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Analogue of ampicillin, is a semisynthetic antibiotic with essentially the all patients who present agar (Biokar®) were prepared and sterilized according to the manufacturers’ instructions. Another drug and may not reflect the rates.

The missed dose and march: This iACG is co-chaired by the UN Deputy Secretary-General and the Director General of WHO and comprises high level representatives of relevant UN agencies, other.

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No adverse events were reported by the group that took the placebo (10 patients). At baseline, no significant differences were observed between the groups for any of the demographic and clinical parameters (Table 1).

Variable SRP A+M Az p ?value Number of patients 12 13 12 ? Mean age (sd) 56.1 (12.8) 52.1 (12.2) 56.3 (9.9) 0.596 Male/Female ratio 5/7 4/9 4/8 0.910 Mean n of teeth 24.8 (3.0) 25.4 (2.8) 25.8 (1.8) 0.687 Mean n of molars 5.8 (2.7) 6.5 (2.6) 6.5 (1.4) 0.737 FMPS (%) 68.8 (17.3) 62.8 (17.9) 64.5 (16.4) 0.678 FMBS (%) 53.3 (12.5) 56.9 (21.0) 46.5 (18.8) 0.351 Mean PPD (mm) 3.93 (0.58) 3.94 (0.64) 3.67 (0.66) 0.505 Mean CAL (mm) 4.36 (0.57) 4.46 (0.77) 4.04 (0.61) 0.280 Mean n of PPD 1–3 mm 82.3 (24.1) 80.9 (27.2) 100.6 (22.1) 0.105 Mean n of PPD 4–6 mm 50.6 (16.6) 56.2 (23.8) 40.6 (15.0) 0.134 Mean n of PPD >6 mm 15.3 (15.8) 15.3 (15.5) 13.3 (17.2) 0.943.

The significance of difference between the groups at baseline was assessed using one?way ANOVA test for all the features except for Male/Female ratio where Fisher's exact test was used.

Irrespective of the treatment group, there were statistically significant reductions in FMPS,

FMBS

and PPD from baseline to 3 months review (p Table 2.

‘All sites’ clinical parameters (mean ± SD) at baseline, review and amoxicillin trihydrate capsules

the

change between the two time points.

In each row, the change between baseline and review was assessed using the paired t?test.

The difference between the groups at three months was assessed using Tukey's multiple comparison test. a Significant difference between baseline and three months review (last column on the right). b Significant difference between the groups at three months.

The reduction of mean PPD in the A+M group was significantly higher than the Az group (p?value. For all three treatment groups, molar plaque score (MPS), molar bleeding score (MBS) and mean PPD showed a significant reduction from baseline to review (p Table 3. ‘Molar sites’ clinical parameters (mean ± SD) at baseline, review and the change between the two time points.

In each row, the change between baseline and review was assessed using the paired t?test.

The difference between the groups at three months was assessed using Tukey's multiple comparison test.

a Significant difference between baseline and three months review (last column on the right).

b Significant difference between the groups at three months.

The reduction of bleeding score and mean PPD was significantly higher in the A+M group than the SRP group (p?value.

The data were subset into categories based on the baseline PPD.

The sites were stratified into

initial

PPD: shallow (1–3 mm); moderate (4–6 mm) and deep (>6 mm).

For each category, changes in PPD and CAL between baseline and three months were determined (Table 4). The change between baseline and review was assessed using the paired t?test. The difference between the groups at three months was assessed

using

Tukey's multiple comparison test.

a Significant difference between baseline and three months review.

b Significant difference between the groups at three months. In the moderate sites, the reduction of mean PPD was significantly

higher

in the A+M group than the SRP group (p?value. Shallow sites (1–3 mm PPD at baseline) For this category, there was no change in PPD on CAL between baseline and three months in any of the treatment groups. There was also no difference between the three groups at three months.

Moderate sites (4–6 mm PPD at baseline) There was a significant reduction in PPD and increase in CAL between baseline and three months in all three treatment groups for initially moderate sites (p. Deep sites (>6 mm PPD at baseline) For the category of deep sites, there was also a significant improvement mean in PPD and CAL between baseline and three months in

all

three treatment groups (p.

This section analyses the mean number of sites with PPD 1–3 mm, 4–6 mm and >6 mm for each treatment group at baseline and at three months review. There was a significant increase in the mean number of sites with shallow PPD (1–3 mm) between baseline and review for all three groups (p 6 mm) a significant reduction in their number was only observed in the two antibiotics groups but not in the SRP group (p = 0.

022

, p ?value = 0.008 for the A+M and Az, respectively) (Fig.

At three months, no difference was detected in the number of shallow, moderate and deep sites between the groups.

However, an additional comparison test was carried out to compare the magnitude of change in the mean number of sites for each PPD categories (number of sites at baseline minus number of sites at review) between treatment groups.

The rationale of this analysis is explained in the Discussion section. This test showed that the A+M group had significantly more change (increase) in the shallow sites compared to the Az group (p. Change in number of sites with PPD 1–3 mm, 4–6 mm, >6 mm in the three treatment groups (Tukey's post hoc comparison test).

