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BACKGROUND: We investigated health-related quality of life (HrQoL) in Filipino people undergoing TB treatment, and whether HrQoL was negatively impacted by comorbidity with undernutrition, diabetes (DM) and anaemia. METHODS: Adult participants were enrolled in public facilities in Metro Manila (three sites) and Negros Occidental (two sites). Multivariate linear regression was used to model the four correlated domain scores from a WHOQOL-BREF questionnaire (physical, psychological, social, environmental). A forward-stepwise approach was used to select a final multivariable model with inclusion based on global tests of significance at P < 0.1. RESULTS: In 446 people on drug-susceptible TB treatment, DM and moderate/severe anaemia were not associated with HrQoL. After adjustment for age, sex, education, food insecurity, treatment adherence, inflammation, Category I or II TB treatment, treatment phase, current side effects and inhibited ability to work, moderate/severe undernutrition (body mass index < 17 kg/m ² ) was associated with lower HrQoL ( P = 0.003) with reduced psychological (coefficient: −1.02, 95% CI −1.54 to −0.51), physical (−0.62, 95% CI −1.14 to −0.09) and environmental domain scores (−0.45, 95% CI −0.88 to −0.01). In 225 patients with known HIV status in Metro Manila, HIV was associated with modestly reduced HrQoL ( P = 0.014). CONCLUSION: Nutritional status and food insecurity represent modifiable risk factors for poor HrQoL that may be alleviated through interventions.
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INT J TUBERC LUNG DIS 24(7):712–719
Q
2020 The Union
http://dx.doi.org/10.5588/ijtld.19.0734
Effects of comorbidities on quality of life in Filipino people with
tuberculosis
T. Edwards,
1,2
L. V. White,
2
N. Lee,
2,3
M. C. Castro,
4
N. R. Saludar,
5
B. N. Faguer,
2
N. D. Fuente,
6
F. Mayoga,
7
K. Ariyoshi,
8
A. M. C. G. Garfin,
9
J. A. Solon,
4
S. E. Cox
2,8,10
1
Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine (LSHTM), London, UK;
2
School of
Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan;
3
Royal Free Hospital, London, UK;
4
Nutrition Center Philippines, Manila,
5
San Lazaro Hospital, Manila,
6
Valladolid Health Center, Valladolid, Negros
Occidental,
7
Bago City Health Center, Bago City, Negros Occidental, the Philippines;
8
Institute of Tropical Medicine,
Nagasaki University, Nagasaki, Japan;
9
National TB Control Programme, Department of Health, Manila, the
Philippines;
10
Faculty of Population Health, LSHTM, London, UK
SUMMARY
BACKGROUND: We investigated health-related quality
of life (HrQoL) in Filipino people undergoing TB
treatment, and whether HrQoL was negatively impacted
by comorbidity with undernutrition, diabetes (DM) and
anaemia.
METHODS: Adult participants were enrolled in public
facilities in Metro Manila (three sites) and Negros
Occidental (two sites). Multivariate linear regression was
used to model the four correlated domain scores from a
WHOQOL-BREF questionnaire (physical, psychological,
social, environmental). A forward-stepwise approach was
used to select a final multivariable model with inclusion
based on global tests of significance at P
,
0.1.
RESULTS: In 446 people on drug-susceptible TB treat-
ment, DM and moderate/severe anaemia were not
associated with HrQoL. After adjustment for age, sex,
education, food insecurity, treatment adherence, inflam-
mation, Category I or II TB treatment, treatment phase,
current side effects and inhibited ability to work,
moderate/severe undernutrition (body mass index
,
17 kg/m
2
) was associated with lower HrQoL (P
¼
0.003)
with reduced psychological (coefficient: 1.02, 95% CI
1.54 to 0.51), physical (0.62, 95% CI 1.14 to
0.09) and environmental domain scores (0.45, 95%
CI 0.88 to 0.01). In 225 patients with known HIV
status in Metro Manila, HIV was associated with
modestly reduced HrQoL (P
¼
0.014).
CONCLUSION: Nutritional status and food insecurity
represent modifiable risk factors for poor HrQoL that
may be alleviated through interventions.
KEY WORDS: tuberculosis; diabetes; malnutrition;
comorbidities; the Philippines; quality of life
TUBERCULOSIS (TB) IS A LEADING cause of
morbidity in many high-burden countries.
1
Although
increasing attention is being paid to the impact of TB
beyond physical health, including psychosocial and
financial impacts, the effects of common comorbid-
ities such as HIV, diabetes (DM), acute malnutrition
and anaemia on the patient’s overall well-being is not
known.
Understanding how TB impacts on quality of life
(QoL) as perceived by individuals, is important for
understanding how to improve patient-centred care
(a component of Pillar 1 in the End TB Strategy
2035).
2
It is also needed to evaluate interventions and
for health policy, since data on health-related QoL
(HrQoL) are used in health economic evaluations.
HrQoL encompasses the physical, mental and social
well-being of individuals. How these are perceived is
dependent on the society and environment of
individuals. Studies in a range of settings have
reported negative impacts of TB disease on an
individual’s HrQoL, using an assortment of mostly
generic tools applicable to different health conditions.
