Cervical cancer prevention in Southern Africa: A review of national cervical cancer screening guidelines in the Southern African development community.

BACKGROUND: Cervical cancer poses a significant burden, particularly in low-and-middle income countries (LMIC) with limited access to healthcare. High-income countries have made progress in prevention, while LMIC face unacceptably high incidence and mortality rates, often lacking official screening recommendations. We analysed the presence and content of cervical cancer screening guidelines for the secondary prevention of cervical cancer in the Southern African Development Community (SADC) and compared it to the current World Health Organization (WHO) guidelines for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. METHODS: A review of national cervical cancer guidelines across the SADC region was conducted. Data was obtained from government websites, international cancer control platforms, and WHO resources. Search terms included "cervical cancer" and "cervical cancer control guidelines", amongst others. There were no limitations on publication years, and the most recent versions of the guidelines were analysed, regardless of language. Each guideline was assessed for specific screening and treatment recommendations, in relation to the current WHO guidelines. Points were assigned for each data element. RESULTS: While most countries contributed data to this analysis there was a notable absence of adherence to the WHO guidelines. The most common screening method was naked eye visual inspection. There was a consensus on the age of screening initiation. Most countries recommended treatment by cryotherapy and loop excision. CONCLUSION: Effective cervical cancer screening programmes, guided by evidence-based recommendations, can enhance early intervention and outcomes. This study highlights the need for standardized and evidence-based cervical cancer screening guidelines in the SADC region, to reduce the burden of cervical cancer and improve the health outcomes of women in these areas.

Introduction of an Alcohol-Related Electronic Screening and Brief Intervention (eSBI) Program to Reduce Hazardous Alcohol Consumption in Namibia's Antiretroviral Treatment (ART) Program.

Alcohol is the most widely abused substance in Namibia and is associated with poor adherence and retention in care among people on antiretroviral therapy (ART). Electronic screening and brief interventions (eSBI) are effective in reducing alcohol consumption in various contexts. We used a mixed methods approach to develop, implement, and evaluate the introduction of an eSBI in two ART clinics in Namibia. Of the 787 participants, 45% reported some alcohol use in the past 12 months and 25% reported hazardous drinking levels. Hazardous drinkers were more likely to be male, separated/widowed/divorced, have a monthly household income > $1000 NAD, and report less than excellent ART adherence. Based on qualitative feedback from participants and providers, ART patients using the eSBI for the first time found it to be a positive and beneficial experience. However, we identified several programmatic considerations that could improve the experience and yield in future implementation studies.

The cardiopulmonary exercise test grey zone; optimising fitness stratification by application of critical difference.

BACKGROUND: Cardiorespiratory fitness can inform patient care, although to what extent natural variation in CRF influences clinical practice remains to be established. We calculated natural variation for cardiopulmonary exercise test (CPET) metrics, which may have implications for fitness stratification. METHODS: In a two-armed experiment, critical difference comprising analytical imprecision and biological variation was calculated for cardiorespiratory fitness and thus defined the magnitude of change required to claim a clinically meaningful change. This metric was retrospectively applied to 213 patients scheduled for colorectal surgery. These patients underwent CPET and the potential for misclassification of fitness was calculated. We created a model with boundaries inclusive of natural variation [critical difference applied to oxygen uptake at anaerobic threshold (V˙O2-AT): 11 ml O2 kg-1 min-1, peak oxygen uptake (V˙O2 peak): 16 ml O2 kg-1 min-1, and ventilatory equivalent for carbon dioxide at AT (V̇E/V̇CO2-AT): 36]. RESULTS: The critical difference for V˙O2-AT, V˙O2 peak, and V˙E/V˙CO2-AT was 19%, 13%, and 10%, respectively, resulting in false negative and false positive rates of up to 28% and 32% for unfit patients. Our model identified boundaries for unfit and fit patients: AT <9.2 and ≥13.6 ml O2 kg-1 min-1, V˙O2 peak <14.2 and ≥18.3 ml kg-1 min-1, V˙E/V˙CO2-AT ≥40.1 and <32.7, between which an area of indeterminate-fitness was established. With natural variation considered, up to 60% of patients presented with indeterminate-fitness. CONCLUSIONS: These findings support a reappraisal of current clinical interpretation of cardiorespiratory fitness highlighting the potential for incorrect fitness stratification when natural variation is not accounted for.

