Evaluation of Tools to Assess Symptoms and Symptom Severity in Patients With Medically Unexplained Physical Symptoms: A Systematic Review and Narrative Synthesis

A substantial portion of patients presenting to healthcare settings exhibit physical symptoms lacking clear, demonstrable organic causes. Accurate assessment of symptom severity is crucial for documenting outcomes and establishing treatment efficacy. This systematic review and narrative synthesis aims to provide researchers with insights into available and validated tools for assessing medically unexplained physical symptoms (MUPS). It involved comprehensive searches across electronic databases, including PubMed, Wiley, and Cochrane, adhering to PRISMA and COSMIN guidelines. The study comprised two phases: Phase 1 systematically reviewed tools for assessing MUPS symptoms and severity, while Phase 2 conducted a narrative synthesis of their measurement properties, focusing on validity and reliability. Out of 14,459 records, 191 articles were identified, leading to the recognition of 16 validated tools for assessing MUPS symptoms and severity. Most tools demonstrated excellent internal consistency and structural validity. However, the majority lacked cross-cultural validity. The choice of tools for the assessment of MUPS will assist clinicians and researchers in determining the severity of MUPS and developing a tailored treatment plan to improve the physical and psychological functioning of these patients.


Introduction And Background
A significant number of patients in healthcare settings present with physical symptoms such as fatigue, pain, gastrointestinal issues, and others that have no clear organic cause [1].Such symptoms are known as medically unexplained physical symptoms (MUPS).While some patients have self-limiting mild symptoms, a significant number of cases develop persistent and severe symptoms over time, leading to significant physical and psychological dysfunction [2].
Assessing the severity of symptoms in MUPS patients is vital for their management and research.Several tools have been used worldwide to assess symptoms and symptom severity among MUPS patients.Therefore, knowledge of these tools is crucial for doctors of different specialties treating MUPS patients.
To date, there has been no systematic review that identifies the instruments to assess MUPS patient symptoms and their severity, along with a synthesis of their methodological quality.This systematic review aims to provide researchers with a bird's-eye view of the available and easy-to-use tools.Identifying these tools would assist clinicians and researchers dealing with MUPS in gauging the severity of the problem and developing customized treatment plans to improve the physical and psychological functioning of these patients.

Review Methods
The study's methodology was registered in PROSPERO (ID-363209).The draft of the manuscript followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [3] and the COSMIN checklist [4].The methodology consisted of two phases.Phase 1 included a systematic review of the tools to assess the symptoms and symptom severity of patients with MUPS, followed by Phase 2, which consisted of a narrative synthesis of the measurement properties of the identified tools (validity and reliability).
Symptoms were defined as the physical features for which the patients were seeking help from the practitioner, whereas, symptom severity is defined as the impact of these symptoms on an individual's physical functioning, mental functioning, and general well-being.
Phase 1: systematic identification of the instruments to measure symptom profile in patients with MUPS Literature Search An electronic search on three databases, PubMed, Cochrane, and Wiley, was performed by the authors (AK and NR) to search for the relevant articles published between January 2000 and January 2022.A search string "(MUPS OR MUS OR 'Unexplained physical symptoms' OR 'medically unexplained physical symptoms') AND (questionnaire OR scale OR tool OR instrument)" was used for searching for relevant indexing terms.We also searched for gray literature on the Open Grey database.A lateral search was also carried out using a reference list and cited literature for primary articles.

Inclusion and Exclusion Criteria
The inclusion criteria include studies measuring the symptoms and/or severity of symptoms in patients with MUPS using an assessment.Out of 30 tools identified, only 16 validated tools were included in this review, as the remaining 14 tools were either in some other language or information regarding the validation process was not accessible, with a population >18-60 years of age.
The exclusion criteria include papers that did not mention the outcomes and studies that did not mention the measures used to assess the symptoms and/or severity of symptoms in MUPS patients or used nonvalidated tools or questionnaires.

Study Selection
Two independent reviewers (TK and AK) carried out the title and abstract screening of the articles selected through the keyword search.The remaining articles were then read completely and were categorized as included (meeting inclusion criteria), excluded (not meeting inclusion criteria), and unclear (disagreement after independent review).The disagreement was resolved by third-party adjudication (PR).The selected articles were then included in the PRISMA flowchart for narrative synthesis.