Some of these studies included an appropriate
comparison population groups of individuals without
TB disease or with latent TB infection or reference
population norms.
3,4
Few studies in people with
active TB disease have included an assessment of the
impact of comorbidities on HrQoL, although a recent
prospective cohort study in India reported a negative
effect of DM using the TB-specific Dhingra and
Rajpal (DR-12) scale.
5
Although the Philippines has a high TB burden, there
are currently limited HrQoL data from the Philippines
or on comorbidities in TB. Within a cross-sectional
study of Filipino people with active TB disease enrolled
in TB-DOTS clinics (ISRCTN12506117), we investi-
Correspondence to: Sharon Cox, Faculty of Population Health, London School of Hygiene & Tropical Medicine, Keppel
Street, London WC1E 7HT, UK; and School of Tropical Medicine and Global Health, Nagasaki University, 1-12-4
Sakamoto, Nagasaki 852-8523, Japan e-mail: sharon.cox@lshtm.ac.uk; sharoncox@nagasaki-u.ac.jp
Article submitted 27 November 2019. Final version accepted 3 February 2020.
gated, as a primary objective, the prevalence of DM and
moderate/severe acute undernutrition and factors asso-
ciated with these comorbidities, reported elsewhere.
6
Here, we report into whether comorbidities of under-
nutrition, DM and moderate or severe anaemia and
HIV infection are associated with reduced HrQoL in
this population, as a secondary objective.
METHODS
Study design
This was a cross-sectional survey, described in detail
elsewhere.
6
Study setting
The Philippines is a middle-income country, estimat-
ed to have the third highest TB incidence (554/
100 000 population) occurring in the context of a low
HIV prevalence, estimated at 2% of incident TB
cases, although HIV testing is low in many areas.
7
The prevalence of undernutrition (body mass index
[BMI] ,18.5 kg/m
2
) in Filipino adults was 10% in
the 2014 National Nutrition Survey. Three public TB-
DOTS clinics in Metro Manila provided data from an
urban setting, including the TB-DOTS Clinic at San
Lazaro Hospital, an infectious disease referral hospi-
tal, serving a predominantly poor population. Metro
Manila is identified as a Category ‘A’ area, with a
high burden of HIV compared to other areas of the
country. Two public TB-DOTS clinics in Negros
Occidental provided data from a rural setting.
Participants
Adults (aged 18 years, excluding pregnant women)
whose TB-DOTS registration date indicated that TB
treatment should be ongoing, were eligible to
participate. Research nurses visited barangays (vil-
lages) to attempt to locate all those whose treatment
was ongoing.
Outcome
The primary outcome of interest was HrQoL assessed
using the World Health Organisation Quality of Life-
BREF (WHOQOL-BREF) assessment,
8,9
. Responses
to 24 of the 26 items in WHO HrQoL-BREF were
used to score four domains: 1) physical, 2) psycho-
logical, 3) social relationships, and 4) environment.
Domain scores were calculated according to the
standard algorithm (with a possible range of 4–20).
9
Higher domain scores reflect better HrQoL.
Data collection and definitions of comorbidity
exposures
Trained multilingual research nurses completed all
study assessments using questionnaires and tools
translated into local languages and extracted infor-
mation recorded on participant’s National TB Pro-
gram treatment cards. Household food security was
assessed using the Adapted US Household Food
Security Survey Module (US HFSSM), previously
validated for use in the Philippines.
10
Data were
entered directly into Open Data Kit software and
uploaded to a secure server daily. Research nurses
conducted anthropometry measurements;
6
weight to
the nearest 0.1 kg; height, mid-upper arm circumfer-
ence (MUAC) and waist and hip circumferences to
the nearest 0.5 cm; and grip strength to the nearest kg
(Jamar Hydraulic Hand Dynamometer; Lafayette
Instruments, IN, USA) using the highest of three
measurements of the dominant hand. Fingerprick
blood samples were used to obtain haemoglobin
(HemoCue 301; ¨
Angelholm, Sweden), glycosylated
haemoglobin (HbA1C) and C-reactive protein (CRP)
(Alere Afinion AS100 Analyzer; Abbott Diagnostics,
Abbott Park, IL, USA) and to conduct HIV screening
(Standard Diagnostics Bioline HIV-1/2 Ag/Ab Combo
Rapid Test kits) for those with unknown status and
who provided additional consent.
Comorbid conditions considered here included
undernutrition, defined as moderate/severe undernu-
trition (BMI ,17.0 kg/m
2
), DM defined as HBA1c
6.5% or receiving treatment for DM at enrolment,
moderate/severe anaemia defined as haemoglobin ,
11 g/dL. HIV co-infection was defined as a positive
screening test result or a previous diagnosis. Other
available data included 1) sociodemographic charac-
teristics: age, sex, urban/rural area study area, marital
status, level of education, distance/time to TB-DOTS
centre, health insurance, level of household food
security, smoking and alcohol consumption and
factors relating to impact of TB on ability to work
and cover expenses; 2) health and TB related factors:
TB category (new vs. relapse etc.), phase of TB
treatment (intensive vs. continuation), current side
effects of TB treatment, adherence to TB treatment in
the previous week, category of medication (Category
I or II), presence of inflammation (CRP .5 g/L) and
hand grip strength as a measure of functional
nutritional status.
