Royal College of General Practitioners - Online Learning Environment

Written by Dr Dirk Pilat

Introduction

Mpox (previously known as monkeypox) is a viral, infectious disease caused by a strain of the monkeypox virus (MPXV). The first human cases were identified in 1970 in the rainforest areas of Central and West Africa. Until 2022, outbreaks were usually limited to this geographical area, with occasional imported cases into non-epidemic countries and human to human transmission only present in a limited number of cases. 

MPXV has two distinct genetic lineages, called clade 1 and 2, both split into types a and b. The 2022-2023 global outbreak of mpox that continues to this day is due to clade 2b and caused 3,822 cases in the UK over the last two years. 

Number of confirmed and highly probable mpox cases by UK nation of residence, 6 May 2022 to 31 July. UKHSA. Contains public sector information licensed under the Open Government Licence v3.0.

The 2022-23 outbreak was driven by human to human MPXV transmission via close contact with infected individuals and continues to this day, albeit in lower levels and particularly among men who have sex with men. In 2024, clade 1b mpox cases were starting to spread outside its traditional geographical location in West Africa with the Democratic Republic of the Congo, Republic of the Congo, Central African Republic, Burundi, Rwanda, Uganda, Kenya, Cameroon and Gabon all affected and around 20,000 cases and potentially 1000 deaths reported in the Democratic Republic of the Congo alone. On 14th August 2024 the World Health Organization declared a public health emergency over mpox and since then two imported cases have been identified in Sweden and Thailand. 

Transmission

Mpox is transmitted through skin to skin contact, inhalation or contact with mucous membranes, through direct contact with skin lesions, coughing and sneezing and contact with clothing or linen used by person with mpox. Sexual contact, kissing, cuddling or other skin-to-skin contact can all cause transmission. 

Signs and symptoms

While short incubation periods have been reported, a contact tracing study from the United Kingdom showed that 95% of people with a potential infection had symptoms within 16-23 days. There have been reports that clade 1b might have a shorter incubation record, but there remains a significant degree of uncertainty. Typical prodrome of the illness are fever, headache, myalgia and joint pain and lymphadenopathy, but proctitis and sore throats have also been reported. In the 2022-23 outbreak the subsequent rash was usually limited to fewer than 20 lesions, but there is anecdotal evidence that the rash associated with clade 1b is more severe with up to several thousand pustules. Similarly, mortality seems to be increased in the new outbreak, though this might be due to the affected population being more vulnerable. The rash initially presents with macules, before developing into papules, vesicles, pseudo-pustules containing solid debris, crusts, and finally scabs, before falling off within 7–14 days. These can be painful and are often located orally or in the genital or anorectal areas.

Mpox lesions in various stages of progression. UKHSA. Contains public sector information licensed under the Open Government Licence v3.0.

Management

Making a diagnosis of mpox can be difficult, as there is a broad range of differential diagnoses for pyrexial maculopapular viral rashes such as chickenpox, measles, bacterial skin infections, scabies and herpes. A travel, contact and sexual history is important to narrow the possible diagnosis down. 

If triaging a patient with suspected mpox or if a patient presents with suspected mpox in general practice, the UK Health Security Agency (UKHSA) suggests isolating the patient in a single room and contacting the local infection service for advice, including appropriate arrangements for transfer into secondary care and immediate precautions in the setting (and who will manage contract tracing and advise on vaccination). When examining a suspected patient, clinical staff should wear face fit tested FFP3 masks, eye protection, long-sleeved splash resistant gowns and gloves to provide care if immediately required. 

Treatment is usually symptomatic, but there are antivirals available in secondary care for those with severe disease or immunocompromised patients. The UKHSA has released guidance for pre- and post-exposure vaccination with the smallpox vaccine for patients, contacts and healthcare workers (see references). 

References

Africa Centres for Disease Control and Prevention (Africa CDC). Africa CDC Epidemic Intelligence Weekly Report, August 2024. [accessed 2 September 2024].

Branda F, Romano C, Ciccozzi M, et al. Mpox: An Overview of Pathogenesis, Diagnosis, and Public Health Implications. J Clin Med. 2024 Apr 12;13(8):2234.

Centers for Disease Control and Prevention (CDC). Clinical Recognition: Key Characteristics for Identifying Mpox. Aug 2023. [accessed 2 September 2024].

Center for Health Security Johns Hopkins University. Situation Update Mpox Virus: Clade I and Clade IIb. 2024. [accessed 2 September 2024].

European Centre for Disease Prevention and Control (ECDC). Factsheet for health professionals on mpox. Aug 2024. [accessed 2 September 2024].

Reardon S. Mpox is spreading rapidly. Here are the questions researchers are racing to answer. Nature. 2024 Sep;633(8028):16-17.

UK Health Security Agency (UKHSA). Clade I mpox virus infection. Aug 2024. [accessed 2 September 2024].

UK Health Security Agency (UKHSA). Mpox: background information. Aug 2024. [accessed 2 September 2024].

UK Health Security Agency (UKHSA). Recommendations for the use of pre-and post-exposure vaccination during a monkeypox incident. Aug 2022. [accessed 2 September 2024].

World Health Organization (WHO). Mpox. Aug 2024. [accessed 2 September 2024].

Written by Dr Dirk Pilat

Topiramate is a sulfamate-substituted monosaccharide discovered in 1979 and first sold in 1996 as an anticonvulsant. In the United Kingdom it is licensed as monotherapy of generalised tonic-clonic seizures or focal seizures with or without secondary generalisation, adjunctive treatment of generalised tonic-clonic seizures or focal seizures with or without secondary generalisation, adjunctive treatment for seizures associated with Lennox-Gastaut syndrome and for migraine prophylaxis (British National Formulary, 2024). In other countries it is used off-label for alcohol use disorders and in combination with phentermine it is licensed as an aid to weight loss in the United States (Fariba & Saadabadi, 2024).  It is well absorbed from the gastrointestinal tract with peak plasma levels usually achieved in 2—3 hours. It interacts with other anticonvulsants and decreases the efficacy of hormonal contraceptives and doses should be reduced in patients with severely impaired renal function, as it is predominately cleared through the kidneys (Spritzer, 2016).

