Improving outcomes in gynaecological cancer: the benefits of subspecialisation.

Over the past 30 years advances in medicine have resulted in increasingly complex care pathways and individualisation of care. As a result, medicine has become subspecialised in many areas, and there is evidence for improved outcomes for patients treated by multidisciplinary teams, as demonstrated in chronic heart failure,[1] stroke,[2] and colorectal cancer.[3]

The 1995 Calman-Hine report, which aimed to improve cancer survival in the UK, recommended setting up co-ordinated care within cancer networks;[4] patients with less common and rare cancers should have care centralised, with patients referred from units to a centre, which could devote a specialist multidisciplinary team to the care of a particular tumour site.

Gynaecological malignancy, arising from the ovary, cervix, endometrium, vulva or vagina, affects 2.2% of the female population by the age of 65 and is the second most common cause of cancer death in women, following breast cancer.[5] In the developed world, most gynaecological cancers are endometrial or ovarian, whereas cervical cancer is more common in the developing world and is the leading cause of gynaecological cancer death worldwide. However, compared with colorectal and breast cancer, gynaecological cancer is relatively uncommon.

Treatment for gynaecological cancers is frequently multimodal, requiring co-ordination of surgical care with chemotherapy and radiotherapy. For some time there has been indirect evidence that women have more favourable outcomes if they are treated by specialist gynaecological oncologists in cancer centres. Gynaecological cancers were one of the first cancer sites to have centralisation of care recommended following the Calman-Hine report, as detailed in the Improving Outcomes in Gynaecological Cancer report in 1999.[6] Furthermore, gynaecological oncology has become a subspecialty within obstetrics and gynaecology in many countries, with the development of specific advanced training programmes to meet the technical challenges of gynaecological cancer surgery and to understand the role of surgery within a multidisciplinary team.

A Cochrane Review by Yin Ling Woo and colleagues, published in the March 2012 issue of The Cochrane Library, evaluates the effect of centralisation of care for women with gynaecological malignancy.[7] Outcomes for women with gynaecological cancer treated by specialist gynaecological oncologists within centres were compared with those receiving care in non-specialist general hospitals. The review identified five studies, including 62,987 women with gynaecological cancer, and concluded that women with gynaecological cancer may have improved outcomes if treated in specialist centres. The findings were stronger for women with ovarian cancer than for the other gynaecological cancers, as several of the studies examined ovarian cancer only. A meta-analysis of data from three of the studies (including over 9000 women) demonstrated that women with ovarian cancer who received care in hospitals with a gynaecological oncologist on site had improved survival compared with those treated in non-specialist hospitals; hazard ratio (HR) of death was 0.90 (95% confidence interval (CI) 0.82 to 0.99).

The review authors noted that all the included studies were from high-income countries (USA, Canada, UK, and the Netherlands), so the findings may not be transferable to other healthcare settings. The review was also limited by the poor quality of the evidence: all included studies were retrospective observational studies and therefore at high risk of bias. However, the studies demonstrated consistent results, which gives some weight to the findings. Another limitation was that only one study, albeit of 48,981 women, included women with gynaecological cancer other than ovarian, and the authors suggested that further studies, ideally from other healthcare settings, should be performed to confirm the benefits of centralising care for women with other gynaecological cancers. The authors thought that the likelihood of selective reporting bias was low, as all studies included overall survival data. However, none of the studies looked at risk of harms or quality of life data, which would be important to women and those commissioning healthcare services.

Gynaecological cancer is another disease for which specialisation seems to improve survival outcomes for patients. Why should this be? Seeking reasons for the benefit of subspecialised care was beyond the scope of the Cochrane Review, but one can speculate on factors that may play a role. Gynaecological cancer surgery can be challenging, involving techniques not routinely encountered by generalists. Even in early-stage ovarian cancer, surgery by a specialist gynaecological oncologist is an important prognostic indicator.[8] For advanced ovarian cancer, several studies have demonstrated that women operated on by a subspecialty trained gynaecological oncologist are more likely to be optimally debulked than women operated on by a general gynaecologist. Interestingly, one study demonstrated that centralisation resulted in a two-fold increase in optimal debulking rates for women with stage III-IV ovarian cancer, but there was no significant change in survival, suggesting that survival in advanced ovarian cancer is influenced primarily by factors other than surgical expertise.[9]

In vulval cancer, a condition for which optimal surgery has a major influence on survival, access to subspecialist surgery due to implementation of Calman-Hine guidelines has improved lymphadenectomy rates and survival.[10] So surgical skill clearly has an effect, and access to appropriately trained multidisciplinary care is important, as demonstrated by Woo and co-authors.[7] Another factor may be that women who are very unwell, with advanced disease and poor performance status, may not be fit for transfer to a specialist centre, although some studies have demonstrated that women treated at specialist centres have more advanced disease.[11]

The authors concluded that it would be important for future studies to have a more robust prospective design, although recognised that a randomised controlled trial may be difficult, but that prospective studies should be performed, with adequate funding and agreed protocols, to evaluate the impact of instigating centralisation of care in the future. Certainly any future studies should ideally examine other gynaecological cancers and outcomes, such as risk of adverse outcomes, quality of life, and cost-benefit analyses, in addition to survival, to inform future healthcare commissioning.