A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

BACKGROUND: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies. PATIENTS AND METHODS: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload. RESULTS: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival. CONCLUSIONS: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

Oxaliplatin/capecitabine vs oxaliplatin/infusional 5-FU in advanced colorectal cancer: the MRC COIN trial.

BACKGROUND: COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC). METHODS: Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment. RESULTS: In total, 64% of 2397 patients received OxCap(± cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (± cetuximab) was associated with more mucositis and infection whereas OxCap(± cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50-80 ml min(-1) on OxCap(± cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function. CONCLUSIONS: Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50-80 ml min(-1) on both regimens require close toxicity monitoring.

Revision interposition arthroplasty of the elbow.

Between 1996 and 2008, nine patients with severe post-traumatic arthritis underwent revision of a failed interposition arthroplasty of the elbow with a further interposition procedure using an allograft of tendo Achillis at a mean of 5.6 years (0.7 to 13.1) after the initial procedure. There were eight men and one woman with a mean age of 47 years (36 to 56). The mean follow-up was 4.7 years (2 to 8). The mean Mayo Elbow Performance score improved from 49 (15 to 65) pre-operatively to 73 (55 to 95) (p = 0.04). The mean Disability of the Arm, Shoulder and Hand score was 26 (7 to 42). One patient was unavailable for clinical follow-up and one underwent total elbow replacement three months post-operatively. Of the remaining patients, one had an excellent, two had good, three fair and one a poor result. Subjectively, five of the nine patients were satisfied. Four continued manual labour. Revision interposition arthroplasty is an option for young, active patients with severe post-traumatic arthritis who require both mobility and durability of the elbow.

Outcome of sliding inguinal hernia repair.

PURPOSE: Sliding inguinal hernias represent a small proportion of inguinal hernias but become more common with advancing age. The most recent review is based on a series published over 50 years ago. There are, however, many case reports of unusual presentations in girls. METHODS: We performed a review of a prospectively kept electronic record of all operations performed at Logan Hospital since 2003 in order to document the clinical characteristics of sliding inguinal hernias in the twenty-first century. RESULTS: Thirty-one males underwent predominantly anterior repair of a sliding hernia after a median of 9 months of symptoms (2.9% of all hernia repairs-32/1,092). Approximately two-thirds of hernias were left sided. There were five minor and two technical complications. Follow-up ranged from 3 weeks to 3 years. Two recurrences have been repaired. CONCLUSIONS: Sliding inguinal hernias continue to test the surgeon's understanding of the inguinal canal's anatomy and technical expertise with a significant rate of technical complications and recurrence.

Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience.

We present the preliminary toxicity data from the MRC COIN trial, a phase III randomised controlled trial of first-line therapy in advanced colorectal cancer, with particular reference to the addition of cetuximab to an oxaliplatin-fluoropyrimidine combination. A total of 804 patients were randomised between March 2005 and July 2006 from 78 centres throughout the United Kingdom. Patients were allocated to oxaliplatin plus fluoropyrimidine chemotherapy with or without the addition of weekly cetuximab. The choice of fluoropyrimidine (either 5-fluorouracil (5FU) or capecitabine) was decided by the treating physician and patient before randomisation. Toxicity data were collected from all patients. Two hundred and three patients received 5FU plus oxaliplatin (OxMdG, 25%), 333 oxaliplatin+capecitabine (Xelox, 41%), 102 received OxMdG+cetuximab (OxMdG+C, 13%) and 166 Xelox+cetuximab (21%). Percent grade 3/4 toxicities included diarrhoea 6, 15, 13 and 25%, nausea/vomiting 3, 7, 7 and 14% for OxMdG, Xelox, OxMdG+C and Xelox+C, respectively. Sixty-day all-cause mortality was 6, 5, 5 and 7%. Statistically significant differences were evident for patients receiving Xelox+cetuximab vs Xelox alone: diarrhoea relative risk (RR) 1.69 (1.17, 2.43, P=0.005) and nausea/vomiting RR 2.01 (1.16, 3.47, P=0.012). The excess toxicity observed in the oxaliplatin-, capecitabine-, cetuximab-treated patients led the trial management group to conclude that a capecitabine dose adjustment was required to maintain safety levels when using this regimen.

Coonrad-Morrey total elbow arthroplasty for tumours of the distal humerus and elbow.

