M)-9-class earthquake 49 days prior. Motivated by this pairing, previous studies investigated its effect on Mount Fuji after both the 2011 M9 Tohoku megaquake and a triggered M5.9 Shizuoka earthquake 4 days later at the foot of the volcano, but reported no potential to erupt. More than 300 years have already passed since the 1707 eruption, and even though consequences to society caused by the next eruption are already being considered, the implications for future volcanism remain uncertain. This study shows how volcanic low-frequency earthquakes (LFEs) in the deep part of the volcano revealed unrecognized activation after the Shizuoka earthquake. Our analyses also show that despite an increase in the rate of occurrence of LFEs, these did not return to pre-earthquake levels, indicating a change in the magma system. Our results demonstrate that the volcanism of Mount Fuji was reactivated by the Shizuoka earthquake, implying that this volcano is sufficiently sensitive to external events that are considered to be enough to trigger eruptions.The relation between earthquakes and volcanic eruptions, each of which is manifested by large-scale tectonic plate and mantle motions, has been widely discussed. Mount Fuji, in Japan, last erupted in 1707, paired with a magnitude ( Many researchers studied how volcanic eruptions are triggered by earthquakes8, motivated by a physical viewpoint in which the stress7 and/or strain8 of an eruption needs to change, with earthquakes causing rapid and sometimes large changes in that stress and/or strain. We draw on a specific case in California, where the 1992 Landers earthquake triggered seismicity at very large distances, including the magmatically active Long Valley caldera region, which also experienced a significant coincident deformation transient6. Another case1 complements the search for direct evidence of the pairing of earthquakes and eruptions, having examined the historical record of large earthquakes and explosive eruptions to show that eruptions occurred in the vicinity of a large earthquake more often than is expected by chance7. In contrast, many large earthquakes have no immediate effect on volcanoes.When earthquakes accompany volcanic eruptions, there is the possibility of a causal relationship between themM) 9.0 Tohoku, Japan earthquake and the following large earthquakes that occurred in eastern Japan caused large changes in stress/strain  from the fall of 2000 to the spring of 200117 changed this situation completely, and the possibility of eruption-related disasters by Mount Fuji has been reassumed while disaster response plans have been developed to counter them18. Therefore, it can be stated that the importance of monitoring the volcanic activity of Mount Fuji is increasing.Mount Fuji is the Japan’s highest mountain and is also an active volcano. In addition, it has repeatedly erupted, causing lava flows into its vicinity several times. In 1707, the large Hoei eruption during the Hoei era also deposited volcanic ash in Tokyo on the east side of Mount FujiM5.9 earthquake that occurred in Shizuoka prefecture 4 days after the Tohoku earthquake. This volcano experienced the 1707 M9-class Hoei earthquake 49 days prior to its eruption. This unique experience led to an evaluation of the Tohoku and Shizuoka earthquakes19, revealing that crustal deformation due to these earthquakes induced changes in stress of Mount Fuji’s magma reservoir in the order of 0.001–1 MPa. The values are considered to be sufficient to trigger an eruption, if that magma is ready to erupt21. However, no LFEs were reportedly activated, suggesting that Mount Fuji did not have the potential to erupt19. It is not easy to characterize LFEs that are ubiquitous and indicative of seismic activities in the deep parts of volcanoes due to their low signal-to-noise ratio22.Mount Fuji exhibited increased seismicity, culminating in the triggered 13, which suggested that the source mechanism of LFEs was quite important to interpret the impact of large earthquakes on the activity of LFEs and deep magmatic processes. We examined if no LFEs beneath Mount Fuji were indeed activated immediately following the Tohoku and Shizuoka earthquakes. A seismic catalog produced in this study revealed that there were LFEs just after the Shizuoka earthquake. Moreover, seismic activation due to this earthquake continued for at least the next eight years, confirmed by using data until 2019. Evidence was shown that the Shizuoka earthquake and crustal deformation19 triggered reactivation of the volcano. Given that Mount Fuji is sensitive to such external influences, it is important to carefully monitor its development, especially when events external to the volcano might cause a disturbance.This study was motivated by previous studiesIn this section, we examine the temporal change in the activity of LFEs beneath Mount Fuji, Japan, and discuss the possibility of an increase in magmatic activities in the lower crust which was triggered by the 2011 Tohoku and Shizuoka earthquakes. We first obtain new catalogs of LFEs, and then apply statistical analyses to examine the temporal changes in LFE activity. Based on the results of these analyses, we conclude that the change in stress caused by the 2011 Shizuoka earthquake enhanced the creation of fractures and resultant change in activity of LFEs around the deep magma reservoir in the lower crust. We also suggest that the activation of LFEs may reflect the sensitivity of Mount Fuji to external disturbances and that the volcano may have the potential to erupt after a 300-year quiescent period.First, we show the influence of the 2011 Japanese earthquakes on LFEs manifested in the magma system of Mount Fuji. Second, we offer support that this magma system was disturbed due to such events, which played a role on activated LFEs. For inference on volcanic hazards of Mount Fuji, implications for future volcanism based on our observations will be discussed later.26 (details of the “CC) to quantify signal similarity range from 0.1 (poor correlation) to 1 (strong correlation and most likely a template LFE). Histograms of CC-values show a tall peak at CC ~ 0.2 , above which LFEs are used for subsequent analysis, should be above the upper noise limit. A low CCth would result in a large number of false detections while a high CCth would result in a reduced number of available LFEs. We selected CCth = 0.25, at the 2-sigma level of a normal distribution, as is expected for the random correlation between signal and noise29. Higher values of CCth = 0.3, 0.35, and 0.5 above the 3-sigma level were also considered to examine the dependence of the result on CCth. Mainly the results for CCth = 0.25 are shown in the text.To resolve the difficulty in detecting LFEs by conventional event‐detection methods, we produced seismicity catalogs using the matched-filter (MF) method, which cross-correlated a template to continuous seismic signalsCCth = 0.25 is about three times larger than in the JMA catalog, which lists about 2,000 LFEs detected in 2003–2019 by a conventional method that is not based on CC  indicates that events with low-frequency signals truly occurred immediately after the Shizuoka earthquake. Given that the number of LFEs in our CCth = 0.5 catalog is about one-fourth of that in the JMA catalog , and the whole period is divided into two adjoining periods to fit the ETAS models separately. This is best applied to cases where there is a clear-cut time instant across which ETAS parameter values change33. To test whether or not there are changes in seismicity pattern at Tc in a given period, the problem of model selection is reduced by using AIC (Akaike Information Criterion)34. We compared AICsingle (AIC for a single ETAS fitting) with AIC2stage (AIC for a two-stage ETAS fitting) to select the model with the smaller value, where AIC2stage = AIC1 + AIC2 .The cumulative number of LFEs as a function of time in Fig. single − AIC2stage), as a function of Tc during 2003–2019  were significantly larger than the extrapolated rates (red) after the Shizuoka earthquake   was visually poor  is followed by aftershocks , while the other three parameters were constants. For details of these parameters, see the ETAS model in “K0 were significantly larger after than before 2011  and  K0 Fig.  to otherThe bottom panel of Fig. CC > 0.25, 0.3, 0.35 and 0.5 , S-wave velocity (VS) as well as VP/VS beneath Mount Fuji, revealed a low-VP, low-VS and low-VP/VS anomaly at depths of 7–17 km, corresponding with the locations of LFEs. The coincidence of the velocity anomaly and the locations of LFEs suggests that supercritical volatile fluids, such as H2O and CO2, may be abundant in the low-VP/VS area and may play an important role in generating LFEs.A seismic survery19: the promotion of bubbling due to pressurization, and changes in stress in surrounding rocks. The first process promotes exsolving volatile components (H2O and CO2) from liquid to gas41. If the magma plumbing system is open or has weak walls that are easily expanded or fractured, increased pressure creates paths for the magma to migrate, so magma pressure will be further reduced and bubbling will be accelerated. In the second process, cracks close to the magma system would be unstable due to stress perturbation. These failures can become paths through which magma flows up, leading to an eruption. Disturbances caused by external fractures, such as the Shizuoka earthquake, may be a key to initiating both processes.Two possible processes leading to an eruption are currently considered for Mount Fuji35 suggested that a complex process occurred beneath Mount Fuji in which the characteristics of its LFEs were due to a variety of focal processes, and where the source mechanism of the largest LFE (M2.3) was explained by non-double-couple components. Among variable LFEs, only those associated with newly-created fractures and reactivated fractures pushed closer to failure by stress changes due to the Shizuoka earthquake, may have become active. The reader might note alternative source processes. LFEs might not always be generated by magma movement. Hydrothermal fluids, as well as the attenuation of higher frequency earthquakes, can create apparent LFEs43.Nakamichi et al.44 before and after the Shizuoka earthquake . While this study presents a case for the interaction of the Mount Fuji volcanic system with tectonic earthquakes, it remains possible that considerable volcano-seismic activity took place without any influence by tectonics for some cases.In 2000–2001, LFE swarms occurred, starting in August 2000, two months after the eruption of Miyakejima volcano, which lies 160 km to the south of Mount Fuji, although