The evidence in gynaecological cancer treatment is consistent in demonstrating benefits from centralisation and is in line with evidence from other diseases (and mirroring results from a new Cochrane Review of colorectal cancer surgery[12]), thus supporting the role of cancer networks and the need for co-ordination of care. These improvements need to be safeguarded in these difficult economic times, and co-operative working between centres and units needs to be protected from the effects of competition, for the benefit of our patients.

Jo Morrison

Dr Jo Morrison (, Consultant in Gynaecological Oncology, Department of Obstetrics and Gynaecology, Musgrove Park Hospital, Taunton, UK


1. Inglis SC, Clark RA, McAlister FA, et al. Which components of heart failure programmes are effective? A systematic review and meta-analysis of the outcomes of structured telephone support or telemonitoring as the primary component of chronic heart failure management in 8323 patients: abridged Cochrane Review. European Journal of Heart Failure 2011;13(9):1028–40.

2. Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database of Systematic Reviews 2007;(4):CD000197.

3. McArdle CS, Hole DJ. Influence of volume and specialization on survival following surgery for colorectal cancer. British Journal of Surgery 2004;91(5):610–7.

4. Expert Advisory Group. A policy framework for commissioning cancer services. London: Department of Health; 1995.

5. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer 2010;127(12):2893–2917.

6. NHS Executive. Guidance on commissioning cancer services: improving outcomes in gynaecological cancers. London: Department of Health; 1999

7. Woo YL, Kyrgiou M, Bryant A, Everett T, Dickinson HO. Centralisation of services for gynaecological cancer. Cochrane Database of Systematic Reviews 2012, Issue 3. Art. No.: CD007945. DOI: 10.1002/14651858.CD007945.pub2.

8. Mayer AR, Chambers SK, Graves E, Holm C, Tseng PC, Nelson BE, et al. Ovarian cancer staging: does it require a gynecologic oncologist? Gynecologic Oncology 1992;47(2):223–7.

9. Bailey J, Murdoch J, Anderson R, Weeks J, Foy C. Stage III and IV ovarian cancer in the South West of England: five-year outcome analysis for cases treated in 1998. International Journal of Gynecological Cancer 2006;16 (suppl 1):25–9.

10. Yap JK, Baker LJ, Balega JZ, Chan KK, Luesley DM. Impact of improving outcome guidance in gynaecological cancer on squamous cell carcinoma of the vulva in the West Midlands, UK. Journal of Obstetrics and Gynaecology 2011;31(8):754–8.

11. Chan JK, Kapp DS, Shin JY, Husain A, Teng NN, Berek JS, et al. Influence of the gynecologic oncologist on the survival of ovarian cancer patients. Obstetrics and Gynecology 2007;109(6):1342–50.

12. Archampong D, Borowski D, Wille-Jørgensen P, Iversen LH. Workload and surgeon’s specialty for outcome after colorectal cancer surgery. Cochrane Database of Systematic Reviews 2012; Issue 3 . Art. No.: CD005391. DOI: 10.1002/14651858.CD005391.pub3

Source: Cochrane library.



Plain language summary

Centralisation of care may prolong survival in women with ovarian cancer, and possibly more generally, gynaecological cancer

Gynaecological cancers are cancers affecting the ovaries, uterus, cervix, vulva, and vagina.  They are the second most common cancers among women, after breast cancer. It is often suggested that outcomes are improved by centralising care within highly specialised services that include expert surgeons, radiologists, pathologists, oncologists who specialise in chemotherapy and radiotherapy, specialist nurses and other health professionals. However, consensus is lacking on whether centralisation of care for gynaecological cancer helps patients to live longer. This review investigated this issue by comparing the survival of women diagnosed with gynaecological cancer who received care from specialised and unspecialised centres.

We used a set of tests to ensure that the evidence the five studies identified reached the quality standard for our analysis.The analysis of three studies combined (meta-analysis), assessing over 9000 women, suggested that institutions with gynaecologic oncologists (specialists in the field of gynaecological cancer treatment) on site may prolong the lives of women with ovarian cancer compared to community or general hospitals. Similarly, another meta-analysis of three studies which assessed well over 50,000 women, found evidence to suggest that teaching centres or regional cancer centres (specialised centres) may prolong the lives of women with gynaecological cancer compared to community or general hospitals. The largest study in this meta-analysis assessed all gynaecological cancers in 48,981 women, so it had major influence on the final result; this means that our findings are likely to be relevant to other gynaecological cancers, besides ovarian cancer.

