Background:PAX2 is a nuclear transcription factor gene that is highly conserved among species. Variants within PAX2 could result in optic nerve colobomas and kidney hypoplasia. However, little clinical and genetic information is currently available about PAX2 variants in Chinese children.Objective: This study aims to further understand the clinical manifestations and genetic characteristics of PAX2 variants in Chinese population.Methods: In this single-center retrospective study, we analyzed the clinical data of 10 children identified as carriers of PAX2 variants by gene sequencing. All the variants found in this study were analyzed using in silico prediction and American College of Medical Genetics and Genomics (ACMG) standards and guidelines.Results: The mean age for developing the first symptom in 10 unrelated children was 7.2 years old. Proteinuria and bilateral kidney dysplasia were found in every patient. Two children underwent kidney histological examination; one child showed high-intensity C1q deposition in the kidney, and the other child showed focal segmental glomerular sclerosis (FSGS). Three children had PAX2-related ocular abnormalities, including nystagmus, retinal exudation, amblyopia, microphthalmia, microcornea, and total blindness. In addition, one patient had the comorbidity of oculocutaneous albinism (OCA). Eight different PAX2 variants were found in ten patients, three of which were reported for the first time.Conclusion: We reported some patients with unique manifestations and comorbidities, and we reported three variants that have not been previously identified. The PAX2 gene is prone to spontaneous variants, and the outcome of patients is unfavorable. Because of the lack of specific therapy, genetic testing should be recommended for individuals with obvious evidence of kidney dysplasia and eye abnormalities, and kidney protective treatment should be initiated early. PAX2 is a member of the PAX family of transcription factors, which localizes to human chromosome band 10q24, spans 84.2 kb, and contains 12 coding exons  and FSGS . Many patients eventually develop kidney failure (KF) and need kidney replacement therapy. However, visual impairment is known to have a wide variation that can be asymmetric, ranging from normal to complete blindness  variant by gene sequencing in our single-center study from May 2017 to April 2021. In our cohort, six patients were admitted to the hospital with proteinuria, three manifested abnormal kidney function, and one presented with kidney ultrasound abnormalities. Before the genetic tests, informed consent was obtained from all families. In addition to these ten patients, we also found one patient with recurrent painless gross hematuria, who had left renal vein entrapment (LRVE) and a PAX2 variant (c.725G > A). However, his kidney structure and function were normal, and the pathogenicity of his variant was uncertain. His symptoms were totally relieved after conservative medical treatment. This result suggested that the LRVE, instead of the PAX2 variant, was the leading cause of his gross hematuria. Because he did not have a confirmed genetic diagnosis, we finally excluded this patient.We enrolled 10 patients with a We retrospectively reviewed the clinical findings of 10 patients, including the onset age, kidney findings, extrarenal manifestations, and kidney histological examination findings. The definitions of the main clinical manifestations, including kidney and ocular symptoms, and the methods of evaluating kidney function are shown in Peripheral blood samples were collected from 10 patients and their parents, and genomic DNA was extracted according to standard procedures. The standard Illumina libraries were prepared by using a DNA Sample Prep Reagent Set . The amplified DNA was captured using the capture kit of urinary system genes. The enrichment libraries were sequenced on Illumina HiSeq 2000, Illumina Nova6000, and MGI DNBSEQ-T7. The raw data were saved in FASTQ format after sequencing. Both Illumina sequencing adapters and low-quality reads (<80 bp) were filtered by cut adaptor software. BWA was used to map the clean reads to the UCSC hg19 human reference genome.In silico prediction of the variants was calculated from the output of the programs Sorting Intolerant from Tolerant (SIFT), Polymorphism Phenotyping v2 (PolyPhen_2), MutationTaster, GERP++, and REVEL. In addition, genomic DNA from all patients’ parents was obtained for Sanger sequencing, which was used to confirm the variants identified by next-generation sequencing (NGS).All variants were identified by GATK or Sentieon and then annotated by ANNOVAR software, as well as the following multiple databases: 1,000 Genomes Project, ESP6500, ExAC, and ExAC-EAS. In downstream analysis, we used five steps to select the potential pathogenic mutations: 1) The mutation reads had to be more than 5, and the mutation ratio had to be no less than 30%. 2) The mutations for which the frequencies were more than 5% in the 1000g, ESP6500 ExAC, and ExAC-EAS database were removed. 3) If the mutations existed in InNormal database (MyGenostics), then they were dropped. 4) The synonymous mutations were removed. 5) After (1), (2), and (3), if the mutations were synonymous and they were reported in HGMD, then they were retained. Then, we performed pathogenicity analysis of the variants according to the ACMG standards and guidelines, and variants were classified as pathogenic, likely pathogenic, uncertain significance, likely benign, or benign . The ACMA total of 10 patients were enrolled in this study, including six boys and four girls, and their cases were sporadic. The ages of the patients on admission ranged from 0.3 to 15.2 years, with an average age of 8.8 years, while the age at the development of the first symptom was 7.2  years old. Six patients  were identified with proteinuria as the first symptom, three patients  were admitted to the hospital due to KF, and kidney hypoplasia was detected in patient 9 after birth. Every patient in our cohort had confirmed congenital kidney hypoplasia and decreased estimated glomerular filtration rate (eGFR).PAX2 variants. Ten patients had varying degrees of proteinuria in our study; three of them (30.0%) presented nephrotic-range proteinuria. Six patients (60.0%) were found to have hematuria. In general, the patients with the PAX2 variants had various clinical manifestations except for proteinuria, but the other nephrotic manifestations, such as edema and hypoproteinemia, were rare. Bilateral kidney dysplasia without ureterectasia was found in all patients by kidney ultrasound examination. Kidney cysts were detected in three patients (30.0%); one patient had multiple cysts, and the other two had a single cyst. The kidney ultrasound results of patients in our single-center study showed that the more severe the kidney dysplasia was, the worse kidney function of the patient. The relevant information is summarized in Proteinuria is the most common kidney manifestation in children with Only two patients underwent histological examinations, but the results were completely different . The kidPAX2 variants. In our cohort, only patients 2 and 8 had subjective ocular abnormalities. Five patients  underwent ophthalmic fundus examination. Patient 2 presented with severe ocular lesions since birth, including microphthalmia, microcornea, congenital amblyopia of the right eye, and congenital blindness of the left eye. After hospitalization, bilateral conjunctival concretions were also discovered in patient 2. Retinal exudation without macular coloboma was detected in patient 7. Furthermore, patient 8 had binocular nystagmus, and the results of the brainstem auditory evoked potential (BAEP) were abnormal, showing suspicious bilateral distal auditory nerves or cochlear dysfunction. In addition to ocular and auditory lesions, malnutrition, obesity, short stature, growth retardation, cholecystolithiasis, and testicular dysgenesis could be observed in our group. Among them, cholecystolithiasis and testicular dysgenesis were rare extrarenal phenotypes that have not been reported before. The relevant information is summarized in Ocular manifestations are the most common extrarenal manifestations in children with PAX2 variant. The ocular symptoms of OCA are mainly reduced pigmentation and congenital nystagmus, which were inconspicuous in patient 2. Therefore, we supposed that the PAX2 variant was the leading cause of the ocular lesions of patient 2.It is worth mentioning that we revealed suspicious OCA in patient 2, such as fair skin, light yellow hair, and eyebrows. The gene test of this patient revealed compound heterozygous variants in the OCA2 gene , originating from his father and his mother, respectively. The variants have both been reported as pathological variants of OCA . This meIn our single-center study, the longest follow-up time of 10 children was 4.4 years, the shortest was 0.67 years, and the average was 2.3 years. Among them, five patients  had developed KF, and the kidney function of three patients deteriorated drastically within a few months but that of the other two patients deteriorated over several years. However, almost all five patients were in adolescence at the onset of KF, and their onset ages ranged from 8.8 to 15.2 years. The kidney function of the remaining five patients was relatively stable. To date, four patients  are undergoing maintenance hemodialysis. The other six patients are receiving oral drug treatment to protect kidney function. None of the patients had new ocular abnormalities.PAX2 variants are summarized in Eight different variants, most of which occurred in exons 2–4, were found in the 10 patients. Among all the variants, variants c.754C > T and c.478_479insT and the large genomic deletions of patient 4 were not previously reported in the Human Gene Variant Database (HGMD) or ClinVar . Accordide novo variants. The variants of two patients (patients 4 and 10) were confirmed to originate from their parents , and they all had decreased eGFR and kidney hypoplasia. Nevertheless, the results of ophthalmic examinations were not the same. They were not related to each other, neither were they relatives. The variant (c.76dupG) was a recurring mutation that had been reported by many studies, rather than a common mutation derived from a single founder. Compared with the three patients in our study, some patients have been reported to have other presentations, such as microcephaly, mental retardation, soft skin, and VUR  previously  developed KF, while the kidney function of the other patients was relatively stable. Although  decades . CompareThere are some limitations to our study. First, our study was retrospective, and most of them had no subjective visual or hearing abnormalities. Therefore, not all the patients had undergone ocular and hearing examinations. Second, only two patients had received a kidney histological examination, and one of them was diagnosed with C1q nephropathy, which is most likely the first report to date. However, the reason for C1q deposition is still unknown and needs to be further explored. Third, except for immediate family members, the other family members’ information was not available in all the patients of our center. However, no suspicious family history was found.PAX2 variants. Patients with PAX2 variants developed KF mainly in adolescence rather than in early life, and the clinical manifestations of those patients were highly heterogeneous. Many patients with PAX2 variants developed KF requiring long-term kidney replacement therapy and even transplantation. Thus, individuals with clear evidence of kidney hypoplasia and ocular abnormalities should be suggested for genetic testing. If such individuals have PAX2 variants, they should be examined for PAX2-related organ damage, closely followed up for kidney function, professionally managed to avoid KF development, and indicated for appropriate genetic counseling.In summary, our study identified three unrecognized variants, two patients with novel presentations, and several novel manifestations of the