Sample size
Sample size for this study was determined by the main
study of undernutrition and DM comorbidity. Of 614
participants with drug-susceptible TB in the main
study, 446 completed QoL interviews.
Statistical methods
Data were analysed using Stata v.15.1 (Stata Corp,
College Station, TX, USA) and R (R Computing,
Vienna, Austria).
11
Characteristics were summarised
for all enrolled participants and for those with
complete HrQoL data. Physical, psychological, social
and environmental domain scores were summarised
as mean (standard deviation [SD]), after observing
data to be approximately normally distributed.
Due to correlation between QoL domain scores
Comorbidities and quality of life in TB 713
within individuals, multivariate linear regression was
used to simultaneously analyse the four QoL out-
comes in the same model. For each independent
variable, regardless of the number of categories,
global tests of association were conducted for
association with the four domains to reduce multiple
testing.
12
Multivariable multivariate linear regression model
building was carried out using a forward stepwise
approach in blocks of related exposures, where
blocks comprised 1) comorbidities, 2) demographic
and socioeconomic indicators, and, 3) TB related
factors. Variables were retained if the global test of
association Pvalue after adjustment for other
variables was ,0.1. Sex was included a priori.In
the final adjusted model, the strength of association
between the independent variables and QoL domain
scores was interpreted with and without Bonferroni’s
adjustment for the number of tests of association in
the final model (a¼0.05/number of tests of
association [covariates] in the final model).
Ethics
Ethical approval was obtained from Institutional
Ethics Review Boards at School of Tropical Medicine
and Global Health, Nagasaki University (Nagasaki,
Japan), London School of Hygiene & Tropical
Medicine (London, UK), Philippines National Ethics
Committee (Manila, The Philippines) and San Lazaro
Hospital in Manila. Written consent was provided by
all participants prior to study enrolment, and
additional written consent was obtained for HIV
screening in accordance with Department of Health
procedures.
RESULTS
Of 614 participants on non-drug-resistant TB regi-
mens enrolled between 8 May and 18 September
2017, 446 were interviewed for HrQoL between 19
May and 18 September 2017. The 446 participant
sub-set included in this analysis (hereafter referred to
as the study population) were similar to the total
study population, except that a greater proportion of
those with HrQoL data were enrolled in urban Metro
Manila than in rural Negros Occidental (Supplemen-
tary Table S1). Males comprised 70% of the study
population and the mean age was 44.8 years (SD
16.7). Participants were significantly older in Negros
Occidental than in Metro Manila (50.5 vs. 41.1 years;
P,0.001), with no difference in age by sex (P¼
0.280). The proportion of participants with previ-
ously treated TB (i.e., those programmatically de-
fined as relapse, treatment after failure, previous
treatment outcome unknown or treatment after loss
to follow-up) was 30.3% (134/443). There was no
evidence that the proportion of previously treated
cases differed by urban/rural area or by sex but did
increase with age, from 17.4% in the 18–40 years age
group, 40% in the 41–65 years’ age group to 45.6%
in the .65 years age group (P,0.001). This is
relevant, because previously treated cases in this
setting were treated with Category II TB treatment
including daily injectable streptomycin during the
intensive phase of treatment.
The prevalence of DM in the study population was
8.3%, with just over half newly captured by the study
protocol (Supplementary Table S1). The prevalence
of moderate and severe undernutrition was 19.7%,
moderate/severe anaemia was 15.7% and self-report-
ed hypertension was 9.0% (Supplementary Table S1).
HIV status was unknown for the majority of
participants in Negros Occidental due to screening
refusal. In Metro Manila, HIV status was known for
238 (88%) of participants, and 68 (28.6%) were
infected. All but 4 had been previously diagnosed,
and 54 were on antiretroviral therapy. Most of these
participants (63/68) were enrolled at San Lazaro
Hospital, an HIV referral centre, accounting for the
high proportion of HIV comorbidity in our urban
study population.
Data were complete for all items on the WHO-
QOL-BREF. Domain scores were approximately
normally distributed, although some skew and
outliers were noted for the psychological domain
(Figure 1). Internal consistency across domain com-
ponents was good for the physical, psychological and
environmental domains (Cronbach’s a.0.7), but
poor for the social relationships’ domain (Cronbach’s
a¼0.46).
For the single (national item) of overall rating of
QoL, 98 (22.0%) rated their QoL as poor or very
poor, and 160 (35.9%) as good or very good. This
compared to 169 (37.9%) who reported being
dissatisfied or very dissatisfied with their health and
118 (26.5%) who were satisfied or very satisfied.
Mean domain scores are shown in Tables 1, S2 and
S3. In univariable, multivariate analysis there was no
evidence of an association between DM, anaemia or
reported hypertension with HrQoL domain scores
(Table 1). However, moderate/severe undernutrition
was significantly associated (P,0.001) with reduced
scores for the physical and psychological domains.