Overall, the findings suggest that centralisation of care may prolong the lives of women with gynaecological cancer, and in particular ovarian cancer. However, the results should be interpreted with caution as all of the studies included in the review could be biased. For example, it is possible that the patients who were treated in specialised centres were less ill to begin with. Another weakness of the review is that only one of the studies included women with gynaecological cancers other than ovarian cancer.

Ideally, further studies in this area are needed.  New studies should be designed to avoid the possibility of bias due to the treatment of women at specialist and non-specialist centres being systematically different. Additionally, studies should assess the impact of centralisation of care on the quality of life of patients.

Most of the available evidence was about ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers and to less developed countries.

Source:Cochrane Library



Pain management for women in labour: an overview of systematic reviews


The pain that women experience during labour is affected by multiple physiological and psychosocial factors and its intensity can vary greatly.  Most women in labour require pain relief. Pain management strategies include non-pharmacological interventions (that aim to help women cope with pain in labour) and pharmacological interventions (that aim to relieve the pain of labour).


To summarise the evidence from Cochrane systematic reviews on the efficacy and safety of non-pharmacological and pharmacological interventions to manage pain in labour. We considered findings from non-Cochrane systematic reviews if there was no relevant Cochrane review.


We searched the Cochrane Database of Systematic Reviews (The Cochrane Library 2011, Issue 5), The Cochrane Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 31 May 2011) and EMBASE (1974 to 31 May 2011) to identify all relevant systematic reviews of randomised controlled trials of pain management in labour. Each of the contributing Cochrane reviews (nine new, six updated) followed a generic protocol with 13 common primary efficacy and safety outcomes. Each Cochrane review included comparisons with placebo, standard care or with a different intervention according to a predefined hierarchy of interventions. Two review authors extracted data and assessed methodological quality, and data were checked by a third author. This overview is a narrative summary of the results obtained from individual reviews.

Main results

We identified 15 Cochrane reviews (255 included trials) and three non-Cochrane reviews (55 included trials) for inclusion within this overview. For all interventions, with available data, results are presented as comparisons of: 1. Intervention versus placebo or standard care; 2. Different forms of the same intervention (e.g. one opioid versus another opioid); 3. One type of intervention versus a different type of intervention (e.g. TENS versus opioid). Not all reviews included results for all comparisons. Most reviews compared the intervention with placebo or standard care, but with the exception of opioids and epidural analgesia, there were few direct comparisons between different forms of the same intervention, and even fewer comparisons between different interventions. Based on these three comparisons, we have categorised interventions into: ” What works” ,“What may work”, and “Insufficient evidence to make a judgement”.


Evidence suggests that epidural, combined spinal epidural (CSE) and inhaled analgesia effectively manage pain in labour, but may give rise to adverse effects. Epidural, and inhaled analgesia effectively relieve pain when compared with placebo or a different type of intervention (epidural versus opioids). Combined-spinal epidurals relieve pain more quickly than traditional or low dose epidurals. Women receiving inhaled analgesia were more likely to experience vomiting, nausea and dizziness.

When compared with placebo or opioids, women receiving epidural analgesia had more instrumental vaginal births and caesarean sections for fetal distress, although there was no difference in the rates of caesarean section overall. Women receiving epidural analgesia were more likely to experience hypotension, motor blockade, fever or urinary retention. Less urinary retention was observed in women receiving CSE than in women receiving traditional epidurals. More women receiving CSE than low-dose epidural experienced pruritus.


There is some evidence to suggest that immersion in water, relaxation, acupuncture, massage and local anaesthetic nerve blocks or non-opioid drugs may improve management of labour pain, with few adverse effects.  Evidence was mainly limited to single trials. These interventions relieved pain and improved satisfaction with pain relief (immersion, relaxation, acupuncture, local anaesthetic nerve blocks, non-opioids) and childbirth experience (immersion, relaxation, non-opioids) when compared with placebo or standard care. Relaxation was associated with fewer assisted vaginal births and acupuncture was associated with fewer assisted vaginal births and caesarean sections.


There is insufficient evidence to make judgements on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, TENS, or parenteral opioids are more effective than placebo or other interventions for pain management in labour. In comparison with other opioids more women receiving pethidine experienced adverse effects including drowsiness and nausea.

Authors’ conclusions

Most methods of non-pharmacological pain management are non-invasive and appear to be safe for mother and baby, however, their efficacy is unclear, due to limited high quality evidence. In many reviews, only one or two trials provided outcome data for analysis and the overall methodological quality of the trials was low. High quality trials are needed.

There is more evidence to support the efficacy of pharmacological methods, but these have more adverse effects. Thus, epidural analgesia provides effective pain relief but at the cost of increased instrumental vaginal birth.