Written by Dr Toni Hazell

Public health authorities have noted a recent rise in both measles and pertussis cases. The first three months of 2024 saw 2,793 laboratory-confirmed cases of pertussis in England (compared to 858 in the whole of 2023), with so far five known deaths, all in infants¹. There have been fewer cases of measles (826 over the same time frame²), but again this is a significant increase when compared to the 212 cases seen in the last quarter of 2023².

Prior to the introduction of vaccination, both of these infections were endemic. There were 800,000 cases of measles per year in the UK³, with 120,000 cases of pertussis per year in England and Wales⁴. Infections and deaths fell when vaccination was introduced, but the success of vaccinations for both infections has been hindered by reduced uptake⁵, with pertussis also affected by immunity that wanes over time. This was illustrated by an increase in cases in 2011/12, despite sustained levels of vaccine coverage over 95%⁶.

Laboratory confirmed cases of pertussis in England in 2024, compared to previous years¹.

Image used under the Open Government v3.0 licence.

Laboratory confirmed cases of measles by month of onset of rash or symptoms reported⁷. 

Image used under the Open Government v3.0 licence.

GPs working at the moment will not have been in clinical practice when these infections were endemic, and so may need a reminder of how to spot them – clinical features are outlined below. Both infections present with a prodrome which is similar to a usual viral upper respiratory infection; diagnosis at this point is probably less likely than when specific features develop later on in the evolution of the illness.

Both illnesses have the potential for unpleasant complications. Patients who have had measles are more susceptible to opportunistic infection for around three years after their recovery, because the measles virus suppresses the immune response. Common complications include otitis media, diarrhoea and pneumonia. Rarer, but potentially more severe, are convulsions, encephalitis and subacute sclerosing panencephalitis. This last condition occurs on average seven years after the measles infection (but has been known up to 30 years later) – it presents with neurological symptoms and is always fatal³. Complications of pertussis include pneumonia, apnoea, seizures and encephalopathy. The strength of the cough can cause pneumothorax, abdominal hernia, rib fracture and subconjunctival haemorrhage. It is particularly risky in newborns – anyone aged under six months with suspected pertussis should be referred to paediatrics and is likely to be admitted⁴.

Key features of measles^3,8:

• Prodrome of upper respiratory tract symptoms and conjunctivitis, which starts 10-12 days after contracting the infection and lasts for 2-4 days, at which point a rash appears.
• Children generally feel unwell, with many references describing them as ‘miserable’.
• Fever, which peaks at around 39°C, coinciding with appearance of the rash.
• Rash with the following features:
  • Starts on the face and behind the ears, before spreading down the body and finally to the extremities.
  • Becomes confluent as it spreads.
  • Erythematous and maculopapular.
  • Lasts in total around one week, fading in any given area around five days after first appearance.
  • May be less prominent (or not appear at all) in those who are immunosuppressed. 
• Koplik spots on the buccal mucosa:
  • 2-3mm across. 
  • Red, with white centres.
  • Pathognomic for measles, but their absence does not exclude the condition.  

• Prodrome of upper respiratory tract symptoms which starts 4-21 days after exposure (usually 7-10 days) and lasts for 1-2 weeks.
• Paroxysmal cough with the following features:
  • Is worse at night and may be associated with a short expiratory burst followed by an inspiratory gasp (the ‘whoop’). 
  • Is violent and uncontrolled, due to attempts to bring up thick mucus. This is not always successful, so the cough may appear dry as mucus remains in the bronchial tree.
  • May be triggered by cold or noise.
  • Associated with post-cough vomiting, with a risk of cyanosis in children and syncope in adults.
• Cough gets worse for 1-2 weeks, stays at the same frequency for another 2-3 weeks and then gradually gets less often. Although pertussis is colloquially known as the ‘100 day cough’, the paroxysmal phase of the cough usually lasts for no longer than 10 weeks, more commonly for six weeks. There is then a convalescent phase lasting 2-3 weeks, in which the cough gradually improves. If another respiratory tract infection is contracted in the few months after pertussis, paroxysm of coughing may recur.
• There is usually no fever. 

Written by Dr Emma Nash

Cough is one of the most frequent reasons for presentation to primary care, particularly in children. Acute cough is most  commonly caused by upper respiratory tract infections; chronic cough (over four weeks) is typically attributed to recurrent respiratory tract infection, asthma or pertussis. However, a wet cough lasting more than four weeks should prompt consideration of protracted bacterial bronchitis, also known as persistent bacterial bronchitis (PBB). First described in a study in 2006, the condition is being increasingly recognised clinically. However, there is no clarity on the underlying mechanisms, making definitive diagnostic and therapeutic guidance elusive. Proposed pathophysiological contributory factors include impaired mucociliary clearance, systemic immune function defects (raised NK-cell levels, altered expression of neutrophil-related mediators), and airway anomalies (tracheobronchomalacia). It is also thought that bacteria may produce a biofilm in the airways. This is a secreted matrix that enhances bacterial attachment to cells and facilitates access to nutrients. It also decreases antibiotic penetration, thus protecting the bacteria and making them harder to eradicate with standard length courses of treatment. 

PBB is initially difficult to distinguish from a viral upper respiratory tract infection. The cough is productive, but the child is systemically well. Although wheeze is variably reported, the evidence is that there is a limited response to bronchodilator therapy, if any. Chest examination is typically normal, but if a wheeze is heard, it is monophonic rather than the polyphonic wheeze found in asthma. Sinus and ear disease is absent.