Data Extraction and Synthesis
Two authors (AB and NR) independently extracted data from the finalized articles.Details such as the name of the tool, number of items, domain assessed, rating scale, time frame, target population, and availability in multiple languages were extracted.The correctness and completeness of the data were done by authors (PR and TK).In case of any discrepancy, a decision was made based on mutual agreement.

Phase 2: narrative synthesis of measurement properties
The measurement properties of the identified tools were taken from the original development and validation studies using lateral search (if and when possible).The information, such as the author's name, study population, and measurement properties, including internal consistency, reliability, measurement error, structural validity, hypothesis validity, cross-cultural validity, criterion validity, and responsiveness, was extracted.

Assessment of Risk of Bias for Measurement Properties
Using the COSMIN checklist, the authors (TK, NR, and AK) assessed the risk of bias for the measurement properties of instruments.As per the COSMIN checklist, the quality of instruments is categorized as very good, adequate, doubtful, or inadequate.The following steps were followed to evaluate the quality of the instrument using the COSMIN checklist: (i) identification of the measurement properties assessed in the study; (ii) understanding of statistical methods used for assessing the measurement properties; (iii) evaluation of the properties according to COSMIN-checklist items; and (iv) grading of each property on the basis of its quality (very good to inadequate).Finally, the methodological quality of a property (e.g., internal consistency) corresponded to the lowest rating given to an item in the COSMIN checklist for that section.For example, if an item on the COSMIN checklist for internal consistency was rated poor, whereas all other items were rated as good, then the final quality for internal consistency was classified as poor.

Identification of MUPS Studies
A total of 14,459 studies were identified in the initial search.Out of these, 191 studies were identified, as shown in the PRISMA flow chart (Figure 1).Studies were randomized controlled trials, observational, and intervention studies.The participant's age ranged from 18 to 60.The studies were conducted in psychiatric and medical settings.

Identification of MUPS Tools to Assess Symptoms and Symptom Severity
From 191 studies, a total of 16 validated tools were included, as presented in Table 1.These tools assessed the symptoms and symptom severity of patients diagnosed with MUPS.

Somatic Symptoms
The most common tool to study somatic symptom severity was the Patient Health Questionnaire-15 (PHQ-15) [5].It comprises 15 somatic symptoms, and the patient is asked to rate them from 0 (not bothered at all) to 2 (bothered a lot).The tool can be self-administered or administered in an interview format.The Bodily Distress Syndrome (BDS) Checklist [17] is another tool comprising 30 items that can be self-administered to screen for somatic symptoms.Other tools that assess the somatic symptoms or can be used as a screening tool for somatization are the Self-reported Somatic Symptom Scale-China (SSS-CN) [6], the Four-Dimensional Symptom Questionnaire (4-DSQ) [20], the Central Sensitization Inventory (CSI) [7], Screening for Somatoform Disorders-7 (SOMS-7 T) [10], the ICD-10 Symptom List [11], and the Somatosensory Amplification Scale (SSAS) [18].
The other components of somatic symptoms, such as pain, were assessed using a short-form McGill Pain Questionnaire (SF-MPQ) [16] and a psychological stress measure [21].The clinical interview schedule [22] assesses the level of fatigue among MUPS patients.Symptoms of hyperventilation were assessed using Nijmegen Hyperventilation List (NHL) tools [12].

Measurement Properties of Instruments: A Narrative Synthesis
The primary development and validation studies were identified using the lateral search to look for the measurement properties of the instruments.Out of 30 tools identified, only 16 validated tools were included in this review, as the remaining 14 tools were either in some other language or the validation papers were not available.The eight properties, namely, internal consistency, reliability, structural validity, hypothesis validity, cross-cultural validity, responsiveness, criterion validity, and measurement error, were assessed.Information regarding the development and validation of only 16 somatic tools could be identified.The internal consistency was calculated using Cronbach's alpha (CA).CA >0.70 was reported for all the somatic instruments.

