Estimating the changing disease burden attributable to smoking in South Africa for 2000, 2006 and 2012.

BACKGROUND: Ongoing quantification of the disease burden attributable to smoking is important to monitor and strengthen tobacco control policies. OBJECTIVES: To estimate the attributable burden due to smoking in South Africa for 2000, 2006 and 2012. METHODS: We estimated attributable burden due to smoking for selected causes of death in South African (SA) adults aged ≥35 years for 2000, 2006 and 2012. We combined smoking prevalence results from 15 national surveys (1998 - 2017) and smoking impact ratios using national mortality rates. Relative risks between smoking and select causes of death were derived from local and international data. RESULTS: Smoking prevalence declined from 25.0% in 1998 (40.5% in males, 10.9% in females) to 19.4% in 2012 (31.9% in males, 7.9% in females), but plateaued after 2010. In 2012 tobacco smoking caused an estimated 31 078 deaths (23 444 in males and 7 634 in females), accounting for 6.9% of total deaths of all ages (17.3% of deaths in adults aged ≥35 years), a 10.5% decline overall since 2000 (7% in males; 18% in females). Age-standardised mortality rates (and disability-adjusted life years (DALYs)) similarly declined in all population groups but remained high in the coloured population. Chronic obstructive pulmonary disease accounted for most tobacco-attributed deaths (6 373), followed by lung cancer (4 923), ischaemic heart disease (4 216), tuberculosis (2 326) and lower respiratory infections (1 950). The distribution of major causes of smoking-attributable deaths shows a middle- to high-income pattern in whites and Asians, and a middle- to low-income pattern in coloureds and black Africans. The role of infectious lung disease (TB and LRIs) has been underappreciated. These diseases comprised 21.0% of deaths among black Africans compared with only 4.3% among whites. It is concerning that smoking rates have plateaued since 2010. CONCLUSION: The gains achieved in reducing smoking prevalence in SA have been eroded since 2010. An increase in excise taxes is the most effective measure for reducing smoking prevalence. The advent of serious respiratory pandemics such as COVID-19 has increased the urgency of considering the role that smoking cessation/abstinence can play in the prevention of, and post-hospital recovery from, any condition.

Antiviral efficacy of entecavir in nucleos(t)ide-naïve patients of Black/African descent with chronic hepatitis B.

This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies.

An approach to a patient with dyspepsia.

Dyspepsia (indigestion) is a non-specific group symptoms related to the upper gastrointestinal tract. Organic disease must be detected and distinguished from non-"ulcer dyspepsia" or "functional" dyspepsia, so that specific treatment can be given.

Traveller's diarrhoea.

Dietary indiscretion is penalized by an increased risk of diarrhoea. Severe dehydration is seldom encountered, and fluid losses are easily corrected with readily available fluids. Drug treatment is either directed at suppressing the pathogen or for its anti-secretory effect.

An approach to the patient with unexplained chest pain.

After coronary artery disease has been excluded as a cause for unexplained chest pain, oesophageal disease must be considered. Ambulatory pH monitoring reveals abnormal oesophageal acid exposure in 50% of patients with recurrent non-cardiac chest pain.

No clinical benefit of adding cisapride to pantoprazole for treatment of gastro-oesophageal reflux disease.

OBJECTIVE: Although a proton pump inhibitor (PPI) and a prokinetic drug are often combined for the medical treatment of gastro-oesophageal reflux disease (GORD), there are few well-conducted clinical studies on the efficacy and tolerability of this therapy. This study investigates whether pantoprazole plus cisapride leads to an additional benefit in comparison to pantoprazole alone. DESIGN AND SETTING: Randomized double-blind prospective multicentre study conducted in patients of 33 hospitals in Ireland, South Africa and the UK. PARTICIPANTS: A total of 350 intention-to-treat (ITT) patients aged 18 years or older with GORD of grade II and III were included in the study. The per-protocol (PP) population comprised 152 patients in the pantoprazole group and 136 in the pantoprazole plus cisapride group. INTERVENTIONS: Patients received either pantoprazole 40 mg once daily or pantoprazole 40 mg once daily plus cisapride 20 mg twice daily. Treatment outcome was assessed after 4 and 8 weeks. The primary criterion was endoscopically confirmed healing after 4 weeks. Additionally, relief of leading symptoms was studied. MAIN OUTCOME MEASURES: The prior null hypothesis was no difference in healing rates between both treatment groups. RESULTS: After 4 weeks of treatment 81% and 82%, and after 8 weeks 89% and 90%, of PP patients treated with pantoprazole or pantoprazole plus cisapride were healed, respectively. Thus, equivalence of the two treatment strategies could be proven. Additionally, improvement of symptom relief showed no significant difference between the two regimens. In contrast to disease grade at baseline, Helicobacter pylori status did not influence the healing rates in our study. Both study medications were tolerated well. CONCLUSION: Addition of cisapride to pantoprazole provides no further benefit in the treatment of GORD.