PBB is a clinical diagnosis. It may be suspected when the first two of the European Respiratory Society criteria are met, and confirmed when all three are met:

1. Presence of continuous chronic wet or productive cough (>four weeks’ duration).

2. Absence of symptoms or signs suggestive of other causes of wet or productive cough (see box 1).

3. Cough resolved following a two-to-four-week course of an appropriate oral antibiotic.

Box 1: Pointers suggestive of causes other than PBB. Symptoms: chest pain, history suggestive of inhaled foreign body, dyspnoea, exertional dyspnoea, haemoptysis, failure to thrive, feeding difficulties, cardiac or neurodevelopmental abnormalities, recurrent sinopulmonary infections, immunodeficiency, or epidemiological risk factors for exposure to tuberculosis. Signs: respiratory distress, digital clubbing, chest wall deformity or auscultatory crackles. Tests (if done): chest radiographic changes (other than perihilar changes/bronchial wall thickening) or lung function abnormalities.

The median age of development is 10 months – 4.8 years and it affects more males than females. PBB is no more common in children with an atopic history, but one study has shown that children who attend childcare are significantly more likely to develop PBB than those who do not. Children with an airway malacia are at increased risk of developing the condition as it is harder to clear mucus when the airways tend to collapse. If this is an underlying factor for a particular child, giving a bronchodilator may exacerbate the symptoms as the airways relax even further. PBB is frequently misdiagnosed, or inadequately treated, resulting in a persistence of symptoms and potential structural damage in the form of bronchiectasis.

Most children who have PBB are not able to expectorate sputum for culture due to their age, so treatment is based on  the sensitivity profiles of the typical pathogens. Haemophilus influenzae is the most common causative organism, followed by Streptococcus pneumoniae and Moraxella catarrhalis. However, sputum culture should be sent, if feasible.

Previously, antibiotic treatment courses have been longer, and there has been much debate over optimal drug choice  and  duration. More recent evidence has shown that two weeks may be adequate in many cases. A further two weeks should be prescribed if the child has improved significantly but is not completely cough free. A minority will need longer courses, but if this is the case, there should be a high index of suspicion for more severe disease such as chronic suppurative lung disease (e.g. cystic fibrosis) or bronchiectasis. Therefore, failure of the cough to respond to four weeks of antibiotics should prompt discussion with a paediatrician for consideration of next steps and whether investigation is needed for underlying causes. A reasonable pathway in primary care would therefore be that a GP suspects PBB because the first two criteria are met, treats with two weeks of antibiotics (and a further two if there is no improvement) and then seek specialist advice if the cough persists after four weeks of antibiotics. Chest x-ray is generally only needed if there is a specific reason, such as focal chest signs of concern. 

Unfortunately, no nationally accepted guidelines exist on treatment choice. The most commonly used antibiotic is oral co-amoxiclav but alternatives such as oral second or third generation cephalosporins, trimethoprim-sulfamethoxazole or a macrolide may be used when there is a history of an IgE-mediated reaction to penicillin. 

It is worth noting that recurrent episodes are common, occurring in up to 76% of cases. Antibiotic prophylaxis may be helpful in children who have more than three recurrences in twelve months. Common choices for prophylaxis are azithromycin three days a week, or co-trimoxazole daily, but this would be on specialist advice.    

References

American Thoracic Society. Protracted Bacterial Bronchitis (PBB) in Children. Am J Respir Crit Care Med. 2018; 198, P11-P12. View patient education sheet on Protracted Bacterial Bronchitis (PBB) in Children. [accessed 20 March 2024]

Bergmann M, Haasenritter J, Beidatsch D, et al. Coughing children in family practice and primary care: a systematic review of prevalence, aetiology and prognosis. BMC Pediatr. 2021 Jun 4;21(1):260. 

Di Filippo P, Scaparrotta A, Petrosino Mi et al. An underestimated cause of chronic cough: The Protracted Bacterial Bronchitis. Ann Thorac Med. 2018 Jan-Mar;13(1):7-13.  

Kansra S. Diagnosis and Management of Children with Protracted Bacterial Bronchitis PBB. Sheffield Children’s Hospital NHS Trust. 2017. Download guideline on Diagnosis and Management of Children with Protracted Bacterial Bronchitis PBB. [accessed 20 March 2024]

Kantar A, Chang A, Shields MD, et al. ERS statement on protracted bacterial bronchitis in children. European Respiratory Journal 2017 Aug; 50(2):1602139.  

Dr Dirk Pilat                                                                                                    

Rabies (from latin ‘to rage’) is a zoonotic, mostly fatal disease caused by a neurotropic virus of the lyssavirus genus.

The disease was first described in Egypt around 2300 BCE and is currently endemic in over 150 countries, with the highest risk of exposure in Africa and Asia. Dogs are the principal host in Africa, Asia and America, but the virus can be present in other wild animals, such as bats, cats, skunks or racoons. The most common way of transmission is the bite of an infected dog or cat, though handling of infected carcasses can cause infection too.

Figure 1. 3D still showing rabies virus by www.scientificanimations.com/is licenced under CC BY-SA 4.0 DEED

Worldwide, around 59,000 people die of rabies each year, mainly in Africa and Asia. In the UK there have been reportedly 26 fatalities since 1946, with the most recent in 2018. There is recent qualitative and quantitative evidence that the perceived risk of exposure to rabies for travellers is low, with vaccination often avoided due to cost implications.

Before the SARS-CoV-2 pandemic, circa 2000 people required post-exposure treatment in England per year, of which 12% were potentially exposed to the two bat species in the UK who harbour the virus. The disease remains prevalent in some countries in Eastern Europe.  