P = .041), urban areas (P = .047), and in patients in long-term care (P = .03). Similarly, no differences were observed for the ability to cope with the pandemic (P > .05). Patients who underwent surgery also had a higher risk of depression , a lower EQ-5 score (P = .001), a higher body mass index (P = .004), greater consumption of drugs (P < .001), especially opiates (P < .001). Patients who underwent surgery constitute a vulnerable population during the COVID-19 pandemic, with poorer quality of life and had a much higher risk of depression. They are also polymedicated and prefrail, adhere well to COVID-19 preventive measures, and do not seem to fear visiting health centers.This observational, cross-sectional case-control study evaluates the impact of coronavirus disease 2019 (COVID-19) on health-related quality of life (HRQoL) in elderly persons who have undergone surgery for adult spinal deformity (ASD). On December 31, 2019, the Chinese authorities first reported severe acute respiratory syndrome coronavirus 2, and on March 11, 2020, it was declared a pandemic. The pandemic seems to have had a negative effect on elderly patients who underwent ASD, in terms of functional and psychological quality of life. We selected patients with ASD aged > 70 years who had undergone surgery between 2010 and 2015 and compared them with age- and sex-matched patients who did not have ASD. We recorded sociodemographic variables, type of surgery, levels of spinal fusion, HRQoL , fear of visiting a health center, fear of leaving one’s house, and adherence to preventive measures. The study population comprised 174 patients , of whom 87 had undergone surgery for ASD. The incidence of COVID-19 was higher in patients aged > 85 years ( The prevalence of adult spinal deformity (ASD) can reach 68% in elderly persons, with a negative impact on health-related quality of life (HRQoL) owing to associated pain and disability. The incidence of ASD is expected to rise gradually as the population ages. When the present article is submitted, >323 million patients will have been infected and >5.5 million will have died, according to the WHO . These figures are unprecedented.On December 31, 2019, the Chinese authorities first reported on a group of patients with respiratory infection of unknown cause that came to be known as severe acute respiratory syndrome coronavirus 2. The World Health Organization (WHO) subsequently termed it coronavirus 2019 disease (COVID-19), and on March 11, 2020, it was declared to be pandemic. Those living in long-term care facilities are particularly affected since they have been subject to considerable nosocomial transmission and frequent outbreaks.Although COVID-19 affects persons of all ages, elderly people who have chronic diseases are especially vulnerable, with more severe clinical pictures and a higher mortality rate.,7The quarantine periods generated a series of risks for mental health, leading to cases of depression, irritability, anxiety, fear, anger, and insomnia, together with the stress associated with loneliness and the fear of contracting the disease and not being able to say goodbye to loved ones. Moreover, many elderly persons do not have the necessary resources to cope with the stressful situation resulting from the COVID-19 pandemic. They lack material resources , social resources , and cognitive/biological resources .However, to date, the negative effects of the pandemic have not been reported in elderly patients who had undergone ASD surgery, in terms of functional and psychological quality of life.The objective of this study was to determine how the pandemic influenced the functional and psychological status and HRQoL in patients who had undergone ASD surgery. Our hypothesis is that these patients, especially the older ones, have suffered a worse adaptation to the pandemic and will have a worse quality of life.We performed an observational, cross-sectional case-control study of patients who underwent surgery for ASD in 2 tertiary hospitals (between January 2010 and December 2015) and compared our findings with those of patients without ASD from the same health care district.The data were collected 2 times: before surgery and after surgery (between April and May 2020).Of the 152 patients who underwent surgery for ASD, 134 fulfilled the inclusion criteria, 28 had died, 16 could not be contacted, and 3 refused to participate in the study. Finally, we included 87 patients who had undergone surgery. The characteristics of the patients and the type of surgery are summarized in Table Our series comprised a total of 174 patients: 87 who underwent surgery for ASD and 87 who did not have ASD.This study was approved by the institutional research ethics committee.All patients gave their written informed consent to be included in the study.Includes patients who underwent surgery for ASD aged > 65 years, with spinal curvature in the coronal plane > 20°, a sagittal vertical axis > 5 cm, pelvic tilt > 25°, or thoracic kyphosis > 60°. The operated patients presented imbalance, with lumbar and radicular pain. All of them had received conservative treatment .Includes patients without ASD aged > 65 years who visited a reference health center with other conditions between October and December 2019. These patients came to the health center for presenting stable chronic diseases that required follow-up, such as diabetes mellitus, dyslipidemia, or hypertension. These were matched by age and sex with those who underwent surgery.We excluded in both groups patients with tumors, infections or deformity , and those who died.Patients who underwent surgery for ASD aged < 65 years, with spinal curvature in the coronal plane < 20°, a sagittal vertical axis < 5 cm, pelvic tilt < 25°, or thoracic kyphosis < 60°. Patients who still had conservative treatment options  or did not want to undergo surgery.Patients with ASD aged < 65 years who visited a reference health center with acute, decompensated, or severe systemic diseases. Patients who were not matched for age and sex with those who underwent surgery.All information was collected by a researcher who did not participate in treatment.We collected sociodemographic and clinical data, as follows: age, sex, body mass index (BMI), smoking history, and levels of spinal fusion (patients who underwent surgery).All participants completed the EuroQol-5D (EQ-5), Geriatric Depression Scale (Yesavage) (GDS), Modified Frailty Index-11 (MFI-11), and Barthel Index Questionnaire (BI). The patients who underwent surgery also completed the following questionnaires: Short Form 12 Health Survey (SF-12), Scoliosis Research Society-22 (SRS-22), and Oswestry Disability Index (ODI).,9Patients’ fear of visiting a health center, fear of leaving their house, and adherence to protective measures were assessed using a single-element scale ranging from 0  to 10 (very much). These scales are inexpensive, valid, and reliable measuring instruments that can be used when assessment via other, more extensive scales is not possible.,11The EQ-5D is used to evaluate HRQoL. It consists of a descriptive system and a visual analog scale (EQ VAS). The descriptive system has 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of severity . The EQ VAS is used to record the self-reported health status on a vertical VAS where the endpoints are labeled “The best health you can imagine” and “The worst health you can imagine.”–14The GDS is one of the most widely used instruments for identifying depression in elderly persons. It comprises 15 dichotomous questions (yes/no), of which 10 are positive and 5 are negative. A score ≥ 5 points indicates that the patient is at risk of depression, and a score > 10 points is considered an indicator of depression.,16The MFI-11 is a simplified form of the Canadian Study of Health and Aging Clinical Frailty Scale. It covers 11 variables or deficits: functional status, dependency, diabetes mellitus, lung problems, congestive heart failure, myocardial infarction, heart surgery, hypertension, previous transient ischemic attack, history of cerebrovascular accident, and peripheral vascular disease. The instrument yields an index ranging from 0 to 1 and classifies a patient as nonfrail (MFI = 0), prefrail (MFI > 0 and < 0.21), and frail (≥0.21).The BI is a generic measure of a patient’s level of independence with respect to basic activities of daily living (ADL). It assigns various scores and weights according to the patient’s ability to perform the activities. The 10 ADLs evaluated are feeding, moving from wheelchair to bed, personal toileting, getting on and off a toilet, bathing/showering, walking on a level surface, ascending and descending stairs, controlling bladder, and controlling bowel. The activities are scored as 0, 5, 10, or 15 points, with an overall range of 0 (completely dependent) to 100 (completely independent).P < .05. Descriptive statistics are expressed as mean and standard deviation. The inferential analysis was performed using the t test and Mann-Whitney test for continuous variables, the χ2 test for categorical variables, and the odds ratio (OR) with 95% confidence interval (CI).The statistical analysis was performed using SPSS version 22.0. Statistical significance was set at The study population comprised 174 patients , of whom 87 had undergone surgery for ASD with a mean of 8.3 (3.5) levels of spinal fusion and 8.5 (2.2) years of follow-up. 57 patients were grade 1, 21 (23.3%) were grade 2, and 9 (10.3%) were grade 3 ; similarly, no differences were recorded in coping with the pandemic (P > .05), fear of visiting a health center (P = .693), fear of leaving one’s house (P = .325), or adherence to protective measures (P = .343). In contrast, we did observe a higher risk of depression, with a GDS of 6.7  and a poorer score in the EQ-5  , took more drugs , especially opiates , had a lower educational level (P = .004), and had significant differences in their place of residence (P < .001) (Table Patients who underwent surgery had a higher BMI (P = .28), were afraid to visit a health center (P = .02), were older (P = .04), had fewer levels of spinal fusion (P = .017), had a higher BMI (P = .03), and usually lived with other persons (P = .013). An American Society of Anesthesiologists score of III was recorded in 56.5% of frail patients (P = .04).Slightly more than a quarter of the patients who underwent surgery (26%) were frail  score of 23.2 ± 5.2 and mental component summary (MCS) score of 46.9 ± 14.5. Eight years after surgery, their situation continued to improve, with a PCS of 31 ± 10 and no variations in the MCS score (46.8 ± 13.6). The PCS score improved by 8 ± 10. Improvements were also recorded in the ODI, SF-physical component, and SRS-22  (Table P = .041), patients living in an urban area (P = .047), and patients living in long-term care facilities (P = .03)  and specific spinal scales (SRS-22 and ODI), a scale to assess depression in elderly persons (GDS), and a scale to assess frailty (MFI-11). Generic approaches were used in order to cover important common domains for the general population, since some patients did not have ASD, and specific approaches were used to evaluate the impact of ASD, depression, and frailty. whereas for patients in the present study, presurgery PCS was 23.2 ± 5.2 and presurgery MCS was 46.9 ± 14.5. Eight years after surgery, patients continue to improve, with a PCS score of 31 ± 10 and no variation in MCS (46.8 ± 13.6), very possibly because of the pandemic.Initial SF-12 values were very low in patients who underwent surgery for ASD. The mean SF-12 score in Spain for patients aged > 75 years is PCS 41.8 and MCS 49.8,The results reported for the EQ-5 were similar to those of the Spanish National Health Survey (ENSE). Patients aged > 75 years have an EQ index of 0.7 and those who underwent surgery have an index of 0.4. They also have a poorer perception of their HRQoL (EQ-5 VAS) 62 vs 49. Therefore, the study population has very high levels of anxiety and depression, with an EQ-5 of 1.9, compared with an EQ-5 of 0.4 for the age-matched general population (ENSE data). However, we cannot say the same for psychological status, since, although statistically significant differences were not recorded in the psychological dimension of SRS-22 or the SF-12, the GDS revealed that more than half of the study population is at risk of depression (GDS > 5), which was more frequent in women and patients who underwent surgery. This finding is most likely due to the strict lockdown measures.,31 Although necessary, self-isolation generates a series of risks for mental health and increases the risk of depressive disorders, post-traumatic stress, and even cognitive impairment.