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\begin{document}


\def\RunningAuthor{Niaz Hussain keerio et al.}
\firstPage{1984}
\articleType{Original Article}
\receivedDate{20 Jun 2021}
\acceptedDate{01 Jul 2021}
\revisedDate{23 Jul 2021}
\journalVolume{2021, 12}
\journalIssue{3}
\journalDoi{ijrps.v12i3.4804}
\copyrightYear{2021}
\def\authorCount{7}
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\title{\textbf{The outcome of natural honey used in chronic ulcers}}
\author{Nizam~Ahmed\textsuperscript{1},  
            Aftab~Alam~Khanzada\textsuperscript{2},  
            Muhammad~Rafique~Joyo\textsuperscript{3},  
            Tanveer~Afzal\textsuperscript{4},  
            Niaz~Hussain~keerio\textsuperscript{*}\textsuperscript{5},  
            Ghazanfar~Ali~Shah\textsuperscript{6}, 
            Syed~Shahid~Noor\textsuperscript{7}~\\[5pt]{\textsuperscript{1}Liaquat University of Medical and Health Science, Jamshoro, Pakistan}~\\{\textsuperscript{2}Red Crescent General Hospital, Hyderabad, Pakistan}~\\{\textsuperscript{3}Bone Care Trauma Centre, Hirabad Hospital, Hyderabad, Pakistan}~\\{\textsuperscript{4}Ameer-ud-Din Medical College, Lahore General Hospital, Lahore, Pakistan}~\\{\textsuperscript{5}Muhammad Medical College and Hospital, Mirpurkhas, Pakistan}~\\{\textsuperscript{6}SMBBIT, Dow University of Medical and Health Sciences Karachi, Pakistan}~\\{\textsuperscript{7}Liaquat National Hospital and Medical College, Karachi, Pakistan}}

\begin{abstract}
The unique characteristics of natural honey obtained in any source in topical chronic nonhealing ulcers have been decreased discomfort, oedema, inflammation, deodorization, disinfect, neo-vascularization, collagen synthesis, granulation, epithelization and hence the ulcer treatment method. In that study, 200 patients were treated in a forward-looking, unrandomized experiment, with persistent, unhealing ulcers found in various areas of their body in the two groups keeping 100 in Group A and used honey dressing and Group B managed without using honey. Natural honey from multiple sources has been used. The main explanation for reduced mobility and loss of work illustrates productivity being pain and fever. The leading causes of healing delays were bacterial infection, necrotic tissue involvement, bedridden state, age, fatigue, Ulcer located near the joint. The quality, the simplicity of application and the efficiency make the control of recurrent nonhealing Ulcers easier for natural honey. For low cost, easy access, and improved healing make it a valuable option for natural honey to handle chronic, nonhealing ulcers, as well as healthy use in diabetic patients.  
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Honey,\newline Non-Healing Ulcers,\newline Wounds
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Niaz~Hussain~keerio~\\ Phone:\ 00923333008501~\\  Email:\ niaz\_h@hotmail.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
        \textsc{DOI:}\ \href{https://doi.org/10.26452/\@journalDoi}{\textcolor{blue}{\underline{\smash{https://doi.org/10.26452/\@journalDoi}}}}\par%
        \vspace*{-11pt}\hrulefill\\{\fontsize{9.12}{10.12}\selectfont Production and Hosted by}\par{IJRPS |~\href{www.ijrps.com}{www.ijrps.com}}\par%
        \vspace*{-2pt}{\fontsize{9.12}{10.12}\selectfont\textcopyright\ \@copyrightYear\ $|$ All rights reserved.}\par%
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        \makeatother
        