It remains important to tailor methods used to each woman’s wishes, needs and circumstances, such as anticipated duration of labour, the infant’s condition, and any augmentation or induction of labour.

A major challenge in compiling this overview, and the individual systematic reviews on which it is based, has been the variation in use of different process and outcome measures in different trials, particularly assessment of pain and its relief, and effects on the neonate after birth. This made it difficult to pool results from otherwise similar studies, and to derive conclusions from the totality of evidence. Other important outcomes have simply not been assessed in trials; thus, despite concerns for 30 years or more about the effects of maternal opioid administration during labour on subsequent neonatal behaviour and its influence on breastfeeding, only two out of 57 trials of opioids reported breastfeeding as an outcome. We therefore strongly recommend that the outcome measures, agreed through wide consultation for this project, are used in all future trials of methods of pain management.

Plain language summary

Pain management for women in labour – an overview

Women’s experience of pain during labour varies greatly. Some women feel little pain whilst others find the pain extremely distressing.  A woman’s position in labour, mobility, and fear and anxiety or, conversely, confidence may influence her experience of pain. Several drug and non-drug interventions are available, and in this overview we have assessed 18 systematic reviews of different interventions used to reduce pain in labour, 15 of these being Cochrane reviews.

Most of the evidence on non-drug interventions was based on just one or two studies and so the findings are not definitive.  However, we found that immersion in water, relaxation, acupuncture and massage all gave pain relief and better satisfaction with pain relief. Immersion and relaxation also gave better satisfaction with childbirth. Both relaxation and acupuncture decreased the use of forceps and ventouse, with acupuncture also decreasing the number of caesarean sections. There was insufficient evidence to make a judgement on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, and TENS are effective for pain relief in labour.

Overall, there were more studies of drug interventions. Inhaled nitrous oxide and oxygen (Entonox®) relieved pain, but some women felt drowsy, nauseous or were sick.  Non-opioid drugs (e.g. sedatives) relieved pain and some gave greater satisfaction with pain relief than placebo or no treatment, but satisfaction with pain relief was less than with opioids. Epidurals relieved pain, but increased the numbers of births needing forceps or ventouse, and the risk of low blood pressure, motor blocks (hindering leg movement), fever and urine retention. Combined spinal-epidurals gave faster pain relief but more women had itching than with epidurals alone, although urinary retention was less likely to be a problem. Local anaesthetic nerve blocks gave satisfaction but caused side effects of giddiness, sweating, tingling, and more babies had low heart rates. Parenteral opioids (injections of pethidine and related drugs) are less effective than epidural but there was insufficient evidence to make a judgement on whether or not they are more effective than other interventions for pain relief in labour.

Overall, women should feel free to choose whatever pain management they feel would help them most during labour. Women who choose non-drug pain management should feel free, if needed, to move onto a drug intervention. During pregnancy, women should be told about the benefits and potential adverse effects on themselves and their babies of the different methods of pain control. Individual studies showed considerable variation in how outcomes such as pain intensity were measured and some important outcomes were rarely or never included (for example, sense of control in labour, breastfeeding, mother and baby interaction, costs and infant outcomes). Further research is needed on the non-drug interventions for pain management in labour.


Source:Cochrane Library.





Maternal Death: The Avoidable Crisis.

Every year, hundreds of thousands of women around the world die avoidable deaths during childbirth, for lack of skilled birth attendants and basic medications, the international medical humanitarian organization Doctors Without Borders/Médecins Sans Frontières (MSF) said in a report released today, in advance of International Women’s Day on March 8.

The report Maternal Death: The Avoidable Crisis details how the provision of emergency obstetric care to pregnant women in acute and chronic humanitarian crises can have a direct impact and save women’s lives. It examines the circumstances for pregnant women in 12 countries where MSF works, in settings ranging from conflict areas to countries with weak health systems, including Pakistan, Somalia, South Sudan, and Haiti. The report highlights the need for emergency medical assistance, particularly when pregnancy complications occur.

The report draws on years of MSF’s experience running and expanding programs to meet the needs of pregnant women, and seeks to draw greater attention to the dearth of emergency obstetric care in a number of crisis areas.

“We know that 15 percent of all pregnancies worldwide will experience a life-threatening complication,” said Kara Blackburn, women’s health advisor for MSF. “Women need access to quality emergency obstetric care whether they live in Sydney, Port-au-Prince, or Mogadishu. The reality is the same for women in a modern hospital in a major city, or for those living in a conflict zone, a refugee camp, or under plastic sheeting following a devastating earthquake.”

Every day, approximately 1,000 women die in childbirth or from pregnancy-related complications – one every 90 seconds, according to the World Health Organization. However, with the help of skilled birth attendants and access to the appropriate drugs and equipment, women’s lives—and the lives of their babies—can be saved.

