrane library, Embase, and Google
  Scholar

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Conti..

• Electronic databases were searched using the
  combinations of the following
• key terms and Mesh terms along with the Boolean
  operators (OR, AND)
• The searching was conducted from inception to
  October 28, 2022 sliding scale, multiple daily
  insulin infusion, continuous subcutaneous insulin
  infusion and insulin pump

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Inclusion and exclusion criteria

• We included all articles conducted any age or sex
  suffering from type 1 or type 2 diabetes mellitus
• comparing CSII with traditional injections in
  type 1 diabetes and type 2 diabetes with English
  language
• who were on insulin treatment (excluding pregnant
  women).
• we include adult and paediatric exclude animal
  study and duplicated and study related with other
  than insulin comparison of MDI and CSII

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Data extraction

• A protocol for data extraction was designed by
  the authors and data were extracted independently
  by two authors (SE and ZT).
• Any disagreements were resolved by consensus
  through discussion Data were extracted on the
  name of the first author and types of diabetics
  mallets, year of publication, author, study
  group, CSII regimen, MDI place of study, study
  design, participants, sample size, outcome of
  each article

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Outcome definition

• The mean out came of this systematic review and
  meta analysis efficacy of MDI slide scale and
  continuous subcutaneous insulin infusion by
  evaluated glycaemic control
• if expressed as a percentage of glycated
  haemoglobin (HbA1 or HbA1c), insulin
  requirements, occurrence of severe and mild
  hypoglycaemic episodes

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Assessment of quality of the studies

• Data from each study included were extracted by
  the two independent reviewers.
• the quality of the included studies using van
  Tulder scale. if there were different outcomes,
  we adjusted the discrepancy in the results
  through discussion

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Data analysis and synthesis

• We conducted a meta-analysis using revman. Forest
  plots were used to estimate pooled prevalence
  with a 95 confidence interval (CI) to provide a
  visual summary of the data.
• To evaluate heterogeneity among studies, the
  Cochrans Q test and I square (I2) indices were
  used.
• A significance threshold of p lt 0.05 was applied
  to the heterogeneity (I2).

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Conti..

• At present heterogeneity, a random-effects model
  was used to compute the overall effect.
• regions on the DM patient glycaemic control.
  Meta-regression was also performed to assess the
  sources of the heterogeneity between the studies.

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Results

• Study selection
• From all database searches, 582 records were
  identified. Forty records removed that is
  ineligible, and three records removed with other
  reason and Seventeen duplicates, were removed
  keeping 522 records
• Moreover, 488 records were removed because the
  titles and abstracts are unrelated to the
  outcomes of the review. The remaining 34 are
  selected for retrieval with in these 25 articles
  were removed and 9 full articles were critically
  assessed for eligibility.

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Conti..

• Then, 3 articles were removed, 2 article are not
  full text and the remaining one was clinical
  trial protocol, then we add 3 articles from other
  source, in the end 9 full articles were selected
  and included in qualitative and quantitative
  analysis
• Characteristics of the included studies
• We included 9 RCTs in the systematic review and
  meta-analysis, with 1530 patients, and mean age
  of 38 years. Table 1 shows the summary of all
  included studies, and the detailed summary of
  each study can be found.

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Conti..

• All patients were diagnosed with T1DM, and T2DM
  clinically, and an open-label study design. Seven
  of the included studies were parallel studies and
  two had a crossover design. were considered for
  this review. Except one study Most study studies
  not specified (NS) their short-acting insulin
• types of insulin pump for CSII and MDI
  treatment. For further detailed information on
  the type of insulin and the type of pumps used,
  see Table 1. MDI treatment was compared with
  different CSII regimens,

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Conti..