    
\section{Introduction}
There is an excellent role of hone in non-healing ulcers in ancient civilization and if used now can create a great impact on public health and country economy \unskip~\citep{1146867:22607373}. Thousands of studies have been done regarding the benefits of using honey in complicated wounds \unskip~\citep{1146867:22607372}. The natural honey chemical composition is complicated. ``The major component of honey comprises of carbohydrates (82\%), glucose (31\%), disaccharides (9\%), maltose, isomaltose, sucrose, turanose and kojibiose etc. oligosaccharides are 4.2\%, including panose, erlose and theanderose'' \unskip~\citep{1146867:22607370}. It contains various enzymes, like ``invertase, which convert sucrose to glucose and fructose'' \unskip~\citep{1146867:22607364}. The glucose oxidases are used to process glucose into gluconolactone, converting it into gluconic acid. H\ensuremath{_{2}}O\ensuremath{_{2\ }}\unskip~\citep{1146867:22607363}. The break-up of catalase H\ensuremath{_{2}}O\ensuremath{_{2}} into H\ensuremath{_{2}}O and of oxygen that holds the wound moist deodorizes and helps to unravel. The natural Honey contains vitamin B2, B5, B6, B9, pantothenic and vitamin C traces \unskip~\citep{1146867:22607366}. The flavonoids present in honey work as an antioxidant \unskip~\citep{1146867:22607379}, other particles like vitamin C, and the effects of catalases and selenium also work as antioxidants. ``Honey also contains organic acids like citric, succinic, lactic, malic, acetic, formic, butanoic, pyroglutamic and aromatic acids'' \unskip~\citep{1146867:22607368}. ``Hydroxymethyl furfural keeps its pH below 5 (3.2-4.5) which encourages blood to release oxygen'' \unskip~\citep{1146867:22607374}. ``Its high osmolarity prevents bacterial growth, reduces swelling and promote healing. Honey also had nitric oxide in traces that boost immunological response, bactericidal and inhibit viral multiplication'' \unskip~\citep{1146867:22607371}. ``On topical application, various evident effects of honey on Ulcer are- provide moist environment and nutrition, reduces local pain, reduces edema and inflammation'' \unskip~\citep{1146867:22607369}, wound management \unskip~\citep{1146867:22607375}, do rapid disinfection and stimulate necrotic tissue removal, stimulate granulation, stimulate neo-vascularization, caused wound contraction and wound healing \unskip~\citep{1146867:22607360}. 

This study objective was to see the result of natural honey on chronic diabetic and non-diabetic ulcers. 
    
\section{Methods}
Our study was prospective non-randomized that was conducted during the period from March 2019 to March 2020 at the Orthopedic Department of Liaquat University of Medical and Health Science, Jamshoro, Pakistan. This study was performed in 200 patients of various ages and genders divided into two groups of 100 each (group-A with honey-dressing and group-B with no honey dressing). Both groups of patients were granted informed consent, and the study was approved by the Ethical Committee of our institute. 

\textbf{Inclusion criteria }

Traumatic wounds, diabetic ulcers, insect bites, venous ulcers and bed sores, age less than 70 years. 

\textbf{Exclusion criteria }

A high risk that the patient and attendants will still drop out and not cooperate with leprosy, TB, malignant Ulcer, HIV and HBsAg positive patients.

Sex, age, profession, cause of Ulcer, related medical problems such as starvation, anemia, HT, DM, cardiovascular disease and so on have all been documented history. Blood profile routine, x-ray chest, diabetes diagram, ECG and any special protocol analysis on all of the subjects under study. Community and sensitivity to ulcer discharge were performed, and results were noted before beginning therapy and on the 15th. Subjective complaints were made, such as ulcer length, aetiology, ulcer pain, nausea, discharge, fever, work lack, reports of prescriptions, hospital stay. Both ulcers have been extensively cleaned with H\ensuremath{_{2}}O\ensuremath{_{2}}, Normal Saline. The essence of honey from different locations, readily available in this area, was eaten and dispersed via ulcers in group A patients and covered immediately with sterile gauze parts so cotton pads could not be dissipated, then bandaged and closed dressing, while in group B patients there was no honey. In the form of Antibiotics, Analgesia, B-complexes and a good quality diet, both patients received fair supporting care. The oral hypoglycemic or insulin injections is pertaining to diabetic patients at the levels of their blood sugar. The research system used as a guide and statistics was used to study patients' age, sex, ulcer etiology, symptomatology, some blood studies (Blood sugar, TLC, Hb, ESR), a culture of discharge, debridement essential, and hospital stays. The following points were noted every fifth day while changing a dressing. Ulcer in two sizes: transverse and longitudinal; slough presence; granulation tissues appearance; ulcer size change; Ulcer snoring; marginal neo-epithelism. Signs of cure is taken from the appearance of red granulated tissue, clearing of the slough, reduction of size and discharge, neo-epithelium in purple at the edges of the Ulcer. 