–36In terms of functioning, our data are consistent with those of other studies, namely, lockdown did not negatively affect patients, as shown by the SRS-22 and SF-12.,38 and that patients with depression may have a heightened perception of pain. They may also be more subject to surgical complications and at risk of further surgery.,41The incidence of depression seems to be higher in patients who underwent surgery, although we are unable to state that spinal surgery is a risk factor. However, we do know that chronic pain increases the risk of depression up to 4-foldMood disorders negatively affect functioning and quality of life. Some studies have shown an inverse correlation between depression and HRQoL and between depression and self-perception of health, with depression acting as a vulnerability factor. Consequently, we can state that depression and quality of life are closely associated. Similarly, we must not forget that ≈20% of patients with chronic diseases can eventually develop a major depressive disorder. In addition, patients who underwent surgery tended to have greater BMI, greater risk of depression, more frequent consumption of drugs (including opiates), and a lower educational level, all of which probably contribute to their lower HRQoL.Among patients who underwent surgery, we found no greater incidence of COVID-19 or differences in ability to cope with the pandemic in terms of fear of visiting a health center, fear of leaving one’s house, or adhering to protective measures. Similarly, we found no differences in levels of anxiety, which were high in both groups. Our results are comparable to those reported elsewhere.We found consumption of drugs to be common, especially in patients undergoing surgery, who took a mean of 9 drugs per day. It is also noteworthy that 52% took opiates. Polymedication affects HRQoL, especially in the case of opiates, which were consumed by more than half of the patients in this study. In addition, despite being very potent analgesics, opiates are associated with impaired functional capacity and an increased number of falls. Misuse of opiates is one of the main causes of accidental death. The United States Centers for Disease Control and Prevention reported that 25% of patients receiving long-term opiate therapy develop opiate use disorder, whose risk is associated with dose and duration of treatment.Polymedication is common in elderly patients and has become a public health problem in developed countries, not only because of its prevalence, which is around 70% in frail persons, or its consequences but also because it is increasingly frequent. Consequently, recent decades have seen an increase in the percentage of patients who are polymedicated, and this seems to be associated with aging of the population and increased morbidity in elderly persons. Polymedication in the elderly is independently associated with increased mortality, poorer HRQoL, and greater dependence. Therefore, it seems necessary to try to reduce consumption of drugs in persons for whom they may do more harm than good, particularly in frail elderly patients , who could benefit from controlled deprescription.,47 Elderly persons have been the most affected population to date, since the conditions they are affected by increase their frailty and leave them vulnerable to greater morbidity if they contract COVID-19.,24Although the incidence of COVID-19 was similar in both groups (10%–13%), we found no statistically significant differences between patients who underwent and did not undergo surgery. This may be because the type of patient was similar in both cases (prefrail), thus making them more susceptible to disease and leading to greater mortality.Biological age is not the same as chronological age. However, the prevalence of frailty increases with age, owing to factors such as the accumulation of health disorders. A study of almost 3000 elderly persons showed that frailty was more common with age and that at age 95 years, practically all patients in the sample were frail owing to an accumulation of health deficits.–52 Very often, they live in social-health care centers, where staff change frequently, with many visitors, and resources are sometimes lacking, thus leaving them very vulnerable.,5,24The residents of care homes have been considerably affected by COVID-19, since they are vulnerable patients with poorer HRQoL, poorer physical health  and mental health , and reduced opportunities for social relationships since many live alone or have few relatives.,54We also recorded more cases in urban areas, as reported elsewhere, possibly owing to the high population density and the high level of local and international interconnectivity, which left patients particularly vulnerable to the spread of the virus. Approximately 90% of cases throughout the world have been in urban areas.,56We found that the frailest patients were the least frightened of visiting a health center, very probably because they see a health center as a safe, controlled place, where they feel protected, especially if they are aware of their frailty. Such patients seem to have a good family support structure since most live with other people and probably do not have to visit a health center alone, thus reducing their anxiety. In addition to these factors, it is worth noting that for many, telemedicine is not a readily available option owing to the scarce use they make of new technology and their low educational level.,58 Fourth, as the study was limited to a single country, it is important to consider variations with other countries, where the pandemic has evolved differently.Our study findings are subject to various limitations. First, as the sample was small, our results should be confirmed in a larger series. Second, the study design was retrospective. Third, the sample was heterogeneous. These limitations affect the vast majority of studies because ASD has various causes.Despite its limitations, ours is the first study to examine in depth the psychological and functional effects of the pandemic using specific scales with a control group comprising patients who did not undergo surgery. Therefore, we were able to evaluate in greater detail the impact of the pandemic on patients who underwent surgery for ASD.Patients who underwent surgery constitute a vulnerable population during the COVID-19 pandemic, with poorer quality of life and had a much higher risk of depression.They were also polymedicated and prefrail. They do not seem to be reticent about visiting a health center and adhere to protective measures.It seems necessary to implement multidisciplinary units to attempt to improve the situation of elderly persons. These should diagnose and treat depression, reduce prescription of drugs, improve functioning, and provide support to frail elderly persons who live alone.We should make every effort to maximize physiological and psychological status before and after surgery to improve the quality of life of elderly patients who undergo surgery for ASD.


At present, there is no established biomarker for the diagnosis of depression. Meanwhile, studies show that acoustic features convey emotional information. Therefore, this study explored differences in acoustic characteristics between depressed patients and healthy individuals to investigate whether these characteristics can identify depression.Participants included 71 patients diagnosed with depression from a regional hospital in Beijing, China, and 62 normal controls from within the greater community. We assessed the clinical symptoms of depression of all participants using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Patient Health Questionnaire (PHQ-9), and recorded the voice of each participant as they read positive, neutral, and negative texts. OpenSMILE was used to analyze their voice acoustics and extract acoustic characteristics from the recordings.p < 0.05). Several mel-frequency cepstral coefficients (MFCCs), including MFCC2, MFCC3, MFCC8, and MFCC9, differed significantly between different emotion tasks; MFCC4 and MFCC7 correlated positively with PHQ-9 scores, and correlations were stable in all emotion tasks. The zero-crossing rate in positive emotion correlated positively with HAMA total score and HAMA somatic anxiety score , and MFCC9 of neutral emotion correlated negatively with HAMD anxiety/somatization scores (r = −0.34). Linear regression showed that the MFCC7-negative was predictive on the PHQ-9 score  and MFCC9-neutral was predictive on HAMD anxiety/somatization score . Logistic regression showed a superior discriminant effect, with a discrimination accuracy of 89.66%.There were significant differences between the depression and control groups in all acoustic characteristics (The acoustic expression of emotion among patients with depression differs from that of normal controls. Some acoustic characteristics are related to the severity of depressive symptoms and may be objective biomarkers of depression. A systematic method of assessing vocal acoustic characteristics could provide an accurate and discreet means of screening for depression; this method may be used instead of—or in conjunction with—traditional screening methods, as it is not subject to the limitations associated with self-reported assessments wherein subjects may be inclined to provide socially acceptable responses rather than being truthful. Depression is a serious mental illness that can result in a significant decline in a patient’s social functioning and quality of life. According to a 2019 epidemiological survey in China, the lifetime prevalence of depression was 3.4%, and the 12-month prevalence was 2.1%—both of which are higher than the prevalence rates for most other psychiatric disorders  is the basic frequency generated by the vibration of the vocal cords. Results from a 4-week sertraline/placebo double-blind controlled trial showed that the mean fundamental frequency of the depression group that responded to the treatment increased from baseline; meanwhile, the frequency remained consistent or decreased from baseline for the depression group that did not respond to the treatment . AdditioAdditionally, although previous studies that used small sample sizes and included limited acoustic characteristics have shown that depressed patients present abnormal acoustic characteristics, no studies to date have verified the correlation between acoustic characteristics and clinical symptoms. Hence, there is a lack of explanation for the