Efficacy and tolerability of 20 mg pantoprazole versus 300 mg ranitidine in patients with mild reflux-oesophagitis: a randomized, double-blind, parallel, and multicentre study.

BACKGROUND AND AIM: The aim of this study was to compare the efficacy and tolerability of low dose pantoprazole (20 mg) (a gastric proton pump inhibitor) with standard dose ranitidine (300 mg) (a histamine-receptor antagonist), in their ability to relieve symptoms and heal oesophageal lesions associated with gastrooesophageal reflux disease (GORD). METHODS: Patients with endoscopically established mild GORD (stage I, modified Savary-Miller classification) were enrolled into a multicentre, randomized, double-blind, parallel-group comparison study (intention-to-treat population, n = 201; age range, 18-82 years). Patients took either oral pantoprazole 20 mg in the morning (n = 101) or ranitidine 300 mg in the evening (n = 100) once daily for 4 weeks or, if the healing was not complete, 8 weeks. Relief from key symptoms (heartburn, acid regurgitation, pain on swallowing) was assessed after 2, 4, and if applicable, 8 weeks. Healing of lesions was confirmed endoscopically after 4 and, if applicable, 8 weeks. RESULTS: Complete relief from key symptoms was noted after 2 weeks in 70/88 (80%) patients treated with pantoprazole vs 45/89 (51%) patients treated with ranitidine ('per-protocol and key-point available' populations, P < 0.001); the corresponding results after 4 weeks were 77/88 (88%) vs 51/88 (58%) (P < 0.001). Complete healing of lesions after 4 weeks of treatment was seen in 74/88 (84%) vs 49/89 (55%) in the pantoprazole and ranitidine group, respectively (P < 0.001, per-protocol); by week 8 the cumulative healing rates were 84/88 (95%) vs 69/89 (78%) in the pantoprazole and ranitidine group, respectively (P < 0.001). For the intention-to-treat populations, the corresponding values for healing after 4 and 8 weeks were 73% vs 49% (P < 0.001) and 83% vs 69% (P < 0.05), respectively. Both study medications were well tolerated. CONCLUSION: Compared to ranitidine 300 mg, the regimen with pantoprazole 20 mg provides faster relief from symptoms and is significantly more effective in healing of oesophageal lesions in patients with mild reflux-oesophagitis. Thus, the low dose of pantoprazole offers a treatment approach which minimizes drug exposure and costs while retaining high efficacy.

Safety and efficacy of pantoprazole 40 mg daily as relapse prophylaxis in patients with healed reflux oesophagitis-a 2-year follow-up.

BACKGROUND: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+, K+-ATPase, necessary for the final step in gastric acid secretion. AIM: To assess safety and efficacy of oral pantoprazole (40 mg o.d.) used as a prophylaxis against relapse in patients with healed reflux oesophagitis during an open-label, 2-year study. METHODS: Outpatients (n=157) with healed stage II or III reflux oesophagitis (Savary-Miller classification) were enrolled into a long-term, multicentre maintenance study. Endoscopy was performed at entry into the study, after 12 and 24 months, or when disease-specific symptoms occurred on more than three consecutive days. Symptoms were assessed at 3-monthly intervals. Endoscopically confirmed relapses (at least stage I) were evaluated as treatment failures. RESULTS: Of the 178 adverse events, experienced by 88 (56%) patients (intention-to-treat population), 12 (7%) were assessed by the investigators as possibly related to the study medication. Median serum gastrin levels increased from a baseline of 46 ng/L to 90 ng/L, reaching a plateau after 9 months. For the intention-to-treat population the endoscopic remission rates after 12 and 24 months were 87% and 76%, respectively (Life-Table survival analysis, Kaplan-Meier). CONCLUSION: Pantoprazole 40 mg proved to be safe and efficacious during a 2-year prophylaxis treatment in patients with healed reflux oesophagitis.

Rapid genomic diversification of Helicobacter pylori.