the change in stress was 1018. Whether the increase in occurrence rate of LFEs  earthquake, LFE, artificial event, etc. The spatial map of events classified as LFEs shows that the area of LFEs around Mount Fuji was separated from other areas of LFEs  showed appropriate spatiotemporal coverage. This becomes particularly important when the source mechanism changes over time. Map and cross-sectional views around Mount Fuji  were mostly distributed within the cluster of LFEs, with all magnitudes between Jan. 2003 and Jul. 2019. A consistent spatial coverage of LFEs (M ≥ 0.9) was found between the pre- and post-Shizuoka-quake periods: the coverage of LFEs (M ≥ 0.9) before the Shizuoka earthquake was observed in the area where LFEs (M ≥ 0.9) had already occurred thus far . The CC between a template and continuous waveform at each sampling time for every component at each station was calculated. After subtracting the hypocenter-to-station travel time of the theoretical S-wave, the time sequences of the correlation function throughout all channels were stacked , above which LFEs are used for our analysis, should be above the upper noise limit. We decided to use CCth = 0.25, 0.3, 0.35, and 0.5 for the following reasons. Histograms of CC-values in Supplementary Fig. CC ~ 0.2. We followed previous studies29, in which the distribution of lower CC-values was modeled by a normally distributed curve that would be expected for random correlations between signals and noise, while the upper tail was considered to represent the presence of well-correlated LFEs. Visual inspection shows that frequencies at and below CC ~ 0.2 are in good agreement with the left-hand side of the normally distributed curve where the mean is 0.19 and its standard deviation is 0.03 , the Soufriere volcano (West Indies), and the Unzen volcano (Japan)29, selected CCth-values > 0.5, by showing normally distributed curves with larger means and standard deviations than those shown in this study. We also examined the case for CCth = 0.5.The 29. Rather, this study’s objective was to resolve the difficulty in detecting smaller LFEs. Our future research will be to conduct in-depth analyses of repeating LFEs for each cluster beneath Mount Fuji, referring to Lamb et al.29, and using a sophisticated MF method that can locate detected LFEs to appreciate if they occurred in the same cluster as the template LFE used to find them.The scope of this study did not permit us to reveal repeating LFEs, nor cyclic activities and cluster characteristic, as were studied by Lamb et al.As a basis of catalog completeness, understanding magnitude scales used in this study is critical. We examined whether large LFEs in our catalog were indeed large, as in the JMA catalog, and vice versa. An LFE in our catalog was paired with that in the JMA catalog if the time difference between them was within two seconds, while ignoring one-to-multiple cases. In this pairing, differences in the locations of LFEs were not considered because, as described in the “Mc) of the processed LFE data. Above Mc, all events are considered to be detected. In particular, underestimates of Mc lead to unreliable ETAS fitting. Attention always needs to be paid to Mc when assessing Mc in each time window. Details of how to compute Mc are provided in the “Analyses of the ETAS model see the “” are criMc was about 0.3 ~ 0.5 for the JMA catalog and about 0.2 ~ 0.3 for the MF catalogs , above which the ETAS model was fitted, we assumed Mth = 0.2, 0.3, and 0.4 , suggesting that the feature generally appears to remain stable  relation50, given by log10N = a-bM, where N is the cumulative number of earthquakes with a magnitude larger than or equal to M, a characterizes seismic activity or earthquake productivity of a region, and constant b is used to describe the relative occurrence of large and small events . Changes in b-values of ordinary earthquakes are known to reflect structural heterogeneity, strength, and temperature in the Earth55, and the b-value is also known to be inversely dependent on differential stress57. We assumed that the GR relation was applicable to not only ordinary earthquakes59 but also LFEs. In this section, the word “earthquake” includes LFEs.To compute 60, which simultaneously calculates the a- and b-values and the completeness magnitude Mc, above which all events are considered to be detected. We always paid attention to a robust estimate of Mc, because it is critical for analyses of the ETAS models  techniqueMc, the EMR technique60 combines the GR relation with a detection rate function. Details are provided next. Statistical modeling was performed separately for completely detected and incompletely detected parts of the frequency-magnitude distribution. The b- and a-values in the GR relation were computed based on earthquakes above a certain magnitude (Mcc). For earthquakes whose magnitudes were smaller than Mcc, it was hypothesized that the detection rate depended on their magnitudes in such a way that large earthquakes were almost entirely detected while smaller ones were detected at lower rates. Earthquakes with M ≥ Mcc were assumed to be detected with a detection rate of 1. To evaluate the fitness of the model to data, the log-likelihood was computed by changing the value of Mcc. The best fitting model was that which maximized the log-likelihood value.To compute 62 was used to facilitate the computation of a, b, and Mc based on the EMR method. Although the package, whose code is open, is written in Mathworks’ commercial software language Matlab®, no knowledge is needed since ZMAP is GUI-driven. ZMAP combines many standard seismological tools. A user can use ZMAP to create a graph of frequency-magnitude distribution with the GR relation with a, b, and Mc values calculated by EMR  and above in a certain region during a specified time interval. Seismic activity includes the background activity at a constant occurrence rate μ (Poisson process). The model assumes that each earthquake (including the aftershock of another earthquake) is followed by aftershocks. Aftershock activity is represented by the Omori-Utsu formula63 in the time domain. The rate of an aftershock occurrence at time t following the i-th earthquake (time ti and magnitude Mi) is given by νi(t) = K0exp{α(Mi-Mth)}(t-ti + c)p- for t > ti, where K0, α, c, and p are constants, which are common to each target aftershock sequence in a region. The rate of occurrence of the whole earthquake series at t becomes i satisfying ti < t. Here, Ht represents the history of occurrence times with associated magnitudes from the data {} before time t. The parameter set θ =  represents the characteristics of seismic activity. The units of the parameters are day−1, day−1, no unit, day, and no unit, respectively. For the case of K0 = 0, the ETAS model reduces to the Poisson model  with unit intensity (occurrence rate) so that visualization can be achieved in two ways64. This has been extended to the program package XETAS31 using GUI.A FORTRAN program package (SASeis2006) associated with a manual for the ETAS analysis was used to calculate maximum likelihood estimates and also to visualize model performanceTc. AIC is used to test whether or not the changes in seismicity pattern at Tc reduces model selection34. In this procedure, we separately fitted the ETAS models for each divided period and then compared their total goodness-of-fit values against the one-fit value over the whole period using the principle of minimum AIC. AIC was calculated from the maximum log-likelihood and number of adjusted parameters.When the stationary ETAS model does not fit a dataset well, the simplest alternative model is a “two-stage ETAS model” that considers different parameter values in subperiods before and after a particular time, referred to as change-point Tc is hypothetically prefixed based on some information other than the occurrence data themselves, such as a notable geophysical event or a notable outside large earthquake, AICsingle (AIC for the model fitted over the whole period) can be compared with AIC2stage (AIC for the 2-stage model fitted on divided periods) to select the model with the smaller value that performs a better fit to the data in the entire target period. If Tc is searched from the target data, the 2-stage model becomes harder to accept. Namely, AIC2stage is compared with AICsingle plus the penalty term 2q to select the model. Here q is the degree of freedom to search for the best candidate Tc from the data. q depends on sample size (number of earthquakes in the target period)65: q increases with sample size and, for example, lies in the 4–5 range for q between 100 and 1000.If 66.Although we adopted AIC for model selection, it cannot always be used for other cases such as the identification of possible earthquake precursors in ionospheric electric content (TEC)69 in such a way that μ and K0 are assigned as a function of t. The function μ(t) and K0(t) are represented by a broken line connecting the respective sequences ) and ) for the i-th earthquake, using a Bayesian function.The standard stationary ETAS model can be temporally extended to the non-stationary ETAS modelK0 were computed, given that other parameters  were constants, where the values for  were obtained as follows. The parameters θ =  were first computed for each time-window, each Mth, and each CCth. Typical values for α, c, p were α = 0.5, c = 0.0015, and p = 2.8. Using these typical values, parameters μ and K0 were recomputed for each time-window, each Mth, and each CCth. The error bars for μ and K0, which can be calculated by XETAS31, are based on error distribution depending on the sample size when the number of LFEs is not large enough65.Although such a sophisticated model is available, a simpler approach was taken to capture essential aspects of the time-dependent background and aftershock activities Fig. –S3. ThisK0 was forced to express time-dependent aftershock activity  were prefixed as constant, resulting in Supplementary Fig. K0, c, p were constant  and intersection (h) of the least-square regression line and the square of the sample correlation coefficient (R2) for Fig. gCCth + h with  =  for M ≥ 0.2 (blue solid line),  for M ≥ 0.3 (red solid line), and  for M ≥ 0.4 (green solid line) before 2011, and  for M ≥ 0.2 (blue dashed line),  for M ≥ 0.3 (red dashed line), and  for M ≥ 0.4 (green dashed line) after 2011.The slope  =  for M ≥ 0.2 (blue solid line),  for M ≥ 0.3 (red solid line), and  for M ≥ 0.4 (green solid line) before 2011, and  for M ≥ 0.2 (blue dashed line),  for M ≥ 0.3 (red dashed line), and  for M ≥ 0.4 (green dashed line) after 2011.Similarly, for Fig. Supplementary Information.