Delivery is the most critical moment for saving women’s and babies’ lives, with most maternal deaths occurring just before, during, or immediately after delivery, often from complications that cannot be predicted ahead of time. Typical—and deadly—complications include hemorrhaging, sepsis (infection), unsafe abortions, eclampsia (hypertension), and obstructed labor, which together account for nearly three quarters of all maternal deaths worldwide. All of these conditions can be prevented or treated.

As an emergency medical organization, MSF has demonstrated that maternal deaths can be reduced, including during humanitarian crises. The organization has invested significantly in developing the technical and logistical capacity to provide life-saving—and free-of-charge—emergency obstetric care.

“It is an ongoing tragedy that we are still seeing so many women die in childbirth, when we know that the provision of quality care at the time of delivery can have a direct impact,” said Blackburn. “We must always remind ourselves that a maternal death is an avoidable death.”

MSF provides emergency obstetric care in approximately 30 countries. In 2010, MSF staff assisted the delivery of more than 150,000 babies.

Source: MSF Newsletter.



Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults.

Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Subcutaneous administration may be preferable to oral for individuals experiencing nausea and/or vomiting
OBJECTIVES: To determine the efficacy and tolerability of subcutaneous sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. SEARCH
METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011.
SELECTION CRITERIA: We included randomised, double-blind, placebo- and/or active-controlled studies using subcutaneous sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or `risk ratio`) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment.
MAIN RESULTS: Thirty-five studies (9365 participants) compared subcutaneous sumatriptan with placebo or an active comparator. Most of the data were for the 6 mg dose. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 6 mg versus placebo the NNTs were 2.9, 2.3, 2.2, and 2.1 for pain-free at one and two hours, and headache relief at one and two hours, respectively, and 6.1 for sustained pain-free at 24 hours. Results for the 4 mg and 8 mg doses were similar to the 6 mg dose, with 6 mg significantly better than 4 mg only for pain-free at one hour, and 8 mg significantly better than 6 mg only for headache relief at one hour. There was no evidence of increased migraine relief if a second dose of sumatriptan 6 mg was given after an inadequate response to the first.Relief of headache-associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than placebo. For the most part, adverse events were transient and mild and were more common with sumatriptan than placebo.Sumatriptan was compared directly with a number of active treatments, including other triptans, acetylsalicylic acid plus metoclopramide, and dihydroergotamine, but there were insufficient data for any pooled analyses.
AUTHORS’ CONCLUSIONS: Subcutaneous sumatriptan is effective as an abortive treatment for acute migraine attacks, quickly relieving pain, nausea, photophobia, phonophobia, and functional disability, but is associated with increased adverse events.

Source: Cochrane database.


An online self-help CBT intervention for chronic lower back pain.

Research has shown that cognitive and behavioral therapies can effectively improve quality of life in chronic pain patients. Unfortunately, many patients lack access to cognitive and behavioral therapy treatments. We developed a pilot version of an interactive online intervention to teach self-management skills for chronic lower back pain, a leading cause of disability and work absenteeism. The objective of this randomized, controlled trial was to evaluate its efficacy.
METHODS: Individuals with chronic lower back pain were recruited over the Internet, screened by phone, and randomly assigned to receive access to the intervention (Wellness Workbook; WW) either immediately (intervention group) or after a 3-week delay (wait-list control). Participants (n=141, 83% female, 23% minority) were asked to complete the WW over 3 weeks. Self-report measures of pain, disability, disabling attitudes and beliefs, self-efficacy for pain control, and mood regulation were completed at baseline, week 3, and week 6.
RESULTS: Controlling for baseline individual differences in the outcome measures, multivariate analysis of covariance revealed that, at week 3, the intervention group scored better than the wait-list control group on all outcomes, including pain severity ratings. At week 6, after both groups had been exposed to the WW, there were no differences between groups. DISCUSSION: Use of this pilot intervention seems to have had positive effects on a number of pain-related outcomes, including disability. Future research will evaluate the effectiveness of the completed intervention, with particular attention to quality of life and disability.

Source: Clinical journal of pain.

Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters.

Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters.
METHODS: Participants with HIV diagnosis seroconversion window of <= 3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status.
RESULTS: Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15-2.71); 3.27 (2.71-3.84); 3.75 (2.25-5.25); and 5.41 (3.41-7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20-2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94-1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75-1.75).
CONCLUSIONS: HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.

Source: Journal of infectious disease.



Performance of the Canadian CT Head Rule and the New Orleans Criteria for predicting any traumatic intracranial injury on computed tomography in a United States Level I trauma center.