Similarly, grip strength as a measure of functional
nutritional status was positively associated with
higher domain scores (P,0.001), while moderate
and severe levels of household food insecurity were
associated with reduced scores (P,0.001; Supple-
mentary Table S2). For those with known HIV status
in Metro Manila, HIV infection was associated with
HrQoL domain scores (P,0.001; Table 1), with
evidence of increased scores for the physical and
environmental domains. We also assessed associa-
tions with indicators of the possible impact of TB on
ability to work, and consequences for household
finances, which both showed evidence of negatively
714 The International Journal of Tuberculosis and Lung Disease
affecting HrQoL scores (P,0.001; Supplementary
Table S2). Finally, TB-specific factors were assessed,
all of which, apart from the basis of diagnosis
(bacteriological vs. clinical) were significantly asso-
ciated (Supplementary Table S3).
Effects for factors retained in the final model are
shown in Table 2.The association between HrQoL
and undernutrition remained after adjustment for
other exposures, with the greatest reduction in the
psychological domain. Moderate or severe food
insecurity showed a dose-response effect of decreased
scores for all domains (Figure 2A). When considering
a Bonferroni adjustment to account for 12 global tests
(aof 0.05/12 ¼0.004), undernutrition and household
food security remained strongly associated with
HrQoL.
When adjusting for area in the model (P,0.001),
effects of adherence and undernutrition were reduced
(global test P¼0.078 and P¼0.058), as these differed
by area (93% in Negros Occidental adhered fully in
Figure 1 Distribution of health-related quality of life domain scores in persons on drug-
susceptible tuberculosis treatment regimens.
Table 1 Domain scores in 446 persons on drug-susceptible TB treatment regimens by clinical comorbid characteristics
n
Health-related quality of life domain, mean (SD) Global
PvaluePhysical Psychological Social Environmental
Overall 446 13.4 (2.4) 13.7 (2.2) 14.6 (2.0) 13.3 (2.0)
Undernutrition None/mild: BMI ,17 kg/m
2
357 13.7 (2.3) 13.8 (2.1) 14.7 (1.9) 13.4 (2.0) ,0.001
Moderate/severe: BMI 17 kg/m
2
88 12.6 (2.5) 12.9 (2.2) 14.5 (2.3) 13.0 (1.9)
Anaemia None/mild: Hb 11 g/dL 373 13.5 (2.4) 13.8 (2.2) 14.7 (2.0) 13.4 (1.9) 0.182
Moderate/severe: Hb ,11 g/dL 70 13.0 (2.4) 13.1 (2.2) 14.3 (2.0) 12.9 (2.0)
Diabetes No: HbA1c ,6.5%, not on treatment 409 13.5 (2.4) 13.7 (2.2) 14.6 (2.0) 13.3 (2.0) 0.590
Yes: HbA1c 6.5% or on treatment 37 13.2 (2.3) 13.6 (2.2) 14.9 (1.8) 13.6 (1.5)
Diabetes diagnosis Not diabetic 409 13.5 (2.4) 13.7 (2.2) 14.6 (2.0) 13.3 (2.0) 0.773
New diagnosis (HbA1c 6.5%,
no previous diagnosis)
19 13.1 (2.2) 13.8 (1.7) 15.2 (1.4) 13.5 (1.6)
Existing diagnosis 18 13.4 (2.5) 13.4 (2.6) 14.6 (2.1) 13.6 (1.5)
Diabetes control Not diabetic 409 13.5 (2.4) 13.7 (2.2) 14.6 (2.0) 13.3 (2.0) 0.570
Controlled: on treatment and
HbA1c ,8.0%
14 13.9 (2.6) 14.0 (2.4) 14.7 (2.0) 13.6 (1.6)
Uncontrolled: HbA1c 8% 23 12.8 (2.0) 13.4 (2.0) 15.1 (1.7) 13.5 (1.5)
Self-reported hypertension No 406 13.5 (2.4) 13.7 (2.2) 14.7 (2.0) 13.4 (2.0) 0.072
Yes 40 12.4 (2.1) 13.2 (2.0) 14.3 (1.9) 12.7 (1.9)
Number of comorbidities
(undernutrition, anaemia,
diabetes, hypertension)
0 262 13.8 (2.4) 14.0 (2.1) 14.8 (1.9) 13.5 (2.0) 0.004
1 137 13.3 (2.4) 13.3 (2.3) 14.5 (2.2) 13.3 (1.9)
2 43 12.1 (1.9) 12.9 (1.9) 14.4 (1.9) 12.6 (1.8)
3 4 12.1 (3.8) 12.3 (2.5) 14.7 (1.9) 12.5 (2.0)
Inflammation No: C-reactive protein ,5 g/L 369 13.7 (2.4) 13.8 (2.2) 14.7 (2.1) 13.4 (2.0) 0.010
Yes: C-reactive protein 5 g/L 34 12.3 (2.6) 12.6 (1.9) 13.7 (1.8) 12.6 (1.8)
Hand grip strength, kg 445 ,0.001
HIV infection (Manila only) No 170 13.5 (2.5) 14.2 (2.1) 14.8 (2.1) 13.1 (2.0) ,0.001
Yes 68 14.5 (1.7) 14.2 (1.9) 14.8 (1.8) 14.7 (1.5)
TB¼tuberculosis; SD ¼standard deviation; BMI¼body mass index; Hb ¼haemoglobin; HbA1c¼glycosyla ted haemoglobin; HIV¼human immunodeficiency virus.