Relative supersaturation (RSS) values for urine crystals are a measure of the risk of urinary stone formation and have been shown to be lowered in foods shown to aid in the management of urolithiasis. In order to calculate RSS in pets, computer programs have been developed to calculate RSS and aid in the understanding of stone formation in veterinary medicine. However, some older programs have not been updated for use in animals, and the specific coefficients used are not publically available. One of the first RSS programs was developed in BASIC computer language and published in 1985 which was called EQUIL2. The EQUIL2 program was updated to a compiled version compatible with a PC platform. However, the formulas could not be read or altered.t-test, calculating the r2 from correlation analysis, Lin’s concordance correlation coefficient, and by a Bland–Altman analysis of outputs from the two programs using urine samples from healthy dogs and cats.This study evaluates a new program with known coefficients to the original EQUIL2 program. The RSS values of the two programs were compared through a Our results show that for both magnesium ammonium phosphate (struvite) and calcium oxalate, the RSS values of the original program could be calculated from the new programs RSS values. Although the actual RSS values were different  the results were highly correlated, finding elevations and reductions in RSS proportionally in the same urine samples. The current work creates a foundation for using the modernized program to calculate RSS and provides a shared method for understanding the risk of struvite and calcium oxalate stone formation. Stones form by precipitation when precursor molecules exceed their saturation level in the urine and inhibitors fail to prevent agglomeration into substantial calculi. The saturation level is the maximum amount of solute that can be dissolved in a solvent at a specific temperature and is influenced by the solvents pH, its milieu of ions and factors influencing precipitation. Within the urinary system of a living mammal, there is an absence of large temperature fluctuations, so the saturation level is mainly dependent on the pH of the solution (urine) and the concentration of the specific molecules. A relative supersaturated solution occurs when more than the usual amount of solute required to form crystals is dissolved in the solution at a stable temperature; this phenomenon occurs when pH changes increase the solubility of the solute as well as the interaction of the molecules in the system serving to stabilize the solution. Therefore, relative supersaturation is defined as the ratio of the actual concentration of a dissolved solute in urine to its theoretical solubility in water . The RSSUrine becomes supersaturated when it contains more material than can be dissolved by water under normal circumstances. Supersaturation is required for stone formation; however, a relative supersaturation above 1 in companion animals’ canine and feline urine may or may not result in stone formation .Urolithiasis is common in humans, affecting about 9% of the population in the United States , while nRelative supersaturation (RSS) is a method for measuring the risk of specific crystal formation in urine and may help predict the risk of urolith formation. The RSS method uses mathematical determinations to predict the predisposition to form stones by analyzing urine pH and the concentrations of different minerals and compounds known to influence the formation of crystals. Risk factors for stone formation include breed, age and genetic makeup. However the controllable food choice and feeding practices also play significant roles . There a4·H2O; struvite), uric acid, and others. The SUPERSAT program was developed in 1969  computed using the new coefficients and the previously established EQUIL2 program for RSS calculations. The goal of the study was to evaluate the relationship between the reported RSS of the two programs thus allowing a comparison of the RSS estimates from EQUIL2 which has previously been used in nutritional research. Also, to provide an understanding of the program we are now making available for general use.2.2.1.ad libitum. During the adaptation phase the dogs and cats were housed collectively by species. The dogs and cats were also housed individually in lodges, to which they had been acclimated via a habituation program, for the 24 h of urine collection. During the collection period all naturally voided urine was collected in bottles containing thymol. A minimum of 30 mL of urine was saved for analysis. Urine was held at body temperature during collection and pH was measured. Aliquots were frozen at-80°C for all other analysis. The protocols were approved by appropriate Animal Care and Use Committees and adhered to the sponsor’s Animal Welfare Policy.The study included urine ion analysis from 380 healthy adult beagle dogs and 494 healthy adult shorthair cats. The health status of the dogs and cats was ascertained by daily observations from animal care technicians and annual evaluations, which included a physical examination, blood work (complete hematology and serum biochemistry panels), urinalysis, and diagnostic imaging . All pets were under the care of a veterinarian  who was consulted on and oversaw any health related concerns. Urinary tract health was under frequent evaluation as the pets urine was frequently evaluated for crystals and signs of infection. Any dog or cat with a urinary tract health-related problem or other systemic disease was not eligible for participation. The dogs and cats were maintained separately in a temperature-controlled facility with natural daylight and opportunities for environmental enrichment and exercise. All dogs and cats were fed to maintain their optimal body weight for at least 2 weeks prior to sampling. Quantities of food offered and refused were weighed and recorded daily. Drinking water was offered 2.2.+2, Cl−, citrate, Mg+2, oxalate, PO4−3, K+, Na+, SO4−2, NH4+, and pH. The specific analyte methods were validated in the laboratory doing the analysis following the FDA Guidelines for Biochemical Analyses. The mineral content of the urine, specifically, Ca, Mg, K, Na and P, are measured using ICP-OES . The minerals  are measured using an Agilent 5,100 Inductively Coupled Plasma—Optical Emission Spectrometer. The urine is prepared by acidifying 500 μL of the urine with dilute hydrochloric acid. The instrument is calibrated using traceable solutions containing each of these elements. The concentrations of chloride, sulfate and citrate are measured simultaneously using hydroxide ion exchange chromatography. Each sample of whole urine is diluted 400:1 with deionized Water . The instrument is calibrated using traceable standards of each ion of interest. The concentration of oxalate in each urine sample is measured using ion exclusion chromatography. The raw urine is acidified using dilute phosphoric Acid prior to freezing to ensure that the oxalate stays in solution. The method used is similar to the previously published method .2.4.t-test; Lin’s concordance correlation coefficient (CCC) .The relationship between values of RSS for CaOx and struvite calculated with the control and new software programs using the measured ion concentrations in urine from dogs and cats was examined using four assessments: a paired nt (CCC) ; calculaan plots . The resn detail . The gra3.3.1.3.1.1.p = <0.01) using the new coefficients.2 of 0.985). The Lin’s CCC was 0.956 showing the agreement between the two values is high. However, the slope was significantly different from 1 . This results in the average difference between the two values as shown in Regression of CaOx values calculated using the new software program could be used to predict CaOx RSS values calculated using the control program with high precision  using the new software program.Summary statistics of RSS values for struvite in dog urine are given in r2 = 0.967). However, the slope significantly different from 1  as shown in Regression of struvite values calculated using the new software program could be used to predict struvite values calculated using the old software program with high precision. The strength of the prediction equation was high  between the two software programs.Summary statistics of RSS values for CaOx values in cat urine samples as determined by the two software programs are given in 2 of 0.987) as shown in As in the case with the canine the relationship of the two software programs was such that the old RSS could be predicted from the results of the new  from the New software as compared to the Control.Summary statistics of RSS values for struvite in cat urine are given in 2 of 0.971, Regression of MAP values calculated using the new software program could be used to predict MAP values calculated using the old software program with high precision  and the EQUIL-HL21 program with new coefficients (New) for calculating the relative supersaturation (RSS) of dog and cat urine with respect to CaOx and struvite. The original programs take up to 15 and 23 user-inputted ion concentrations, respectively. However, these programs are robustly designed to calculate RSS in other sample types  and for multiple stone types. As such not all input variables have meaning in the urine samples or stone types considered here. This study used the analytes which are present in urine and expected to have an influence on struvite or CaOx supersaturation. The data from this work show that the two programs are highly related in that knowing the RSS from the New calculation allows one to calculate the RSS from the Control program. However, they do not produce identical results. The difference is due to the different thermodynamic stability constants used in the computations by the two programs.The RSS values for CaOx in dogs were significantly higher using the Control program compared with the New software. This relationship generated the slope of 1.181 so that the increase was found consistently with the higher values showing the greatest differences. For the RSS of CaOx in cat urine, the agreement between the programs was good with a slope of 1.048 (Control/New). For RSS of struvite in dog urine, the slope was 3.08 with higher values in the Control program as compared to the New. Similarly, for RSS of struvite in cat urine the slope was 3.314 showing clear differences and higher values of RSS using the Control program.We hypothesize the discrepancies in the data obtained using the two programs can be explained by the slightly different coefficients and thermodynamic stability constants used for computations between the two programs. The greater divergence in RSS at higher values indicates that a constant factor in the algorithms is responsible, although the contribution of super-anion binding sites may play a role for CaOx . Also, iThe study was designed to document the RSS values generated by the two software programs and determine the level of alignment between the values generated by both. The study therefore, does not give information on what program generates values that best represent clinical manifestations or laboratory investigations. Moreover, a limitation in this work is that urine from healthy dogs and cats, which were not known stone formers, was used to determine the range of RSS. This limits the evaluation of the algorithms. The study does provide evidence that when comparing RSS values the comparisons should be made using values calculated by the same program or through understanding the relationship between the two programs used. We also freely offer the program to researchers , so thataruplab.com, 500 Chipeta Way, Salt Lake City, UT) or a program offered by Royal Canin, using human, dog and cat urine have been reported (Comparisons between the Control program and other methods regarding their ability to predict urine supersaturation are available in the scientific literature , 44, 45.reported . Values reported . The SUPreported  for calcreported . Howeverreported . These sThis study has a limitation in that it did not use all possible analytes for predicting RSS and did not have any pets with urolithiasis as data points to evaluate what RSS prediction value is associated with stone formation. Furthermore, there is the general limitation of all RSS values as actual stone formation is dependent on nucleation and the surface energy of the solid phases of stone-salts , 49.In conclusion, this study shows that the relative supersaturation of dog and cat urine with respect to CaOx or struvite can be calculated using either of these programs. Although the programs are highly related they are not interchangeable. The advantage of the new program is that it is compatible with modern operating systems and can serve as an open-source platform for use by the veterinary research community.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of Hill’s Pet Nutrition, Inc. Written informed consent was obtained from the owner for the participation of the animals in this study.JB was responsible for statistical analysis. PW was responsible for the coefficients used and the new program to calculate relative super saturation. All authors contributed to the writing and editing of the manuscript and agreed to be accountable for the content of the work.This research was funded by Hill’s Pet Nutrition, Inc. The funding agency provided funds for the consultants and the bio-archive data for analysis.RA, SD, JM, PW, and DJ were employed by Hill’s Pet Nutrition, Inc. JB was employed by Alpha Statistical Consulting.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 COVID-19 pandemic mandated a robust expansion of our program’s telemedicine bandwidth. Despite the lifting of pandemic restrictions, the number of telemedicine visits has stayed consistent, which is a credit to both the quality of care provided and to the convenience of receiving care via computer or smartphone. We sought to quantify some aspects of this convenience to more thoroughly understand the benefits of our program's expansion.We examined home addresses for all patients seen via telemedicine from June, 2021 through May, 2022. We estimated the distance that telemedicine saved each patient by searching a navigation website for the most time efficient route from their hometown to our burn center. Patients who lived in the same city as our center were assigned a distance of 1 mile. Hours saved were estimated by assuming a driving speed of 70 miles per hour. Fuel money saved was estimated by assuming an average fuel economy of 24.2 miles per gallon and an average gas price of $3.61. The overall carbon footprint was estimated by assuming an average CO2 emission of 411 grams/mile.1,794 patient visits were conducted via telemedicine over this 12 month span. The total estimated amount of roundtrip travel saved was 621,718 miles which equated to 8,882 hours and $92,744 dollars saved. The carbon footprint saved was 255.5 metric tonnes. On average, our telemedicine program saved an estimated 4.95 hours and $51.70 in gasoline per patient-visit.Even when ignoring the potential hurdles of transportation access, family care, missed time at work, and parking fees there are clear quantifiable reasons behind the program’s popularity. The environmental benefit is an important byproduct of its convenience.Our telemedicine program requires dedicated staffing and significant patience with technology but has remained popular due to the outlined advantages and has facilitated the expansion of our program into a broader catchment area.