Helicobacter pylori was cultured from antrum and corpus gastric biopsies from 65 patients originating from two separate groups: (i) a geographically linked group and (ii) a geographically nonlinked group. Genomic DNA was recovered from the clinical isolates and subjected to restriction fragment length polymorphism (RFLP) analysis after digestion with DraI. Southern blots were probed with the oligonucleotide (GTG)5, the riboprobe pKK3535, and the cagA gene probe pMC3. (GTG)5 and cagA DNA fingerprints and ribopatterns suggested that most of the patients were infected with their own unique strain; however, some were infected with multiple strains. Minor genomic differences were detected in many antrum/corpus sample pairs (clonal variants), suggesting rapid evolutionary change in domains detected by (GTG)5. The high degree of genomic diversity detected by (GTG)5 may reflect structural versatility of these domains. The genomic diversity indicates that infection by H. pylori in a defined community does not appear to be limited to certain RFLP types.

Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter Eradication for Lesion Prevention.

BACKGROUND: The effect of Helicobacter pylori in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H. pylori eradication in patients with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs. METHODS: 285 patients were randomly assigned omeprazole 20 mg, amoxycillin 1000 mg, and clarithromycin 500 mg, twice daily (n=142, H. pylori eradication treatment), or omeprazole with placebo antibiotics (n=143, controls) for 1 week. All patients received omeprazole 20 mg once daily for 3 weeks until endoscopy, and, if the ulcer was not healed, 40 mg once daily until repeat endoscopy at 8 weeks. Ulcer-free patients with mild dyspepsia continued NSAIDs but not antiulcer treatment. We investigated ulcers with endoscopy at 1, 3, and 6 months and with carbon-13-labelled urea breath test at 3 months. FINDINGS: The estimated probability of being ulcer-free at 6 months was 0.56 (95% CI 0.47-0.65) on eradication treatment and 0.53 (0.44-0.62) on on control treatment (p=0.80). Time to treatment failure did not differ between groups for ulcers or dyspepsia alone, per-protocol analysis, or final H. pylori status. 66% (58-74) of the eradication group compared with 14% (8-20) of the control group had a final negative H. pylori result (p<0.001). Fewer baseline gastric ulcers healed among eradication-treatment patients than among controls (72 vs 100% at 8 weeks, p=0.006). INTERPRETATION: H. pylori eradication in long-term users of NSAIDs with past or current peptic ulcer or troublesome dyspepsia led to impaired healing of gastric ulcers and did not affect the rate of peptic ulcers or dyspepsia over 6 months.

Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin.

BACKGROUND: Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication. AIM: To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies. METHODS: Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14-17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site). RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal. CONCLUSION: An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.

Two-week course of pantoprazole combined with 1 week of amoxycillin and clarithromycin is effective in Helicobacter pylori eradication and duodenal ulcer healing.

BACKGROUND: Experience with proton pump inhibitor-based triple therapy is predominantly with omeprazole-containing regimens. AIM: To investigate the efficacy of a pantoprazole-based regimen, with either a 1 or 2-week course of antibiotic co-therapy, in eradicating H. pylori, healing duodenal ulcers and to assess the antibiotic sensitivity profiles of isolated H. pylori strains. METHODS: A single-blind, multicentre, parallel group comparison of patients with endoscopically proven, H. pylori associated, active duodenal ulceration. All patients received pantoprazole, 40 mg b.d. for 2 weeks. Patients were randomized to receive either 1 or 2 weeks of therapy with amoxycillin, 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry, at 14 days and a minimum of 4 weeks after cessation of all therapy. H. pylori status was determined by urease reaction, histological assessment and culture from antral and body biopsies. Antibiotic sensitivity was determined using the agar dilution technique. RESULTS: Sixty-seven patients were randomized. One week co-therapy (n=33): eradication efficacy, ITT= 79% (95% CI: 61-91%); ulcer healing efficacy (at 6-week visit)=88% (95% CI: 72-97%). Two-week co-therapy (n=34): eradication efficacy, ITT=91% (95% CI: 76-98%: ulcer healing efficacy= 88% (95% CI: 73-97%). Both regimens were well tolerated and no primary antibiotic resistance was noted. CONCLUSION: Pantoprazole-based triple therapy, with either 1 or 2 weeks of co-therapy with amoxycillin and clarithromycin, is effective in eradicating H. pylori and healing duodenal ulceration.

A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group.

BACKGROUND: Suppressing acid secretion is thought o reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain. METHODS: We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to double-blind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach, and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432 patients in whom treatment was successful to maintenance treatment with either 20 mg of omeprazole per day or 150 mg of ranitidine twice a day for six months. RESULTS: At eight weeks, treatment was successful in 80 percent (140 of 174) of the patients in the group given 20 mg of omeprazole per day, 79 percent (148 of 187) of those given 40 mg of omeprazole per day, and 63 percent (110 of 174) of those given ranitidine (P<0.001 for the comparison with 20 mg of omeprazole and P=0.001 for the comparison with 40 mg of omeprazole). The rates of healing of all types of lesions were higher with omeprazole than with ranitidine. During maintenance therapy, the estimated proportion of patients in remission at the end of six months was 72 percent in the omeprazole group and 59 percent in the ranitidine group. The rates of adverse events were similar between groups during both phases. Both medications were well tolerated. CONCLUSIONS: In patients with regular use of NSAIDs, omeprazole healed and prevented ulcers more effectively than did ranitidine.

