Use of Microorganisms Metabolic Engineering for Production Optimization of Drugs Review write a “systematic review article” with the same format and shape

Use of Microorganisms Metabolic Engineering for Production Optimization of Drugs Review write a “systematic review article” with the same format and shape as the attached file named Sample. every section should have the standard systematic review article sections like abstract, background, methods, results, discussion and conclusions. and each section should have the standard systematic review article content. for example; for the method section, the research timeline (for example articles used in this review are from 2009-2020), database used, keywords and what type of articles used should be mentioned exactly as it does in the sample file.the 19 reference article files have been attached as well. please use them to write this article. Masnoon et al. BMC Geriatrics (2017) 17:230
DOI 10.1186/s12877-017-0621-2
RESEARCH ARTICLE
Open Access
What is polypharmacy? A systematic review
of definitions
Nashwa Masnoon1,2* , Sepehr Shakib3,4, Lisa Kalisch-Ellett1 and Gillian E. Caughey1,3,4
Abstract
Background: Multimorbidity and the associated use of multiple medicines (polypharmacy), is common in the older
population. Despite this, there is no consensus definition for polypharmacy. A systematic review was conducted to
identify and summarise polypharmacy definitions in existing literature.
Methods: The reporting of this systematic review conforms to the Preferred Reporting Items for Systematic reviews
and Meta-Analyses (PRISMA) checklist. MEDLINE (Ovid), EMBASE and Cochrane were systematically searched, as well
as grey literature, to identify articles which defined the term polypharmacy (without any limits on the types of
definitions) and were in English, published between 1st January 2000 and 30th May 2016. Definitions were
categorised as i. numerical only (using the number of medications to define polypharmacy), ii. numerical with an
associated duration of therapy or healthcare setting (such as during hospital stay) or iii. Descriptive (using a brief
description to define polypharmacy).
Results: A total of 1156 articles were identified and 110 articles met the inclusion criteria. Articles not only defined
polypharmacy but associated terms such as minor and major polypharmacy. As a result, a total of 138 definitions of
polypharmacy and associated terms were obtained. There were 111 numerical only definitions (80.4% of all
definitions), 15 numerical definitions which incorporated a duration of therapy or healthcare setting (10.9%) and 12
descriptive definitions (8.7%). The most commonly reported definition of polypharmacy was the numerical
definition of five or more medications daily (n = 51, 46.4% of articles), with definitions ranging from two or more to
11 or more medicines. Only 6.4% of articles classified the distinction between appropriate and inappropriate
polypharmacy, using descriptive definitions to make this distinction.
Conclusions: Polypharmacy definitions were variable. Numerical definitions of polypharmacy did not account for specific
comorbidities present and make it difficult to assess safety and appropriateness of therapy in the clinical setting.
Keywords: Polypharmacy, Multimorbidity, Comorbidity, Inappropriate prescribing, Aged, Systematic review
Background
Multimorbidity, commonly defined as the co-existence
of two or more chronic health conditions, is common in
the older population [1]. The presence of multiple
chronic conditions increases the complexity of therapeutic management for both health professionals and
patients, and impacts negatively on health outcomes.
Multimorbidity is associated with decreased quality of
* Correspondence: Nashwa.Masnoon@mymail.unisa.edu.au
1
Quality Use of Medicines and Pharmacy Research Centre, School of
Pharmacy and Medical Sciences, University of South Australia, Frome Road,
Adelaide, South Australia, Australia
2
Department of Pharmacy, Royal Adelaide Hospital, North Terrace, Adelaide,
South Australia, Australia
Full list of author information is available at the end of the article
life, self-rated health, mobility and functional ability as
well as increases in hospitalisations, physiological distress, use of health care resources, mortality and costs
[2–4]. Globally, the health burden of multimorbidity is
expected to rise significantly as a result of the growing
number of older people and increasing numbers of
people living with multimorbidity [5].
The use of multiple medicines, commonly referred to
as polypharmacy is common in the older population
with multimorbidity, as one or more medicines may be
used to treat each condition. Polypharmacy is associated
with adverse outcomes including mortality, falls, adverse
drug reactions, increased length of stay in hospital and
readmission to hospital soon after discharge [6–8]. The
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
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Masnoon et al. BMC Geriatrics (2017) 17:230
risk of adverse effects and harm increases with increasing numbers of medications [9]. Harm can result due to
a multitude of factors including drug-drug interactions
and drug-disease interactions. Older patients are at even
greater risk of adverse effects due to decreased renal and
hepatic function, lower lean body mass, reduced hearing,
vision, cognition and mobility [10].