The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors’ aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types.A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death.Thirty nine studies were included . Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) , major complications , and early allograft dysfunction (EAD)  and improved 1-year graft survival  in ECD-OLT. HMP also reduced primary non-function (PNF)  and acute rejection . NMP only reduced major complications in ECD-OLT , without favorable effects on other complications and survival. NRP lowered the overall risk of NAS , PNF , and EAD  and meanwhile improved 1-year graft survival  in control DCD-OLT.HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist. HighlightsWe accurately evaluate the benefits of different machine perfusion (MP) methods  on different donor types.HMP significantly reduces the risk of non-anastomotic biliary stricture (NAS), major complications, and early allograft dysfunction (EAD), meanwhile improves 1-year graft survival in all DBD-OLT (donor after brainstem death-orthotopic liver transplantation), DCD-OLT (donation after circulatory death-OLT), and ECD-OLT (extended criteria donor-OLT).NMP only reduces the risk of major complications in ECD-OLT, and failed to improve survival in all donor types.NRP lowers the occurrences of NAS, PNF (primary non-function), and EAD, meanwhile markedly elevates 1-year graft and patient survival rates in cDCD-OLT (controlled DCD-OLT).2, which could additionally increase the donor pool by up to 20–50% in some centers. However, ECD livers are frequently associated with high risk of postoperative short-term and long-term complications, as high-risk donors are more vulnerable to ischemia-reperfusion injury (IRI)3. Especially, primary non-function (PNF), early graft failure, and non-anastomotic biliary stricture (NAS), that are the frequent cause of early patient death, have always been the Achilles heel for ECD utilization. The discrepancy between the increasing need for ECD and the high perioperative complications of ECD has become a hard nut to crack in OLT. Therefore, new strategies for safe use of ECD grafts are urgently needed.Orthotopic liver transplantation (OLT) is the only well-established treatment for end-stage liver disease, but many patients died on the waiting list due to severe shortage of donors. To address shortfalls in the supply of standard criteria donors, many transplant centers have progressively extended the criteria to accept marginal livers or extended criteria donors (ECD)4. By allowing for ex-situ nutrients supply, organ resuscitation, and viability evaluation, all hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP) have been shown to outperform SCS through modulating IRI6, repairing liver grafts, and thus reducing post-OLT complications, so more margin donors can be saved to combat the organ shortages.Static cold storage (SCS) remains the gold standard for organ preservation worldwide due to its simplicity, low cost, and convenience for transport. However, it cannot satisfy the requirements of high-quality preservation for ECD grafts. To expand the donor pool and mitigate the drawbacks of ECD, machine perfusion (MP) has emerged as a promising preservation method since it can greatly alleviate IRI and thus reduce the discarded rates7. The concept of NRP was introduced to reduce IRI during non-touching period before procurement. Recent studies suggested NRP as a safe alternative to in-situ cooling and rapid procurement8, which could also reduce certain post-transplant complications such as NAS and early allograft dysfunction (EAD)10. However, these results are not so convincing as they are inconsistent.In some countries, donation after circulatory death (DCD) donors has extremely high discarding rates due to long functional warm ischemia time (WIT) under ethical principle and requirements. To address this, the VITTAL trial has attempted to use NMP to rescue declined livers to push the boundaries in utilization of high-risk grafts, but the outcomes in DCD grafts were not satisfactory10. However, these meta-analyses are vague about the effectiveness of MP on different graft types. The preferred MP method for certain type of donor remains unclear, especially for ECD. These add to confusion in donor grafts management and cause unnecessary medical waste. In recent 2 years, a considerable number of high-quality researches on MP are updated. It is needed to summarize and confirm the selection criteria of different MP strategies for different donor types, especially for ECD.All HMP, NMP, and NRP could theoretically improve OLT outcomes through protecting grafts from IRI. However, more convincing evidence is still needed. Currently, the number of randomized controlled trials (RCTs) on MP is still limited, and heterogeneity makes the results remain controversial. Previous meta-analyses have demonstrated the importance of MP in reducing EAD and NASThe aim of this study was to appraise and condense the available literature reporting OLT outcomes when comparing HMP, NMP, and NRP with SCS to (i) assess the effects of different MP strategies on improving OLT outcomes in different donor types and (ii) preliminarily explore the preferred MP strategy for ECD grafts.11   and AMSTAR  Guidelines12 .This systematic review and meta-analysis was conducted in April 2023 on the basis of the PRISMAThe literature search was carried out on PubMed, Cochrane Library, EMBASE, ClinicalTrials.gov, and Web of Science, using the following search algorithm ‘ AND MeSH terms (liver)’ in ‘All fields’. No language or date restrictions were applied. The reference lists of selected studies and previous reviews were manually reviewed to identify all relevant articles. Abstracts were screened and full-text articles were evaluated for eligibility by two independent reviewers. If a disagreement occurred between the reviewers, the senior author was consulted to reach a final decision together.Adult OLT studies  comparing the outcomes of HMP, NMP, or NRP versus SCS were included.Studies were excluded if: (a) articles with less than 10 transplanted livers; (b) studies using more than one perfusion technique [e.g. sequential hypothermic oxygenated perfusion (HOPE) and NMP]; (c) studies contained living or split donor or multivisceral transplantation or simultaneous liver–kidney transplantation or pediatric transplantation; (d) studies without controls or the control group was not SCS; (e) overlapping studies from the same center; (f) articles without the interest outcomes; (g) animal experiments, reviews, editorials, letters or case reports, book chapters, and abstracts.The primary outcomes extracted were NAS, major complications, EAD, and 1-year patient and graft survival. Secondary outcomes were acute cellular rejection (ACR), PNF, post-reperfusion syndrome (PRS), acute kidney injury (AKI), renal replacement therapy (RRT), and hepatic artery thrombosis (HAT).13. Major complication defined as major complications defined by a Clavien–Dindo grade ≥3. ECD were defined as donors with hemodynamic deterioration, donor age >65 years, donor body mass index >30 kg/m2, serum bilirubin >3 mg/dl, Aspartate Aminotransferase or Alanine Aminotransferase above three times the upper reference threshold, sodium >165 mmol/l, intensive care unit (ICU) stay >7 days, steatosis >40%, cold ischemic time (CIT) >12 h1. Detailed definitions of primary and secondary endpoints can be found in the Supplementary Materials .NAS was defined as any irregularity or narrowing of the intrahepatic or extrahepatic donor bile ducts within 12 months following OLT, and it must be documented by Endoscopic Retrograde Cholangiopancreatography, percutaneous transhepatic cholangiogram, surgically placed biliary catheter, or magnetic resonance cholangiopancreatogramData extraction was performed using a predetermined Microsoft Excel template. The data included characteristics of the study , donor and recipient characteristics , MP parameters , and the outcomes above. Any differences in data extraction were settled by discussion and consultation with the senior authors.Two reviewers determined independently the risk of bias according to the Risk of Bias in Nonrandomized Studies of Interventions tool for cohort studies and the Risk of Bias tool 2 (RoB2) or RCTs.Q and the I2 statistics. A meta-analysis was conducted using random-effects model or fixed-effects model, with fixed-effects model used if heterogeneity was less than 50%. First, we focused on the effects of HMP, NMP, or NRP on all donor types. Subsequently, subgroup analysis was used to explore the effects on ECD, DCD, or donor after brainstem death (DBD). Possible sources of heterogeneity were explored by subgroup analysis and sensitivity analysis. When analyzing NRP studies, we further divided DCD into controlled DCD (cDCD) and uncontrolled DCD (uDCD). Finally, we conducted the meta-analysis using only RCTs to verify the stability of the results. The statistical package R version 4.2.0 was used for statistical analysis. A two-tailed P<0.05 was considered as statistically significant.Results were expressed as odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was analyzed using Cochran’s 46 were eligible in the systematic review, including nine RCTs46 and 30 cohort studies47. A total of 6254 livers were included: 3970 SCS (control group), 608 grafts with HMP, 709 with NMP, and 968 with NRP, of which 1122 livers were from RCTs. Study information, recipient and donor demographics, and perfusion characteristics are summarized in Tables S3–S7 . Detailed distribution of baseline characteristics is described in Supplementary Page 1 . A PRISMA flow chart for included studies is presented in Figure http://links.lww.com/JS9/A885) and S2 . Overall, all RCTs had a low risk of bias. Non-randomized cohort studies had at least moderate risk bias [Tables S1 and S2 ].Literature search finally identified 1714 records, and 101 full-text articles were assessed for eligibility. In total, 39 studies46 were involved in meta-analyses, including four RCTs46. No significant heterogeneity was observed. For overall effects on all donor types, HMP was associated with significant improvements in NAS , major complication , and EAD . One-year graft survival  and 1-year patient survival  were significantly improved in HMP compared with SCS [Figs S1  and S2 ].Fourteen HMP studies46 reported the effects of HMP on ECD, including three RCTs46. HMP remarkably reduced the risk of NAS in ECD-OLT compared with SCS ; this benefit was maintained significant in major complications  and EAD . HMP was also significantly associated with improved 1-year graft survival  and 1-year patient survival  compared with SCS in ECD subgroup ; and this benefit was maintained in EAD  . One-year graft survival was significantly improved in HMP-DCD . However, there was no significant difference in 1-year patient survival between HMP-DCD and SCS-DCD  . Compared with SCS, HMP remarkably reduced the risk of