Risk of Bias Assessment of Instruments: A Quality Assessment
Most of the tools assessing the somatic symptoms had very good internal consistency and structural validity.The reliability of the majority of the tools was found to be adequate.Approximately half of the tools revealed very good convergent validity.However, cross-cultural validity was not reported for the majority of the tools.A detailed description of the tools is presented in the Appendices section.

Discussion
This systematic review identifies the instruments used in the literature to assess the symptoms and symptom severity among patients of MUPS and provides a narrative synthesis of their measurement properties.The standardized tools may help clinicians and researchers to generate data across diverse population groups and draw reliable conclusions.
MUPS patients are presented with somatic complaints varying from mild to severe.Patients with such symptoms constantly juggle from one physician to another, contributing to the overutilization of healthcare services.In literature, instruments for the assessment of somatic symptoms and their severity have been defined as generic (somatic complaints or somatic symptom severity) or condition-specific (dyspepsia, pain, fatigue).Patient Health Questionnaire-15 (PHQ-15) is the most widely used tool to assess somatization or somatic severity.The instrument is highly valid and reliable and can be self-administered.However, in most cases, the tool is often coupled with other psychiatric instruments to capture the greater aspect of the problem.
The Stress and Crisis Inventory-93 (SCI-93) [9] can assess the severity of stress symptoms related to the autonomic nervous system.This self-reported tool can also assess symptoms due to the impact of trauma.
The tool has high internal consistency and structural, convergent, and criterion validity.
The pain and physical discomfort among MUPS patients can be evaluated using Somatosensory Amplification Scale (SSAS).The instrument helps in assessing bodily sensations.The three components gauged using this tool are body hypervigilance, rare and weak body sensations, and emotional reaction to the sensations [18].The tool is easy to self-administer and has extremely well-established validity and reliability.Lastly, the Checklist Individual Strength (CIS) is a reliable, valid, and easy-to-administer tool for assessing fatigue severity, concentration problems, and reduced motivation.
All the above-stated tools are self-administered and have been developed on a Likert scale.They can be used to capture the overall somatic domain in MUPS patients as they depict very good psychometric properties.
Recent studies from India highlight the unique perspectives of patients, caregivers, and healthcare professionals regarding MUPS [23].These insights underscore the necessity for locally tailored evaluation modules, recognizing the distinct symptom presentations in Indian populations compared to the West [24,25].In response, certain researchers have formulated comprehensive treatment modules, coupled with yoga therapy, to address the needs of these patients effectively [26,27].

Limitations and strengths
Some limitations of the present review should be considered.We evaluated only three databases through electronic searches.We did not look for unpublished data or other algorithmic search engines like Google Scholar.We limited ourselves to studies from 2000 onwards, though there may have been some studies on the topic before 2000.We did not delve into different sub-populations that presented with MUPS, such as adolescents and geriatric populations.Lastly, we considered somatic symptoms to be synonymous with MUPS.Despite the limitations, the systematic assessment and narrative synthesis of the tools may be a handy resource for researchers and clinicians working in the field of MUPS.

Recommendation for future research
This review found that most of the tools identified have not been cross-culturally validated.The symptoms of MUPS may differ from culture to culture, as patients provide their perception or meaning to their symptoms.Therefore, either these tools should be validated culturally before administering, or a tool should be developed and validated according to the symptoms presented in a particular cultural setting.

Conclusions
A systematic review has been done to identify the validated tools used to assess the symptoms and symptom severity in MUPS patients.A narrative synthesis has also been performed to assess the methodological quality of the tools.A bird-eye view of the standardized tools has been provided, which can be used by clinicians and public health researchers for the assessment of MUPS patients at baseline and to assess the effectiveness and efficacy of treatment to improve their physical and psychological well-being.

FIGURE 1 :
FIGURE 1: PRISMA flowchart PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

TABLE 1 : List of validated tools
NA: not available, HVS: hyperventilation syndrome, CDC: Centers for Disease Control and Prevention, CFS: chronic fatigue syndrome, SCAN: Schedules for Clinical Assessment in Neuropsychiatry

TABLE 6 : Risk of bias assessment of instruments (criterion validity)
NA: not available

TABLE 7 : Risk of bias assessment of instruments (responsiveness)
NA: not available