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J P Matthews

Publications and source records attributed to J P Matthews.

At least 19 recordsLinked to original sources

A phase II study of dexamethasone, ifosfamide, cisplatin and etoposide (DICE) as salvage chemotherapy for patients with relapsed and refractory lymphoma.

The 4-day combination of dexamethasone, ifosfamide, cisplatin, and etoposide (DICE) is a salvage regimen for lymphoma. We report a prospective phase II multi-center trial of a modified DICE regimen in relapsed or refractory Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), constituting a single day of intravenous administration followed by 3 days of oral administration, aimed at reducing inpatient days without losing efficacy. Forty patients (median age 56, range 25 - 79) were included: 28 (70%) NHL, 9 (23%) HL and 3 (8%) CLL. Fifty-three per cent had received 2 prior treatment regimens. International Prognostic Index (IPI) was 2 in 75% of NHL patients. Patients aged 55 and those with previous autologous stem cell transplantation (ASCT) started on a lower-dose regimen, with dose escalation possible in 2 patients. Overall response rate was 41%. Thirty-eight per cent of patients had stable disease. With a median of 3.1 years of follow-up, estimated progression-free survival (PFS) and overall survival (OS) rates at 3 years were 15% and 43% respectively. OS was longer in the < 55 compared to the 55 age cohort (P = 0.0091), longer for HL than NHL (P = 0.59 and 0.039 respectively) and longer for Low/Low-Int IPI than High/High-Int IPI (P = 0.0074 and 0.0009 respectively). Median duration of inpatient stay was 3 days. There were no treatment-related deaths. In conclusion, this modification of DICE is an effective and well tolerated salvage regimen, even in this poor prognosis group of patients. Further clinical studies of DICE in first relapse and in older patients, possibly with the addition of rituximab, are warranted.

Adult↗

Rapid screening for depression--validation of the Brief Case-Find for Depression (BCD) in medical oncology and palliative care patients.

Depression in oncology patients is under-recognised and associated with poor outcomes. Screening can increase case recognition. The Brief Case-Find for Depression (BCD) is a four-question, interviewer-administered instrument that has been previously validated in a general medical setting. The primary aim of this study was to validate the BCD in a medical oncology/palliative care setting, primarily by comparing its association with physical illness measures and with the Primary Care Evaluation of Mental Disorders (PRIME-MD), the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Eligible adult oncology patients gave informed consent and completed the above measures and a pain scale. Agreement between the BCD and other instruments was assessed. Construct validity was determined by comparing depressed/nondepressed patients with respect to performance status, symptoms, pain score and functional impairment. A total of 100 patients had a median age of 58 (range 21-90) and ECOG performance status (PS) 2 (0-4). In all, 60% had metastatic disease. The therapeutic goal was curative/adjuvant in 39% and palliative in 61%. Prevalence of depression according to the various measures was: BCD 34%, PRIME-MD 12%, BDI 19% and HADS 14%. In total, 45% of patients responded positively to a single-item screening question. The BCD showed fair agreement with the PRIME-MD (kappa=0.21), moderate agreement with the BDI (kappa=0.43) and fair agreement with the HADS (kappa=0.27). Against the PRIME-MD diagnosis of depression, the BCD had greater sensitivity, but lesser specificity and overall agreement, compared with the BDI and depression scale of the HADS. Patients with probable depression (according to BCD) had inferior PS (P=0.0064), increased pain (P=0.045) and greater impairment of functioning (PRIME-MD: P=0.0003). There was no association with gender, age, disease status or therapeutic goal. Depression is common in oncology patients. The BCD is a quick, easy-to-administer screen for depression, which has reasonable psychometric properties in this population.

Adult↗

Optimum trephine length in the assessment of bone marrow involvement in patients with diffuse large cell lymphoma.