• All 9 studies included in this analysis reported
  glucose control as the main outcome.
• However, the significant difference disappeared
  in the overall studies are (p0.05).
• Moreover, significant difference was found in
  mean change of HbA1c () (mean difference from
  baseline to end of study) between the patient
  treated with CSII and MDI in the overall analysis
  (WMD-0.02, 97 CI1.02 to 47.01, p0.05,

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Discussion

• Based on the general result of this systematic
  review and meta-analysis, the following
  conclusions can be drawn on CSII therapy in
  patients with type 1 and type 2 diabetes
  mellitus.
• In adult, elderly and young patients with
  diabetes mellitus, CSII treatment in comparison
  to MDI therapy leads to better glycaemic control
  without a rise in hypoglycaemic events and with
  lower insulin requirements.
• CSII can thus be considered a valuable therapy
  option in adult patients with type 1 diabetes
  mellitus. In patients with type 2 diabetes
  mellitus treatment with CSII is better glycaemic
  control

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Conti

• CSII can thus be considered a valuable therapy
  option in adult patients with type 1 diabetes
  mellitus. In patients with type 2 diabetes
  mellitus treatment with CSII is better glycaemic
  control
• when compared with MDI therapy. Also, there was
  no difference in hypoglycaemic events and insulin
  requirements between the two treatments. It can
  therefore be generalized that in patients with
  type 2 diabetes mellitus CSII application is more
  effective than MDI treatment.

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Conti..

• Results from studies investigating patients with
  type 1 diabetes mellitus suggested a beneficial
  effect of CSII therapy compared with MDI therapy
  in terms of glycated haemoglobin,
• but because of the small number of patients under
  investigation and the short duration of the
  included trials, conclusions on adolescent
  patients are less firm than for adult patients
  with type 1 diabetes mellitus.

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Conti..

• There is also no clear information about
  hypoglycaemia in adolescents because of the
  insufficient reporting of such events.
• Due to the very limited data available, no
  meaningful inferences could be drawn on the
  possible effects of CSII treatment in younger
  children.
• Even though this review, bringing together
  evidence for three important patient groups, is,
  to our knowledge, one of the most comprehensive
  on the topic to date, there are some limitations
  warranting caution in interpreting the validity
  of the results.

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Conti ..

• To investigate this heterogeneity several
  sensitivity analyses were performed.
• The positive effect of CSII treatment was
  likewise seen in trials that lasted for less than
  or more than 6 months. Comparing the studies
  according to their design, the result remained
  statistically significant in favour of CSII
  treatment in both parallel and crossover trials.
• While in studies using HbA1c measurements CSII
  treatment resulted in a statistically significant
  lower HbA1c value, in (the older) studies using
  HbA1 to measure glycaemic control the difference
  between the treatment groups was not
  statistically significant..

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• today probably the most commonly used bolus
  insulin type, were used, clear clinically
  relevant superiority was unproven.
• However, none of these sensitivity analyses could
  explain the observed heterogeneity, different
  CSII pumps, etc.)
• It should also be noted that the heterogeneity is
  not so much caused by qualitatively different
  results, but by quantitative differences.
• From these limitations it is clear that the
  results obtained from this meta-analysis have to
  be interpreted cautiously even though they are
  consistent with previously published
  meta-analyses

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Conti..

• In terms of insulin requirements, there is no any
  meta analysis was done because it is not
  relevant, insulin requirement is only a relevant
  outcome for the healthcare system but not
• relevant for the individual patient. In any case,
  a meta-analysis would not have helped interpret
  the data more effectively, due to differences in
  reporting

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Conti

• In addition, even in these studies, where
  short-acting insulin analogues, today probably
  the most commonly used bolus insulin type, were
  used, clear clinically relevant superiority was
  unproven.
• However, none of these sensitivity analyses could
  explain the observed heterogeneity, which is most
  probably caused by a combination of several
  confounding factors (studies dating back to 1982,
  low study quality, different study designs, small
  treatment groups, different CSII pumps, etc.). .