This study compared the clinical performance of the Canadian CT Head Rule (CCHR) and the New Orleans Criteria (NOC) for detecting any traumatic intracranial lesion on computed tomography (CT) in patients with a Glasgow Coma Scale (GCS) score of 15. Also assessed were ability to detect patients with “clinically important“ brain injury and patients requiring neurosurgical intervention. Additionally, the performance of the CCHR was assessed in a larger cohort of those presenting with GCS of 13 to 15.
METHODS: This prospective cohort study was conducted in a U.S. Level I trauma center and enrolled a consecutive sample of mildly head-injured adults who presented to the emergency department (ED) with witnessed loss of consciousness, disorientation or amnesia, and GCS 13 to 15. The rules were compared in the group of patients with GCS 15. The primary outcome was prediction of “any traumatic intracranial injury“ on CT. Secondary outcomes included “clinically important brain injury“ on CT and need for neurosurgical intervention.
RESULTS: Among the 431 enrolled patients, 314 patients (73%) had a GCS of 15, and 22 of the 314 (7%) had evidence of a traumatic intracranial lesion on CT. There were 11 of 314 (3.5%) who had “clinically important“ brain injury, and 3 of 314 (1.0%) required neurosurgical intervention. The NOC and CCHR both had 100% sensitivity (95% confidence interval [CI] = 82% to 100%), but the CCHR was more specific for detecting any traumatic intracranial lesion on CT, with a specificity of 36.3% (95% CI = 31% to 42%) versus 10.2% (95% CI = 7% to 14%) for NOC. For “clinically important“ brain lesions, the CCHR and the NOC had similar sensitivity (both 100%; 95% CI = 68% to 100%), but the specificity was 35% (95% CI = 30% to 41%) for CCHR and 9.9% (95% CI = 7% to 14%) for NOC. When the rules were compared for predicting need for neurosurgical intervention, the sensitivity was equivalent at 100% (95% CI = 31% to 100%) but the CCHR had a higher specificity at 80.7% (95% CI = 76% to 85%) versus 9.6% (95% CI = 7% to 14%) for NOC. Among all 431 patients with a GCS score 13 to 15, the CCHR had sensitivities of 100% (95% CI = 84% to 100%) for 27 patients with clinically important brain injury and 100% (95% CI = 46% to 100%) for five patients requiring neurosurgical intervention.
CONCLUSIONS: In a U.S. sample of mildly head-injured patients, the CCHR and the NOC had equivalently high sensitivities for detecting any traumatic intracranial lesion on CT, clinically important brain injury, and neurosurgical intervention, but the CCHR was more specific. A larger cohort will be needed to validate these findings.

Source:Acedemic Emergency medicine.



Five Things You Need To Know When Deciding On A Cholesterol-Lowering Drug.

Recent news has caused millions of Americans to question whether they should be taking statin drugs, used for lowering cholesterol and preventing heart disease. TheFood and Drug Administration (FDA)recently announced safety labeling changes for statins and a prominent cardiologist warned in the New York Times that too many people are taking statin drugs.

The concerns affect many people since these blockbuster drugs are practically ubiquitous. Government studies indicate that there is a one in four chance that you are taking these medications if you are 45 years and older. About half of American men and a third of American women in the 65 to 74 years age range are taking statins.

Available products include single ingredient products ((atorvastatin), Lescol (fluvastatin), Mevacor (lovastatin), Altoprev (lovastatin extended-release), Livalo (pitavastatin), Pravachol (pravastatin), Crestor (rosuvastatin), and Zocor (simvastatin) and combination products (Advicor (lovastatin/niacin extended-release), Simcor (simvastatin/niacin extended-release), and Vytorin (simvastatin/ezetimibe)). Together they account for $14 billion in U.S. sales.

If you are taking statins, what should you do about this new information? Here are five key things to consider.

1. It is your decision.

First and foremost, this is your decision. Medicine is often defined by decisions with trade-offs and uncertainty. Choices about medications can be particularly challenging when they concern prevention. When you choose to take a drug for prevention, you have decided that the risks of the drug are more than offset by its future benefit.

Your doctors and health care professionals can guide you, but you deserve to be informed about the decision and make the choice that feels most comfortable to you. You do not know if you will be the person who avoids a heart attack or will suffer a side effect. You should have the information about what you are likely to gain by taking the medication – and what risks you are incurring. The decision to take the drug should mean that you believe that you are more likely to benefit from the drug than to be harmed by it. And even if a drug has a benefit for you, you have a right to decide whether it is right for you.


Moreover, in decisions about drugs for prevention, it is important to remember that lifestyle choices (e.g., not smoking, being active, eating healthy, and keeping your weight under control) should be a part of any strategy to lower risk of heart disease.

2. Statins reduce risk.

Among all prevention drugs, statins are among the most effective in lowering risk. These drugs have been shown, with quite a lot of evidence, to reduce the risk of heart attacks and deaths in a wide range of patients. Those taking statins have about a 20% lower risk of a heart attack and 10% lower risk of death. Higher dose and higher potency statins tend to reduce risk of heart disease a bit more.