postoperative major complications  and EAD . HMP was significantly associated with improved 1-year graft survival  and 1-year patient survival  in DBD grafts [Fig. S3 ].Nine articles45 studies reported the effects of NMP on OLT outcomes, including five RCTs43. Overall risk of NAS  and EAD  was significantly lower in NMP than SCS, but no difference was observed in major complications . High heterogeneity was observed among the included studies for these endpoints [Fig. S4 ]. No differences were found in 1-year graft survival  and patient survival  [Figs S4  and S5 ].A total of 1623 NMP studies reported the outcomes of ECD-OLT. The risk of NAS  and EAD  was similar between NMP-ECD and SCS-ECD. Instead, major complications were significantly reduced in NMP-ECD . No differences were observed in 1-year graft survival  and 1-year patient survival  between NMP and SCS . In the meta-analysis of three studies20, EAD was significantly reduced in NMP-DCD   in NMP-DBD. No statistical difference was found in 1-year graft survival  and 1-year patient survival between NMP-DBD and SCS-DBD  [Fig. S6 ].Five studies44 included both DBD and DCD grafts. As these studies did not report the outcomes separately according donor types, we specifically performed a subgroup analysis of NMP studies including both DBD and DCD. There were no differences in NAS , major complications , EAD , 1-year graft survival , and 1-year patient survival  between NMP and SCS in this subgroup [Fig. S7 ].Eight NMP studies42 studies investigated the impacts of NRP on OLT outcomes, currently no RCTs were available on this topic. Seven studies42 investigated NRP-cDCD grafts, with three41 using SCS-cDCD as controls and the remaining four42 using SCS-DBD as controls. NRP-uDCD was investigated in three studies40 with SCS-DBD as control.Though tenhttp://links.lww.com/JS9/A885) and S9 ], NRP significantly reduced the overall risk of EAD . However, there were no significant differences in NAS  and major complications  between NRP and SCS. One-year graft survival  and 1-year patient survival  were also similar between NRR and SCS. The heterogeneity was high in these outcomes [Figs S8  and S9 ].In pooled analysis .In subgroup analysis of HMP-RCTs, HMP was associated with a significant reduction in NAS , major complications , and EAD . However, NMP showed no benefits on 1-year graft survival  and 1-year patient survival  [Fig. S11 ].In subgroup analysis of NMP-RCTs, NMP significantly reduced NAS  and ACR  and tended to reduce PRS  and HAT  compared to SCS [Figs S12  and S13 ]. In a subgroup analysis of ACR, HMP significantly reduced ACR only in ECD-DCD grafts  but not in ECD-DBD grafts . No differences were observed in AKI and RRT between HMP and SCS (P>0.05).In a pooled analysis, HMP significantly decreased the risk of PNF  but had no effects on reducing PRS, ACR, RRT, and HAT (P>0.05) [Figs S14  and S15 ].NMP tended to reduce the risk of PNF  and HAT  but had no effects on reducing PRS and RRT (P>0.05) [Fig. S16 ].NRP significantly reduced the rates of ACR  on different donor types, we performed a meta-analysis according to DBD, DCD, and ECD. Our results show first that HMP, NMP, and NRP are all effective to improve OLT outcomes, but their protective effects vary to a certain degree on different donor types. Compared with SCS, HMP could comprehensively improve OLT outcomes, including reducing the risk of NAS, EAD, major complications, PNF, PRS, and ACR and meanwhile improve 1-year graft/patient survival, with the strongest effects seen in ECD. Second, NMP could reduce major complications in ECD and EAD in DCD. Third, NRP significantly reduced NAS, EAD, PNF, and HAT and improved 1-year graft survival in cDCD.P =0.03, Fig. S12 ] and NAS risk by 57%  compared with SCS, indicating HMP’s excellent effects against IRI. More interestingly and beyond our expectation, we also found HMP’s significant effects on reducing ACR , which was consistent with Maspero’s findings48. Better still, our data further suggested that HMP’s benefits on ACR were only limited in DCD  but not in DBD and ECD-DBD grafts (P>0.05), which needs further study to clarify this phenomenon. Graft survival is another important endpoint for MP’s trials. In our study, HMP significantly improved 1-year graft survival in all DBD, DCD, and ECD subgroups, demonstrating its long-lasting and outstanding protection on long-term outcomes. In Patrono’s study35, HMP is even associated with improved 5-year overall graft survival in elderly donors (>75 years old). A noteworthy study by Muller et al.49 highlights the significance of flavin mononucleotide in HMP setting as a reliable marker to determine the ‘transplantability’ and facilitate proper clinical decisions regarding the acceptance of high-risk grafts. Taken these results together, HMP has the potential to be the preferred preservation strategy for DCD or ECD grafts.The issue of improving preservation quality is at the core of transplantation, especially for high-risk grafts. ECD are increasingly used due to severe organ shortage, but many ECD livers are still declined due to high risk of PNF or severe complications. MP has the potential to address this dilemma, and various protocols are currently investigated in clinical trials. However, MP’s benefits on ECD lack quantitative investigation, and the priority of different MP methods remains unknown. Our study first demonstrated that there is an overall improvement in HMP-OLT outcomes, including reducing various short-term complications and improving graft survival. This effect is significant in all DBD, DCD, and ECD, with the strongest effects seen with ECD. PNF and NAS are two critical IRI-related complications, which could directly reflect the preservation quality. Our study first showed that HMP significantly reduced PNF risk by 60% . No benefits on graft/patient survival were observed in DBD, DCD, and ECD by NMP. Unlike HMP’s and NRP’s multiple benefits on OLT outcomes compared with SCS, our pooled data suggested that NMP might not provide optimal protection against IRI, especially for DCD and ECD grafts after a period of cold storage. In a recent study reporting 78 NMP-livers followed-up for 7 years by Hefler et al.44, no differences in long-term survival, major complications or biliary complications were observed (P>0.05). Even in ischemia-free OLT, continuous NMP ‘without any ischemia’ still failed to improve survival43. These results indicated that only NMP alone might be not enough for high-risk grafts. Though allowing ex-situ viability assessment at 37°C, NMP may still be associated with continuous warm ischemia of donor liver because the organ is metabolically active and current technology may not achieve sufficient hepatic perfusion compared with that in-situ. Therefore, this may partly explain the relatively high rates of NAS in NMP-DCD livers and limited benefits on survival50. Besides potential insufficient perfusion, user or device error might cause serious consequences in NMP, leading to graft loss. For this reason, it has been proposed that NMP should best be preceded by a short period of HMP as sequential HMP&NMP for high-risk DCD livers indeed demonstrated excellent results and low NAS risk51. Following HMP, a longer preservation time will allow NMP to modulate the quality of marginal donor by delivering various drugs, anti-oxidants, and siRNA, providing the possibility for organ repair, immune regulation, and even ectopic regeneration. Combined HMP and NMP strategy will be a very meaningful and promising attempt. More studies are warranted to further clarify NMP’s selection criteria for ECD and expand the boundary of this promising field.NMP is a landmark development in overcoming logistical challenges in OLT. NMP can not only resuscitate grafts to reduce IRI but also allow to facilitate viability assessment and decision-making of marginal grafts. According to Nasralla’sDCD Figs , 5, with52. Our data showed that NRP remarkably reduced the risk of PNF, NAS, EAD, and HAT in cDCD grafts. Surprisingly, our pooled data suggested that NRP could remarkably reduce PNF and HAT risk in NRP-cDCD compared with SCS-cDCD , suggesting that there is some kind of upper limit to NRP’s benefits under long time warm ischemia. Patrono et al.53 demonstrated that a combination of NRP and HMP for cDCD achieves comparable outcomes to standard SCS-DBD. This perfusion strategy has the potential to leverage the advantages of both NRP and HMP, while simultaneously addressing their respective limitations to optimize the prognosis of uDCD-OLT53. However, further multicenter RCTs are needed to validate the benefits of sequential perfusion strategies combining NRP with HMP or NMP.Although using uDCD greatly expands the donor pool, its use in high-risk patients needs to be more cautious, and the protocols of NRP in uDCD-OLT should be more stringent. In contrast to cDCD, 1-year graft and patient survival in NRP-uDCD is still inferior to SCS-DBD .In future, appropriate perfusion methods are required to be clarified to maximize clinical benefits for corresponding donor types. Theoretically, there could be an optimum perfusion strategy for a specific type of donors and even for each donor. Currently in the early periods of MP application, preliminary clinical trials were mainly designed to compared the efficacy and feasibility of different MP approaches with SCS as the clinical standard. A direct comparison between different MP techniques is still lacking, especially for current two main paradigms – NMP versus HOPE. Our results suggested the superiority of HMP on DCD and ECD. But owing to insufficient data of NMP-ECD studies, the superiority of HMP to NMP needs to be verified. Recently, the first multicenter RCT to test the effects of NMP versus HOPE on ECD-DBD livers is on recruitment and will help to answer this academic problem , the National Key R&D Program of China (2022YFA1104900), the National Natural Science Foundation of China (82200702 and 31972926), and the Guangdong Basic and Applied Basic Research Foundation (2020A1515111111).K.Z., Y.N., A.L.: study concept and design; A.L., Y.N., W.C., S.C., and L.Z.: acquisition of data; A.L., W.C., and P.C.: analysis and interpretation of data; A.L., Y.N., P.C.: drafting of the manuscript; Y.N. and K.Z.: critical revision of the manuscript for important intellectual content; Y.N. and K.Z.: administrative, technical, or material support; and K.Z.: study supervision. All authors have made a significant contribution to this study and have approved the final manuscript.The authors declare that they have no conflicts of interest.The review protocol was registered prospectively with the National Institute for Health Research (PROSPERO) system and is available online with registration number CRD42023391864.Kebo Zhong and Yu Nie.The data, code, and other materials are available from the corresponding author upon reasonable request. The data that support the findings of this study are openly available in PubMed.Not commissioned, externally peer-reviewed.