After an incubation time of typically three to 12 weeks, infection with the virus can cause a slow but progressive encephalitis with early symptoms being headache, fever, and malaise. The patient may then develop the characteristic symptoms of hydrophobia, hallucinations, and features of mania before progressing to paralysis and coma. Rabies is almost always fatal, and there is currently no specific treatment other than symptom control.

Pre-exposure prophylaxis via vaccination before travelling (or for those with occupational hazards) into endemic areas is a safe and effective method of protecting people from rabies, with the Green Book recommending an individual risk assessment of potential exposure prior to travelling.

Post-exposure management should consist of wound treatment (running tap water over the wound for several minutes, washing with soap or detergent and application of a dressing with disinfectants (such as 40 to 70% alcohol, tincture, or aqueous solution of povidone-iodine) and treatment with either an accelerated course of rabies vaccine or administration of human rabies immunoglobulin. The decision about which course of post-exposure treatment to administer depends on the categories of exposure, which animal was involved and in which country the incident occurred. Advice on who to contact in a suspected case of rabies can be obtained in this table from the Green Book.

Guidance Rabies: the green book, chapter 27, p11. Contains public sector information licensed under the Open Government Licence v3.0.

Tetanus is a disease caused by the neurotoxin produced by the bacterium Clostridium tetani. The spores of the bacterium are ubiquitous in soil throughout the world and enter contaminated wounds or minor abrasions. In low- and middle-income countries, both maternal (tetanus during pregnancy or within 6 weeks of the end of pregnancy via birth, miscarriage, or abortion) and neonatal tetanus (infection occurs via the umbilical stump) are likely significantly under-reported, but it is estimated that in 2015 about 35,000 deaths were due to neonatal tetanus and 57,000 adults were reported to have died. In high income countries, older people and people who inject drugs are the most likely to contract the disease. Migrants from countries with poor vaccination programmes can be particularly susceptible. Between 2001 and 2022, 147 cases of tetanus were reported to the UK Health Security Agency.

Figure 2.Opisthotonus in a patient suffering from tetanus - Painting by Sir Charles Bell - 1809. In public domain.

Under anaerobic conditions the spores germinate, and the newly formed bacteria produce a highly toxic neurotoxin that is transported retrogradely along the axonal pathways, reducing motor nerve inhibition. After an incubation time of up to 21 days, localised or general spasms (such as back arching, known as opisthotonos) can occur, with trismus and ‘risus sardonicus’ being early signs. This can be associated with dysphagia due to laryngeal and pharyngeal spasms. Testing is available via wound samples or serology but should not delay treatment. The UK Health Security Agency defines a probable case as “In the absence of a more likely diagnosis, an acute illness with muscle spasms or hypertonia, and diagnosis of tetanus by a health care provider”.

Treatment requires thorough cleaning and debridement of the wound, antibiotics and in severe cases mechanical ventilation under neuromuscular blocking agents.

Fortunately, a safe and efficient vaccine exists and has been in regular use since 1961. By the 1970s the disease had almost disappeared in children under 15. These days, it is part of the United Kingdom’s routine immunisation schedule.

Patients with tetanus prone wounds might, depending on their vaccination status, receive a reinforcing dose of tetanus vaccine and – if indicated – a dose of human tetanus immunoglobulin after their wound has been thoroughly cleaned. The Green Book categorises tetanus prone wounds as:

• puncture-type injuries acquired in a contaminated environment and likely therefore to contain tetanus spores e.g. gardening injuries and wounds containing foreign bodies
• compound fractures
• wounds or burns with systemic sepsis
• certain animal bites and scratches - although smaller bites from domestic pets are generally puncture injuries, animal saliva should not contain tetanus spores unless the animal has been routing in soil or lives in an agricultural setting.

High-risk tetanus wounds include any of the above with either:

• heavy contamination with material likely to contain tetanus spores e.g. soil, manure
• wounds or burns that show extensive devitalised tissue
• wounds or burns that require surgical intervention that is delayed for more than six hours are high risk even if the contamination was not initially heavy.

 

Guidance Tetanus: the green book, chapter 30, Table 30.1, p.10. Contains public sector information licensed under the Open Government Licence v3.0.
 

References

Marano, C et al. (2019). Perceptions of rabies risk: a survey of travellers and travel clinics from Canada, Germany, Sweden and the UK. Journal of Travel Medicine, Vol 26, Suppl 1, S3–S9, DOI: 10.1093/jtm/tay062

Singh,R et al.(2017). Rabies – epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review, Veterinary Quarterly, 37:1, 212-251, DOI: 10.1080/01652176.2017.1343516

United Kingdom Health Security Agency (2023). Guidance on the management of suspected tetanus cases and the assessment and management of tetanus-prone wounds. https://www.gov.uk/government/publications/tetanus-advice-for-health-professionals/guidance-on-the-management-of-suspected-tetanus-cases-and-the-assessment-and-management-of-tetanus-prone-wounds (Accessed 14.11.2023)

United Kingdom Health Security Agency (2023). Rabies: the green book, chapter 27. https://www.gov.uk/government/publications/rabies-the-green-book-chapter-27 (Accessed 13.11.2023)

United Kingdom Health Security Agency (2022). Tetanus: the green book, chapter 30. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1080599/Green_Book_on_immunisation_chapter_30_tetanus.pdf  (Accessed 14.11.2023)

Yen, LM; Thwaites, CL (2019). Tetanus. Lancet 2019; 393: 1657–68 http://dx.doi.org/10.1016/S0140-6736(18)33131-3

Written by Dr Dirk Pilat

The Hepatitis E virus (HEV) is the most common cause for acute viral hepatitis worldwide, a fact that is not widely known in the United Kingdom. It is a small RNA virus that has various genotypes, though the most important are HEV 1&2 – the most common types in low-income countries – and HEV 3, which occurs in Europe, the Americas and Australia.

