***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The persistent diarrhoea-malnutrition syndrome ( PDM ) remains a leading cause of morbidity and mortality in hospitals in re source -poor countries . In view of the benefits of elemental or oligomeric feeds in inflammatory bowel diseases , we performed a r and omized controlled trial of an exclusive diet of amino acid-based elemental feed ( AAF ) compared with st and ard nutritional rehabilitation ( based on skimmed milk and then soya ) for PDM . Treatment was given for 4 weeks in the malnutrition ward of the University Teaching Hospital , Lusaka , in a single-blind study . Intestinal and systemic infections were treated with routine therapies . The main outcome measures were weight gain , recovery from diarrhoea , and mortality .  Two hundred children ( 106 HIV seropositive , 90 HIV seronegative ) were r and omized ; 155 children completed therapy , 39 died , and six were lost to follow-up . At r and omization , they were severely malnourished : median baseline weight-for-age z-score was -4.0 ( interquartile range , IQR -4.4 , -3.5 ) ; 9 per cent were underweight , 23 per cent had marasmus , 47 per cent had kwashiorkor , and 21 per cent had marasmic-kwashiorkor .  Weight gain was greater in the AAF group ( median gain in weight-for-age z-score was 1.23 , IQR 0.89 - 1.57 ) compared with the control group ( 0.87 , IQR 0.47 - 1.25 ; p=0.002 ) , although calorie intakes were higher in the control group . The increase in haemoglobin concentration was also greater in the AAF group ( 0.8 g/dl , IQR 0 - 1.8 ) than in the control group ( 0.3 , IQR -0.6 , -1.6 ; p=0.04 ) . Diarrhoea frequency and global recovery scores improved equally in both treatment groups and mortality did not differ . A diet of reduced molecular complexity was associated with significantly improved weight gain In order to evaluate strategies to reduce HIV transmission through breast milk and optimize both maternal and infant health among HIV-infected women and their infants , we design ed and implemented a large , r and omized clinical trial in Lilongwe , Malawi . The development of protocol s for large , r and omized clinical trials is a complicated and lengthy process often requiring alterations to the original research design . Many factors lead to delays and changes , including study site-specific priorities , new scientific information becoming available , the involvement of national and international human subject committees and monitoring boards , and alterations in medical practice and guidance at local , national , and international levels . When planning and implementing a clinical study in a re source -limited setting , additional factors must be taken into account , including local customs and program needs , language and socio-cultural barriers , high background rates of malnutrition and endemic diseases , extreme poverty , lack of personnel , and limited infrastructure . Investigators must be prepared to modify the protocol as necessary in order to ensure participant safety and successful implementation of study procedures . This paper describes the process of design ing , implementing , and subsequently modifying the  Breastfeeding , Antiretrovirals , and Nutrition , ( BAN ) Study , a large , on-going , r and omized breastfeeding intervention trial of HIV-infected women and their infants conducted at a single-site in Lilongwe , Malawi . We highlight some of the successes , challenges , and lessons learned at different stages during the conduct of the trial Summary Background HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione ( GSH ) , a major antioxidant . The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis . Whey proteins are rich in cysteine as well as in GSH precursor peptides . Aim of the study In order to evaluate the effects of whey supplementation on plasma GSH levels , HIV-infected patients were treated with whey proteins for a period of six months . Methods In a double blind clinical trial , 30 patients were r and omized to a daily dose of 45 g whey proteins of either Protectamin ® ( Fresenius Kabi , Germany ) or Immunocal ® ( Immunotec , Europe ) for 2 weeks . Eighteen patients ( 16 male , 42 ± 9.4 yr , 249 ± 99 CD4 + lymphocytes/l ) continued the trial with a daily dose of 45 g of Protectamin for six months . Results Pre-therapy , total plasma GSH levels  ( Protectamin : 1.92 ± 0.6 μM ; Immunocal : 1.99 ± 0.9 μM ) were less than normal ( 2.64 ± 0.7 μM , p = 0.03 ) . After two weeks of whey protein  supplementation , plasma total GSH levels increased in the Protectamin group by 44 ± 56 % ( 2.79 ± 1.1 μM , p = 0.004 ) , while the difference in the Immunocal group did not reach significance ( + 24.5 ± 59 % , 2.51 ± 1.48 μM , p = 0.43 ) . Consequently , all patients continuing the trial were openly switched to Protectamin . After six months , total GSH plasma levels were still significantly elevated compared to baseline ( day 1 : 1.95 ± 0.8 μM vs. month 1 : 2.18 ± 0.8 μM , p = 0.19 ; month 3 : 2.39 ± 0.9 μM , p = 0.056 ; month 6 : 2.47 ± 0.8 μM , p = 0.033 ) . Body weight , T-cell counts , and other clinical parameters did not change . The most common mild side effect was intestinal disturbance ; severe adverse events did not occur . Conclusion Supplementation with whey proteins persistently increased plasma glutathione levels in patients with advanced HIV-infection . The treatment was well tolerated . A larger long-term trial is clearly warranted to evaluate whether this positive influence on the glutathione metabolism translates into a more favorable course of the disease In tuberculosis ( TB ) , the production of nitric oxide ( NO ) is confirmed but its importance in host defense is debated . Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production . Smear positive TB patients from Gondar , Ethiopia ( n = 180 ) were r and omized to a food supplementation rich in arginine ( peanuts , equivalent to 1 g of arginine/day ) or with a low arginine content ( wheat crackers , locally called daboqolo ) during four weeks . The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion , weight gain , sedimentation rate , reduction of cough and chest X-ray improvement as well as levels of NO in urine ( uNO ) or exhaled air ( eNO ) at two months . There was no effect of the intervention on the primary outcome ( OR 1.44 , 95 % CI : 0.69 - 3.0 , p = 0.39 ) or secondary outcomes . In the subgroup analysis according to HIV status , peanut supplemented HIV+/TB patients showed increased cure rate ( 83.8 % ( 31/37 ) vs 53.1 % ( 17/32 ) , p < 0.01 ) . A low baseline eNO ( < 10 ppb ) in HIV+/TB patients was associated with a decreased cure rate . We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect . In the subgroup of HIV positive TB patients , it significantly increased the cure rate and as an additional finding in this subgroup , low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies Objective : We tested the hypothesis that concentrated formula ( CF ) begun within the first 2 weeks of life increases growth in infants born to human immunodeficiency virus (HIV)–infected mothers . Material s and Methods : HIV-exposed infants from the United States , the Bahamas , and Brazil were r and omized in a double-blind , controlled trial to receive either a CF ( 87 kcal/100 mL [ 26 kcal/oz ] ) or a st and ard formula ( SF ; 67 kcal/100 mL [ 20 kcal/oz ] ) for 8 weeks . This article presents results for infants who were not determined to be HIV infected based on testing at 4 weeks . Primary outcomes were safety , tolerability , and growth in weight and length . Results : Two thous and ninety-seven infants were enrolled , of whom 1998 were uninfected and had study formula dispensed . At weeks 4 and 8 , uninfected infants receiving CF showed higher energy intake than those who were receiving SF ( P < 0.001 ) . By week 8 , uninfected infants assigned to CF weighed more than infants receiving SF . There were no consistent differences in measures of tolerability , and rates of discontinuation or perceived formula intolerance were similar between treatment groups . Conclusions : A CF is well tolerated and results in increased weight gain compared with SF . Until the HIV status of an infant is reliably determined , early introduction of a CF in HIV-exposed children may have beneficial effects on growth . The role of early nutritional intervention remains to be determined for individuals living in countries with endemic malnutrition for whom formula feeding is a viable option We studied the effects of enteral supplements on protein and energy intakes , body composition , energy expenditure , and gastrointestinal histology in 49 subjects with human immunodeficiency virus-associated weight loss ( 12.7 + /- 0.9 % of body wt ) . We also determined whether a stable-isotope mass spectrometric measurement at baseline might predict the short-term response of fat-free mass ( FFM ) measured by bioelectrical impedance analysis .  