\begin{table*}[!htbp]
\caption{\boldmath {Sex and Age distribution} }
\label{tw-1213178422fa}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.275\linewidth-2\tabcolsep}p{\dimexpr.2271\linewidth-2\tabcolsep}p{\dimexpr.22509999999999998\linewidth-2\tabcolsep}p{\dimexpr.2728\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Age (years) & Male & Female & Total (\%)\\
\tblmidrule 
0-20 &
  16 &
  13 &
  14.50\\
21-40 &
  44 &
  27 &
  35.50\\
41-60 &
  40 &
  23 &
  31.50\\
{\textgreater}60 &
  20 &
  17 &
  18.50\\
Total &
  120 &
  80 &
  100\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Type of ulcers as per etiology} }
\label{tw-9f9b200d7053}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.46900000000000006\linewidth-2\tabcolsep}p{\dimexpr.2719\linewidth-2\tabcolsep}p{\dimexpr.2591\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Etiology & \multicolumn{2}{p{\dimexpr(.531\linewidth-2\tabcolsep)}}{\cAlignHack No. of patients}\\
\rowcolor{kwdboxcolor} & \cAlignHack Group A & \cAlignHack Group B\\
\tblmidrule 
Traumatic Ulcer &
  \cAlignHack 46 &
  \cAlignHack 46\\
Insect bite ulcer &
  \cAlignHack 9 &
  \cAlignHack 9\\
Diabetic Ulcer &
  \cAlignHack 28 &
  \cAlignHack 28\\
Bed sores &
  \cAlignHack 7 &
  \cAlignHack 7\\
Venous Ulcer &
  \cAlignHack 10 &
  \cAlignHack 10\\
Total &
  \cAlignHack 100 &
  \cAlignHack 100\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Symptoms as per patient} }
\label{tw-b021d601bb2e}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.4606\linewidth-2\tabcolsep}p{\dimexpr.5394\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Symptoms & No. of patients\\
\tblmidrule 
Pain &
  107\\
Discharge &
  123\\
Fever &
  57\\
Bleeding &
  31\\
Maggots &
  23\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Investigations} }
\label{tw-0b71b3b5a47c}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3205\linewidth-2\tabcolsep}p{\dimexpr.1982\linewidth-2\tabcolsep}p{\dimexpr.29349999999999994\linewidth-2\tabcolsep}p{\dimexpr.1878\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Name with \mbox{}\protect\newline normal value & No. of \mbox{}\protect\newline patients & Abnormal Value & No of \mbox{}\protect\newline patients\\
\tblmidrule 
TLC (4000-10000/mm\ensuremath{^{3}}) &
  133 &
  {\textgreater}10000/mm &
  367\\
BS-R (80-120mg\%) &
  138 &
  {\textgreater}120 mg\% &
  62\\
Hb ({\textgreater}10 gm\%) &
  122 &
  {\textless}10 gm\% &
  78\\
ESR (2-20 mm1\ensuremath{^{st}} hour) &
  139 &
  {\textgreater}20 mm 1\ensuremath{^{st}} hour &
  61\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Culture of discharge} }
\label{tw-add9f0901371}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3807000000000001\linewidth-2\tabcolsep}p{\dimexpr.2189\linewidth-2\tabcolsep}p{\dimexpr.23129999999999995\linewidth-2\tabcolsep}p{\dimexpr.1691\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor} & \multicolumn{3}{p{\dimexpr(.6192999999999999\linewidth-2\tabcolsep)}}{\cAlignHack On 15\ensuremath{^{th}} day}\\
\rowcolor{kwdboxcolor}Pathogens & Patients & Group A & Group B\\
\tblmidrule 
Staphylococcus &
  49 &
  Nil &
  Nil\\
Streptococcus &
  19 &
  11 &
  16\\
Klebsiella &
  34 &
  12 &
  13\\
Proteus &
  23 &
  14 &
  -\\
E. Coli &
  20 &
  Nil &
  11\\
Pseudomonas &
  17 &
  Nil &
  Nil\\
Sterile &
  25 &
  52 &
  38\\
Mixed type &
  13 &
  11 &
  -\\
Total &
  200 &
  100 &
  100\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {No of patients required Debridement} }
\label{tw-a662e017b742}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.47519999999999996\linewidth-2\tabcolsep}p{\dimexpr.22840000000000003\linewidth-2\tabcolsep}p{\dimexpr.29640000000000008\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor} & \multicolumn{2}{p{\dimexpr(.5248000000000001\linewidth-2\tabcolsep)}}{\cAlignHack No. of patients}\\
\rowcolor{kwdboxcolor}No. of debridements & \cAlignHack Group A & \cAlignHack Group B\\
\tblmidrule 
1 &
  \cAlignHack 37 &
  \cAlignHack 43\\
2 &
  \cAlignHack 23 &
  \cAlignHack 25\\
{\textgreater}2 &
  \cAlignHack 13 &
  \cAlignHack 15\\
0 &
  \cAlignHack 27 &
  \cAlignHack 17\\
Total &
  \cAlignHack 100 &
  \cAlignHack 100\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Number of patients admitted in Hospital} }
\label{tw-bfe91073f382}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.4649\linewidth-2\tabcolsep}p{\dimexpr.24479999999999993\linewidth-2\tabcolsep}p{\dimexpr.29029999999999998\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Days range & \multicolumn{2}{p{\dimexpr(.5350999999999999\linewidth-2\tabcolsep)}}{\cAlignHack No of patients}\\
\rowcolor{kwdboxcolor} & \cAlignHack Group A & \cAlignHack Group B\\
\tblmidrule 
0-10 &
  \cAlignHack 12 &
  \cAlignHack 8\\
11-20 &
  \cAlignHack 26 &
  \cAlignHack 15\\
21-30 &
  \cAlignHack 35 &
  \cAlignHack 31\\
{\textgreater}30 &
  \cAlignHack 27 &
  \cAlignHack 46\\
Total &
  \cAlignHack 100 &
  \cAlignHack 100\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

    
\section{Results}
In our study, out of 200 patients, most were affected in the 3\ensuremath{^{rd}} and 4\ensuremath{^{th}} decade of life (35.50\%), and the male-female ratio was 1.6:1.0 (Table~\ref{tw-1213178422fa}). Most ulcers cause was road traffic accidents (46.00\%), which precede diabetic Ulcer (28.00\%) (Table~\ref{tw-9f9b200d7053}). 