BACKGROUND: The National Cancer Institute has recommended a bone marrow biopsy length of >/=20 mm for the staging and surveillance of patients with non-Hodgkin's lymphoma. However, there are few published data to support this recommendation, particularly the role of examining multiple levels. PATIENTS AND METHODS: Bone marrow biopsies from 172 patients with newly diagnosed diffuse large cell lymphoma (DLCL) entered in two consecutive trials of the Australasian Leukaemia and Lymphoma Group were analysed. The original haematoxylin and eosin-stained trephine biopsy and two or more deeper sections cut at 0.1-0.2 mm intervals were assessed with respect to the morphology, extent and pattern of lymphomatous involvement. The rate of positive diagnosis was correlated with the length of the biopsy specimen and the number of sections examined. RESULTS: Forty-seven biopsies (27%) demonstrated marrow involvement on examination of a mean of four trephine biopsy sections. The rate of positivity increased with the examination of multiple levels and correlated with increasing trephine length but was not dependent on the number of sites sampled. Twenty per cent of biopsies <20 mm in length were positive for lymphoma; this increased to 35% for biopsies >/=20 mm (P = 0.023). CONCLUSIONS: Morphological bone marrow involvement in DLCL is optimally demonstrated by a 20-mm long trephine biopsy from a single site which is examined at multiple levels (four or more). This obviates the need for bilateral sampling, thereby reducing patient morbidity from the procedure. This study provides evidence to support the National Cancer Institute recommendations regarding trephine biopsy in the staging of DLCL, providing multiple levels are examined.

Biopsy↗

Uptake of psychosocial referrals in an outpatient cancer setting: improving service accessibility via the referral process.

The object of this study was to identify factors which influence the uptake of psychosocial services in an ambulatory cancer setting and to identify potential barriers to the access of support services in the referral process. To this end, 202 individuals attending outpatient clinics of a cancer hospital were randomised to the intervention arm of a study to assess the impact of providing co-ordinated, targeted psychosocial referrals and interventions. Qualitative and quantitative analysis of the reasons for failure to offer services and for nonacceptance of services was undertaken. Individuals accepted 22% of offered services, refused 38% of offered services, indicated that services were in place in 31% of cases, and were not offered 9% of identified services. The major response from patients refusing services was "not now". Female patients ( P < 0.01), and individuals with a moderate to high level of depression ( P = 0.02), were more likely to accept services. A variety of factors impact on decisions on utilisation of support services. Recommendations on how individuals' access to these services might be improved are offered, based on an analysis of the reasons given by patients for refusal.

Aged↗

F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma: powerful correlation with survival and high impact on treatment.

BACKGROUND: Successful treatment of nonsmall cell lung carcinoma (NSCLC) with radical radiotherapy (RT) requires accurate delineation of tumor extent. Conventional computed tomography-based noninvasive staging often estimates intrathoracic thoracic tumor extent incorrectly and fails to detect distant metastasis. High sensitivity and specificity are reported for F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) staging in potentially resectable NSCLC. The authors investigated FDG-PET staging in radical RT candidates with unresectable NSCLC. METHODS: The authors prospectively studied 153 consecutive patients with unresectable NSCLC who were candidates for radical RT after conventional staging and had PET scans. Patients were allocated both "before PET" and "after PET" stages. Subsequent management was recorded. Survival analysis was used to compare validity of pre-PET and post-PET staging. RESULTS: After PET, 107 patients (70%) actually received radical therapies (radical RT with or without concurrent chemotherapy, n = 102; radical surgery, n = 5); 46 patients (30%) received palliative treatment because of PET-detected distant metastasis (n = 28; 18%) or extensive locoregional disease (n = 18; 12%). Palliative therapies were RT (n = 33), chemotherapy (n = 12), or supportive care (n = 1). All five surgically treated patients underwent potentially curative resections after downstaging by PET. For radically treated patients, post-PET stage (P = 0.0041) but not pre-PET stage (P = 0.19) was strongly associated with survival. Radically treated patients survived longer than those treated palliatively (P = 0.02; 1-year survival, 69% and 44%, respectively; 2-year survival, 44% radical; no palliative patients had 2-yr follow-up). CONCLUSIONS: Positron emission tomography-assisted staging detected unsuspected metastasis in 20%, strongly influenced choice of treatment strategy, frequently impacted RT planning, and was a powerful predictor of survival. Potential impact of FDG-PET is even greater in radical RT candidates with NSCLC than in surgical candidates.

Adult↗

High rate of detection of unsuspected distant metastases by pet in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy.