psychopathology of abnormal acoustic characteristics. It is unclear whether acoustic features can partly reflect the severity of emotional symptoms and whether the severity of depression can be evaluated by certain acoustic features.To address this limitation, the present study surveyed a relatively large sample of depressed patients and healthy controls. Using MFCC, ZCR, HNR, and F0, which are known to reflect the emotional changes of the voice, we aimed to verify the relationship between acoustic characteristics and severity of depression and the significance of acoustic characteristics in disease discrimination. We also conducted a preliminary exploration of the psychopathological mechanism of abnormal acoustic characteristics.We hypothesized that the acoustic characteristics of depressed patients and normal people differ and are related to depressive symptoms and that acoustic characteristics can help distinguish depressed patients from normal individuals to some extent. If acoustic characteristics can be used as objective biomarkers of depression to provide a diagnostic reference, it may help decrease the rate of misdiagnosis and missed diagnosis, promote early identification and treatment of depression, and ultimately improve the patient’s prognosis. Since acoustic characteristics can be obtained automatically, exploring the acoustic characteristics that can predict the severity of anxiety and depression was conducive to promoting the intelligent evaluation of depressive disorder severity. Moreover, it can also promote the development of artificial intelligence ability to identify depression and provide Internet-based medical treatment to patients, which can have far-reaching implications.We recruited 71 patients from Beijing Huilongguan Hospital from 2018 to 2020. An experienced psychiatrist conducted detailed mental and physical examinations of the participants. The inclusion criteria were as follows: (1) diagnosed with depression according to the Diagnostic and Statistical Manual of Mental Disorders (DSM–IV), (2) aged 18–60 years, (3) attained junior high school education or above, and (4) able to read Chinese fluently. The exclusion criteria were as follows: (1) diagnosed with severe cerebrovascular disease, brain injury, and other nervous system diseases; (2) having a serious physical disease; (3) having accompanying substance abuse (except tobacco) problems; and (4) diagnosed with acute nasolaryngology and respiratory system diseases affecting the vocal cords. Sixty-two healthy controls with no current or previous mental illness were recruited from the surrounding community and screened by the Mini-International Neuropsychiatric Interview. The remaining inclusion and exclusion criteria were the same as those used in the patient group.This study was approved by the Ethics Committee of Beijing Huilongguan Hospital. A specific psychiatrist explained the details of the study to all the participants; meanwhile, their information was strictly confidential. Audio data would be stored on a specific hard disk. Participants took part in voluntarily and there would be no penalty for withdrawal at any time. Written informed consent was obtained from all participants.All participants provided their general information, and the depression group completed clinical symptom evaluation questionnaires, including the 17-item Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), and Patient Health Questionnaire (PHQ-9). The HAMD-17 is a commonly used depression rating scale comprising 17 symptom items across five domains including anxiety/somatization, weight, cognitive impairment, retardation, sleep disturbance , 22. TheAll participants were seated in a noise-controlled room (background sound less than 30 dB). After a 3-min rest period, voices were recorded using a fixed ISK BM-5000 microphone . The participants were asked to read three paragraphs in their natural tone. Each paragraph contained about 200 Chinese characters, which described one of the three different emotions: positive, negative, and neutral. The positive emotion text depicted scenes from the Chinese New Year and included words such as “happy,” “smile,” “play games,” “delicious,” “singing and dancing,” and so on. The negative emotion text included “punishment,” “trouble,” “worry,” “anxious,” “worry,” “slander,” “pain,” “dark clouds,” and so on. The neutral emotion text described a bridge using location, shape, and other descriptors that did not contain any emotion-related words. Word stimulations can induce different emotional and physiological responses , 26 and t-test was used for comparison between groups. Categorical data were analyzed using the chi-square test. Multivariate analysis of variance was used to compare the differences in acoustic characteristics between groups, with gender, age, and education level as covariates. To address the problem of multiple comparisons (15 acoustic features), a false discovery rate (FDR) procedure was further performed at a q-value of 0.05 over all acoustic features together. Spearman correlation analysis was performed to explore the relationship between depression symptom scores and acoustic characteristics. Further, multiple linear regression was conducted to explore the relation between clinical symptom and acoustic characteristics.All statistical analyses were performed using the SPSS 21.0. For normally distributed continuous variables, the independent sample via logistic regression (LR) and support vector machine (SVM) models, respectively, both of which were used frequently in previous studies. Due to its superior discriminant effect, the LR model was selected for further analysis. All machine learning processes were completed with scikit-learn in Python 3.8. All parameters were performed by default to avoid the influence of manual intervention on discrimination results. The f_classif method in the feature_selection module of scikit-learn was used to screen all of acoustic features. The LR analysis was performed again based on the 20 selected variables, while analyzing the contribution of each variable to the classification. We performed a 10-fold cross validation of the classification and divided the dataset into the training set and the test set at a 7:3 ratio. The test data was only used for the validation of the discriminant model and were not used in any training process. Figures were generated from Matplotlib, a popular data visualization package for Python , which survived FDR-correction. For η2 0.01, 0.06, and 0.14 were considered small, moderate, and large effect sizes, respectively. ZCR, F0, MFCC1-5, MFCC7-10 showed a large effect size, and the remaining features showed a moderate effect size. Only MFCC2, MFCC3, MFCC8, and MFCC9 had statistically significant conditional main effects in the positive, neutral, and negative emotion tasks , but none of the acoustic characteristics had a group × condition interaction effect —with gender, age, and education level as covariates—showed significant inter-group main effects of all of the acoustic characteristics (n effect .r = 0.31) and with the HAMA somatic anxiety subscale score (r = 0.34). MFCC9 in the neutral task showed a negative correlation with the anxiety/somatization subscale score of the HAMD (r = −0.34). The remaining acoustic characteristics did not show a significant correlation with depressive symptoms (Since there were significant differences between the groups for each acoustic characteristic indicator, we performed a Spearman correlation analysis for all acoustic features and the PHQ-9, HAMA, and HAMD scores. The results showed that MFCC4 and MFCC7 had significant positive correlations with the PHQ-9 score, regardless of the positive, neutral, or negative emotion tasks. ZCR in the positive condition task showed a significant correlation with the HAMA total score (symptoms .F = 7.25, R2 = 0.20, p = 0.01 (In linear regression, the PHQ-9 score was a dependent variable, while age, gender, education, MFCC4, and MFCC7 were independent variables. To avoid high collinearity of the same features under different emotion tasks, we selected MFCC4-neutral and MFCC7-negative, which had the highest correlation coefficient with the PHQ-9 score. Stepwise method was used. The result showed statistically significant effects, p = 0.01 .F = 4.15, R2 = 0.11, p = 0.049 (Then, the HAMD anxiety/somatization score was used as a dependent variable, while MFCC9-neutral, age, gender, and education were independent variables. Similarly, stepwise method was used. Here too, linear regression showed statistically significant effects,  = 0.049 .The LR model showed better discriminant results than SVM between the depression and control groups, with a discrimination accuracy of 89.66% and AUC of 0.98. A recall of 0.94 signified that 94% of depression patients were predicted as the depressed group, and precision of 0.89 signified that 89% of participants in the predicted depressed group were actually depression patients. Further, 83% of the healthy controls were predicted to be in the control group, and 91% of the participants in the predicted control group were actually healthy controls. The discrimination accuracy of the SVM model and the AUC were 86.21% and 0.95, respectively see .There were significant differences in acoustic characteristics between the depression and normal control groups, after controlling for gender, age, and education. Only MFCC2, MFCC3, MFCC8, and MFCC9 showed differences during the positive, neutral, and negative emotion tasks. This suggests that there are differences in some acoustic features under different implicit emotional task patterns. Taguchi et al. also found that MFCC2 was higher in depressed patients than in normal controls, which is consistent with our results, but they did not report an association between MFCC and depressive symptom severity . These iPatients with depression often have autonomic nervous function disorders, and the muscle tone of their vocal tract can be affected by the disease, which may be one of the factors that distinguish depressed patients’ acoustic characteristics from those of healthy individuals. Patients with depression often feel tired, and a study suggests that sympathetic nervous system activity is enhanced, and parasympathetic nervous system activity is weakened during fatigue . ChangesSpeakers can constantly monitor and adjust their voice by using their speech as feedback in the auditory circuit . In the 1A receptor agonists, dose-dependently reduce isolation-induced ultrasound vocalizations in rats (Rats express their emotions through ultrasonic vocalizations, and different emotions correspond to different frequencies of ultrasound; ultrasonic vocalizations in anxious conditions due to isolation are associated with 5-HT. Drugs that act on the 5-HT receptor, such as some serotonin reuptake inhibitors and serotonin 5-HT in rats . Seroton in rats . The aboAlthough the findings of this study have implications for improving the diagnosis of depression, there are some inherent limitations to the study design. First, the exploratory cross-sectional design of this study precluded causal inferences. Longitudinal follow-ups of patients with depression, including observation of the entire course of disease with and without drug treatment, need to be carried out in the future. Second, the clinical symptom assessment in this study was simple; future studies should include more dimensions of depression, including the assessment of suicide risk and autonomic nervous function. Third, the experimental paradigm of this study was relatively simple and warrants further expansion to simulate different scenarios, help gain a comprehensive understanding of the changes in the acoustic characteristics of depressed patients, and fully evaluate their accuracy as objective biomarkers of depression. Furthermore, this study only included Chinese Mandarin samples, whether the specific language or other cultural factors may influence the generalizability of the results is still unclear. Finally, although we performed a 10-fold cross validation, a larger sample size and independent validation datasets may be more effective for verifying our conclusions.The change in acoustic characteristics in patients with depression may not be caused by a single factor, and the specific underlying mechanism remains unclear. However, the acoustic characteristics of depressed patients were significantly different from those of the normal control group in this study, and the accuracy of depression classification based on acoustic features was very high. These findings suggest that acoustic characteristics may become objective biomarkers of depression; this may help clinicians make objective diagnosis of depression, reduce the rate of missed diagnosis and misdiagnosis, and promote the development of Internet medical treatment.