Thirty-nine subjects completed the study after being r and omly assigned to receive either a whole-protein-based ( n = 22 ) or a peptide-based ( n = 17 ) formula . A nonsupplemented , nonr and omly assigned group ( n = 13 ) was followed concurrently . Both formulas were well tolerated . Voluntary intakes of energy and protein from nonsupplement sources decreased significantly during supplementation [ by 819 - 1638 kJ ( 196 - 382 kcal)/d and 5.6 - 14.4 g protein/d , respectively ; P < 0.01 ] but to a lesser extent than the intake from the supplement [ 2300 - 2510 kJ(550 - 600 kcal)/d and 19 - 28 g protein/d , respectively ] , so that net increases in intakes of protein and energy ( P < 0.03 ) , as well as of several vitamins and trace elements were increased . Nevertheless , the mean FFM did not increase for the group as a whole , although there was considerable interindividual heterogeneity . Changes in FFM at 6 wk were significantly inversely correlated ( r = 0.65 , P < 0.01 ) with baseline synthesis of fat ( de novo hepatic lipogenesis ) , but not with other potential measures of energy intake ( insulin-like growth factor 1 or its binding protein ) or inflammation ( soluble tumor necrosis factor receptors I or II ) . The prospect i ve identification of FFM response by measurement of de novo hepatic lipogenesis supported the hypothesis that the subset of wasting patients whose FFM is unresponsive to nutrient supplementation have altered nutrient metabolism BACKGROUND HIV patients with wasting are at increased risk of opportunistic complications and fatality . OBJECTIVE We hypothesized that augmenting dietary intake with high-biologic-value protein would enhance weight and lean tissue in weight-stable subjects with a prior unintentional weight loss of > 3 % . DESIGN Fifty-nine subjects with HIV RNA concentrations < 5000 copies/mL were r and omly assigned to receive a 280-kcal supplement containing 40 g whey protein or a matched isocaloric control supplement without added protein twice daily for 12 wk . RESULTS Before the study , intake of total energy and protein exceeded estimated requirements ( 44.3 + /- 12.6 kcal x kg(-1 ) x d(-1 ) and 1.69 + /- 0.55 g x kg(-1 ) x d(-1 ) , respectively ) . Both supplements failed to increase total energy intake because of decreases in self-selected food intake . Changes in weight ( 0.8 + /- 2.4 and 0.7 + /- 2.4 kg ) and lean body mass ( 0.3 + /- 1.4 and 0.3 + /- 1.5 kg ) did not differ significantly between the whey protein and control groups , respectively . Waist-to-hip ratio improved more with whey protein ( -0.02 + /- 0.05 ) than with the control ( 0.01 + /- 0.03 ; P = 0.025 ) at week 6 but not at week 12 . Fasting triacylglycerol increased by 39 + /- 98 mg/dL with the control supplement and decreased by 16 + /- 62 mg/dL with whey protein at week 12 ( P = 0.03 ) . CD4 lymphocytes increased by 31 + /- 84 
    Output:
    
A nutritional supplement enhanced with protein did not significantly alter the risk of death compared to st and ard nutritional care in children with prolonged diarrhoea .
In general supplementation with specific macronutrients such as amino acids , whey protein concentration or Spirulina did not significantly alter clinical , anthropometric or immunological outcomes compared with placebo in HIV-infected adults and children .
AUTHORS ' CONCLUSIONS Given the current evidence base , which is limited to fourteen relatively small trials all evaluating different macronutrient supplements in different population s at different stages of HIV infection and with varying treatment status , no firm conclusions can be drawn about the effects of macronutrient supplementation on morbidity and mortality in people living with HIV .
It is , however , promising to see more studies being conducted in low-income countries , and particularly in children , where macronutrient supplementation both pre-antiretroviral treatment and in conjunction with antiretroviral treatment might prove to be beneficial