PURPOSE: Most radical radiotherapy (RT) candidates with non-small-cell lung cancer (NSCLC) have Stage III disease and ultimately die with distant metastases. We tested the hypothesis that positron emission tomography (PET) using 18-F fluorodeoxyglucose (FDG) would detect more unsuspected metastases in apparent Stage III disease than in Stages I-II. METHODS AND MATERIALS: Staging FDG-PET was performed for 167 NSCLC patients, with Stage I-III by conventional workup, who were candidates for curative therapy with surgery (n = 8), radical chemo/RT or RT (n = 156), or preoperative chemo/RT (n = 3). Each patient was allocated a conventional "pre-PET stage" and a "post-PET stage" that relied on PET when discordance with conventional staging occurred. RESULTS: Stage distribution pre-PET was n = 39 (Stage I), n = 28 (Stage II), and n = 100 (Stage III). In 32 patients (19%), PET detected distant metastasis, most commonly abdominal with 17 cases (adrenal, n = 7; liver, n = 4; other, n = 6). Other sites included lung (n = 10) and bone (n = 6). PET-detected metastasis increased with increasing pre-PET stage from I (7.5%) through II (18%) to III (24%, p = 0.016), and, in particular, was significantly higher in Stage III (p = 0.039). Biopsy confirmation was not routine, but progression occurred at PET-detected metastatic sites or other metastatic sites in all but 3 of the 32 patients by last review. CONCLUSION: PET staging is recommended for radical RT candidates with NSCLC. The highest yield of unexpected distant metastases is observed in Stage III.

Adult↗

Association between high interleukin-6 levels and adverse outcome after autologous haemopoietic stem cell transplantation.

We studied interleukin-6 (IL-6) levels on the day of transplantation in 31 patients undergoing autologous haemopoietic stem cell transplantation (SCT) (either peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation (BMT)) for neoplastic diseases to determine if there was a relationship between IL-6 level and rate of haemopoietic recovery, length of stay in hospital, and survival. There was no apparent delay in post-transplant recovery associated with elevated IL-6 levels. However, increased values of IL-6 tended to be associated with an increased length of stay in hospital (P = 0.083). There was a highly significant adverse association between higher IL-6 levels and survival following transplantation (P = 0.0001). This association remained significant (P = 0.013) in the uniform subgroup of patients with malignant lymphoma with chemosensitive disease who had undergone BMT (that is, excluding patients who had undergone PBSCT) (n = 13). Knowledge of IL-6 levels on the day of transplant has the potential to provide valuable prognostic information in patients undergoing autologous haemopoietic SCT.

Adult↗

Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia.

Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.

Acute Disease↗

(18)F-FDG PET provides high-impact and powerful prognostic stratification in staging newly diagnosed non-small cell lung cancer.

UNLABELLED: Survival of lung cancer patients remains poor despite increasingly aggressive treatment. Conventional staging has well-described limitations. (18)F-FDG PET has been shown to stage lung cancer more accurately than does CT scanning, but the impact on patient treatment and outcome is poorly defined. This study evaluated this impact in routine clinical practice within a tertiary oncology facility. METHODS: For 153 consecutive patients with newly diagnosed non-small cell lung cancer, the treatment plan based on conventional staging methods was compared with the treatment plan based on incorporation of PET findings. Survival was analyzed using the Cox proportional hazards regression model. RESULTS: For broad groupings of stage, 10% of cases were downstaged and 33% upstaged by PET. When assessable, the PET stage was confirmed in 89% of patients. PET had a high impact on 54 patients (35%), including 34 whose therapy was changed from curative to palliative, 6 whose therapy was changed from palliative to curative, and 14 whose treatment modality was changed but not the treatment intent. For 39 patients (25%), a previously selected therapy was altered because of the PET findings. The Cox model indicated that the pre-PET stage was significantly associated with survival (P = 0.013) but that the post-PET stage provided much stronger prognostic stratification (P < 0.0001) and remained significant after adjustment for treatment delivered. CONCLUSION: Staging that incorporated PET provided a more accurate prognostic stratification than did staging based on conventional investigations. Further, the additional information provided by PET significantly and appropriately changed management in the majority of patients.