Maternal mortality comprises about 10% of all deaths among women of reproductive age (15–49 years). More than 90% of such deaths occur in low- and middle-income countries (LMIC). In this study, we aimed to document lessons learnt and best practices toward sustainability of the m-mama program for reducing maternal and newborn mortality in Tanzania. We conducted a qualitative study from February to March 2022 in Kahama and Kishapu district councils of Shinyanga region. A total of 20 Key Informant Interviews (KII) and four Focused Group Discussions (FGDs) were conducted among key stakeholders. The participants included implementing partners and beneficiaries, Community Care groups (CCGs) facilitators, health facility staff, drivers and dispatchers. We gathered data on their experience with the program, services offered, and recommendations to improve program sustainability. We based the discussion of our findings on the integrated sustainability framework (ISF). Thematic analysis was conducted to summarize the results. To ensure the sustainability of the program, these were recommended. First, active involvement of the government to complement community efforts, through the provision and maintenance of resources including a timely and inclusive budget, dedicated staff, infrastructure development and maintenance. Secondly, support from different stakeholders through a well-coordinated partnership with the government and local facilities. Third, continued capacity building for implementers, health care workers (HCWs) and community health workers (CHWs) and community awareness to increase program trust and services utilization. Dissemination and sharing of evidence and lesson learnt from successful program activities and close monitoring of implemented activities is necessary to ensure smooth, well-coordinated delivery of proposed strategies. Considering the temporality of the external funding, for successful implementation of the program, we propose a package of three key actions; first, strengthening government ownership and engagement at an earlier stage, secondly, promoting community awareness and commitment and lastly, maintaining a well-coordinated multi-stakeholder’ involvement during program implementation. Maternal and neonatal mortality remains a global health problem . DespiteMaternal mortality is linked with the three-delay model proposed by Thaddeus and Maine . The firImproving maternal health is one of the sustainable development goals (SDGs). Specifically, it is target number 3.1  with the aim of reducing maternal mortality ratio (MMR) to below 70 deaths per 100,000 live births in 2030 . ExpeditWith much efforts invested into implementing evidence-based interventions in LMICs, most of which are externally funded, it is essential to ensure that such programs are long lived and the community continues to benefit beyond initial Implementation . SustainTanzania has witnessed a steady decline in neonatal and child mortality, but not maternal mortality . CounterA qualitative study was conducted between February and March 2022 in Kahama and Kishapu districts of Shinyanga region, Northern Tanzania. Kahama and Kishapu are among the 6 municipalities in Shinyanga where m-mama program was implemented. In 2015, Shinyanga was reported as one of the regions with higher MMR of 446 deaths per 100,000 live births than the national average of 432/100,000 live births .The m-mama program was implemented in the Mwanza and Shinyanga regions in Tanzania in various phases. The program began in 2013 as the Mobilizing Maternal Health project. It aimed to address broad, systemic challenges through a coordinated horizontal program approach that extends from the community, lower-level health facilities up to the hospital level. It has been implemented in close collaboration with government partners at the Ministry of Health (MoH) and the President’s Office Regional Administration and Local Government (PO-RALG), selected health facility governing bodies, and communities. The program focused on proof of concept and identifying cost effective solutions to address maternal and neonatal mortality. In the current phase, the program started in 2017 to expand m-mama program into the entire Shinyanga region with a total of six councils and approximately 1.9 million population. It focused on the ownership and sustainability of the program by local government authorities beyond the donor supported services. Touch Foundation, Pathfinder International and respective Regional and Council Health Management Teams (R/CHMT) were the key implementers of the m-mama program.m-mama program interventions included the Emergency transportation system (EmTS) and technical and operational support of the health system. The EmTs was designed in concert with the Ministry of Health (MoH), Reproductive and Child Health Services (RCHS) division and the Regional Health Management Team (RHMT). This innovative method utilized technology to remotely triage patients and dispatch an ambulance or community taxi driver to transfer the patient to a health facility. It aimed to address the second and third delays .With the aim of providing holistic care for women and newborns, m-mama program also provided technical and operational support. This included the establishment of Community Care Groups (CCGs) to address the first delay by influencing proper health-seeking behaviors in the community. Also, the program supported health facilities in Shinyanga region to improve the quality of Maternal, Neonatal and Child Health (MNCH) care at Basic Emergency Obstetric and Neonatal Care (BEmONC) dispensaries, health centers and hospital level by building the capacity of health providers, providing equipment and improving detection and referral of high-risk and complicated pregnancies. This assured provision of high-quality care for women and newborns upon reaching the appropriate health facility. Concurrently, Touch Foundation helped to build clinical and structural capacity at the health centers and district hospital level for the provision of Comprehensive Emergency Obstetric and Neonatal Care (CEmONC) services so that together the activities supported a continuum of care for women to access MNCH services at all levels of the health care system.We adopted the integrated sustainability framework (ISF) inductively to synthesize themes and subthemes on program sustainability. With the ISF, the important constructs listed as factors influencing program sustainability across settings are the outer context, inner context, the processes, characteristics of the interventionists, and characteristics of the intervention . The ISFi.e., support from different stakeholders as significant contributor in supporting program continuation), the inner contextual factors , the intervention characteristics  and the intervention process .The themes selected and developed in our study were analysed and interpreted using the domains of the ISF in the dynamic context as shown in Respondents in the current evaluation study categorized in five groups. The first group included government officials at national, regional and district levels. At national level, stakeholders from PO-RALG and Safe motherhood from the MoH were interviewed. Also, government officials, coordinators and officers at regional and district level were included.Program staff from m-mama, Pathfinder and Touch Foundation at administerial level as well as m-mama Program implementers form the second group of study participants. These are; District Transport Officers, Emergency Transport System Focal persons and Dispatch supervisors. Thirdly, at community level, we involved Community Care Group (CCGs) facilitators responsible in facilitating and supervising CCGs. The fourth group were the program implementing partners at the local facilities and communities, these are the health care workers (nurses and doctors) at health facility level, and drivers and dispatchers included to assess the emergency transportation system employed in improving health facility accessibility. The last group included the beneficiaries of the m-mama program, these were selected women or mothers at community level and their spouses.Purposive sampling was conducted from the level of region to health facility. Purposive sampling is commonly and widely used in qualitative research to obtain information-rich individuals to ensure in-depth understanding of the subject of interest . It invoAt the regional level, two of the six councils covered by the program were purposively selected to be included in the evaluation; Kahama MC and Kishapu DC were the selected councils. Then, at the council level, one health facility was selected purposively from each council. Staff from selected health facilities were recruited through support from the district council. CCG facilitators and supervisors, drivers, dispatchers and beneficiaries were recruited both at the health facilities and in the community with the support of staff from the health facilities.A total of four (4) experienced research assistants fluent in English and Swahili languages were recruited and trained by senior researchers involved in this evaluation on the qualitative study design, interviewing techniques and type of data to be collected. One day was used to pre-test the tools as part of training and validation of the tool. They were also oriented on the ethical considerations pertinent to this study. Interview guides were developed using extensive review of the interventional activities during the program implementation and review of literature on sustainability. The major sustainability questions are reported in We used two qualitative data collection methods, 38 Key Informant Interviews (KII) were conducted among key stakeholders, implementing partners and beneficiaries. Seven (7) Focused Group Discussions (FGDs) were completed for CCG facilitators, facility staff, drivers and dispatchers to gather data on their experience with the program, services offered, and recommendations to improve sustainability of the services implemented under m-mama program. On average, six (6) participants were included in each FDGs. Research assistants had no prior relationship with all the interviewees; before starting KIIs and FDGs, researchers used a few minutes for introductions to ensure rapport and trust from the participants. All KIIs and FDGs were conducted considering participants’ conveniences and preferences. For health facility staff and dispatchers, FDGs were conducted at a selected venue in the respective facilities. Similarly, FDGs with drivers and CCGs were conducted in the health facilities where m-mama program was implemented. For key stakeholders and implementing partners, we conducted the KIIs in their respective offices. On average, the interviews lasted for 45 to 60 minutes.All the KIIs and FDGs were conducted in either English or Swahili and they were audio-tape recorded after consent was sought. KIIs and FDGs were transcribed verbatim in Swahili and in English and translation was done for data collected in Swahili. Transcriptions were done immediately within 24 hours to allow for any clarifications and to assess data saturation. Two members of the research team reviewed the transcripts interactively and inductively determined themes and subthemes. Thematic analysis was used as highlighted in five stages; data familiarization, generating initial codes, determining themes from codes, reviewing themes and lastly results presentation . For illArrangements were made throughout the research process to ensure maintenance of the standards of conducting qualitative research as reported elsewhere . During All research assistants were selected based on the experience in conducting interviews in our setting. A three-day training was conducted for research assistants and one day used for the pretesting and validating of tools. All KIIs and FDGs were audio-recorded to ensure that all the information is captured. Transcriptions were done simultaneously and reviewed by at least one investigator daily to check for quality. During data analysis, transcripts were read repetitively and emerging themes recorded in a codebook. Two investigators conducted data coding and one experienced colleague reviewed the codebook. All the transcripts and codebook were stored in an encrypted file which only investigators had access to.Ethical approval for this evaluation was granted by the Muhimbili University of Health and Allied Sciences Research and Ethics Committee. Permission to collect data from Shinyanga region was granted by the President’s Office Regional and Local Government Authority and the office of the Regional Medical Officer in Shinyanga. Written informed consents to audio-record and participation in the study were obtained from participants before data collection. Participants were given space to decide about their participation. They were also informed that their participation is voluntary and they may wish to withdraw their participation at any point. Privacy and confidentiality were maintained. The data obtained from this program evaluation were kept as strictly confidential, were accessible to only the named investigators and has been stored on password-protected computers.A total of 80 participants were enrolled in this study; Of these, thirty-eight 38  were involved in administrative works at district, regional or national levels. Support from different stakeholders as significant contributor in supporting program continuation was reported in the outer context. Related to the inner context is the government commitment through provision and maintenance of resources. Regarding the processes involved in the implementation of the intervention, continued capacity building and community awareness was suggested, as well as close monitoring of the implemented activities to ensure smooth and well-coordinated delivery of the proposed strategies. The perceived need and benefit of the intervention is included in the intervention characteristics domain  for funding by the government; participants highlighted that the priorities should be placed at the council level to make sure that the program activities are well budgeted.