While in many instances the use of multiple medicines or polypharmacy may be clinically appropriate, it
is important to identify patients with inappropriate
polypharmacy that may place patients at increased risk
of adverse events and poor health outcomes. Studies
have suggested a shift towards adopting the term
‘appropriate polypharmacy’ in order to differentiate
between the prescribing of ‘many’ and ‘too many’ drugs
instead of a simple numerical count of medications,
which is of limited value in practice [11, 12]. In order
to make this distinction between appropriate and
inappropriate polypharmacy, the term polypharmacy
needs to be clearly defined. We therefore conducted a
systematic review to explore the definitions of polypharmacy in existing literature. We additionally aimed
to explore whether articles differentiated between
appropriate and inappropriate polypharmacy and how
this distinction was made.
Methods
Data sources and search strategy
The reporting of this systematic review conforms to the
PRISMA (Preferred Reporting Items for Systematic
reviews and Meta-Analyses) checklist.
MEDLINE (Ovid), EMBASE and Cochrane databases were searched between 1st January 2000 and
30th May 2016.
The following search terms (Medical Subject Headings
or MESH and keywords) were used in EMBASE and
MEDLINE (Ovid):
polypharmacy/ (MESH) OR multiple medication*
OR multiple medicine* OR multiple drug* (key
words) OR many medication* OR many medicine*
OR many drug* (key words) (for all articles referring
to polypharmacy) AND.
defin* (key word) or explan* (keyword) (for all articles
defining or explaining polypharmacy).
For the review of the Cochrane database, the term
“polypharmacy” was searched.
The search was limited to primary research articles
which defined the term polypharmacy in any shape
or form, conducted in humans and published in
English between the years 2000 and 2016. Articles
were considered if the abstracts were available in
English and were published or in press. Reference
lists of relevant articles and grey literature were
Page 2 of 10
screened to identify other relevant articles. The
search strategy was developed in consultation with a
librarian specialising in health databases, with a predetermined protocol developed collaboratively with
the authors for methods to search and select relevant articles.
Study selection and data extraction
Articles that met the inclusion criteria and provided a
definition of polypharmacy were included. One author
(NM) conducted the initial database search and primary
screening of article titles and abstracts and articles were
categorised as: relevant, irrelevant or unsure. Three reviewers (NM, SS, GC) discussed the appropriateness of
inclusion of each article classed as relevant or unsure.
Once all relevant articles were identified, one author
(NM) reviewed full texts of all identified articles and extracted the data. A pre-defined data extraction template
was developed by all authors and then applied to ensure
consistent data extraction from each of the identified
studies. Data items extracted included the definitions of
polypharmacy and associated terms such as minor,
moderate and excessive polypharmacy and whether
studies distinguished between appropriate and inappropriate polypharmacy and if so, how this distinction was
made or defined. The definitions of polypharmacy and
associated terms were categorised as: i. numerical only
(using the number of medications to define polypharmacy), ii. numerical for a given duration of therapy or
healthcare setting for e.g. during hospital stay or iii.
Descriptive (using a brief description to define polypharmacy). Once the primary data extraction was complete
all authors reviewed the content analysis for each of the
extracted studies, with data further categorised and
summarised in tables.
Results
A total of 1156 articles were identified and 110 articles
met the full inclusion criteria for this systematic review
[10–119]. Fig. 1 shows a flowchart of study selection according to the PRISMA checklist.
Studies not only defined polypharmacy but also used
associated terms to define the level of polypharmacy;
including minor (8 studies, 7.3%), moderate (1 study,
0.9%), major (12 studies, 10.9%), hyper (2 studies, 1.8%),
excessive (10 studies, 9.1%), severe (1 study, 0.9%),
appropriate (1 study, 0.9%), rational polypharmacy and
indiscriminate prescribing (1 study, 0.9%), persistent (1
study, 0.9%), chronic (1 study, 0.9%), and pseudopolypharmacy (1 study, 0.9%). As a result, a total of 138 definitions of polypharmacy and associated terms were
obtained. There were 111 numerical only definitions
(80.4% of all definitions), 15 numerical definitions which
Masnoon et al. BMC Geriatrics (2017) 17:230
Page 3 of 10
Fig. 1 Study selection flowchart according to PRISMA checklist
incorporated a duration of therapy or healthcare setting
(10.9%) and 12 descriptive definitions (8.7%). Table 1
presents a breakdown of the number of definitions for
each term.