A trial of lansoprazole in refractory gastric ulcer.

BACKGROUND: The proton-pump inhibitor, lansoprazole, a more potent gastric acid inhibitor with a longer action than H2-receptor antagonists, should heal refractory gastric ulcers more effectively. METHODS: Lansoprazole's efficacy in healing refractory gastric ulcer(s) (i.e. after 6 weeks of treatment with H2-receptor antagonists, antacids or sucralfate at recommended dosages, and/or a relapse within 1 year of documented gastric ulcer), was compared by a two-dose regimen in a four-centre, randomized, parallel group study. One hundred and eighteen patients (59 per group) with an endoscopically confirmed gastric ulcer > or = 3 mm, received lansoprazole 30 or 60 mg daily. We assessed efficacy endoscopically at 4 and 8 weeks, and again after documented healing during a maintenance phase of lansoprazole 30 mg/day at 2 and 4 months. RESULTS: Demographic and anthropometric data were comparable. Healing rates at 4 weeks were 63% (30 mg) vs. 66% (60 mg) (95% CI, -14 to 21%) and cumulatively at 8 weeks, 83% (30 mg) vs. 81% (60 mg) (95% CI, -12 to 16%). Two and 4 months after documented healing, 86% and 78% of intention-to-treat patients remained in remission. CONCLUSION: Lansoprazole 30 or 60 mg/day appear equally effective in healing refractory gastric ulcers, while maintenance therapy of 30 mg/day effectively prevented an ulcer relapse.

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+-ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel-Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.

Clinical characteristics of and prognosis in acute transmural anterior, transmural inferior and non-transmural myocardial infarction. A comparative retrospective study.

This retrospective study was undertaken to determine whether there was any difference in the clinical characteristics of and prognosis in white patients admitted to the Intensive Coronary Care Unit (ICCU) at Tygerberg Hospital with acute non-transmural, transmural anterior and transmural inferior myocardial infarction (MI). The three groups were carefully matched, taking into consideration the possible influence of previous MI and congestive cardiac failure (CCF). There were 187 patients with non-transmural MI, and 176 with transmural anterior and 209 with transmural inferior MI. Patients with acute transmural anterior MI had the worst prognosis while at the ICCU, at 3 months' follow-up and at long-term follow-up (mean 22,2 months). This group had the greatest frequency of CCF, cardiogenic shock, acute pericarditis, ventricular premature beats, ventricular tachycardia, left anterior hemiblock and complete left bundle-branch block and the highest mortality. Acute transmural inferior MI was responsible for the highest frequency of ventricular fibrillation in the ICCU and had a worse prognosis than non-transmural MI. Acute non-transmural MI resulted in the highest incidence of early and late myocardial reinfarction; although death in the ICCU was least frequent, mortality among this group had increased dramatically by 3 months' follow-up. Hence, acute non-transmural MI is not benign and an unstable period exists for 3 months thereafter. Because of this, more aggressive diagnostic measures should be instituted during this period in order possibly to improve prognosis in this group. It would appear that this is the first such study undertaken in South Africa.

Syphilitic coronary ostial stenosis. Case reports.

Two young Coloured men with proven syphilitic coronary ostial stenosis had severe angina pectoris unresponsive to conventional medication. One underwent an aortic valve replacement for severe aortic insufficiency associated with subtotal ostial occlusion of the right coronary artery (RCA), which was corrected by an aortocoronary bypass graft; the left coronary artery (LCA) ostium was normal and patent. The other patient had total occlusion of the LCA ostium which resulted in an extensive transmural anteroseptal and anterolateral myocardial infarction; the RCA ostium was unaffected and the aortic valve appeared normal. He was considered unsuitable for cardiac surgery and continued to receive anti-anginal drug therapy with quite satisfactory improvement in symptoms. Non-atheromatous coronary artery disease must always be sought for and excluded when a non-White patient presents with symptoms of ischaemic heart disease. Although atheromatous coronary artery involvement is becoming increasingly prevalent among 'westernized' Black and Coloured subjects, it is still relatively unusual in comparison with the extremely high incidence in the White population.