Aged↗

The utility of (18)F-FDG PET for suspected recurrent non-small cell lung cancer after potentially curative therapy: impact on management and prognostic stratification.

UNLABELLED: After potentially curative therapy of non-small cell lung cancer (NSCLC), masses or symptoms suggestive of relapse are common but may be difficult to characterize. Early detection is important because salvage therapies are available for localized recurrence. This study evaluated whether (18)F-FDG PET is useful and predictive of outcome in this setting. METHODS: For 63 consecutive patients with suspected relapse >6 mo after definitive treatment of NSCLC, the apparent extent of disease on conventional restaging was compared with that on FDG PET. Patients with already confirmed systemic metastases were excluded unless locally aggressive treatment of these was being considered. Serial imaging and pathologic results were obtained during a median follow-up of 19 mo to validate diagnostic findings. Prognostic significance was tested using the Cox proportional hazards regression model. RESULTS: PET had positive findings in 41 of 42 patients with confirmed relapse (sensitivity, 98%). No disease was evident during a minimum follow-up of 12 mo in 14 of 15 patients with clinically suspected relapse but negative PET findings (negative predictive value, 93%). PET induced a major management change in 40 patients (63%), including 6 whose treatment was changed from curative to palliative, 3 whose treatment was changed from palliative to curative, and 9 for whom negative PET findings prevented active management. Both the presence (P = 0.012) and the extent (P < 0.0001) of relapse on PET were highly significant prognostic factors. There was also significant prognostic stratification based on the treatment delivered after the PET study (P = 0.011), but after adjustment for this treatment, PET status remained highly predictive of survival. CONCLUSION: PET better assesses the status of disease and stratifies prognosis than does conventional staging, affects patient management, and should be incorporated into paradigms for suspected recurrence of NSCLC.

Aged↗

A randomised crossover trial of chemotherapy in the home: patient preferences and cost analysis.

OBJECTIVES: To determine patient preferences and cost differences between home-based and hospital-based chemotherapy. DESIGN: Randomised crossover trial. SETTING: A tertiary cancer hospital in Melbourne, Victoria. PARTICIPANTS: 20 patients who required chemotherapy suitable for administration at home. INTERVENTIONS: Patients were assigned at random to receive their first chemotherapy treatment in either the home or the hospital and the second treatment in the alternative setting. MAIN OUTCOME MEASURES: Patient preference, costs. RESULTS: There was universal agreement by the 20 patients in the randomised trial that home-based chemotherapy was the preferred option (P < 0.0001). No problems were nominated by the patients as being associated with home-based chemotherapy. Home-based treatment was estimated to result in an increased cost of $83 (P = 0.0002) for each chemotherapy treatment compared with hospital-based treatment. Reported advantages for chemotherapy in the home included the elimination of travel, reduction in treatment-associated anxiety, reduction in the burden on carers and family, and the ability to continue other duties. There were no significant complications associated with administration of chemotherapy in the home. CONCLUSIONS: Patients prefer home-based chemotherapy to hospital-based treatment. The future of chemotherapy-in-the-home programs in Australia will depend on whether patient preferences are deemed to offset any potential increase in costs.

Aged↗

Characteristics of 49 patients who survived for 5 years following radical radiation therapy for non-small cell lung cancer: the potential for cure.