Comorbidities and quality of life in TB 715
Table 2 Multivariable multivariate regression analysis in 392 persons on drug-susceptible TB treatment regimens*
Health-related quality of life domain, linear regression coefficient (95% CI)
Physical Psychological Social Environmental Global Pvalue
Sex Female
Male –0.88 (–1.44 to –0.32)
–0.42 (–0.97 to 0.13) –0.14 (–0.68 to 0.39) –0.21 (–0.68 to 0.25) 0.039
Age, years 18–40
41–65 –0.18 (–0.70 to 0.33) –0.50 (–1.00 to 0.01) –0.19 (–0.68 to 0.30) –0.48 (–0.90 to -0.05)
0.073
.65 –0.75 (–1.54 to 0.04) –0.96 (–1.74 to –0.18)
–0.82 (–1.57 to –0.06)
–0.48 (–1.14 to 0.18)
Maximum education obtained Primary
Secondary 0.42 (–0.11 to 0.95) 0.42 (–0.10 to 0.94) 0.24 (–0.26 to 0.75) 0.39 (–0.05 to 0.83) ,0.001
Tertiary 1.01 (0.35 to 1.66)
0.40 (–0.24 to 1.04) –0.10 (–0.72 to 0.52) 1.20 (0.66 to 1.74)
Vocational 0.13 (–1.24 to 1.49) –0.62 (–1.96 to 0.72) 0.07 (–1.23 to 1.37) 0.49 (–0.64 to 1.62)
Household food security Secure
Moderate insecurity –0.66 (–1.20 to –0.12)
–0.57 (–1.10 to –0.03)
–0.64 (–1.16 to –0.12)
–0.93 (–1.38 to –0.48)
,0.001
Severe insecurity –0.78 (–1.35 to –0.22)
–0.82 (–1.38 to –0.27)
–1.00 (–1.53 to –0.46)
–1.25 (–1.71 to –0.78)
Moderate/severe undernutrition
§
No: BMI ,17 kg/m
2
Yes: BMI 17 kg/m
2
–0.62 (–1.14 to –0.09)
–1.02 (–1.54 to –0.51)
–0.20 (–0.70 to 0.30) –0.45 (–0.88 to –0.01)
0.003
Inflammation No: CRP ,5g/L
Yes: CRP .5 g/L –0.96 (–1.73 to –0.19)
–1.14 (–1.90 to –0.39)
–0.97 (–1.71 to –0.24) –0.90 (–1.54 to –0.27)
0.017
Hand grip strength 0.05 (0.02 to 0.08)
0.00 (–0.03 to 0.03) –0.00 (–0.03 to 0.03) –0.01 (–0.03 to 0.01) ,0.001
Phase of treatment Intensive
Continuation 0.51 (0.06 to 0.97)
0.28 (–0.16 to 0.73) –0.09 (–0.52 to 0.34) –0.14 (–0.51 to 0.24) 0.025
TB treatment category Category 1
Category 2 –0.65 (–1.11 to –0.19)
–0.46 (–0.92 to –0.01)
–0.75 (–1.19 to –0.31)
–0.22 (–0.60 to 0.17) 0.002
Current treatment side effects No
Yes 0.76 (0.30 to 1.22)
0.41 (–0.04 to 0.86) 0.16 (–0.27 to 0.60) 0.41 (0.03 to 0.79)
0.026
Ability to work affected No
Yes –0.48 (–0.91 to –0.05)
–0.72 (–1.15 to –0.30)
–0.74 (–1.15 to –0.33
) –0.20 (–0.56 to 0.16) ,0.001
Number of days adherent in last 7 days 0.03 (–0.05 to 0.11) –0.06 (–0.14 to 0.02) 0.01 (–0.07 to 0.09) 0.10 (0.03 to 0.17)
,0.001
* Based on n¼392 after exclusion of missing values (missing values: total ¼5; BMI ¼1; grip strength ¼1; work ability ¼2; adherence ¼4; CRP ¼43).
From multivariable multivariate linear regression.
Indicates 95% CIs excluding the null effect.
TB ¼tuberculosis; CI ¼confidence interval; BMI ¼body mass index; CRP ¼C-reactive protein.
716 The International Journal of Tuberculosis and Lung Disease
the last 7 days compared to 62% in Manila, v
2
P,
0.001; and 30% vs. 15% severe/moderate undernu-
trition in Negros Occidental and Manila, P¼0.002).
Household food security was not associated with
undernutrition overall but did differ by area (approx-
imately two thirds moderate/severe food insecurity in
Negros compared to one third in Manila, P,0.001).
Undernutrition and recent adherence were retained in
the model over area as more specifically measured
covariates of interest.
The final model was fitted to participants from
Metro Manilla with known HIV status and non-
missing values for factors in the final model
(Supplementary Table S4). After adjustment, HIV
Figure 2 A) Adjusted effects on HrQoL domain scores in persons on drug-susceptible TB treatment regimens; B) adjusted effects on
HrQoL domain scores in persons on drug-susceptible TB treatment regimens registered in clinics in Metro Manilla with known HIV
status. Undernutrition: moderate/severe: BMI 17 kg/m
2
compared to mild/normal: BMI ,17 kg/m
2
; moderate and severe
household food insecurity compared to mild/no insecurity. Inflammation: CRP 5 g/L compared to CRP ,5 g/L. Category II compared
to Category I TB treatment regimen (Category II includes daily streptomycin injections in the intensive phase). HrQoL ¼health-related
quality of life; CRP ¼C-reactive protein.