The drugs with the strongest evidence of benefit are atorvastatin, lovastatin, pravastatin, simvastatin, and rosuvastatin.

This benefit is important because not all drugs that lower cholesterol or improve risk factors actually reduce the risk of heart disease. And some drugs even paradoxically increase risk. Questions remain about the effects on risk of many other lipid lowering drugs, such as niacin, fibrates, and ezetimibe.

3. Statins have risks.

Statins, like all drugs, have potential side effects. That is, although they are generally safe, they can cause harm in some people. Some of these side effects are well documented. In some people statins can cause muscle aches, soreness and weakness. This side effect is not uncommon and may occur in as many as one in ten people taking these medications. These symptoms usually resolve after discontinuing the drug – and they may not occur with another type of statin.

The new FDA announcement stated that there are rare reports of reversible memory loss and confusion, side effects that were considered not serious and went away when the drug was stopped. The reports about these side effects were submitted to the FDA by doctors and their relationship to statins is not certain.

The FDA also reported that blood sugar levels sometimes rise with statin therapy, but the importance of the finding is not known. For perspective, a recent study found that increases in blood sugar by a blood pressure drug, chlorthalidone, did not increase risk as much as would have been expected. Statins can very rarely also have more dramatic side effects such as life-threatening muscle damage or liver disease.

Finally, statins are generally drugs that are prescribed for a lifetime. Their effect over decades of use has yet to be determined.

Despite these risks, the trials showed a substantial benefit to these drugs – which is what has led them to be widely prescribed. But the drugs do cause harm for some even as they confer benefit for others.

4. Your risk matters.

Although the guidelines tend to focus on cholesterol levels in the decision to take statins, your overall risk of heart disease may be a more important factor in your decision. Since statins lower risk for people regardless of their cholesterol level, your benefit from the drug will depend on your risk of heart disease. If you have a low risk of heart disease, then you will have little to gain from treatment. A 20% reduction in a low risk of a heart attack may not mean much. The higher your risk, the more you have to gain.

Colleagues and I did a study and found that prescribing statins based on risk rather than cholesterol levels would lead to more lives being saved by treating fewer people. You can calculate your risk of heart disease from some online resources ( or For many people a risk of less than 1% a year is considered low.

If you have heart disease, your risk of future events is higher and the benefit from statin therapy is generally considered substantial. In that case you do not even need to calculate your risk.

5. Minimize the statin risk.

If you do take statins, you have some choices that can minimize your risk.

First, you should be alert to symptoms that may signal a side effect. Talk to your doctor if you develop muscle aches, weakness or any new symptoms that concern you.

Second, lower doses are better. People with a higher risk of heart disease or with heart disease may benefit more from higher dose or higher potency statins (such as atorvastatin) but others may do better with a lower dose or less potent statin. These drugs tend to have fewer side effects.

Third, be aware that some other drugs you are taking may increase the risk of statins. Some drugs can markedly raise the risk of side effects of statins and you should ask your doctor about possible interactions if you are taking other medications. Also, for some statins, grapefruit juice can make the statin drugs more potent – though it is not clear if this raises the risk of side effects.

Finally, pravastatin appears not to increase blood sugar levels – so if this is a concern of yours, then you might want to try this medication. This statin is also less affected by other medications.

Bottom line: Statins are capable of remarkable reductions in the risk of heart disease and death. During the increase in their use there has been a marked decline in heart attacks and deaths from heart disease. The people with the most to gain are those with an increased risk of heart disease. If you are one such individual, and if your risk cannot be lowered by lifestyle changes, then statins are an excellent option. But it is your choice – and if you do take them, then be alert for side effects and minimize your risk.

The new information from the FDA or the admonitions from some experts does not fundamentally change the decision you have to make. Side effects are rare – but you should only take any drug if you are convinced that the benefits substantially outweigh the potential harms.

Harlan M. Krumholz MD, SM is the Harold H. Hines, Jr. Professor of Medicine and Epidemiology and Public Health at Yale University School of Medicine.

Source:Forbes Medicine

Research group suggests Madagascar’s unique animals arrived on rafts.

Ever since the island of  was first visited by people, some two thousand years ago, there has been speculation about the unique plants and animals that live on the world’s fourth largest island; one where roughly ninety percent of the wildlife is found nowhere else. For many years, it was believed they came to be there during the time when the island was still physically connected to Africa, but that reasoning has fallen by the wayside as it has been shown that the island separated some 88 million years ago, while most of the animals that live there didn’t arrive till just 60 million years ago, forcing evolutionary scientists to search for other explanations. Now new evidence by an international group of researchers is proposing that the animals got there by floating on rafts during a time when prevailing currents would have made the journey more plausible. They have published a paper on their ideas in the Proceedings of the National Academy of Sciences.