We reviewed 20 patients who had undergone a Coonrad-Morrey total elbow arthroplasty after resection of a primary or metastatic tumour from the elbow or distal humerus between 1980 and 2002. Eighteen patients underwent reconstruction for palliative treatment with restoration of function after intralesional surgery and two after excision of a primary bone tumour. The mean follow-up was 30 months (1 to 192). Five patients (25%) were alive at the final follow-up; 14 (70%) had died of their disease and one of unrelated causes. Local control was achieved in 15 patients (75%). The mean Mayo Elbow Performance Score improved from 22 (5 to 45) to 75 points (55 to 95). Four reconstructions (20%) failed and required revision. Seven patients (35%) had early complications, the most frequent being nerve injury (25%). There were no infections or wound complications although 18 patients (90%) had radiotherapy, chemotherapy or both. The Coonrad-Morrey total elbow arthroplasty provides good relief from pain and a good functional outcome after resection of tumours of the elbow. The rates of complications involving local recurrence of tumour (25%) and nerve injury (25%) are of concern.

A conservative femoral replacement for total hip arthroplasty. A prospective study.

Between 1985 and 1993, 146 patients (162 hips) had total hip replacement (THR) using a conservative uncemented femoral component. The mean age of the patients was 50.8 years and the mean follow-up was 6.2 years (2 to 13). One patient was lost to follow-up, one died within two years of surgery and one had a revision procedure after a fracture sustained in a road-traffic accident. For the remaining 159, Kaplan-Meier survival analysis was calculated for the incidence of revision because of mechanical loosening or osteolysis. Survival without mechanical loosening at both five and ten years was 98.2%. Survival without osteolysis was 99% at five and 91% at ten years. The Harris hip score improved from a mean of 66.3 before to 90.4 at follow-up. Of particular note is the lack of thigh pain in this group. Radiological analysis showed that 139 stems (88%) had no measurable subsidence, 8 (5%) had less than 2 mm and 12 (7%) had more than 2 mm. Two of the eight and one of the 12 were revised for mechanical loosening. Nine hips were revised for late loosening associated with osteolysis. No reaming of the femoral canal was associated with statistically significant less blood loss compared with a comparable control group of uncemented implants (p < 0.0001). Our study suggests that using a conservative femoral implant does not protect against wear debris but the reliable mechanical stability (98.2%) makes this an attractive design of implant particularly for young patients.

Soluble adhesion molecules in clinical ischaemic injury.

BACKGROUND: Neutrophil adhesion is a prerequisite for ischaemic injury. In vitro research has shown that soluble adhesion molecules have an inhibitory effect on neutrophil binding AIMS: To determine whether the circulating forms of adhesion molecules are consumed during skeletal muscle ischaemic injury in man. METHODS: The response of the circulating forms of adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and L-selectin to ischaemia and reperfusion was investigated in 23 patients during surgery involving aortic cross-clamping and in 20 volunteers with tourniquet-induced forearm ischaemia. RESULTS: In the aortic model the levels of circulating ICAM-1 fell from an initial value of 250 +/- 20 to 210 +/- 13 ng/ml (p < 0.05) and soluble L-selectin fell from 642 +/- 62 to 487 +/- 49 ng/ml during ischaemia (p < 0.05). There was a similar pattern of reduced levels of circulating adhesion molecules in the model of forearm ischaemia. However the recovery of these molecules during the reperfusion period differed between the two models. CONCLUSIONS: Soluble L-selectin and soluble ICAM-1 appear to be utilised during clinical models of ischaemia. This supports previous in vitro studies suggesting a role in competitive inhibition and these circulating molecules may be clinically important inhibitors of leukocyte adhesion.

Semiconstrained total elbow arthroplasty in the context of treated previous infection.

Previous infection has been considered a strict contraindication to implantation or reimplantation of an elbow prosthesis. The purpose of this study was to investigate whether these patients can in fact be successfully treated with a prosthetic arthroplasty given previous treatment of the infection. Ten consecutive prosthetic arthroplasties performed in patients with documented infections in the elbow were retrospectively reviewed. Seven of the patients had infectious complications of total elbow arthroplasties that led to resection. Two patients had previous infections from septic joints and 1 from open reduction internal fixation. The median interval of time from infection treatment to final implant was 45 months (3.8 years). All arthroplasties were performed by the same surgeon with a modified Coonrad-Morrey, semiconstrained prosthesis. Patients were monitored for clinical signs of infection including radiographic and serologic studies and clinical evaluation based on the Mayo Elbow Performance Score. Mean surveillance was 4 years (range 2.8 to 5.4 years). Eight of the 10 cases have not shown signs of infection at the latest assessment. Two have had recurrent infections. The time interval from the original infection to latest implantation did not correlate with infection recurrence. Among those 8 without recurrent infection, 7 had excellent and 1 had satisfactory results according to the Mayo Elbow Performance Score. The recurrent infections were rated as failures. The average score was 32 before and 81 after surgery. The average pain score was 15 before surgery, and the average postoperative pain score was 40. Salvage of previously infected elbows with prosthetic arthroplasty can provide excellent results in a significant proportion of patients. Although the procedure offers superior functional outcomes compared with the alternative treatment options, it is technically demanding.