A most common cause of restricted mobility was Pain and fever (Table~\ref{tw-b021d601bb2e}). 127 days was the chronic average time for ulcer and 63 days absence from work. Most of Sugar (DM) patients with more than 120 blood sugar were 31\%, TLC more than10000/mm3 (33.50\%), hemoglobin more than 10\% (39\%) and ESR{\textgreater}20 mm in 30.5\% cases (Table~\ref{tw-0b71b3b5a47c}). C/S report of discharge before starting treatment was \textit{staphylococcus aurous } (24.50\%) after than by \textit{Klebsiella } (17\%), but 2wks after getting treatment culture came negative in 52 \% in group-A, and it was only 38\% in group B (Table~\ref{tw-add9f0901371}). It was observed that there was no increased in blood sugar after local use of natural honey.

73\% of patients needed multiple cleanings and debridement in the A group while 83\% in the B group. 27\% of A group and 17\% of B group patients didn't required any procedure (Table~\ref{tw-a662e017b742}). Only a few patients' complaints of local irritation after few minutes of local hone application, which settled without any treatment. It was noted that in Group B higher than Group A (Table~\ref{tw-bfe91073f382}).
    
\section{Discussion}
 This was a randomized study, and 200 patients were equally included in two groups with chronic Ulcer situated on different body parts. In 65\% of patients has foot ulcers. ``Trauma was a main etiological factor due to RTA'' \unskip~\citep{1146867:22607362}, ``domestic violence or accidents (56.50\%), followed by diabetic Ulcer in 28\%, which was also found a major cause of delayed healing'' \unskip~\citep{1146867:22607367}. insect bite ulcer, Venous Ulcer, and bed sores also are big contributors in ulcers \unskip~\citep{1146867:22607361}. 3\ensuremath{^{rd}} and 4\ensuremath{^{th}} decade of life is the duration of life in which most peoples were affected. Males were affected more than females (1.6:1.0). Pain and fever was the most common cause of restricted mobility and were increased by infection \unskip~\citep{1146867:22607376}. In Pakistan male is the main earning member of the family, and when he is affected, the whole family affected finically. Ulcer C/S shows that Klebsiella and Staphylococcus aureus and are the major pathogens, and after two weeks of treatment, 38\% of patients of group-A became negative. Almost 72\% percent of patients required multiple debridements, 27\% of patients were not taken for multiple de-bridements of group A as compared to group B, which was 17\% \unskip~\citep{1146867:22607365}. Skin grafting was done for 59\% of patients \unskip~\citep{1146867:22607378}, and total hospital stay was higher in group B as compared to group A. This is also observed that there is no increased in blood sugar level while using a local honey application, specially, in diabetic patients. Only 15\% of a patient's informed that they felt local irritation which was resolved in few minutes time duration; otherwise, no other complication was noted.

The primary cause of delay in the process of healing Ulcer's detection, which was discovered after deterioration, was a bacterial infection, the involvement of necrotic tissue, bedridden conditions, old age, fatigue, diabetes mellitus, and an ulcer near the joint was apparent \unskip~\citep{1146867:22607377}. The ulcer cure was tested by evaluating its size \unskip~\citep{1146867:22607380}, red granulation tissue appearance and marginal neo-epithelization.

This research was constrained because it was not randomized, and therefore it was not possible to establish continuity between etiology, form and site and size of the Ulcer. Secondly, the overall sample size was 200. This research was constrained because it was not randomized, and therefore it was not possible to establish continuity between etiology, form and site and size of the Ulcer. Secondly, the overall sample size was 200. 
    
\section{Conclusion}
Honey originating from any local source decreases pain, nausea, oedema and deodorization, fast disinfection; induces slow removal; facilitates neovascularization; greatly accelerates granulation, synthesis of collagen, epithelization; and supports ulcer cure. Insect bites and wound causing from an accident is the main cause of ulcers. The quality, simple usability and easy application make natural sweetness a better option in chronic ulcer management. Due to use of honey, it does not increase the glucose level in a diabetic patient. Natural honey is cost-efficient, easily accessible, and improved healing make it a valuable option for natural honey to handle chronic, nonhealing ulcers, as well as healthy use in diabetic patients.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest for this study.

\textbf{Funding Support}

The authors declare that they have no funding support for this study. 
    

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