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limitation

• It should also be noted that the heterogeneity is
  not so much caused by qualitatively different
  results, but by quantitative differences
• From these limitations it is clear that the
  results obtained from this meta-analysis have to
  be interpreted cautiously even though they are
  consistent with previously published
  meta-analyses
• In terms of insulin requirements, there is no any
  meta-analysis was done because it is not
  relevant, insulin requirement is only a relevant
  outcome for the healthcare system but not
  relevant for the individual patient. In any case,
  a meta-analysis would not have helped interpret
  the data more effectively, due to differences in
  reporting

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Conclusion

• based on the systemic and meta analysis conducted
  on efficacy of multiple daily insulin and
  continuous subcutaneous insulin infusion in
  patient with diabetics mallitus as a conclusion
  the efficacy of continuous subcutaneous insulin
  infusion is more effective than multiple daily
  insulin so it is preferable to use CSII to
  control hyperglycaemia

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• Appraisal section

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• Critical Appraisal on an article entitled
• Continuous subcutaneous insulin infusion versus
  multiple daily injections in children and young
  people at diagnosis of type 1 diabetes the SCIPI
  RCT
• By shimelis Engida
• Adviser Mr zelalem Tilahun (B.Pharm ,MSc, asst
  prof)

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Outline

• Background and Overview
• Methods
• Results
• The Students Discussion and Conclusions
• EBL Critical Appraisal Checklist

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Background and overview

• Article Title/Citation
• Continuous subcutaneous insulin infusion versus
  multiple daily injections in children and young
  people at diagnosis of type 1 diabetes the SCIPI
  
• Blair J, McKay A, Rid yard C, Thorn borough K,
  Bedson E, Peak M, Didi M, Annan F, Gregory JW,
  Hughes D, Gamble C RCT. Health technology
  assessment. 2018 Aug 31 22.

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• Study objectives
• To compare glycaemic control during treatment
  with CSII and MDI
• to determine safety and effect on blood sugar
  control

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• Background
• The risk of developing long-term complications of
  type 1 diabetes (T1D) is related to glycaemic
  control and is reduced by the use of intensive
  insulin treatment regimens multiple daily
  injections (MDI) ( 4) and continuous
  subcutaneous insulin infusion (CSII). Despite a
  lack of evidence that the more expensive
  treatment with CSII is superior to MDI, both
  treatments are used widely within the NHS.
• Funding Sources
• Funding for this study was provided by the Health
  Technology Assessment programme of the National
  Institute for Health Research.

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Methods

• Study design and methodology
• open-label two-arm multicentre RCT comparing use
  of CSII with use of MDI in children and young
  people aged 7 months to 15 years who were newly
  diagnosed withT1DM
• Open-label randomised controlled trial with an
  internal pilot and 12-month follow-up with 1 1
  web-based
• block randomisation stratified by age and centre.

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Patient selection and enrolment

• Patients were eligible to participate in the
  study if they met the following inclusion
  criteria-
• The patient has newly diagnosed T1D
• The patient is aged 7 months to 15 years.
• The parent/legal representative of the patient
  is willing to give consent for the study.
• The parent/legal representative of the patient
  is able to comply with the treatment regimen and
  study visits

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• Participants with the following characteristics
  were excluded from the trial-
• previous treatment for T1D
• Haemoglobinopathy
• co-existing pathology conditions likely to affect
  glycaemic control
• psychological or psychiatric disorders
• receipt of medication likely to affect glycaemic
  control
• allergy to a component of insulin aspart or
  insulin glargine

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• Outcome measures/endpoints
• The primary outcome was glycosylated haemoglobin
  (HbA1c) concentration at 12 months.
• The secondary outcomes were (1) HbA1c
  concentrations of lt 48 mmol/mol, (2) severe
  hypoglycaemia,(3) diabetic ketoacidosis (DKA),
  (4) T1D- or treatment-related adverse events
  (AEs), (5) change in body mass index and height
  standard deviation score, (6) insulin
  requirements, (7) QoL and (8) partial remission
  rate.
• The economic outcome was the incremental cost per
  quality-adjusted life-year (QALY) gained

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• Statistical analysis
• Primary analysis used the intention-to-treat
  (ITT) principle. A 0.05 level of statistical
  significance and 95 confidence intervals (CIs)
  are used throughout.
• The statistical analysis plan was developed prior
  to analysis and All analyses were conducted using
  SAS software (version 9.2 SAS Institute Inc.,
  Cary, NC, USA).
• SAS and all other SAS Institute Inc. product or
  service names are registered trademarks or
  trademarks of SAS Institute Inc. in the USA and
  other countries. indicates USA registration.