Comorbidities and quality of life in TB 717
was associated with QoL overall (P¼0.014, Figure
2B) with the largest observed negative impact on
psychological domain, followed by environmental
domain. In this model, the effects of undernutrition
and adherence were absent, but food insecurity
remained a strong risk factor for reduced QoL (P,
0.001). In this sub-group, HIV was strongly associ-
ated with increased level of education (P,0.001),
which likely represents a proxy for socio-economic
status (60% of those with tertiary education had
HIV) and sex (40% of male participants vs. 3% of
women had HIV, P,0.001 and the previously
observed effect of sex on QoL was not seen in this
sub-group).
DISCUSSION
We focussed on the effect of DM and undernutrition
on HrQoL as more common comorbid conditions.
The prevalence of undernutrition is much higher than
in the general adult population (10% BMI ,18.5),
13
while the national prevalence of DM is estimated at
5.8%.
14
Furthermore, diagnosis and management of
DM and undernutrition are recommended for inte-
grated patient centred care, but current implementa-
tion is limited.
2,15
In this population, we observed that undernutrition
was independently associated with lower perceived
QoL in the physical, psychological and environmen-
tal domains. No effects were observed for DM or
anaemia. Furthermore, we explored if effects of DM
may be limited to those with existing diagnoses or
those with uncontrolled (HbA1c 8%) compared to
controlled DM, but saw no evidence of associations,
although low numbers of observations will have
limited the probability of detecting all but large
effects. In addition to undernutrition, household food
insecurity was associated in a dose-response manner
with reduced scores across all four domains. In a
previous cross-sectional study of HrQoL using the
Short Form-8 (a shorter version of the Short Form-36)
in 520 Filipino TB patients enrolled in TB-DOTS in
Metro Manila, the mental component summary
score, but not the physical component summary
score, was independently associated with increasing
BMI.
16
Although the use of financial or in-kind
support for travel or food as incentives or enablers for
persons undergoing TB treatment are widely advo-
cated to increase treatment uptake and completion
and as means of poverty alleviation,
17
no such
programmes were available at the time of our study
for patients enrolled in non-MDR-TB treatment
regimens. Therefore, we could not investigate if such
provisions might impact QoL, and if mediated
through effects on nutritional status or household
food security. We are not aware of any studies that
have assessed this. In India, large increases in
WHOQOL-BREF domain scores were observed
between start of TB treatment and end of the
intensive phase and end of treatment.
18
The mean
scores at treatment completion were the most
comparable to those we observed (scores transformed
onto the 0–100 scale of 66 [environment domain] to
80 [physical domain]), equivalent to approximately
14.5 and 16.5 on the 4–20 scale we report). Over the
course of treatment, the largest improvement in QoL
was observed for the physical domain (nearly
doubled), but comorbidities were not assessed.
18
Another study in India (using the TB-specific Dhingra
& Rajpal DR-12 scale), reported decreased scores in
the socio-psychological and exercise adaptation
domains in persons with DM aged over 50 years;
while uncontrolled versus controlled DM was asso-
ciated with lower scores, but only at the end of TB
treatment.
5
Despite a high prevalence of severe
undernutrition (23% BMI ,15 kg/m
2
), a possible
effect of this important comorbidity was not report-
ed.
5
Within our sub-set of participants with known
HIV status, living with HIV infection initially
appeared to be associated with increased QoL
domain scores, but after adjustment, this association
trended towards decreased scores, likely due to
confounding by age and education, which were
higher in those with HIV and also positively
associated with QoL domain scores, Thus, compared
to other studies in Ethiopia the impact of comorbid
HIV appeared to be limited.
19,20
As the majority of
those living with HIV were already in care at the same
site as their TB treatment and receiving antiretroviral
therapy, this suggests that in the context of adequate
care, the additional impact of comorbid HIV in TB is
not necessarily great. The level of impact may vary
depending on the extent of integrated management of
the two conditions and availability of coping/support
mechanisms for HIV care.
Although there is evidence that QoL scores increase
with duration of treatment, they may not resolve to
pre-disease levels due to the increasingly recognised
long-term effects of TB disease, including chronic
lung disorders, requiring long-term further manage-
ment.
21
Simple physical therapy rehabilitation inter-
ventions may be beneficial in improving lung function
and also QoL, especially in the physical domain.
22
Potential limitations of this study include the lack
of normative data in representative Filipino adults to
compare our observations with and low internal
consistency across the items in the social relation-
ships’ domain, so perhaps more contextual adapta-
tion of the tool is needed. Further limitations include
those inherent in cross-sectional studies. However,
selection bias was minimised by the inclusion of
participants across the range of treatment duration
and frequency of attending TB-DOTS clinics. Mea-
surement bias was minimised by trained study nurses
assessing nutritional status and screening of DM,
rather than relying on routinely collected data, but a
718 The International Journal of Tuberculosis and Lung Disease
single measurement of HbA1c 6.5% may have
resulted in misclassification of DM from temporary
glucose dysregulation induced by TB.