A+M had a significantly more increase in

the

shallow sites compared to the Az group (p.

It is well established that the primary aetiology of periodontal disease is plaque biofilm.

The qualitative

composition

of supra and subgingival plaque in chronic periodontitis and the role of specific periodontal pathogens (orange and red complex) has been thoroughly investigated.

42-44 Therefore, the goal of treatment of periodontal disease is the suppression of periodontal pathogens to levels that are low enough to resolve inflammation and establish periodontal health. 3, 33 Scaling and root planing (SRP) remains to the standard treatment of chronic periodontitis. 4, 5 However, SRP is not always sufficient in reducing periodontal pathogens to levels that are low enough to produce satisfactory periodontal clinical outcomes such as pocket depth reduction

and

gain of clinical attachment levels.

Incomplete removal of subgingival pathogens is related to initial probing pocket depth, the location and morphology of the lesion and the anatomy of the tooth. 33 Studies demonstrated that the persistence of specific bacterial species after scaling and root planing is associated with further bone loss and attachment loss. 45, 46 Hence, the use of adjunctive systemic AB targeting periodontal pathogens can be advantageous.

This double?blinded placebo?controlled

preliminary

trial was designed to evaluate the clinical effects of SRP alone, SRP with adjunctive A+M and SRP with adjunctive Az for patients with generalized moderate to advanced chronic periodontitis.

Between the two time points, all treatment groups showed a significant reduction in the full mouth plaque score (FMPS) and full mouth bleeding score (FMBS).

None of the groups showed a FMBS greater than 20% at three?months review (19.5%, 16.2% and 13.9% for the SRP, A+M and Az, respectively).

The mean PPD also reduced significantly in the three groups.

A significant gain in attachment was observed in the SRP and A+M groups, but not the Az group.

This cannot be interpreted that Az has not led to

increase

in attachment levels. The small sample size could have contributed to the lack of significant changes in attachment levels in the Az group. In addition, the mean CAL in the Az group at baseline was lower than the mean CAL of the other

two

groups.

Although this difference at baseline was not statistically significant, clinically it may have had an effect on the end result. Clinical and microbiological studies show that non?surgical treatment leads to improvement of clinical parameters (BOP, PPD reduction and gain in CAL) 4, 5 and in microbial profiles 47 of chronic periodontitis patients. The improvements are also more pronounced in the deeper sites.

The only difference noted between the groups at

three

months was that the A+M showed a higher reduction in PPD than the Az group (p 39 In this study, patients were then divided into four groups: subjects receiving SRP alone or with systemically administered Az, metronidazole, or a sub?antimicrobial dose of doxycycline (SDD). Significantly greater pocket depth reduction and CAL gain in the initially PPD >6 mm was observed in the metronidazole or Az subjects compared to the other two groups. The largest percentage of sites showing attachment gain >2 mm at 12 months was in the Az group.

A number of randomized control trials (RCTs) and systematic reviews showed the additional clinical benefits of adjunctive antibiotics (AB) when compared to SRP only. Despite the large heterogeneity in the designs of the studies (type of patients, type of non?surgical treatment, time of administration of the drugs, dose and duration of drug administration and follow?up time), the results of these studies showed the additional benefit of the AB.

In regards to A+M, the additional reduction in BOP, PPD and CAL has been demonstrated for patients with chronic periodontitis, 48, 49 as well as aggressive periodontitis.

28, 50, 51 A large multicentre randomized controlled trial conducted over 24 months demonstrated significantly more clinical attachment gain and probing depth reduction in the A+M compared to the placebo group.

25 The additional clinical

benefit

of adjunctive A+M for chronic and aggressive periodontitis patients has been demonstrated in meta?analyses.

30, 31, 52 Collectively, all these studies showed that A+M will lead to a higher reduction in mean PPD and more gain in CAL than SRP with more clinical significance in the deeper sites. As for Az, very few RCTs looked at the effect of Az on chronic periodontitis patients.

Most of the trials that evaluated the effect of Az were either on patients with aggressive periodontitis or patients who had an imprecise description of the diagnosis of their cases.

Many of the studies were also not properly controlled and/or included smokers as well as non?smokers. Two RCTs that evaluated the effect of Az in CP patients were conducted by Oteo et al .

illustrated that the adjunctive use of systemic Az exhibited significant clinical (PPD reduction and CAL gain) and microbiological (reduction in Aa and frequency of detection of Pg ) benefits. 13 On the

other

hand, the one?year trial by Sampaio et al ., did not find additional benefit for Az with SRP in comparison to SRP only. 14 A recent meta?analysis indicated that a potential benefit of

systemic

azithromycin as adjunctive to non?surgical periodontal treatment may exist for chronic periodontitis but not aggressive periodontitis. However, the authors warned of some risk of bias in some of the studies.

Furthermore, there was no evidence of superiority of Az over A+M. A number of longitudinal studies have shown that non?surgical root debridement of molar teeth (compared to non?molar teeth) results in less favourable clinical and microbiologic outcomes. 54, 55 Sites with furcation involvement consistently demonstrated greater proportions of periodontopathogens, higher frequency of attachment loss 54-57 and higher frequency of tooth loss.



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