“The government should support the review of guideline. The CCHP at the councils should capture transport costs, if the costs are not captured in the CCHP, it will not be recognized by the government, this will make the funds available to sustain the program”- stakeholder, Pathfinder“Regarding sustainability, as councils we have to include the program in the budget so that we continue to get services from the drivers because they were trained and they are willing to volunteer so that we support each other in reaching our clients”- Medical officer, KishapuDelayed funding from the government affects the sustainability of the program activities. One of the reported concerns was payments of community drivers involved in the emergency transportation.“We still use this program, we still continue to sustain it but as I told you, the challenge is with our financial systems for paying these drivers, it becomes difficult at times, program sustainability will be inadequate compared to when they were paid by the funders, on the spot. They were paid as they transfer clients, this encouraged them to work. Currently, we only work with the drivers that are considerate and willing to help but not all of them are patient enough to continue providing services.”– HCWs FGD, KishapuThe delay of payments to the drivers causes them to leave the program activities and subsequently creating human resource shortage. This is demonstrated in the quote below:“Another thing, I don’t know how to tell you this, most of the drivers currently have ran away because of the payment issues. If the driver transfers the patient, they are supposed to be paid by the facility, at the facility, they will have to wait for the basket funds for them to be paid.”Dispatcher General, Kishapu- Most of the community mobilization activities were done by the community health workers (CHWs). Most of these are not regularly paid by the government. The provision of incentives to the CHWs and dispatchers was reported as another initiative towards sustaining the new program interventions especially community-based activities.“…due to the fact that they thought if we continue with this work, we might receive some income, some continue, and some had to stop. In order to help them earn at least an income, we can include them in the budget if possible. Initially results based financing (RBF) was helpful in this but currently RBF is unpredictable.”- Community stakeholder, Kahama“For these NGOs or the government, the government should see the role of including them in the monthly budget, those community-based workers, because they are doing volunteering work up to today. Since this is very important, lifesaving and it raises the national economy, if the mortality and morbidity are reduced, these people would be contributing in productive works so they should remember the people supporting the women…”- FDG, KahamaThe m-mama emergency transportation program was mainly implemented through the available ambulances at the facilities and the community taxes. However, the ambulances at the facilities needed some renovations. The need to increase the number of ambulances was suggested by one of the stakeholders. It was argued that depending on community taxies alone is risky because they can be unpredictable.“For this program to be sustained, the major thing is to increase the number of ambulances, I think ambulances are more important. Community tax drivers have other responsibilities, they have signed the contract but they have other responsibilities as humans. They may fall sick, or travel e.t.c, but with the ambulances in many facilities, it helps with the facility activities. Even if I go to holiday, someone else will keep working so it is more sustainable. It is different from relying on the community tax drives only. To make it easy, they should bring more ambulances in the facilities.”–Medical Officer, KahamaThe government is called to improve the infrastructure especially roads. Good roads will enable smooth operation of the emergency transportation. Also, they will enable the transportation of medical supplies to the health facilities so that patients can get the services they need on time.“For the councils near me, for instance, Msalala and Ushetu, infrastructures are still a big challenge especially for small cars, there was a day a car got stuck and the patient was delayed for about 8 hours and it had to be dragged. You might transfer the patient experiencing complications and you find the roads are bad and you get stuck… the infrastructures are not friendly at all…”- Officer, KahamaTo curb the challenge of poor transport infrastructures, it was suggested that the government considers increasing the number of CEMONC centers so that reaching the health centers take a considerably short time.“For what I think, improving the infrastructures with the way our district is, it may take a long time, but more CEMONC centers should be built, so that we reduce the distance, this is one of the ways to solve the problem”CCG facilitator, Kishapu–Throughout the implementation of the program and towards the end of program, the m-mama program team trained and involved the respective councils to promote the ownership of the program and government preparedness to take full responsibility of the program. However, participants thought that the donors are still needed for the program to achieve the desired impact and ensure sustainability."With regards to EmTS, if stakeholders would support, it means the project would be going on well, but for them to drop and leave the health facilities, it was too early. Therefore, they should continue to handle it because the government has many things to do. We should not say that the responsibilities of the project go back to the government. They have shown the way on what has to be done but sustainability is a challenge,”CCG facilitator, Kishapu- Regular program monitoring from the m-mama supporters and innovators was suggested so that the government continues to learn from the innovators and m-mama stakeholders. It was also perceived that the m-mama program is “their project, they started it” so it is crucial that they continue supporting it.“For what I see, what is needed is continued support, even if the donors’ contract has ended, they are supposed to continue supporting because this is their projects, they started it. So, they should continue for some time to see how the program progresses while receiving support from the government too… Even now the government has taken over, but we had more drivers showing up initially when the donors were still supporting. They should observe what causes the drivers to exit the program, they should implement what the donors used to do and maintain it so that the program is sustained.”- Facility Based Coordinator, KahamaThe government resources were seen as inadequate to ensure sustainability of the program, a call was made for other stakeholders to supplement what is implemented by the government.“… For instance, for what I see, the services are ongoing but to a low standard because initially, the government was working with support from the stakeholders, for instance the referral system was there before, and even now it is there, but extent of service delivery is low because the high cost might overburden the system. For instance, the ambulances were very few so the funder introduces community taxes; so if the government fails to pay the tax drivers, then these services will not be provided adequately and we will end up depending on ambulances only. We might go back to how it was in the past before the program. The stakeholder’s involvement will really help because now the program is preforming poorly.”–FDG, KishapuCapacity building as one of the core program activities provided during implementation of the m-mama program played a role in reducing maternal and neonatal deaths. This learning environment supported by the funders and stakeholders was seen as an initiative towards better maternal and child health outcomes."We wish that the project is brought back and continues to support us. It helped us to provide education to the community, and community members have started to understand what is supposed to be done. So, if they continue to support through this project, to reduce maternal and neonatal deaths, save lives of mothers and children, we will be happier,”- a Community Based Coordinator reported.Not only the involvement of multiple stakeholders is needed but also a well-coordinated partnership between the government and these stakeholders to ensure proper planning and utilization of resources“The government is the key player in the Ministry of Health, it is stakeholders’ responsibility to see where the government has limited ability so that they can proceed from there. I don’t think it’s wise if the government provides gloves and the program also provides gloves (laughing), there will be overstock and it won’t have much impact. The important thing here is observing where the government efforts have ended so that the stakeholdesr can complement”Medical Officer, Kahama- However, others thought that the government is swamped with many responsibilities, therefore the donors should continue to support the program so that the community can continue to enjoy its success and benefits.“Maybe if they can use the method they used initially, because it was Touch and pathfinder, they were good, they were the ones paying the drivers for a significant proportion and the drivers were paid timely. If they can improve and revert to how it was, then all will be well.”hospital attendant, Kishapu–“So, what to consider is… if the program is progressing well, they should strive to handle it themselves, the government has so much to do, we shouldn’t leave this to the government. Of course, they have shed some light on what is supposed to be done and how it should be done, but based only on that, sustainability will be low.”CCG facilitator, Kishapu- To continuously reap the benefits of this program, health care workers advised on the presence of regular capacity building and refresher trainings to ensure the possibility of responding to challenges faced during program implementation timely and efficiently.“When it comes to training, I think they have done enough and we have understood. But there should be regular, short term refreshment courses to discuss on solving the challenges we meet, it shouldn’t take so long like 6 months but it can be every two months to evaluate on the challenges faced and address them timely.”–dispatcher, KahamaRegarding the trainings that were primarily done by the government, the commitment to make the curriculums more practical was suggested. The trainings are inherent responsibilities of the government and the respective councils; the m-mama program promoted timely and regular conduction of these trainings but the role lies inherently on the respective councils as stated;“This is more of the government commitment; it is not a project issue. The government needs to change the curriculum for BEmONC, CEmONC and Neonatal Intensive care to be more practical rather than theory classes. This is championed by the MoH.”- stakeholder, PathfinderRaising awareness of the community can contribute in stimulating the utilization of the program activities; this is crucial to ensure that the program is sustained. The community care groups led by the CHWs were the most utilized platforms for raising awareness among expecting mothers and encouraging proper practices towards safe delivery.