CONCLUSION
Evidence of the psychosocial effects of undernutri-
tion, additional to direct biomedical effects on TB
treatment outcomes provides further evidence to 1)
support the need for nutrition interventions; 2)
include additional outcomes such as HrQoL and
mental health-related measures to determine impacts
of nutrition interventions; and, 3) identify individuals
who might benefit from additional psychosocial
support. The measurement of household food inse-
curity within TB programmes may be a sensitive
indicator of household poverty and stress, which may
be alleviated through social protection mechanisms
aimed at the whole household and directly or
indirectly improving household food security and
potentially HrQoL.
Acknowledgements
The authors thank participants, their families, TB-DOTS clinic
staff and research nurses: AKQ Llantada, RMT Garcia, MA
Savaadra, CD Alvarez, RJ Juson and M Lourdes with support from
C Berido for their contributions in making this work possible.
Electronic data solutions were provided by London School of
Hygiene & Tropical Medicine Open Research Kits (London, UK)
(odk.lshtm.ac.uk).
This work was supported by funding from Nagasaki University
(Nagasaki, Japan) to SEC.
Conflicts of interest: none declared.
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3539
Comorbidities and quality of life in TB 719
RE
´SUME
´
CONTEXTE : En raison de la faible quantit´e des donn´ees
existantes, nous avons ´evalu´e la qualit´e de vie li´ee `ala
sant´e (HrQoL) des Philippins suivant un traitement
antituberculeux ; et si ce dernier ´etait n ´egativement
affect´e par des comorbidit´es telles que la malnutrition, le
diab`ete et l’an´emie.
ME
´THODES : Les participants adultes ont ´et´e recrut ´es
dans des ´etablissements publics du Grand Manille (3sites)
et de Negros occidental (2 sites). Nous avons utilis´eune
egression lin´eaire multivari´ee pour modeler les quatre
scores de domaine corr´el ´es du questionnaire
WHOQHOL-BREF (physique, psychologique, social,
environnemental). La m´ethode ascendante pas `a pas a
´et´e utilis´ee pour choisir un mod`ele multivari´e final avec
inclusion bas´ee sur des tests de signification dont P
,
0,1.
RE
´SULTATS : Chez 446 personnes sous traitement
contre la tuberculose pharmacosensible, le diab`ete et
l’an´emie mod´er´ee ou s´ev`ere n’ont pas ´et ´e associ ´es avec la
HrQoL. Apr`es pond ´eration de l’ ˆage, du sexe, du niveau
d’´education atteint, de l’ins´ecurit ´e alimentaire, de
l’adh´esion au traitement, de l’inflammation, de la
cat´egorie de traitement antituberculeux (I ou II), de la
phase de traitement, des effets secondaires
contemporains au traitement et r ´eduction de la
capacit´e`a travailler, la sous-nutrition mod´er´ee ou
ev`ere (indice de masse corporelle
,
17 kg/m
2
)a´et´e
associ´ee `a une HrQoL plus faible (P
¼
0.003) avec une
eduction des scores pour les domaines psychologiques
(coefficient 1,02 ; IC 95% 1,54 `a 0,51), physiques
(coefficient 0,62 ; IC 95% 1,14 `a0,09)et
environnementaux (coefficient 0,45 ; IC 95% 0,88 `a
0,01). Chez 225 patients du Grand Manille dont le statut
VIH ´etait connu, la s ´eropositivit ´ea´et ´e associ ´e avec une
HrQoL mod´er´ement r´eduite (P
¼
0.014).
CONCLUSIONS : Le statut nutritionnel et l’ins´ecurit´e
alimentaire repr´esentent des facteurs de risques ´evitables
vis-`a-vis de la HrQoL qui peuvent att´enu´es au travers
d’interventions.
RESUMEN
MARCO DE REFERENCIA: Dada la escasez de datos, se
investig ´o la calidad de vida relacionada con la salud
(HrQoL) en las personas de Filipinas que recib´ıan
tratamiento contra la TB y si una comorbilidad por
desnutrici ´on, diabetes o anemia la afectaban de manera
negativa.
ME
´TODOS: Los adultos participantes se inscribieron en
establecimientos p ´ublicos en Gran Manila (tres centros)
y en Negros Occidental (dos centros). Mediante una
regresi ´on lineal multivariante se modelizaron las
correlaciones de las puntuaciones de las cuatro
dimensiones del cuestionario WHOQOL-BREF (f´ısica,
psicol ´ogica, social y ambiental). Se utiliz ´ounm´etodo de
regresi ´on escalonada anter ´ograda a fin de escoger un
modelo multivariante final con inclusiones basadas en
las pruebas generales de significaci ´on con P
,
0,1.