Out of the 110 identified articles, 81 (73.6%) included
only a numerical definition of polypharmacy (i.e. did not
specify duration of therapy or healthcare setting). Nine
articles (8.2%) included numerical definitions of polypharmacy for a given duration of time or healthcare setting and nine articles (8.2%) included descriptive
definitions of polypharmacy. Four articles included two
categories of polypharmacy definitions: two articles
(1.8%) included both numerical only definitions and numerical definitions of polypharmacy for a duration of
time or healthcare setting and two articles (1.8%) included both numerical only and descriptive definitions
of polypharmacy.
Numerical only definitions of polypharmacy in existing
literature
Table 2 shows the various numerical only categorisations
of polypharmacy and associated terms and the number
of studies using these definitions.
There was a wide range of variability in the definitions
of polypharmacy as well as associated terms such as
minor, moderate and major polypharmacy. The most
commonly used term was polypharmacy, but there was
variation with regard to the actual definition of polypharmacy, which ranged from two or more medications
to 11 or more medications [13, 90]. The most commonly
used definition for polypharmacy was five or more medications daily, with 46.4% (n = 51) of studies using this
definition [11, 24–73]. The second most common definition for polypharmacy was six or more medications,
with ten studies using this definition [10, 74–82]. Only
Masnoon et al. BMC Geriatrics (2017) 17:230
Page 4 of 10
Table 1 Breakdown of polypharmacy definitions according to
the category of definition
Table 2 Various numerical only definitions of polypharmacy
and associated terms in existing literature
Term
Numerical Numerical in a
Descriptive Total number
only
given duration
of definitions
of time or setting
Term
Number of
medications
Polypharmacy
81
Polypharmacy
9
9
99
Number of
studies
References
≥2
1
[13]
2 to 9
1
[14]
≥3
1
[15]
3 to 6
1
[16]
Minor Polypharmacy
8
0
0
8
Moderate
polypharmacy
1
0
0
1
Major polypharmacy
11
1
0
12
≥4
6
[17–22]
Hyperpolypharmacy
1
1
0
2
≥ 4 or ≥ 5
1
[23]
Excessive
polypharmacy
8
2
0
10
≥5
51
[11, 24–73]
10
[10, 74–82]
Severe polypharmacy
1
0
0
1
≥6
Persistent
polypharmacy
0
1
0
1
≥7
2
[83, 84]
5 to 9
3
[85–87]
≥9
1
[88]
≥ 10
1
[89]
≥ 11
1
[90]
number of
drug classes
1
[91]
2 to 4
6
[92–97]
2 to 3
1
[98]
0 to 4
1
[99]
Chronic polypharmacy 0
1
0
1
Appropriate
polypharmacy
0
1
1
0
Rational polypharmacy 0
and indiscriminate
prescribing
0
1
1
Pseudopolypharmacy
0
0
1
1

Total number of
definitions according to
category of definition
111
15
12
138
one study defined polypharmacy as the number of drug
classes used by a patient [91].
Minor Polypharmacy
Moderate polypharmacy
4 to 5
1
[98]
Major polypharmacy
≥5
6
[92–95,
97, 100]
Numerical definitions of polypharmacy incorporating a
duration of therapy or healthcare setting
Eleven studies (10.0% of all studies) used numerical definitions of polypharmacy which incorporated a duration of
therapy in the definition and four studies (3.6%) used
definitions of polypharmacy which incorporated a healthcare setting (Table 3). The definitions of polypharmacy involving a duration of therapy, ranged from use of two or
more medications for more than 240 days (‘long term
use’) to five to nine medications used for 90 days or more
[101, 108]. Polypharmacy definitions incorporating a
healthcare setting included the use of five or more medications at hospital discharge, and the use of 10 or more
medications during hospital stay [106, 110].
Descriptive definitions of polypharmacy
Twelve studies used descriptive definitions of polypharmacy (Table 4). Some studies used different wording but
conveyed the same definition of polypharmacy. For example, the definitions “Co-prescribing multiple medications” [113] and “Simultaneous and long term use of
different drugs by the same individual” [77] describe
polypharmacy as the use of multiple medications concurrently. Other studies alluded to a different issue of
medications being appropriate or inappropriate for a
given patient [10, 79, 114–118].