HEV is responsible for about 20 million infections worldwide each year, of which 3 million will be symptomatic and 56,000 lethal. In the United Kingdom, the UK Health Security Agency (UKHSA) follows up confirmed Hepatitis E infections to investigate non-travel related cases of HEV in England and Wales while Public Health Scotland (PHS) monitors HEV infections within their territory.

HEV 1&2 are obligate human pathogens and usually transmitted faecal – orally by contaminated drinking water, while HEV 3 is usually transmitted via inadequately cooked pork, molluscs, or seafood. 90% of pigs in the UK have antibodies to HEV, and around 20% have been known to have an active infection at the time of slaughter. Within Europe the prevalence varies, though there are geographic hotspots with human seroprevalence of >50%. In 2019, UKHSA reported 1202 confirmed HEV infections, PHS reported 158 (>100 cases more than Hepatis A) though due to its often asymptomatic nature, it is reported to be significantly underdiagnosed.

The presentation of acute HEV infections depends on the location of the patient and the genome responsible: In resource poor countries it usually affects young people 15-35 years of age who experience  an acute, self-limiting hepatitis due to HEV1 (Asia) or 2 (Central America). Preterm women are particularly affected, with papers quoting mortality rates of up to 25% and preterm deliveries in 66%. 

This transmission electron micrograph depicts numerous, spheroid-shaped, hepatitis-E viruses (HEV), also known as Orthohepevirus A. Image used with permission from Centers for Disease Control and Prevention (CDC).

During the first 2 weeks of hepatitis E illness:

• avoid preparing food for others
• limit contact with others if possible, especially pregnant women, or people with chronic liver disease

Close contacts should:

• wash hands thoroughly with soap and warm water and then dry properly after contact with an infected person
• wash hands after going to the toilet, before preparing, serving and eating food

Immunosuppressed patients such as transplant recipients, HIV-positive patients or people receiving chemotherapy for haematological malignancies can develop chronic HEV infections and might get treated with ribavirin.

Pregnant women should contact their obstetric team for advice.

As there is currently no licensed vaccine for Hepatitis E in the United Kingdom, prevention is key. UKHSA suggests:

• cooking meat and meat products thoroughly
• avoid eating raw or undercooked meat and shellfish
• washing hands thoroughly before preparing, serving and eating food.

When travelling to countries with poor sanitation:

• boil all drinking water, including water for brushing teeth
• avoid eating raw or undercooked meat and shellfish.

In primary care, a good travel history can be key to diagnose a patient with an unexplained rise in liver function tests and prodromal symptoms.

References:

Aslan, TA; Balaban, HY (2020). Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World Journal of Gastroenterology. October 7; 26(37): 5543-5560

Horvatits, T; Schulze zur Wisch, J et al. (2019). The clinical perspective on Hepatitis E. Viruses 11, 617

Public Health Scotland: Ten-year gastrointestinal and zoonoses data tables (2023). https://publichealthscotland.scot/publications/ten-year-gastrointestinal-and-zoonoses-data-tables/ten-year-gastrointestinal-and-zoonoses-data-tables-march-2023/ (Accessed 15.08.2023)

UKHSA: Hepatitis E: symptoms, transmission, treatment and prevention (2020). https://www.gov.uk/government/publications/hepatitis-e-symptoms-transmission-prevention-treatment/hepatitis-e-symptoms-transmission-treatment-and-prevention (Accessed 15.08.2023)

Webb, GW; Dalton, HR (2019). Hepatitis E: an underestimated emerging threat. Therapeutic Advances in Infectious Disease Vol. 6: 1–18

Written by Dr Toni Hazell 

Menopause is defined as a biological stage in a woman’s life when menstruation stops permanently, due to the loss of ovarian follicular activity. It is a retrospective diagnosis, made 12 months after the last period, which often follows several years of perimenopause in which periods can be irregular and menopausal symptoms may be felt. The average age of the menopause in the UK is 51. An early menopause is one that happens before 45. Premature ovarian insufficiency (POI) is defined as the transient or permanent loss of ovarian function below the age of 40¹. Care for women with POI should be holistic – as well as the risks to physical health, POI can be very distressing, particularly for those women who do not feel that they have completed their family.

A woman with POI may have an absolutely reduced number of ovarian follicles, or there may be remaining follicles which are not functioning properly. 90% of POI is idiopathic, but the following causes of a reduction or poor function of the follicles may be found in up to 10% of women²:

• Chromosomal disorders (e.g. Fragile X and Turner syndrome)
• Autoimmune disease (e.g. thyroiditis and Addison’s)
• Iatrogenic (e.g. due to the use of chemotherapy or pelvic radiotherapy or surgical after oophorectomy)
• Metabolic disorders (e.g. galactosaemia)
• Toxins such as cigarette smoke and some chemicals and pesticides can speed up follicle depletion
• Infection (e.g. mumps, TB and malaria – this is rare).

POI should be suspected in women who are under than 40 who have at least four months of amenorrhoea, with an estimated FSH level of more than 30 IU/L on two blood samples taken 4 – 6 weeks apart^1,2,3. If the diagnosis is in doubt, then a referral should be done⁴. Referral might be to a specialist menopause clinic, to endocrinology or to gynaecology, depending on your specific concerns and what pathways you have available locally. A full history should be taken, including:

• a review of menopausal symptoms
• other possible causes (including pregnancy)
• lifestyle factors (smoking, alcohol, exercise, nutrition)
• the need for contraception (women with POI still have a small risk of ovulation)
• smear status
• family history of POI, venous thromboembolism or breast cancer
• the woman’s thoughts about HRT use
• any co-morbidities which might be relevant when considering HRT use
• osteoporosis risk – consider a baseline assessment of bone mineral density, with a repeat 2-3 years after diagnosis³.