Today, the distance between Madagascar and Africa is about 250 miles (400 kilometers), far enough to make the journey by raft virtually impossible due to a lack of fresh water to drink, not to mention overheating and sunburn. But, say the researchers, some 60 million years ago, things were different. During that time, the island was in a slightly different position. In particular, its northernmost edge hadn’t started creeping into the southern equatorial current, which means ocean currents would have been able to flow from west to east, which would have helped tremendously. If the animals were to ride over, they would have done so accidentally due to finding themselves marooned on a raft made of natural vegetation torn from the ground during a cyclone, examples of which have been seen often enough in modern times to prove that it can happen. If such a situation did occur, it’s possible the small raft could have been blown far out to sea by a storm that also deposited enough water on the raft to allow any animals aboard to survive the trip from Africa, or even Asia.

The researchers came to these conclusions after building a database of all the animals on the island and then working backwards using genetic evidence to pinpoint almost precisely the time frame that they diverged from their African cousins. Once they had that, they studied research findings regarding conditions on the Earth in that area and found that it was likely that the ocean currents could have been flowing east to west due to tectonic shifting.

The research team suggests that the animals would also have had time on their side. Over a span of millions of years, a rare event such as animals floating over could have occurred often enough to account for the animals that did make it over and who eventually began reproducing.

The team also points out that once the island shifted enough to change ocean currents, the numbers of animals reaching Madagascar diminished greatly, which explains why those that did make the trip lived in almost complete isolation, giving rise to the evolution of such exotic species.

How, when, and from where Madagascar’s vertebrates arrived on the island is poorly known, and a comprehensive explanation for the distribution of its organisms has yet to emerge. We begin to break that impasse by analyzing vertebrate arrival patterns implied by currently existing taxa. For each of 81 clades, we compiled arrival date, source, and ancestor type (obligate freshwater, terrestrial, facultative swimmer, or volant). We analyzed changes in arrival rates, with and without adjusting for clade extinction. Probability of successful transoceanic dispersal is negatively correlated with distance traveled and influenced by ocean currents and ancestor type. Obligate rafters show a decrease in probability of successful transoceanic dispersal from the Paleocene onward, reaching the lowest levels after the mid-Miocene. This finding is consistent with a paleoceanographic model [Ali JR, Huber M (2010)Nature 463:653–656] that predicts Early Cenozoic surface currents periodically conducive to rafting or swimming from Africa, followed by a reconfiguration to present-day flow 15–20 million years ago that significantly diminished the ability for transoceanic dispersal to Madagascar from the adjacent mainland.





New Studies Aimed at Colorectal Cancer Detection and Prevention.

Research focuses on colonoscopy, fecal immunochemical testing, and stool DNA testing.

Randomized trials of screening colonoscopy have been initiated in northern Europe, Spain, and the U.S.. In the Spanish and U.S. trials, participants not assigned to colonoscopy are undergoing fecal immunochemical testing (FIT). Researchers from the Spanish trial have now reported results from the first round of screening. Participation rates were lower in the colonoscopy group than the FIT group (25% vs. 34%). Of people who underwent FIT, 7% had positive tests that were followed by colonoscopy. In intention-to-screen analyses, colorectal cancer (CRC) was found in equal numbers of participants in the two groups (0.1%), but advanced adenomas were found in twice as many colonoscopy participants as FIT participants (2% vs. 1%).

In the U.S. National Polyp Study, researchers evaluated the effects of colonoscopic removal of adenomatous polyps. Patients underwent colonoscopy between 1980 and 1990 to further evaluate symptoms or other positive tests. Among 2602 patients in whom adenomas were removed, 20-year cumulative mortality from CRC was 0.8%. According to population-based registry data, expected CRC mortality was 1.5%; thus, colonoscopic removal of adenomas lowered mortality by roughly 50%.

Research on stool DNA testing — which should identify colorectal neoplasia more accurately than fecal occult blood testing — is also moving forward. U.S. investigators applied a “next-generation” DNA test (which detects 6 neoplasia-associated genes in exfoliated tumor cells) to stool samples from 293 people with normal colonoscopies, 133 patients with advanced adenomas, and 252 patients with CRC (mostly nonmetastatic); stool samples were obtained prior to colonoscopy or surgery. When specificity was set at 90%, sensitivity was 85% for cancer and 54% for adenomas 1 cm. Sensitivity rose to 77% for adenomas >2 cm.

Comment: The first of these studies — with its low participation rates — illustrates the difficulties of conducting a randomized trial of colorectal cancer screening. Although the second study supports the efficacy of colonoscopic polypectomy to prevent cancer-related deaths, it is not a randomized screening trial. And the third study suggests that stool DNA screening might eventually enable us to limit colonoscopy to those most likely to benefit.

Source: Journal Watch General Medicine