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Result

• Enrolment baseline characteristics
• A total of 293 participants, with a median age of
  9.8 years (minimum 0.7 years, maximum 16 years),
  were
• randomised (CSII, n 149 MDI, n 144) between
  May 2011 and January 2015. Primary outcome data
• were available for 97 of participants (CSII, n
  143 MDI, n 142)

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• Summary of primary secondary outcomes
• The primary outcome measure was glycaemic control
  (HbA1c) concentrations 12 months after diagnosis.
• Secondary outcome Percentage of participants in
  each group with a glycosylated haemoglobin level
  of lt 48 mmol/mol at 12 months after diagnosis at
  the time the SCIPI study protocol was written

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Authors Discussion

• successful therapies that should be embraced and
  encouraged. However, the authors also recognised
  that parents may feel pressurised to allow use of
  CSII in their children, given the strong advocacy
  for CSII therapy from support groups
• some health-care providers. Perhaps most
  importantly, physicians reported social benefits
  of the use of CSII allowing adolescent patients
  to become more independent and reducing parental
  stress around the unpredictable eating habits of
  young children and the need for frequent insulin
  injections.
• The physicians also felt that CSII therapy
  facilitated the physicianpatient relationship.
  In order to fully understand the drivers behind
  the widespread adoption of CSII, tools will need
  to be developed that accurately harness this
  information.

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Conclusions

• In this study, we did not record whether or not
  patients used CSII to its full potential. It is
  possible that enhanced CSII use would have
  resulted in improved glycaemic control and that
  this may be achievable through further education,
  training and support in the community. There may
  be a place for researching these elements of CSII
  use. However, such a package of care is likely to
  require increased investment, and this additional
  cost needs to be considered in the light of the
  health economic data reported in the SCIPI study.
  Very significant improvements in glycaemic
  control would be necessary for CSII to be seen as
  cost effective. Should such a project be
  undertaken, it would be essential to also examine
  the effect of enhanced education and support in
  the community on glycaemic control in children
  treated with MDI

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The Students Discussion and Conclusions

• Study strengths
• Title
• The title was self-descriptive, precise to the
  subject matter and quite clear
• Abstract
• It is well stated and precise and also attractive
  and it includes all information that is
  background, objective
• method results and key word lists

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• Introduction
• The authors explained and addressed the basic
  scientific background in this section.
• They highlighted previously published articles
  and they raised their concerns, gaps, insights
  and rationality for their work
• Method
• The methodology section was well organized. They
  had a clear inclusion and exclusion criterias,
  the measurement of outcome was legitimate for the
  objectives settled and the end points were
  clearly mentioned. The trial was approved by
  Ethical committee and statistical procedure used
  for analysis of data was specific

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• Results
• The data was presented by percentage and several
  tables. Follow up information was well presented
  and they used several tables to present their
  findings.
• Discussion/ Conclusion
• It was well elaborated section of the manuscript.
  The authors compare their findings with several
  other similar studies and they try to indicate
  interesting future study areas. They also had
  indicated their insights and reasonings in this
  section

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• Reference
• The manuscript had one hundreds fifty-eight
  citations
• All of them were well referenced
• Study weakness
• The weakness of the study me be prone for ethical
  valuation and may not get all data in the
  research because the research does not state the
  device and insulin type which use during the
  study and

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Applicability and impact on healthcare providers
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• Additional thoughts/Comments

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Conclusions and Recommendations
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• Acknowledgment

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