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Beijing Huilongguan Hospital. The patients/participants provided their written informed consent to participate in this study.S-PT, Z-RW, and Y-LT contributed to the conception and design of the study. QZ performed the statistical analysis and wrote the first draft of the manuscript. S-PT reviewed and revised the manuscript. H-ZF, Y-LZ, and Z-XT organized the database. Y-LL, LL, and Y-XW contributed to provision of study materials and patients. All authors contributed to the manuscript revision, as well as read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The prevalence of chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by the aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at the improved management of infected wounds, a variety of wound dressings that incorporate antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound-care market. However, many wound-care professionals agree that none of these wound dressings show comprehensive or optimal antimicrobial activity. This manuscript summarizes and discusses studies on PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties that are relevant to the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound-healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies. Wounds can be viewed as a disruption of the normal anatomical structure and function of any bodily tissue or organ. They can occur following injury by physical, chemical or thermal means, or as the result of underlying pathological conditions. In open wounds, the protective body surface (skin or mucous membranes) is broken, allowing entry of foreign material into the tissues, including microorganisms. Wound healing, i.e., the process by which the normal structure and function of destroyed or damaged tissues is restored, is an extremely complex and dynamic biological process that can be divided into the following four sequential, yet overlapping, processes: (i) hemostasis, i.e., stoppage of bleeding; (ii) inflammation, a primary defense mechanism against the invasion of microorganisms; (iii) proliferation of keratinocytes, fibroblasts, macrophages and endothelial cells and migration from the wound edges into the gap in the dermal layers created by the wound, to restore skin continuity and function through the formation of new tissues and blood vessels; (iv) remodeling of these new tissues, converting the initial fibrin-rich blood clot into a collagen-rich scar ,2. As a Attenuation or disruption of any of the cellular or molecular mechanisms underlying the above-mentioned sequence of processes can compromise wound closure, with wound healing usually stalling in the inflammatory phase. Advanced age and diabetes are primary risk factors for developing chronic, non-healing wounds, but failure to achieve wound healing in a timely and orderly manner may also be due to several other factors, such as other pathological conditions , repeated insults, poor primary treatment, necrosis and excessive levels of inflammatory cytokines and exudate. Chronic wounds caused by pathological conditions, also known as ulcers, have a high prevalence worldwide, most notably venous leg ulcers and diabetic foot ulcers, for which the worldwide prevalence is 3% and 6.3% of the adult population, respectively [Chronic wounds are often severely colonized by bacteria and fungi and may become infected. The formation of biofilms in polymicrobial infections shields bacteria from antimicrobial agents and from the immune response and is one of the causes of wound-healing failure, which can result in the widening of wounds, in the need for surgical intervention and in life-threatening events . In the The simplest approach to replace the barrier function of intact skin is the application of a dressing, such as cotton gauze. Ideally, traditional wound dressings (WDs) should possess the following characteristics ,7: (i) sThe WD market is expected to represent USD 11.2 billion by 2025 , driven Of the commercially available AMDs, more than a dozen contain the antiseptic PHMB. Among the advantages of using PHMB in AMDs are its high stability ,19 and bAcetobacter xylinum (A. xylinum) and designated bacterial cellulose [(i)Precipitation by immersion in a non-solvent, in which precipitation occurs due to the exchange of the solvent in the polymer solution by a non-solvent miscible with the solvent present in a coagulation bath;(ii)Precipitation in non-solvent vapor, in which phase inversion occurs inside a closed chamber in which the non-solvent is in the vapor phase and causes precipitation of the polymer in the solution;(iii)Solvent evaporation , in which the solvent of a polymer solution cast on a substrate is allowed to evaporate or is removed by heating the polymer solution in an oven;(iv)Thermally induced phase separation, in which a solvent that dissolves the polymer at a given temperature loses this ability when the temperature is decreased, with the solvent being subsequently removed by extraction, evaporation or lyophilization (freeze-drying);(v)Crosslinking, in which a polymer in solution is insolubilized by the formation of chemical bonds or by physical interactions between its molecular chains.The matrices of commercially available WDs of known composition are all made of one or more natural polymers, modified natural polymers or synthetic polymers. These polymeric matrices, which commonly have the form of a sheet or pad, act as selective membranes, controlling mass transport of a particular species across them. In particular, they prevent the transport of microorganisms and other foreign agents present in the outside environment to the wound, while allowing transport of water vapor, oxygen and carbon dioxide to or from the outside environment. Membranes for WDs are most commonly produced by the following methods : (i) weaellulose . Currentellulose ,25. In pellulose ,27. In t2 capture and sensing [PHMB is a synthetic polydispersed mixture of polymers that has been widely employed as an antiseptic since the 1950s. In addition to its use in wound antisepsis ,29,30. I sensing , uranium sensing  and sewa sensing . As a pr sensing .Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) [Acanthamoeba spp. [Herpes simplex [PHMB is effective against a wide spectrum of both Gram-positive and Gram-negative bacteria, including difficult to control bacterial strains, such as methicillin-resistant ci (VRE) , althougci (VRE) . Of noteci (VRE) . On the ci (VRE) . PHMB isci (VRE) , amoeboieba spp. , envelop simplex  and huma simplex , and non simplex .Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and the highest to the Gram-positive bacteria Pseudomonas aeruginosa (P. aeruginosa). MIC and MBC values may be higher when bacteria form biofilms, as suggested by the results of a study that show that the antimicrobial activity of a commercial PRWD was higher in a planktonic cell model than in an immobilized cell model used to mimic biofilms [®  contains PHMB at a concentration of 0.03% or 0.04%, and Prontosan®, in all its three formats , contains 0.1% PHMB (in combination with a betaine antiseptic). In rats, acute skin toxicity was only observed for a concentration of 5% [PHMB’s minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against bacteria commonly found in wounds are presented in biofilms . PHMB isbiofilms ,44,50, abiofilms , most nobiofilms . HoweverPHMB is commonly synthesized as a hydrochloride salt by polycondensation of 1,6-hexanemethylenediamine and sodium dicyanamide, but can also be synthesized through other routes . The polDue to the occurrence of polymerization, depolymerization and repolymerization reactions during its synthesis, a polydisperse polymer is obtained. Reported molecular weight (MW) values range from below 500 g/mol up to ca. 4200 g/mol , and MW Ka values above 13 [2+ ions that stabilize the lipid bilayer and its hydrophobic hexamethylene portion is able to sink into the cell membrane, resulting in increased membrane permeability and, ultimately, membrane disruption [PHMB is also structurally related to naturally occurring antimicrobial peptides (AMPs) , which sabove 13 ), attachsruption ,56,60,61sruption . The spesruption .In terms of physical and chemical properties, PHMB exhibits good thermal and hydrolytic stability ,19. It iA first proposal for the medical use of a PHMB-releasing membrane can be found in a 1984 patent filed by Johnson & Johnson  for the ® PHMB, its employment in 32 patients with hard-to-heal wounds  reduced bacterial load and pain and resulted in the effective management of exudate levels [TM AMD drain sponge extended the number of days during which tracheostomy sites remained free of pathogens, compared to a non-AMD dressing, while normal flora remained unaffected [® X + PHMB was assessed in case studies of patients with traumatic and surgical wounds, pressure and leg ulcers, and burns, where it reduced infection, exudate levels and pain, while increasing granulation tissue and epithelialization and improved necrotic tissue debridement [S. aureus and keratinocytes, Suprasorb® X + PHMB protected keratinocytes from damage by reducing the number of viable bacterial cells [® X + PHMB showed better and faster pain reduction and the need for fewer WD changes [® X + PHMB and a silver-containing WD were both effective in reducing pain and bacterial burden in the treatment of critically colonized and locally infected wounds, but Suprasorb® X + PHMB exhibited superior antimicrobial properties [®, a commercial AMD with the antiseptic CHX [e levels . CelluDre levels . In clinaffected . Kendallaffected . In vivoaffected , and itsaffected . Kerlix™affected , includiaffected  and MRSAaffected ,75. In haffected ,77. In taffected . Howeveraffected . Suprasoridement . In a coal cells . In a pr changes . Additiooperties . Finallyptic CHX .The first publications that reported the preparation and assessment of PRMs for AMDs date back to the early 2010s. Since then, a total of 28 PRMs have been described in the literature . In the N-isopropylacrylamide)/N-tert-butylacrylamide/acryloyl-lysine (PNIPAAm/NtBAAm/A-Lys) copolymer. The latter case explores the thermally induced contraction of a PNIPAAm-based hydrogel to favor drug release at human body temperatures. This type of stimuli-reacting system is sometimes described as “smart”. Another interesting strategy involved the inclusion of a protease in a gelatin-based matrix to decrease the membrane’s crosslinking degree over time.A variety of polymers and polymer mixtures were employed in the preparation of the 28 PRMs. Some of these polymers, such as cotton, bacterial cellulose and polyurethanes (PURs), are also employed in the preparation of commercial PRWDs , while oSome of the polymer membranes in PRMs were non-woven bacterial cellulose membranes produced by bacteria. The remaining membranes were prepared using a variety of methods , mostly There are three main approaches for loading a drug into a membrane , which aContrary to all of the PRWDs for which this information was provided, which were consistently loaded by impregnation , all of w/v). In the cases that employed woven membranes in which PHMB was not loaded by soaking, PHMB was added to a solution that was applied as a coating on the membrane, by either spray or dip coating (membrane immersed in a drug-containing solution for a short period). An additional approach was the addition of PHMB at concentrations ranging from 0.2 to 0.4 wt% to the growth medium employed in the production of a bacterial cellulose membrane by Gluconacetobacter xylinus , which resulted in a bacterial cellulose/PHMB composite. Loading by addition was employed with PRMs prepared by electrospinning and by phase inversion. A comparison of the employed PHMB concentrations is not possible since, in these studies, the PHMB concentrations in the solutions employed in membrane preparation were expressed using different concentration units that cannot be interconverted , which a® C, or are sterilized in the last step in their manufacture  by gamma radiation , ethylene oxide , steam (autoclaving) or dry heat , among other possible sterilization methods. Regarding the PRMs, none of the membranes were prepared using aseptic processing and only two (PRM8 and PRM16) underwent terminal sterilization , as in the case of, for instance, Suprasorblization . SteriliThe extent of the characterization of the PRMs varied considerably, as can be observed in As can be observed in Of the physical properties covered by the various parts of EN 13726, only absorbency  and MVTR (moisture vapor transmission rate) were included in the characterization of at least some of the PRMs . It must2 solution that contains 42 mM Na+ and 2.5 mM Ca2+) retained per 100 cm2 of sample or, in the case of wound cavity-filling WDs, per gram of sample. This standard also specifies the conditions for preconditioning the samples (21 °C and 60 ± 15% relative humidity (RH)) before the assay, the temperature of test solution A during immersion (37 °C) and the duration of the immersion (30 min) [2/24 h was obtained for these two PRMs, which is comparable to the lower MVTR values obtained for a set of commercial WDs studied under this standard, which ranged from 50 to 9360g/m2/24 h [2/24 h was obtained. However, a different assay method was employed, still in accordance with the ASTM standard. In this method, the designated “Procedure A—Desiccant Method”  . In the (30 min) . Regardi(30 min) . The ran(30 min) ). Once a/m2/24 h ,128. Wit Method” a, anhydrAir and oxygen permeabilities were also determined for three PRMs. Absorbency, MVTR and air permeability can all affect the PRMs’ ability to control exudate levels. To prevent excessive exudate in the wound bed, which can result in tissue maceration , WDs mus3/m2/12 h (or 0.001 cm3/cm2/s) was obtained following the Chinese GB/T 19789-2005 standard [3/cm2/s and 0.5 cm3/cm2/s, respectively, at a 125 Pa pressure differential), which might be due to the already mentioned differences in morphology, fiber diameter and porosity. The values obtained in both cases were within the range of values obtained with a set of commercial WDs assayed by the same method—from below 0.02 to above 78 cm3/cm2/s, the minimum and maximum values for the employed instrument, albeit at a slightly lower (100 Pa) pressure differential [For the bacterial cellulose-based PRM13, an oxygen transmission rate of 48 cmstandard , at 37 °standard , which wstandard , which werential . As suchUpon application of a medicated WD to an open wound, the bioactive agent is released to the wound exudate. Thus, results of in vitro PHMB release studies can be used to predict the validity of the PRMs. Drug release kinetics are affected by characteristics of the release medium, such as pH , viscosi(i)Distilled water;(ii)2·2H2O 0.33 g/L;A salt solution composed of NaCl 8.6 g/L, KCl 0.3 g/L and CaCl(iii)A 50 mM tris(hydroxymethyl)aminomethane (TRIS) solution at pH 7.4;(iv)PBS. The exact composition varies slightly according to the laboratory; a common composition is 140 mM NaCl, 10 mM phosphate buffer, and 3 mM KCl, with a pH of 7.4 at 25 °C ;(v)“Simulated body fluid”, whose composition was not provided.The exact composition of exudate varies with wound origin, type, size and location, as well as with the phase of the wound-healing process . It is mWater can hardly classify as an exudate model, as it differs radically from exudate, namely in terms of electrolyte composition, ionic strength, osmolality, pH and buffering capacity, to name a few parameters. The salt solution contained the major ions present in exudate, but has no buffering capacity. In turn, the TRIS solution was buffered by a non-biological molecule, but lacked the major ions present in exudate. PBS, which was employed in half of the drug-release studies with PRMs, had ion concentrations, osmolarities and pH values  within the ranges reported for exudate. However, PBS differs significantly from exudate, namely in terms of viscosity, which is much lower (as was the case for water and the other two solutions). The composition of the “simulated body fluid” was not detailed. More complex exudate models that contain proteins, lipids and saccharides besides salts were proposed ,162,163.In most studies with PRMs , the pH The main driving force for drug release in non-erodible, drug-loaded membranes, such as those employed as medicated WDs, is a drug concentration gradient between the drug-containing matrix and the release medium, which is affected by the swelling and relaxation of the membrane matrix. The maximum drug-release rate will occur under conditions in which the accumulation of the drug in the release medium is considered negligible and, as such, it will not affect the dissolution of further drug molecules that are released. These conditions are designated infinite sink conditions (or just sink conditions). In pharmaceutical science studies, it is considered that infinite sink conditions normally occur when the volume of the release medium is, at least, 3 to 10 times the saturation volume for the drug under study . When th2/day [2/day, and that this value can double in the presence of infection [2/day), as a compromise between physiological relevance and assay duration [Fluid leaking out of blood vessels is naturally drained and recirculated. However, in wounds, additional fluid leakage and consequent exudate accumulation occur, due to the inflammatory response that takes place, which is characterized by increased capillary permeability. Even though there is no internationally accepted standard to measure exudate production, no accepted reference “normal” rate of exudate production, and as wound exudate production varies with the wound-healing phase and wound origin, type, size and location, as well as with local and systemic factors ,148, rep2/day , taking 2/day . The SMTnfection , employsduration , which cMany studies with PRMs did not mention the medium volume employed. Within those that mentioned it, only three studies employed low volumes between 1 and 3 mL , with the remaining ranging from 10 to 60 mL . AdditioFranz diffusion cells  are a tyMost of the drug release kinetic curves obtained with PRMs showed an initial burst release, where most of the PHMB was released, followed by a plateau . This buAnother type of release curves obtained showed two release phases . They were obtained with PRM8, PRM11b, PRM13 and PRM21 . With thIn a drug-release system, the drug-release duration, i.e., the time it takes for the cumulative released drug concentration to become constant, and the concentration of the released active drug determine the duration of the therapeutic activity of the system and, in the case of medicated WD, they may affect WD-changing frequency. Longer therapeutic activity is favorable, since it offers a lower frequency of WD change that, in turn, lowers wound exposure and favors wound stabilization, improving patient well-being and lowering costs ,181. To PHMB release durations of PRMs varied from a minimum of 0.5 h to a maximum of 20 days, with the most common duration in the range of 1–24 h . As diffmax, the cumulative concentration of the drug released when equilibrium between the drug inside the membrane and the outside milieu was attained, corresponding to the plateau of the drug-release curve), as the release medium volumes employed were much larger than the exudate volumes  and E. coli [S. aureus and P. aeruginosa as the most common association [Candida albicans  [E. coli and P. aeruginosa were the most employed bacteria in the Gram-negative group, while in the Gram-positive group, S. aureus was the most employed. P. mirabilis, which is also commonly found in infected wounds, was never employed.A large number of bacterial species can be found in infected wounds, most frequently  E. coli ,183. Polociation . Fungi albicans) ,184. WitP. aeruginosa, the Gram-positive S. aureus and the yeast C. albicans into separate samples of the AMD under evaluation. These test suspensions are prepared in a solution that contains heat-inactivated fetal calf serum (FCS), peptone and NaCl, used to simulate wound exudate. After a contact time of 24 h at 30–34 °C, the antimicrobial activity is stopped by the addition of a neutralizing solution and the number of bacteria or yeast recovered from the AMD is determined and compared to that of a negative control.Several types of assays have been developed to evaluate or screen the in vitro antimicrobial activity of a substance . The appTo evaluate the antimicrobial activity of PRMs, the most commonly employed assays were the agar disc diffusion assay and the inoculation assay . In the P. aeruginosa, although active against other bacteria; (ii) the PRM20 membrane loaded by impregnation with 0.1% PHMB that, although active against several bacterial species and strains in a biofilm assay, did not show activity against a particular Staphylococcus epidermidis (S. epidermidis) strain, and (iii) the PRM21 membrane loaded by addition of PHMB in the range 0.1–0.5 wt%, for which no activity was detected against P. aeruginosa, Acinetobacter baumannii (A. baumannii) or against Bacillus subtilis (B. subtilis) biofilms. In these cases, P. aeruginosa was the bacterial species that most often resisted antibacterial activity. This bacterial species is known for its remarkable resistance to antibiotics [It is not possible to establish a correlation between antibacterial activity and the amount of PHMB loaded per unit mass of PRM samples, since very few studies determined the drug-loading yield . Additioibiotics .w/v (PRM5), with the remaining active PRMs loaded by adding PHMB concentrations in the range 0.04–0.4% w/v. When wt% was used, the minimum PHMB concentration that resulted in antibacterial activity was 0.1 wt% for the PRM21 membrane. However, for the PRM10 membrane, antibacterial activity was only observed for a PHMB concentration of 10 wt%. This PRM corresponds to a membrane composed of chitosan and PLA. As carboxylic groups in PLA have a pKa value below 7, PLA will be negatively charged at physiological pH and the positively charged PHMB (and chitosan) will interact and bind to PLA. As such, this PRM may require loading with higher PHMB concentrations to exhibit antibacterial activity. However, other PRMs that contain negatively charged polymers, such as PRM5 (PLA) or PRM18/PRM19 , did not require high PHMB concentrations, suggesting