Those who have worked in primary care for decades will be aware of the changing demand for hormone replacement therapy (HRT) over the years, with a significant decline in the early 2000s⁵, associated with concerns about cardiovascular risk and breast cancer, often based on studies looking at different populations from those who are prescribed HRT in the UK. This has been reversed in the last few years, with a 35% increase in HRT items prescribed from 2020/21 to 2021/22⁶. It is vital that healthcare professionals understand the key difference between prescribing HRT for women who go through their menopause at a normal age, and those with POI, as the risk/benefit analysis is completely different. For women with POI, HRT is merely replacing the hormones that an average woman would have had naturally and reducing the excess risk of osteoporosis that comes with POI. For the vast majority there appears to be no excess risk of breast cancer arising from the use of HRT up to the age of 50³. Both NICE⁴ and the British Menopause Society³ (BMS) are clear that this cohort of women should be offered HRT unless there is a clear absolute or relative contraindication, the main one being a history of a hormone sensitive cancer such as breast cancer. All the data that we have suggests that transdermal oestrogen does not increase the risk of venous thromboembolism (VTE) in women who have their menopause at a normal age^3,4 – the BMS acknowledges the limited data in women with POI but says that the transdermal route should be considered in women with POI who are at an increased risk of VTE, for example due to obesity. Transdermal oestrogen, when used with micronised progesterone, is also ‘unlikely to significantly increase VTE risk above the individual’s intrinsic risk’⁷ for those who have a personal or family history of VTE.

The decision as to whether to refer a woman with POI to a specialist menopause clinic will depend on several factors. These may include the level of suspicion of an underlying cause, the confidence of the GP to manage POI, the woman’s desire for ongoing fertility, a need for specialist psychological input and any individual risk factors for HRT. For women with a history of a hormone sensitive cancer, a referral to discuss the risks and benefits of HRT would be sensible, and this discussion might usefully include her oncologist.

Women who go through their menopause at a normal age are advised to use contraception for one year after their last period (if that happens over the age of 50), or two years if their last period is under the age of 50. Women with POI have a higher risk of spontaneous ovulation and conception and have around a 5 – 10% change of spontaneous natural conception³. Contraception is therefore advised if they do not want to become pregnant and some will prefer to use combined hormonal contraception (CHC) instead of HRT – either are suitable options for oestrogen replacement (assuming no contraindications to combined hormonal contraception), although HRT may be more beneficial for bone health and cardiovascular risk³. They should continue to have smear tests at the normal frequency for their age. If a woman has no need for contraception (e.g. post sterilisation) and has no other licensed indications (e.g. menstrual symptoms) and is using CHC because she prefers it to HRT, then this will be unlicensed.

A diagnosis of POI can have physical, social, and psychological impacts on a woman and her family so holistic care is important. Signposting to a charity such as The Daisy Network⁸ and to reliable sources of information such as the Women’s Health Concern⁹, Rock My Menopause¹⁰, the RCOG menopause hub¹¹, and articles on the website Patient¹² may help her to feel more in control. GPs who wish to learn more about menopause might want to start with the RCGP course on the subject, consisting of a half-hour eLearning module, a short screencast and a podcast¹³. Access Menopause eLearning course via the following link https://elearning.rcgp.org.uk/course/info.php?id=663

Declaration of interests – Dr. Hazell does both paid and unpaid work for the PCWHF, who host Rock My Menopause, and also works for the website Patient.

References (all viewed 26.5.23)

1)     NICE CKS. Menopause. Last updated September 2022. https://cks.nice.org.uk/topics/menopause/

2)     Daisy network. What is POI. https://www.daisynetwork.org/about-poi/what-is-poi/

3)     British Menopause Society. Premature Ovarian Insufficiency. April 2020. https://thebms.org.uk/publications/consensus-statements/premature-ovarian-insufficiency/

4)     NICE. NG23. Menopause: diagnosis and management. Last updated December 2019. https://www.nice.org.uk/guidance/ng23

5)     Cagnacci A, Venier M. The Controversial History of Hormone Replacement Therapy. Medicina (Kaunas). 2019 Sep 18;55(9):602

6)     NHSBSA Statistics and Data Science. Hormone replacement therapy – England. October 2022. https://www.nhsbsa.nhs.uk/statistical-collections/hormone-replacement-therapy-england/hormone-replacement-therapy-england-april-2015-june-2022

7)     Hamoda H, Panay N, Pedder H et al. The British Menopause Society & Women's Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reprod Health. 2020 Dec;26(4):181-209

8)     The Daisy Network. https://www.daisynetwork.org/

9)     Women’s Health Concern. https://www.womens-health-concern.org/

10)  Rock My Menopause. Premature ovarian insufficiency factsheet. https://rockmymenopause.com/portfolio-item/premature-ovarian-insufficiency

11)  RCOG. Menopause and later life. https://www.rcog.org.uk/for-the-public/menopause-and-later-life/

12)  Patient. What it’s like to go through early menopause. Last updated June 2019. https://patient.info/news-and-features/what-its-like-to-go-through-early-menopause

13)  RCGP eLearning. Menopause. September 2022.  https://elearning.rcgp.org.uk/course/view.php?id=663

14) Eunice Kennedy Shriver National Institute of Child Health and Human Development. What causes POI? https://www.nichd.nih.gov/health/topics/poi/conditioninfo/causes

You might have read recently in the daily and medical press that there has been an outbreak of diphtheria among asylum seekers in England. Even though refugees are often young, physically fit males, they can have complex health needs after their long journeys, such as untreated communicable diseases. Since June 2022 there has been an increase in diphtheria cases, and as of December 2022 62 cases of diphtheria had been confirmed, with half of the cases being cutaneous. Before mass vaccination, diphtheria was once one of the most feared childhood diseases in the UK, with more than 61,000 cases and 3,283 deaths in 1940.