RESULTADOS: De 446 personas en tratamiento por TB
farmacosensible, la presencia de diabetes y anemia
moderada o grave no se relacion ´o con la HrQoL. Tras
corregir con respecto a la edad, el sexo, el grado de
instrucci ´on, la inseguridad alimentaria, el cumplimiento
terap´eutico, la inflamaci ´on, la Categor´ıa I o II del
tratamiento antituberculoso, la fase del tratamiento, los
efectos secundarios actuales y la alteraci ´on de la
capacidad de trabajar, se observ ´o que la desnutrici ´on
moderada o grave (´ındice de masa corporal
,
17 kg/m
2
)
se relacionaba con una HrQoL inferior (P
¼
0,003), con
disminuci ´on de la puntuaci ´on de la esfera psicol ´ogica
(coeficiente –1,02; IC 95% –1,5 a 0,51), f´ısica (–0,62;
–1,14 a 0,09) y ambiental (–0,45; –0,88 a 0,01). De 225
pacientes con situaci ´on conocida frente al virus de la
inmunodeficiencia humana (VIH) en Gran Manila, la
infecci ´on por el VIH se asoci ´o con una leve disminuci ´on
de la HrQoL (P
¼
0,014).
CONCLUSIO
´N: El estado nutricional y la inseguridad
alimentaria representan factores de riesgo modificables
de una HrQoL deficiente, que se pueden mejorar con las
intervenciones.
Comorbidities and quality of life in TB i
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... TB co-infection worsens the symptoms of HIV and advances the disease to the next stage, which can further deteriorate the HRQoL [70]. Additionally, studies have found that TB patients are negatively impacted by comorbidities such as undernutrition, diabetes mellitus (DM), anemia, or HIV infection [76,77]. ...
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Objective: To determine the prevalence of diabetes mellitus (DM), assess its influence on health-related quality of life (HRQoL) among TB patients. Methods: In this prospective study, eligible patients at three primary health care centers in urban slum region of South Delhi, India, underwent blood glucose screening at treatment initiation. HRQoL scores were determined by conducting face-to-face interviews using Dhingra and Rajpal (DR-12) scale at pretreatment, end of intensive phase and end of the treatment. Results: In 316 patients, the overall DM prevalence was 15.8%, of whom 9.5% were known to have diabetes and 6.3% were diagnosed at TB treatment initiation. DM was more common among patients of older age (p<0.001), with higher BMI (p<0.001), with PTB (p=0.02), and with poor psychological status. HRQoL was significantly poor in the socio-psychological and exercise adaptation domains in DM patients ˃50 years of age at each visit. Older age, poor literacy, loss in workdays, alcohol use and socioeconomic status significantly predict poor HRQoL scores in DM patients. Uncontrolled DM patients demonstrated poor HRQoL at the end of the intensive phase (P=0.04) of treatment and at its completion (P=0.03) compared to those with controlled DM. Conclusion: Addressing screening measures and glycaemic control along with social determinants such as literacy level and alcohol consumption could be an important means of improving the HRQoL of TB with DM patients. This article is protected by copyright. All rights reserved.
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Health-related quality of life (HRQOL) among pulmonary tuberculosis (PTB) patients has not been investigated in the Philippines. This study aimed to describe HRQOL among PTB patients and to determine factors that are associated with HRQOL. A cross-sectional survey was conducted at 10 public health centers and 2 non-government organization clinics in District I, Tondo, Manila. Face-to-face interviews using a structured questionnaire including Short Form-8, Duke-UNC Functional Social Support Questionnaire, and Medical Research Council (MRC) dyspnea scale were performed with 561 PTB patients from September to November 2012. HRQOL among PTB patients was generally impaired. Factors associated with lower physical component summary were exposure to secondhand smoke (SHS) (P = 0.038), positive sputum smear result (P = 0.027), not working (P = 0.038), lower education level (P < 0.01), number of symptoms (P < 0.01), number of adverse drug reactions (ADRs) (P < 0.01), higher score on the MRC dyspnea scale (P < 0.01), and low perceived social support (P = 0.027). Lower body mass index (P = 0.016), non-SHS exposure (P = 0.033), number of symptoms (P < 0.01), number of ADRs (P < 0.01), low perceived social support (P < 0.01), and negative perception for waiting time in the clinic (P = 0.026) were identified to be factors significantly associated with lower mental component summary. Socioeconomic status including SHS exposure and low perceived social support, in addition to clinical factors, may be associated with poor HRQOL. Further study would be needed to assess our findings.
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Newly diagnosed pulmonary tuberculosis (PTB) patients starting treatment under the Revised National Tuberculosis Control Programme (RNTCP) in a North Indian city. To quantify impairment in health-related quality of life (HRQoL) of PTB patients at the time of diagnosis and during treatment, and to assess the utility of these assessments as a measure of outcome under programme conditions. HRQoL was assessed using the Hindi version of the 26-item World Health Organization Quality of Life (WHOQOL-BREF) scale at the start and end of the intensive phase and at completion of treatment. Four domain scores-physical, psychological, social relationships and environment-were calculated and compared between groups, based on different patient and disease characteristics. Psychometric evaluation was conducted by assessing acceptability, validity and responsiveness of the questionnaire. A total of 2654 HRQoL assessments were performed among 1034 patients. Domain scores were generally better among men, urban residents, younger patients, patients with higher socio-economic status and those with less severe disease. The WHOQOL-BREF demonstrated good psychometric properties, and domain scores improved with treatment. Residual HRQoL impairment was noted in some patients even at treatment completion. HRQoL is impaired in patients with PTB, and improves rapidly and significantly with programme-based treatment. HRQoL assessment can be used as an adjunct outcome measure for patients treated by the RNTCP.