that the presence of negatively charged polymers in the membrane may not be the only factor that justifies the use of high PHMB concentrations.In loading by soaking or impregnation, the lowest PHMB concentration that resulted in PRMs with antibacterial activity was 0.04% . Most of the remaining active PRMs were loaded with PHMB concentrations in the range 0.1–1% . In loadS. aureus, A. baumannii, and Klebsiella pneumoniae (K. pneumoniae) lasted for 3–4 days, while for the two highest PHMB concentrations (1 and 2%), the activity lasted for 7–8 days.Most antibacterial assays were short-term assays, with 24 h being the most employed contact time. Two studies employed long contact times of 7 and 9 days, with daily renewal of the agar plate with the test bacteria, which will simulate exudate turnover in the wound. In one of these long-term studies, the antibacterial activity of PRM9 lasted for just 1 day, although it was evaluated for 7 days. In the other long-term study, it was possible to achieve long-term antibacterial activity; for the lowest PHMB concentration employed (0.1%), antibacterial activity against ®) against Gram-positive and Gram-negative bacteria, (ii) comparable to that of a silver-based AMD (Acticoat®) for Gram-negative bacteria, but inferior against P. aeruginosa, and (iii) comparable to that of a commercial PRWD loaded by impregnation with the same PHMB concentration (Suprasorb® X + PHMB) for Gram-positive bacteria, with the exception of B. subtilis, to which it was inferior, and for Gram-negative bacteria, with the exception of P. aeruginosa, to which it was also inferior. PRM12 also demonstrated antibacterial activity comparable to that of Suprasorb® X + PHMB that contained a PHMB concentration 3- or 7.5-times higher, and PRM14 was superior to a commercial silver-based WD (Actisorb® Silver 220), when loaded with PHMB concentrations in the range of 5–35 wt%. In a large-scale study that employed a large number of bacterial species and strains, PRM20 loaded with 0.1% PHMB exhibited antibacterial activity that was superior to a commercial silver-based AMD (Aquacel® Ag), but was slightly inferior to equivalent membranes loaded with the antiseptics octinidine (OCT) and PVP-I, although these were loaded with much higher antiseptic concentrations .In a few cases where the activity of PRMs was compared to that of commercial AMDs , in geneE. coli, P. aeruginosa, B. subtilis and S. aureus for storage periods in the range of 1–6 months. For A. baumannii, although it was not active after storage for 1, 2 and 3 months, it was active after 6 months of storage. A commercial AMD that was assayed in parallel maintained its antibacterial activity for up to 6 months of storage.A different type of study looked at the storage stability of the antibacterial activity, which is an important aspect when developing AMDs for commercial use. In the only study of this type, the PRM8 membrane  maintainC. albicans, although weakly, and its antifungal activity depended on the culture medium employed, being higher in an exudate model. The growth of the same fungus was also inhibited by the PRM21 membrane. The remaining study was concerned about fungal growth during the storage of the PRM13 membrane in a humid environment. No fungal growth was observed for 6 weeks, in contrast to the equivalent samples not loaded with PHMB.Although wounds can be colonized by both bacteria and fungi, which both contribute to delayed wound healing , the antP. aeruginosa and S. aureus, being less active against S. aureus. For mixed-species biofilms, PRM11b was able to completely eradicate the biofilm, but only after 48 h of contact. In a large-scale study that employed the PRM20 membrane, antimicrobial activity with partial eradication of the biofilm was observed after 24 h for the tested bacterial strains, with the exception of a single strain of E. epidermidis grown in TSB (tryptic soy broth). The antimicrobial activity depended on the medium employed, being higher in the artificial exudate medium employed than in TSB, highlighting the importance of the wound exudate model selected. This PRM exhibited better performance than a silver-based commercial AMD (Aquacel® Ag), but slightly inferior performance than the equivalent membranes loaded with OCT and PVP-I, although containing much higher concentrations.Almost all of the reported in vitro antibacterial activity assays with PRMs employed single bacterial cultures in planktonic form or as colonies on agar . As in c®, a PVP-I-based AMD, and of Acticoat®, a silver-based AMD, a flatbed perfusion biofilm device  was studied in the colony drip-flow biofilm model  and to WDs without antibacterial agents [P. aeruginosa and S. aureus [Dynamic biofilm models have been developed for the study of the antibiofilm activity of antimicrobial substances. Although not employed to study PRMs, this type of model has already been employed to evaluate the antibacterial activity of commercial AMDs. In an evaluation of Inadinem device a that coemployed . Inadinelm model b with bil agents . After t. aureus . The AMDP. aeruginosa [A. baumannii was employed to evaluate the PRM15 membrane. When this PRM was assayed in vitro  , AMDs inOnly twelve PRMs were tested for biocompatibility . Except Depending on the concentration, PHMB may exhibit in vitro cytotoxicity . In PHMBw/v in relation to the formulation volume, up to 5 wt%, when expressed in relation to the polymer mass in the formulation, and up to 0.3 wt% in relation to the solution mass  were observed in the subcutaneous evaluation and no sensitization was detected in the study with human volunteers. The irritation potential of the PRM17 membrane was evaluated by employing an assay that is out of the scope of the ISO 10993-23:2021 standard, dedicated to the evaluation of irritation effects of substances [Among the PRMs, two studies have evaluated other categories of biological effects covered by the ISO 10993 standard, in addition to cytotoxicity . The mosbstances , which wbstances . Upon apAlthough it could be advantageous if WDs possessed hemostatic capacity, evaluation of the hemostatic capacity of PRMs was reported in a single case. The PAm-based PRM18 woven membrane coated with alginate that contained silver nanoparticles (AgNPs) and PHMB accelerated blood clotting when evaluated with a qualitative blood-clotting assay, in which fresh, non-anticoagulated human blood was applied to the membrane and clot formation was visually evaluated.Antimicrobial activity and absence of cytotoxicity do not necessarily equate with improved wound healing. It is also critical that PMRs do not adversely affect the healing process. Thus, wound-healing testing should be regarded as a fundamental component of the characterization of AMDs. The evaluation of wound-healing capacity is largely carried out in vivo, using animal models. The most frequently employed laboratory animals are mice, rats, pigs and rabbits . Pig wou®). This result agrees with in vitro studies that show that the migration capacity of keratinocytes and fibroblasts is not affected when treated with low PHMB concentrations (0.001%) [As can be observed in (0.001%) .These two in vitro wound healing assays are not the most representative models of a wound. In the Boyden’s chamber assay, cell–cell and cell–matrix interactions are not reproduced, as cells are added as suspensions; in the wound-scratch assay, as it is a two-dimensional model, it does not adequately represent the complexity of a wound. Other models that more closely resemble a wound are three-dimensional (3D) models in which cell-free 3D zones are created in 3D cell cultures in collagen matrices . These c®). With this wound-healing model, in addition to wound size or area, other parameters that were taken as indicators of wound healing were the area of the wound covered by collagen [® and the PRM15 membrane showed no effect on the neovascularization capacity or on the levels of inflammatory factors when compared to the unloaded membrane.In the in vivo wound-healing evaluation of PMRs, rats were consistently used and wounds were induced either by heat or surgically . These tcollagen , the occcollagen  , a PRWD that appears to have been discontinued (COPA® AMD), and three PRWDs without a tradename. Two of these clinical trials with PRWDs without a tradename—registry nos. NCT02652169 and NCT02643680 of the American clinical trials registry database [A search carried out on 20/11/2022 using the European , Americadatabase —employedA search using the Google Patents search engine  carried Research on PRMs for their application as AMDs has resulted in a number of membranes that were characterized to different extents. The drug-release studies carried out employed in vitro models and conditions that were far from approaching the physiological conditions and, in many cases, information concerning the conditions under which the studies were carried out was incomplete or missing. With very few exceptions, the effect of sterilization was not considered. As the type of sink conditions employed was not mentioned, as it is likely that non-sink conditions will prevail in wounds covered with a WD, and as sterilization may alter the drug release kinetics, the obtained drug-release results are unlikely to have physiological significance. Thus, a full account of the conditions employed in drug-release assays with PRMs is desired, as well as the use of in vitro models for drug-release studies that better simulate physiological conditions.The physical characterization of the PRMs fell short of an essential physical characterization of WDs and different assays and assay conditions were employed to evaluate the same property, precluding a comparison of the results. In general, the PRMs showed antibacterial activity against the several bacterial species and strains tested, mostly employing single bacterial cultures in planktonic form, in colonies on agar or as static biofilms. Since the most representative models of the infected wound bed are multi-species biofilms under dynamic conditions, an evaluation of the antibacterial activity of the PRMs that uses this more realistic in vitro model or in vivo models is missing. In a few cases in which the antibacterial activity was compared to that of commercial PRWDs or to other types of AMDs, usually, it was comparable or superior. In general, no cytotoxicity was detected and, when detected, it occurred for PRMs that were loaded using the highest PHMB concentrations. Some PRMs were evaluated for wound-healing capacity, by mostly employing in vivo rodent wound-healing models, but also in two human and in one animal case study. All PRMs that were evaluated for wound-healing capacity resulted in successful outcomes and performed better than the selected non-medicated WDs or commercial AMDs, showing faster wound closure. As such, they show promise for further development. In fact, two AMDs that are likely to be based on two PRMs are undergoing clinical trials.The next generation of PRMs may well include the use of PHMB in some novel types of WDs. Among them is the use of PHMB (i) associated with nanocarriers, (ii) on WDs prepared by additive manufacturing and (iii) on smart electronic WD platforms. With the exception of the recent use of PHMB encapsulated in nanoliposomes in PRM19, the use of nanocarriers in combination with PHMB remains unexplored; a small number of studies with PHMB that involve nanocarriers exist ,215,216,