Figure 1 Corynebacteriæ diphtheriæ 
Source: CDC
This image is in the public domain and thus free of any copyright restrictions. Use of this image does not constitute this blog’s endorsement or recommendation by the U.S. Government, Department of Health and Human Services, or Centers for Disease Control and Prevention.

Diphtheria is caused by the non-sporing, non-encapsulated, and non-motile Gram positive bacillus Corynebacteriæ diphtheriæ and Corynebacteriæ ulcerans. Respiratory diphtheria presents with a pharyngitis that often will be associated with a visible greyish membrane and enlarged anterior cervical lymph nodes with perinodal swelling, causing the classic bullneck appearance. Laryngeal diphtheria can be associated with progressive hoarseness and stridor, while nasal diphtheria can present with uni- or bilateral discharge and crustiness. As diphtheria has become increasingly rare in the United Kingdom, thanks to a successful immunisation campaign, it’s not always instantly recognisable for clinicians.

Figure 2 Bullneck appearance

Source: CDC
This image is in the public domain and thus free of any copyright restrictions. Use of this image does not constitute this blog’s endorsement or recommendation by the U.S. Government, Department of Health and Human Services, or Centers for Disease Control and Prevention.

The incubation period for diphtheria is usually 2 to 5 days but may be longer. The commonest mode of transmission of C. diphtheriæ is via droplet spread from a person with respiratory diphtheria; prolonged close contact is usually required for spread.

Cutaneous diphtheria usually starts as a vesicular rash and then forms one or more clearly demarcated ulcer that can be covered in a blueish-grey membrane. Patients may have both cutaneous and respiratory disease.

Figure 4 cutaneous diphtheria 
Source: CDC
This image is in the public domain and thus free of any copyright restrictions. Use of this image does not constitute this blog’s endorsement or recommendation by the U.S. Government, Department of Health and Human Services, or Centers for Disease Control and Prevention.

 

Figure 3 respiratory diphtheria by User: Dileepunnikri is licenced under CC BY-SA 3.0 via Wikimedia Commons.

 

Swabs should be collected from patients and sent to a local diagnostic laboratory with appropriate clinical details.

All suspected cases have to be notified to the UK Health Security Agency. Patients might be referred to the local specialist infectious disease team for face-to-face assessment and review. Treatment options include diphtheria anti-toxin intravenously and macrolide antibiotics.

 

References

Knights, F; Munir, S (2022). Initial health assessments for newly arrived migrants, refugees, and asylum seekers. BMJ 2022;377:e068821 https://doi.org/10.1136/bmj-2021-068821 

British Medical Association (2022). Unique health challenges for refugees and asylum seekers. https://www.bma.org.uk/advice-and-support/ethics/refugees-overseas-visitors-and-vulnerable-migrants/refugee-and-asylum-seeker-patient-health-toolkit/unique-health-challenges-for-refugees-and-asylum-seekers (Accessed 19.01.2023)

UK Health Security Agency (2022): Infectious diseases in asylum seekers: actions for health professionals. https://www.gov.uk/guidance/infectious-diseases-in-asylum-seekers-actions-for-health-professionals (Accessed 19.01.2023)

UK Health Security Agency (2022): Public health control and management of diphtheria in England. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1117027/diphtheria-guidelines-2022_v17_111122.pdf (Accessed 19.01.2023)

It is now over 40 years ago since a rare lung infection, Pneumocystis carinii was noticed in five young, previously healthy men who lived in Los Angeles¹. The article describing this cluster or cases was the first hint of a global epidemic of human immunodeficiency virus (HIV), which at the time led inexorably to acquired immune deficiency syndrome (AIDS) and almost certain death.

Fast forward to 2022 and HIV has become a treatable chronic disease – those who are adherent to antiretroviral therapy (ART) with an undetectable viral load can expect a normal or near-normal life span² and no longer have to worry about passing the virus to a sexual partner, as this is impossible for those on effective treatment³.

The most important factor in reducing morbidity and mortality is early diagnosis and early initiation of ART. Progress of the virus is measured by monitoring the viral load and CD4 count (a type of T lymphocytes). If HIV is diagnosed late (when the CD4 count has dropped below 350 cells/mm³), there is a ten-fold increase in risk of the patient dying in the year after diagnosis^4,5 and if this doesn’t happen, they still have a likely ten-year reduction in life expectancy². It is estimated that 6,600 people in England have undiagnosed HIV, making up approximately 6% of the total population of people with HIV in England⁶. This group will have a poor prognosis if they remain undiagnosed, and risk unknowingly passing the virus to their sexual partners.

NICE guidance advises that we offer and recommend HIV testing based on local prevalence, which can be seen on this map of diagnosed HIV prevalence per 1,000 population aged 15 – 59 years in England in 2015. There are hotspots of high prevalence (2-5 cases per 1,000) and extremely high prevalence (>5 cases per 1,000) in various cities including London, Brighton and Manchester – healthcare professionals in these areas should be aware of the recommendation to offer routine HIV tests as laid out in the table below⁷, which also covers the clinical situations in which any healthcare professional should offer a test, regardless of local prevalence.