Instability of the elbow treated with semiconstrained total elbow arthroplasty.

The results of nineteen semiconstrained modified Coonrad-Morrey total elbow arthroplasties performed in nineteen patients to treat instability were evaluated at an average of seventy-two months (range, twenty-five to 128 months) postoperatively. Preoperatively, all patients had either a flail elbow or gross instability of the elbow that prevented useful function of the extremity. The instability of sixteen elbows was the result of a traumatic injury or of the treatment of such an injury. The most recent result was satisfactory for sixteen elbows and unsatisfactory for three. The average overall Mayo elbow performance score increased from 44 points preoperatively to 86 points postoperatively. At the most recent follow-up examination, no elbow was unstable. The average arc of flexion was from 25 degrees (range, 0 to 60 degrees) to 128 degrees (range, 30 to 142 degrees), which represented a 58-degree increase from the preoperative average arc. Sixteen patients had little or no pain after the arthroplasty. There were four complications in four patients. Three complications (loosening of the humeral component in one patient and a fracture of the ulnar component in two) occurred postoperatively; all three were treated with a revision procedure. The other complication (a fracture of the olecranon) occurred intraoperatively and was treated with tension-band fixation; the most recent outcome was not affected. Radiographically, one patient had complete (type-V) radiolucency about the humeral component. None of the nine patients for whom true anteroposterior radiographs were available had evidence of wear of the bushings. The bone graft behind the anterior flange of the humeral prosthesis was mature in fourteen elbows, incomplete in two, and resorbed in two. One patient was excluded from this analysis because radiographs were not available. Instability of the elbow resulting in the inability to use the extremity is a challenging clinical situation. However, in patients who are more than sixty years old and in selected patients who are less than sixty years old but who have extensive loss of bone as a result of severe injury, have had multiple operations, or have rheumatoid arthritis, total elbow arthroplasty with a linked, semiconstrained prosthesis reestablishes a mobile, stable joint without premature loosening or failure of the components. In our experience, the use of customized implants, maintenance of the muscular attachments to the epicondyles, and reconstruction of the epicondyles to the implant were unnecessary.

Total elbow arthroplasty in primary osteoarthritis of the elbow.

Primary osteoarthritis of the elbow is an infrequent condition typically managed by some form of debridement. There is no comment in the literature regarding prosthetic replacement for this condition. We report 5 patients (mean age, 68), with a minimum assessment of 3 years (range, 37-125 years) after total elbow arthroplasty. Complications in 4 patients included subluxation, fracture of a humeral component with particulate synovitis, heterotopic ossification, recurrent osteophyte formation, and transient ulnar neuropathy. Although revision was required in 2 of the 5, currently all experience had satisfactory outcomes. While replacement has proven ultimately to be a successful option for this high-demand patient group because of the high complication rate, we do not recommend replacement unless alternate operative options are deemed unacceptable.

Rheological properties and function of blood cells in stored bank blood and salvaged blood.

The technique involving filtration of diluted blood enables the separate analysis of the flow properties of different cell subpopulations. This study was designed to assess the changes occurring in the flow properties and function of blood cells in stored bank blood and salvaged blood compared to patient blood in a given clinical situation. We measured hydrogen peroxide production by neutrophils and the filterability, through 5 microm Nucleopore filters, of isolated red blood cells and of diluted blood. Samples were obtained from patients undergoing aortic surgery and blood intended for transfusion: either salvaged during surgery or stored bank blood. Both salvaged and bank blood were much less filterable than patient blood, with reduced deformability of both red and white blood cells. However, salvaged blood contained highly activated neutrophils with a prolonged transit time of the 'fast-flowing' cells in the analysis compared to bank blood. Bank blood contained significantly more particles which acted as pore-blockers. Cells in bank and salvaged blood therefore have markedly abnormal flow and biochemical properties compared to patient blood.

Infection after total elbow arthroplasty.