Background: Improved health care and rising life expectancy are creating a growing pool of old age people all over the world, including Africa. Malnutrition in the old age people is associated with both short- and long-term negative health outcomes. However, the reported burdens of malnutrition are fragmented and inconsistent, where more compiled evidence is warranted to aid decision-makers. Hence, this paper is aimed to estimate the pooled prevalence of malnutrition among old age people in Africa.Methods: A systematic search for research reporting the prevalence of malnutrition among old age people (aged above 60 years) was conducted from HINARI/PubMed and Google Scholar databases using combination keywords. Published articles in English language starting from January 2000 to October 2021 were screened. We presented the results based on the standard for reporting systematic review and meta-analysis of observational studies. A random-effect meta-analysis was done to estimate the prevalence of malnutrition along with the 95% confidence intervals. The publication bias was assessed using the funnel plot.Results: A total of 1,442 studies were retrieved based on the search strategy, where only 36 studies  reported from 11 African countries were included for meta-analysis. The reported prevalence of malnutrition ranges from 2.2 to 77.3% across Africa. Overall, the pooled prevalence of malnutrition was 18% . The prevalence is higher in the Central Africa , in the community , and among advanced age .Conclusion: The prevalence of malnutrition in African old age people is high and differs by setting, assessment tool, and country of residence. Hence, due attention to geriatric nutrition is mandatory, and the need for a valid, reliable, and simple screening tool should be thought of. The global demographic structure of the population is changing dramatically, notably in Africa, due to several social and economic milestones . These rIn Africa, the risk of malnutrition among older people is a major challenge to the health care system and needs special and urgent attention. The usual food production practices, marketing style, and living standards have all contributed to an increase in the use of low-cost, packaged products that are high in fat, energy, and salt and yet low in nutritional quality. More importantly, poor infrastructure and limited resources, combined with conflict and poor access to healthcare services, are factors that contribute to the overwhelming levels of malnutrition and food insecurity on the continent . The lacWhile any age group may suffer from malnutrition, it is most common among old age people due to the changes in physiological, psychosocial, and health characteristics of individuals in this age group . FurtherTimely diagnosis of malnutrition and risk factors is crucial for public health interventions targeting old age people. In addition, previous studies reported that the prevalence of malnutrition among old age people varies between 1.1% and 72.2% in different settings , where sBefore the beginning of this systematic review, we conducted a systematic search of review papers from the Cochrane Library, the International Prospective Register of Systematic Reviews (PROSPERO), and the Joanna Briggs Institute (JBI), and no review had been conducted on malnutrition among old age people in Africa. Then, relevant publications were searched systematically from HINARI, PubMed, and Google Scholar databases from 01 January 2000 to 16 October 2021. We employed the search through relevant combinations of MeSH terms and related keywords, such as “malnutrition”, “obesity”, “overweight”, “old age people”, “older adults”, “elderly”, and “Africa” as indicated in Based on the condition, context, and population (CoCoPop) framework  we incluvia email. Contacted authors requested full-text papers until 31 October 2021. However, if both strategies were not possible, the study was removed from the review.Qualitative studies, study protocols, abstracts, opinions, commentaries, case reports, review papers, and studies on African-Americans who do not live on the African continent were all excluded from the review. Duplicated articles and those reporting malnutrition in post-intervention were excluded. Articles without access to the full text were managed using two strategies. First, when outcome data were not reported, we tried to calculate from other additional information in the publications. If not, second method was to contact the corresponding author Studies that measured malnutrition with any standard and validated tools, including questionnaires such as Patient-Generated Subjective Global Assessment (PG-SGA), Mini Nutritional Assessment (MNA), Subjective Global Assessment tools (SGA), or Nutritional Screening Checklist (NCL), anthropometric , or biochemical indices  were considered. We used the reported prevalence of malnutrition or undernutrition based on the standard definition set for each nutritional assessment method.A two-step process was used to select the relevant publications. First, the scan of the titles and abstracts was conducted for the inclusion of references that meet the eligibility criteria. If there were any uncertainties about the relevance of a study, the entire text was retrieved. Second, the full texts were then used to make a judgement on whether or not the study should be included in the review. The two authors work individually on all aspects of the selection process. Disagreements were settled through conversation.The selected studies were critically appraised using a ten-item rating checklist designed for research reporting prevalence , where bData extraction was performed by two independent authors using a prespecified standard format prepared in Excel from the full-text articles. The extract comprised the following information: general , participants , and study details . Morbidity was coded as one or multi when a single or multiple underlying health conditions were an inclusion criterion.The pre-coded extracted data in excel format was exported to STATA software version 14  for desc2) test. The I2 values of 25, 50, and 75% with a p-value less than 0.10 represent low, medium, and high heterogeneity, respectively , relevant nutritional assessment method, and language (other than English). Furthermore, 237 articles were found during the full-text screening. Finally, 37 and 36 articles were selected for qualitative (systematic review) and quantitative analysis , respectively. A total of 37 studies reported the prevalence of malnutrition among old age people. While 34 studies (92%) were published within the last 10 years between 2011 and 2020, the remaining 8% were issued between 2001 and 2010. All the included studies were reported from 11 African countries, where more than half  were from four countries: Ethiopia, Egypt, Nigeria, and South Africa.Seven studies (18.9%) were from Ethiopia  and six versus noninstitutional (versus low economic classes (n = 22) were conducted in community settings, while 11 studies were conducted among institutionalized elders.Except for three studies . While 18 studies employed various anthropometric measurements such as BMI, MUAC, and CC separately or in combinations to assess malnutrition. One study used an interviewer-administered Nutritional Screening Checklist (NCL) (n = 23) of the studies reported single (n = 8) or multiple (n = 15) underlying clinical conditions such as fracture, heart disease, dementia, Parkinson’s disease, or cancer  were females. The included studies had sample sizes ranging from 40  to 2,219st (NCL)  and anotst (NCL) . Two-thir cancer .Based on the quality assessment checklist, studies were either in moderate (6-8 points)  or high-The prevalence of malnutrition varied highly across the studies conducted in different countries, assessment tools used, and healthcare settings. We presented an overview of the findings from various studies using two assessment tools in the section below.n = 5), the community (n = 10), a long-term care center (n = 1), and a daycare center (n = 1), utilized body mass index (BMI) as a nutritional assessment tool. As low as zero (2). Furthermore, the highest prevalence of undernutrition (25.6%) was reported in a Tanzanian hospital   and MNA (n = 20). Since the full-and short-form of MNA and NCL tools are similar in the interpretation of the outcome variable, they were treated as similar tools. The random pooled prevalence of malnutrition in Africa was 18%  .df = 35 and p-value < 0.001; I2 = 98.1%; Tau-square (τ2 = 0.01).As illustrated in Moreover, a minimal publication bias has been noted in the published studies. Studies with lower standard error and larger sample size might be included, as indicated in of the funnel and Egger’s publication plots . Smallerp = 0.008), suggesting publication bias. Here, the positive coefficient indicates that small studies overestimate the effect size. However, no study appeared to have a significant impact on the summary effect size in the sensitivity analysis, strongly suggesting that the effect estimate is consistent across groups and potentially giving a reliable estimate of the outcome.Furthermore, Egger’s regression asymmetry test value was 3.50 (p = 0.430)  as compared to other regions of the continent. Similarly, the community old age people , older age groups , and those with no reported clinical condition  had a higher malnutrition burden than their counterparts. The prevalence estimates showed a statistically significant variation among all subgroups except for the assessment tools used (= 0.430) .p = 0.049) predicting the prevalence of malnutrition in the meta-regression analysis.However, only the study setting was statistically significant  in our review used BMI as a nutritional assessment tool for old age people. Similar studies in Africa still preferred to use BMI for old age people where 19.9% and 30% of subjects were undernourished, overweight or obese, respectively . This is in the range of the ones reported from the world, ranging from 0.8 to 24.6%  . The disp < 0.001; T2 = 0.01; I2 = 98.1%). Sensitivity analysis did not improve this heterogeneity, which is consistent with other previous findings . These findings are consistent with the reviews from India  predictor of malnutrition prevalence. This is, however, different from the reviews conducted in India  and assessment tools  were statistically significant predictors of the malnutrition prevalence, respectively. The variation might be due to the difference in assessment tools used between the studies.In the subgroup analysis, the prevalence of malnutrition showed a great variation depending on the study regions, study settings, age groups, and clinical conditions of study participants. Malnutrition was found to be prevalent in central Africa (3.76%), in older age groups (3.54%), with no documented clinical condition (3.16%), and in community-dwellers (3.12%). The prevalence was statistically significant in all subgroups except between the assessment tools used (om India  and the om India . While tin India  and the in India  where th2 = 98.08%), the interpretation of the current study needs precaution. Being limited to including only English literature and not including research published in books might limit the generalizability of the estimate.To our knowledge, this is the first systemic review and meta-analysis that provides a comprehensive estimate of the prevalence of malnutrition among old age people in Africa, including more recent studies conducted in the continent. Even though this review has its strengths, it is not without limitations. Due to the inherent heterogeneity among the included studies (IThis systematic review and meta-analysis showed high malnutrition prevalence among old age people which warrants a targeted policy intervention. The prevalence varied greatly depending on the study setting, the tool used, and the country of residence. To better monitor and evaluate, the use of a more reliable, valid, and standardized malnutrition assessment tool is strongly recommended.