“… Our community needs to be educated adequately, some of the things we observe are due to lack of education, when you provide education at community level, the fruits and benefits are great as I said earlier….”- CHW, KahamaSince the CCGs were led by the members of the community, they were perceived to be easily sustainable.“In forming these community groups, we used community care group facilitators, these are known in the particular societies in engaging and mobilizing their communities well… This was intentionally done so that sustainability is feasible, it is the community members themselves making the initiative to have such groups, we therefore expect that the knowledge is retained in the community and they maintain the services.”- stakeholder, Pathfinder“Also empowering the community has been a great success in raising awareness, women are now referring themselves through the community care groups”- stakeholder, Touch FoundationTo ensure that all community members are covered by the program, it was suggested that the media platforms such as local radios be used to educate the community on the maternal and newborn health services provided.“We can do advocacy, we may use the local radios, we can have sessions, health education, we can also organize community campaigns to educate the society on the presentation and what to do if they see such and such signs. So, both these things will help in informing the community on what to do in case of emergencies.”–medical officer, KahamaCommunity awareness to increase trust of the program and ultimately maintain the utilization of the services even without funders involved is crucial.“But the community should cooperate and continue calling and utilizing the services. We usually have the perception that the program can only succeed if it is a white person leading it, but if it’s just African, people start to think nothing will work. So, they shouldn’t stop using this program, they should continue calling, we will continue serving them for 24 hours, seven days a week. The community leaders should keep helping us…”- Transport Focal Person, Shinyanga MCThe m-mama program provided a toll-free contact number available 24 hours for reporting on maternal or neonatal emergencies. It was suggested that efforts on the provision of continuous community awareness should also include reminders on the toll-free numbers as other villagers may not know these numbers.“Also, to improve and strengthen this program, education should be provided regularly in the community, we might assume that the toll-free number have been distributed but other people have never received them so it is important that we educate them frequently after every few months in the villages. People are informed and given the toll-free number…”–HCWs FDGs, KishapuEveryone in the community should be aware and involved in the emergency transportation system. A call was made for the community leaders to be directly involved in increasing the visibility of the program and promote its utilization through the local platforms such as annual meetings.“The community leaders should continue helping us. We still go back, asking them to encourage their societies in the community or government meetings, one of the agenda there should be to inform them that this program is to save the lives of mothers and newborns. Despite the donors exiting, the government has taken over and it is implementing it a hundred percent.”- Transport Focal Person, Kahama MCMale involvement is another area that was reported to play a key role in services utilization by the community. Community awareness activities were emphasized to be inclusive of males as they are the “main decision makers” in the families.“We should find a way to make men feel as they are part of the program, because they used to think it is only for women and newborns, this brought up challenges… If we could then educate them too and not only women so that they are also involved, to include them even in the community groups. They used to say those are just for women, and their stuff, we should involve them because they are the main decision makers”–CCG facilitator, KishapuThe need to continuously gather evidence throughout the program and share the impact with the decision makers was suggested so that people in the central government can understand what is happening and share the story in high level meetings to get a policy buy-in.“Another lesson learned is that collaboration with the government is key, a key success factor, their enthusiasm is key to success, getting their buy in, that this isn’t something that only we are doing, we are doing it together”– Program manager, Touch foundation“In record keeping, the data that we keep, I know there are challenges. If we maintain those data well, others can visit and see what we do and learn through such data. This will help to showcase how this program helps a lot of people.”- dispatcher, KishapuAll service providers should be informed of the program and its contents. Orientation of the new staff employed in the facilities is crucial to ensure the continuity of care for patients and introduction of the program for those not in the cycle.“For instance, I can say in the facility, if we get extra workers, we usually organize a meeting, we orient them on what will be going on so that if they are the ones on duty at the facility, they can provide services. When they come, we inform them on the ongoing support and organizations we work with…”–HCWs FDG, KishapuHaving actual evidence through gathered data and regular program outcomes monitoring is not only essential for sustainability but may also promote program scale up.“We need to keep gathering evidence, we have communicated with the ministry and there is an agreement for us to expand into Lindi and Morogoro and have agreed for us to expand to 14 other regions. Direct financing did not come overnight, you need to gather evidence for them to see. We need to be do doing mid-term evaluations, if we don’t gather evidence well, we will fail to convince people”–stakeholder, PORALGThe role of monitoring and evaluation was perceived as a paramount continuous process that will assist government and implementers to document lessons for future reference. This can be done through continuous learning and improving from the identified gaps, taking note of the lessons learnt throughout the process“Aah, we need to stick to what we have now and maintain them, also to improve when we see there are gaps. Also, after implementing such interventions, to monitor on the remaining challenges and see how we can tackle them so that we can learn and implement what we have.”–medical officer, KahamaThe current study aimed to document lessons learnt and best practices toward sustainability of the m-mama innovative program for reducing maternal and newborn mortality in Tanzania. We report the following as factors perceived to promote the sustainability of the program by various stakeholders and beneficiaries of the m-mama program. First is the active involvement of the government through the provision and maintenance of resources including a timely and inclusive budget and infrastructure development and maintenance. Secondly, the support from different stakeholders through a well-coordinated partnership. The third factor is continued capacity building for implementers, health care workers and CHWs and community awareness to increase program trust and boost utilization. Then fourthly, striving to disseminate and share evidence and lesson learnt from such successful program activities and lastly, close monitoring of implemented activities to ensure smooth and well-coordinated delivery of proposed program strategies.Active involvement of the government through provision and maintenance of resources including a timely and inclusive budget and infrastructure development and maintenance is crucial. Program support and leadership from the inner system is a key construct and factor towards sustainability . ProgramAlthough sustainability is a multistage and multilevel approach, the emphasis is on the government for coordination, relevant policy and provision of resources . The curParticipants in this study highlighted the role of involving other stakeholders in attaining the program goal; specifically, a well-coordinated partnership between the government, donors and the community at large. This finding is consistent with previous studies that report synergies and multisectoral collaborations as facilitators of program implementation and sustainability . StakehoA concept of working within the available resources has been reported in Africa; this assures that the needed framework and funding environment for program implementation is existing hence it is convenient for the program to be sustained even without external funding or support , 32. HowInvolving the community in the implementation of program activities was reported as a key role that heightens the uptake of services and promote sustainment. Involving the local community has been shown to promote the quick adaptation of the intervention to local contexts which is crucial for program sustainability , 36. ComResponses from our findings highlight that some beneficiaries were not well informed about the ongoing interventions for maternal and newborn health such as presence of toll-free number for emergency calls. Some stakeholders suggested increasing community awareness of the program and the role of upholding maternal health through CHWs and the use of media. The CCGs were also the main source of information for most program beneficiaries in our study. Health promotion can also be done through direct community involvement coupled with capacity building as the source of information to recognize emergency signs and symptoms in perinatal period .Regular monitoring of the program activities was perceived as an influencing factor for sustainability. Consistently, continuous reporting of program implementation progress and performance feedback including the challenges during implementation and lessons learnt contribute towards proper program sustainability . AdditioThe strength of our study is in the use of qualitative method in understanding the value of stakeholders’ perspectives including program beneficiaries on program sustainability. We also built our findings in alignment with the validated integrated sustainability framework. The ISF model integrates a wide range of constructs that are proven to promote program sustainability in a long run. The participants recruited had a deeper and long-standing understanding of the m-mama program hence providing great insight on the what can be done to ensure sustainment. However, our study is not without limitations; Despite the benefit of using purposive sampling, this may have caused selection bias. However, we selected diverse array of stakeholders at all levels of implementation hence allowing triangulation of data in our study. Also, the evidence gathered did not cover all the essential constructs of sustainability on the ISF; however, considering the role of local contexts, some constructs may carry more weight in our context compared to what has been reported elsewhere.The current study provides context specific qualitative empirical findings in terms of stakeholders’ perspectives on sustaining the m-mama innovative program for maternal and child health. Our findings uphold the crucial role of government preparedness, involvement and support in ensuring the institutionalization of externally funded programs. Stakeholders’ involvement should not stop at the implementation stage but ensure a well coordination partnership during the adaptation stage to promote accountability and adherence to initial implementation plans. We also highlighted the evident role of community mobilization and involvement in program ownership and continuation. Building capacity for HCWs as local program implementers and close monitoring of the program outcomes for future reference and feedback. Given the crucial role of donor funding in implementing health related programs in developing countries, we emphasize on strategies to maintaining programs’ benefits for future projects. We therefore suggest the inclusion of sustainability planning during the design stage and importantly, engaging the community and local government in the design and implementation stages to foster program ownership. Nevertheless, designing self-funding models for emergence transportation through community contributions and involvement of other local stakeholders can be helpful to reduce dependence on the government. Continuing sensitization and raising community awareness on the importance of the designed program in health may assist in demand creation and promoting community engagement and local support for the newly implemented and continuing projects.