The purpose of this study was to review our experience with the treatment of twenty-five infections (in twenty-five patients) after total elbow arthroplasty and to examine indications for salvage of the prosthesis compared with those for resection arthroplasty. The patients were divided into three groups on the basis of treatment. Group I comprised fourteen patients who were managed with multiple, extensive irrigation and debridement procedures with retention of the original components. The primary indication for retention of the prosthesis was evidence that it was well fixed as determined both radiographically and intraoperatively. Group II comprised six patients who had removal of the prosthesis and debridement followed by immediate or staged reimplantation. Group III comprised five patients who were managed with resection arthroplasty. The infection was successfully eradicated in seven of the fourteen elbows that had salvage of the prosthesis with irrigation and debridement. The results were strongly dependent on the causative organism; attempts at debridement failed in the four elbows that were infected with Staphylococcus epidermidis compared with three of the ten that were infected with another organism. Four of the six patients in Group II had successful reimplantation of a prosthesis; in three, the infection had been caused by an organism other than Staphylococcus epidermidis. Only one of the three patients who had a Staphylococcus epidermidis infection had a successful reimplantation. None of the five patients who had a resection arthroplasty had signs of infection at the latest follow-up examination. We concluded that salvage of the prosthesis with extensive irrigation and debridement in the presence of an infection about the elbow can be reasonably successful if the infecting organism is not Staphylococcus epidermidis and if the components are well fixed. When removal of the components is warranted, staged reimplantation can also be highly successful when the infecting organism is not Staphylococcus epidermidis. However, the repeated operations necessary to retain a prosthesis and the high rates of complications seen with this approach--and the relatively good rates of satisfaction obtained with resection arthroplasty--suggest that resection arthroplasty remains the procedure of choice in medically frail patients or in patients for whom function of the elbow is less of a concern.

Total elbow arthroplasty: revision with use of a non-custom semiconstrained prosthesis.

The results of revision elbow arthroplasty with use of the semiconstrained Mayo-modified Coonrad implant in forty-one patients were reviewed retrospectively. The average duration of follow-up was six years (range, two to thirteen years). At the time of the latest follow-up evaluation, thirty-eight patients were able to perform activities of daily living, one had a stiff elbow because of heterotopic ossification, one had weakness secondary to an injury of the radial nerve, and one had an unstable elbow after removal of the prosthesis because of recurrent aseptic loosening. Fourteen patients sustained either a fracture or a perforation of the cortex at the time of removal of the primary implant. Three of these patients had an injury of the radial nerve; the injury was due to extravasation of the cement from a cortical defect in two of them and was sustained during removal of the cement in one. Eight patients had an intraoperative or postoperative complication that necessitated additional operative intervention. Postoperatively, twenty-two patients had complete relief of pain and sixteen had mild discomfort. Three patients remained disabled: one, because of pain secondary to loosening of the component; one, because of a pre-existing nerve injury; and one, because of the residual effects of an intraoperative injury of the radial nerve. The average Mayo elbow performance score was 87 +/- 16 points at the latest follow-up evaluation, compared with 44 +/- 17 points preoperatively (p < 0.0001). Revision elbow arthroplasty restored function to the patients who had had a failed prosthesis without infection.

Neutrophil elastase, von Willebrand factor, soluble thrombomodulin and percutaneous oxygen in peripheral atherosclerosis.

OBJECTIVES: To test the hypothesis that endothelial cell damage and hypoxia are related to the activity of neutrophil elastase in patients with peripheral atherosclerosis. DESIGN: A cross-sectional serological study in a tertiary referral, University Hospital. MATERIALS: Venous blood was obtained from 22 patients with peripheral vascular disease and an equal number of age and sex matched controls. METHODS: Neutrophil elastase and two markers of endothelial cell damage (von Willebrand factor and soluble thrombomodulin) were measured in plasma by ELISA. Hypoxia was measured by percutaneous oxygen (by oximeter) at the dorsum of the foot. RESULTS: Patients had higher von Willebrand factor, higher soluble thrombomodulin and higher elastase but lower percutaneous oxygen (all p < 0.001). In the patient's group, there were significant inverse correlates between von Willebrand factor and percutaneous oxygen (p = 0.004) and between soluble thrombomodulin and percutaneous oxygen (p = 0.011) while elastase correlated positively with soluble thrombomodulin (p = 0.023). CONCLUSIONS: Our data support the hypothesis that release of elastase from activated neutrophils relates to endothelial cell damage. This may contribute to hypoxia and may result in the deterioration in clinically assessed atherosclerosis.