PURPOSE: To investigate the long-term curative potential of radical radiation therapy (RT) for non-small cell lung cancer (NSCLC) by studying characteristics of patients from a large prospective database who survived >5 years after RT, and by analyzing survival beyond 5 years. METHODS AND MATERIALS: Five-year survivors were identified from a database containing information on 488 patients given radical RT following presentation to the Peter MacCallum Cancer Institute with NSCLC between 1984 and 1990. Additional data were obtained from case notes of survivors. RT was computed tomography (CT)-planned, conventionally-fractionated, and given without chemotherapy. RESULTS: Actuarial survival for 49 5-year survivors was 65% at 10 years. Five 5-year survivors had documented disease progression within the first 5 years and subsequently died. Of 44 patients free-from-progression (FFP) at 5 years, an estimated 81% remained FFP in the second 5 years. Age and histology were not significant prognostic factors, and only 22 patients (4.5%) had weight loss >10%. For 277 patients who had not undergone thoracotomy, median RT dose was 60 Gy and survival at 5 and 10 years was 7% and 3%, respectively. For 207 patients who received radical RT post-thoracotomy, median dose was 60 Gy and survival at 5 and 10 years was 24% and 18%, respectively. Five-year survivors of post-thoracotomy RT had been treated for gross residual disease (n = 10), positive-margin (n = 6), or probable microscopic residual disease (n = 17). Failure to regain ECOG performance status = 0 post-thoracotomy was associated with reduced survival (p<0.0012). FFP in the second 5 years was superior for patients who had postoperative radiotherapy (90%) compared to patients without thoracotomy (62%, p = 0.008). CONCLUSION: Most patients FFP >5 years after radical RT for NSCLC remained FFP in the following 5 years and were apparently cured. RT alone can cure small but significant numbers of patients. Long-term results of combined chemotherapy/RT protocols, which are associated with increased median survival, are awaited for comparison.

Aged↗

Varicella-zoster infection after allogeneic bone marrow transplantation: incidence, risk factors and prevention with low-dose aciclovir and ganciclovir.

We examined the incidence of herpes varicella-zoster virus (VZV) infection in 151 patients undergoing allogeneic BMT between August 1990 and September 1997 and who survived at least 3 months. Median follow-up was 17 (range 3.3-80.7) months. Herpes simplex virus antibody positive (HSV+) patients received aciclovir 1200 mg p.o. daily or 750 mg i.v. daily, in divided doses from day 0 to engraftment. Ganciclovir (5 mg/kg i.v. three times per week) was given in CMV+ patients (or if the donor was CMV+) from engraftment to day 84. Ganciclovir was continued or recommenced if a dose of greater than 20 mg of prednisone was used for the treatment of GVHD otherwise aciclovir was recommenced. In HSV+ patients not receiving ganciclovir, aciclovir 600 mg p.o. daily in divided doses was given until at least 6 months after BMT. Thirty-two patients developed VZV infection from 4.1 to 28 months after transplant. The estimated cumulative incidence of VZV was 13% (95% confidence interval 6-19%) at 12 months, 32% (22-42%) at 24 months and 38% (27-50%) at 28 months, with no further cases beyond that time. No patient developed VZV whilst receiving aciclovir or ganciclovir (P < 0.0001). However, there was a rapid onset of VZV following cessation of antiviral therapy (33% (20-46%) at 1 year post cessation). The presence of GVHD and the prior duration of antiviral prophylaxis were significant and independent risk factors for the development of VZV. Age, underlying disease, conditioning therapy or donor type were not. We conclude that 3-6 months of low-dose aciclovir and ganciclovir are effective at delaying the onset of VZV after allogeneic BMT, but may not affect the overall incidence of infection. Prolonged prophylaxis may be warranted in patients at high risk of infection, for example those patients with GVHD.

2-Aminopurine↗

Non-surgical periodontal treatment with and without adjunctive metronidazole in smokers and non-smokers.

AIM: To determine whether adjunctive metronidazole therapy would compensate for the poorer treatment response to scaling and root planing reported in smokers. METHOD: A single-blind, randomised clinical trial of 28 smokers and 56 non-smokers, stratified for periodontitis disease severity and randomly allocated to 3 treatment groups: (1) Scaling and root planing using an ultrasonic scaler with local anaesthesia (SRP), (2) SRP+ metronidazole tabs 200 mg tds for 7 days, (3) SRP + 2 subgingival applications of 25% metronidazole gel. Probing depths (PD) and attachment levels (AL) were recorded with a Florida probe at baseline, 2 months and 6 months post treatment by a single examiner who was unaware of the treatment modality. Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance. RESULTS: Reductions in probing depth at 6 months were significantly less (p < 0.001) in the smokers (mean 1.23 mm, 95% confidence intervals = 1.05 to 1.40 mm) than in the non-smokers (1.92, 1.75 to 2.09 mm). Attachment level gains were approximately 0.55 mm and there was no statistically significant difference between smokers and non-smokers. There were no differences in any clinical measure in response to the three treatment regimens at 2 or 6 months for either smokers or non-smokers. A reduction in the proportion of spirochaetes was observed at 6 months which was less in smokers than in non-smokers (p = 0.034). Multiple linear regression analysis on probing depth at 6 months demonstrated that smoking was a significant explanatory factor (p < 0.001) for poor treatment outcome, whilst the presence or absence of adjunctive metronidazole was not (p = 0.620). CONCLUSION: This study confirms that smokers have a poorer treatment response to SRP, regardless of the application of either systemic or locally applied adjunctive metronidazole.