≥6
3
[96, 98, 101]
5 to 9
1
[99]
≥ 11
1
[74]
Hyperpolypharmacy
≥ 10
1
[102]
Excessive polypharmacy
≥ 10
7
[30, 58, 65,
70, 85–87]
≥ 21
1
[74]
≥ 10
1
[99]
Severe polypharmacy
Appropriate and inappropriate polypharmacy
Only seven studies (6.4% of all studies) defined appropriate or rational polypharmacy, or recognised the distinction between appropriate and inappropriate medications
[10, 79, 114–118]. These studies either defined polypharmacy using a brief description only (n = 3) [79, 115, 117]
or used a brief description and polypharmacy tools such
as the Beers criteria and the Medication Appropriateness
Index (MAI) (n = 4 studies) [10, 114, 116, 118]. An
example of a polypharmacy definition which recognised
the use of appropriate and inappropriate medications is
“polypharmacy ranges from the use of a large number of
medications, to the use of potentially inappropriate
medications, medication underuse and duplication” and
“potentially inappropriate medications” [114]. Out of the
two studies defining polypharmacy as “potentially
Masnoon et al. BMC Geriatrics (2017) 17:230
Page 5 of 10
Table 3 Numerical definitions of polypharmacy and associated terms by duration of therapy/ healthcare setting
Term
Number of medications
Number of studies
References
Polypharmacy
≥ 2 for > 240 days (long term)
1
[101]
≥ 5 medications in the same month
1
[103]
> 5 medications for ≥ 90 days
1
[104]
≥ 5 medications in the same quarter of a year
1
[105]
≥ 5 medicines at hospital discharge
1
[106]
5 to 9 medicines on the day of maximum number of prescriptions of the study year
(on the day of the study year when the number of medications prescribed was highest)
1
[107]
5 to 9 medications for ≥ 90 days
1
[108]
5 to 9 medicines during hospital stay
1
[109]
≥ 10 medicines during hospital stay
1
[110]
Major polypharmacy
≥ 10 on the day of maximum number of prescriptions of the study year (on the day
of the study year when the number of medications prescribed was highest)
1
[107]
Hyperpolypharmacy
≥ 10 medications for ≥90 days
1
[108]
≥ 10 medications in the same quarter of a year
1
[105]
≥ 10 medications during hospital stay
1
[109]
Persistent polypharmacy
≥ 5 medications for 181 days
1
[52]
Chronic polypharmacy
≥ 5 medications in 1 month for 6 months (consecutive or not) in a year
1
[111]
Excessive polypharmacy
inappropriate medications”, one study simply mentioned
“potentially inappropriate medications” without further
explanation [79] and the other study included examples
of potentially inappropriate medications from existing
literature such as duplication of medications, drug-drug
interactions, medications used to treat side effects of
other medications and medications which are
unnecessary for a specific patient [10]. Only one study
explicitly defined appropriate polypharmacy, which was
defined as “the optimisation of medications for patients
with complex and/or multiple conditions where
medicine usage agrees with best evidence” [117].
Four studies (3.6%) used polypharmacy tools or
criteria to identify potentially inappropriate medications [10, 114, 116, 118]. The Beers criteria as an
indicator of potentially inappropriate medications
were used in all four (three studies used Beers criteria
2003 and one used Beers criteria 1997) [10, 114, 116, 118].
One study used the Medication Appropriateness Index
(MAI) and the Healthcare Effectiveness Data and
Table 4 Descriptive definitions of polypharmacy and associated terms
Term
Definition
Number of studies
References
Polypharmacy
Patients visiting multiple pharmacies to obtain medications
1
[112]
Coprescribing multiple medications
1
[113]
Simultaneous and long term use of different drugs by the same individual
1
[77]
Polypharmacy definition ranges from the use of a large number of medications,
to the use of potentially inappropriate medications, medication underuse and
medication duplication
1
[114]
Potentially inappropriate medications
2
[10, 79]
Use of multiple medications concurrently and the use of additional medications
to correct adverse effects
1
[115]
Use of medications which are not clinically indicated
1
[116]
More drugs being prescribed or taken than are clinically appropriate in the
context of a patient’s comorbidities
1
[12]
Appropriate polypharmacy
Optimisation of medications for patients with complex and/or multiple
conditions where medicine usage agrees with best evidence
1
[117]
Rational polypharmacy and
indiscriminate prescribing
Rational polypharmacy recognizes legitimate prescribing and indiscriminate
prescribing suggests inappropriate prescribing (the terms “legitimate prescribing”
and “inappropriate prescribing” were not explained)
1
[118]
Pseudopolypharmacy
Patients being recorded as taking more medications than they are actually taking
1
[119]
Masnoon et al. BMC Geriatrics (2017) 17:230
Information Set (HEDIS) [114]. None of the studies
explicitly identified the need to distinguish between
appropriate and inappropriate polypharmacy based on
the pharmacology of medications involved, how they
interact with each other and comorbidities for a
specific patient.
Of the 110 studies included in the review, only one
highlighted the inconsistencies in the definitions of
polypharmacy in the literature. The authors of this
study suggested that polypharmacy be defined as
patients visiting multiple pharmacies which may be
associated w…
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