Administration, Oral↗

A phase I/II study of intensive dose escalation of cytarabine in combination with idarubicin and etoposide in induction and consolidation treatment of adult acute myeloid leukemia. Australian Leukaemia Study Group (ALSG).

To determine the safety and efficacy of the combination of idarubicin, cytarabine and etoposide ("ICE") for induction and consolidation treatment of acute myeloid leukemia (AML), and of dose-intensification of cytarabine in this setting, 54 previously untreated patients in three cohorts were studied by sequential dose escalation of cytarabine, in combination with standard doses of idarubicin and etoposide. Cytarabine was given to Cohort 1 at the conventional dosage of 100 mg/m2 per day by continuous infusion for 7 days in induction and 5 days in consolidation; to Cohort 2 at high-dose (HiDAC) (3 g/m2 intravenously twice daily on days 1, 3, 5 and 7) during induction with conventional dosage during consolidation; to Cohort 3 HiDAC was given for both induction and consolidation. In addition, Cohort 3 patients received lenograstim (Granocyte; rHuG-CSF) after both induction and consolidation courses. We found that there was no significant difference between the three cohorts in hematological toxicity in induction, but that HiDAC was associated with a greater incidence of gastro-intestinal toxicities. There was no difference in induction mortality between the three cohorts, which was 11% overall. Consolidation with HiDAC led to a significant increase in hematological toxicity. Overall, the complete remission (CR) rate was 80% with no significant difference between the three regimens. The estimated disease free survival at 3 years was 28%, 67% and 54% respectively for Cohorts 1, 2 and 3 with an estimated overall survival of 38%, 63% and 47%. We conclude that cytarabine dosage can be escalated safely in combination with idarubicin and etoposide in both induction and consolidation. The combination is effective for induction treatment of AML and its side-effects appear similar to those of standard regimens. Whether its use offers long-term benefits compared with standard regimens is the subject of ongoing controlled randomized studies.

Adolescent↗

Adjunctive systemic and locally delivered metronidazole in the treatment of periodontitis: a controlled clinical study.

OBJECTIVE: To compare clinical and microbiological responses following non-surgical treatment of moderate to advanced adult periodontitis using subgingival scaling with and without adjunctive topical or systemic metronidazole. DESIGN: A single blind randomised clinical trial of 90 subjects, stratified for periodontitis disease severity and smoking status, divided into three treatment groups: 1. Subgingival scaling using ultrasonic scalers and local anaesthesia; 2. Subgingival scaling using ultrasonic scalers and local anaesthesia plus seven days of systemic metronidazole (200 mg tds); 3. Subgingival scaling using ultrasonic scalers and local anaesthesia plus two applications of 25% metronidazole gel one week apart in all sites with probing depths more than 4 mm. Evaluations were made before treatment, and 8 weeks and 24 weeks post treatment. MAIN OUTCOME MEASURES: Probing depths, probing attachment levels and bleeding on probing were measured using a Florida probe. Bacterial morphotypes were evaluated with darkfield microscopy. Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance. RESULTS: 84 subjects completed the trial and the three treatment groups did not differ at baseline for any clinical parameter. Mean probing depths were reduced following treatment by greater than 1.6 mm (Group 1 = 1.68 mm, Group 2 = 1.62 mm, Group 3 = 1.74 mm at six months post treatment) but no significant differences were detected between treatment groups at any time point. Similarly, no significant differences were detectable between treatments for changes in mean probing attachment levels, bleeding on probing, plaque scores or proportions of bacterial morphotypes. CONCLUSIONS: This study does not support the routine use of adjunctive metronidazole in the non-surgical treatment of periodontitis.

Administration, Oral↗