 

Map from HIV in the UK 2016 Report, Public Health England⁸

Image used under the Open Government Licence v3.0

Prevalence level	When to offer a test
High	On admission to hospital or attendance at an emergency department if blood tests are being done for another reason. On registration with a new GP. If blood tests are being done in primary care for another reason and the person has not had an HIV test in the last year.
Extremely high	As per advice for high prevalence areas. Should also be considered opportunistically in every consultation at a GP surgery based on clinical judgment and on every admission to hospital or visit to an emergency department.
Any prevalence	Has symptoms for which HIV is part of the differential diagnosis. From a country with a high rate of HIV infection or has sexual contact with someone from such a country, or someone who is in a high-risk group for HIV for another reason e.g., female partners of men who have sex with men. Is a man or trans woman who has sex with men and has not been tested in the last year. Discloses chemsex (the use of drugs as part of sexual activity) or use of injected drugs. Is diagnosed with, or requests a test for, a sexually transmitted infection. Is attending a first appointment for termination of pregnancy or treatment of lymphoma, tuberculosis or hepatitis B or C.

In primary care we should be aware that HIV may present at seroconversion, or later as the CD4 count drops and symptoms of immunodeficiency start to emerge.

Seroconversion occurs between 10 days and six weeks after infection with HIV and may be very mild. It is difficult to diagnose as clinical features can be non-specific, including a fever, sore throat, malaise and arthralgia. A maculopapular rash, particularly in combination with a fever, should alert us to the possibility of seroconversion². Traditionally we have considered there to be a 12 week ‘window period’ for HIV testing – the time in which a person may have contracted HIV, but still have a negative test as they have not yet made enough antibodies for the test to be positive. Many labs now use combined antibody/antigen tests which shorten the window period, but unless you are familiar with the tests used locally, it is safest to advise that anyone who may be in the early stages of HIV repeats their test at least 12 weeks after any encounter where they think they may have caught the virus.

Later symptoms are listed in the British HIV Association list of ‘clinical indicator diseases’, which are defined by the fact that patients with these conditions have at least a 1 in 1000 likelihood of having undiagnosed HIV⁹. They include diagnoses and incidental findings which are commonly seen in general practice, such as unexplained fever, lymphadenopathy, chronic diarrhoea or weight loss, unexplained low white cell count or platelet count and any cervical dysplasia or community acquired pneumonia. We should also consider testing for various skin conditions, including seborrhoeic dermatitis, shingles and severe psoriasis, and for those with lung cancer or lymphoma.

It is not all that often that we can point to a specific consultation in primary care and say “I saved a life today”. Picking up a case of HIV and getting a patient on to antiretrovirals is a truly life-saving measure, for which an increase in testing is vital. 

 

References (all accessed 9.10.22)

1. HIV.gov. A timeline of HIV and AIDS. https://www.hiv.gov/hiv-basics/overview/history/hiv-and-aids-timeline#year-1981

2. NICE CKS. HIV infection and AIDS. 2021. https://cks.nice.org.uk/topics/hiv-infection-aids/

3. National Institute of Allergy and Infectious Diseases. HIV Undetectable=untransmissible, or Treatment as Prevention. 2019. https://www.niaid.nih.gov/diseases-conditions/treatment-prevention

4. The Lancet HIV. Time to tackle late diagnosis. Lancet HIV. 2022 Mar;9(3): e139

5. UK Health Security Agency. Leaving it late: why are people still dying from HIV in the UK? 2014.

6. Public Health England. Trends in HIV testing, new diagnoses and people receiving HIV-related care in the United Kingdom: data to the end of December 2019. 2020. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/959330/hpr2020_hiv19.pdf

7. NICE NG60. HIV testing: increasing update among people who may have undiagnosed HIV. 2016. https://www.nice.org.uk/guidance/ng60/chapter/Recommendations#offering-and-recommending-hiv-testing-in-different-settings

8. Public Health England. HIV in the UK 2016 Report. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/602942/HIV_in_the_UK_report.pdf

9. British HIV Association. British HIV Association/British Association for Sexual Health and HIV/British Infection Association Adult HIV Testing Guidelines 2020. 2020. Appendix 1. https://www.bhiva.org/file/5f68c0dd7aefb/HIV-testing-guidelines-2020.pdf

Introduction

Constipation is a common, frequently encountered gastrointestinal disorder affecting approximately one third of adults 60 years and older, with over half of nursing home residents affected. Constipation can have significant consequences: in susceptible and frail older people, excessive straining can trigger a syncopal episode and coronary or cerebral ischaemia. In severe cases, constipation can lead to anorexia, nausea and pain and ultimately can cause a stercoral ulcer, leading to perforation and death. Stercoral ulcers are due to hard, impacted faeces causing pressure necrosis of the distal colon, leading to ulceration and subsequent perforation of the intestinal wall.

Constipation often causes a reduction in the quality of life, with general health, vitality, social functioning and mental health all affected. Risk factors for constipation include female sex, older age, inactivity, low calorie intake, a low-fibre diet, polypharmacy, and low income. The incidence of constipation is three times higher in women, and women are twice as likely as men to see their primary care team for constipation.

Symptoms

Patients usually complain of ‘straining’ when opening their bowels, difficulty passing stools, incomplete evacuation or both. This is often associated with hard stools, abdominal bloating pain and distention. The stool frequency may be normal.

Primary constipation

Primary constipation includes the subtypes of normal transit, slow transit and disorders of defaecation, all of unknown causes. Histology of the colon of older adults shows more tightly packed collagen fibres and a reduced number of myenteric neurons, but these changes are not considered to be major contributors to the development of constipation.

Secondary constipation

Secondary causes of constipation include medication use, chronic disease processes and psychosocial issues. Opioids, calcium channel blockers, oral iron supplements, antacids and anticholinergics are common causes for medication-induced constipation, while hypothyroidism, hypercalcaemia, Parkinson’s disease and colorectal carcinoma can all cause secondary constipation.

Assessment

Patients should always be assessed for red flags that might indicate an underlying malignancy, such as:

·       persistent unexplained change in bowel habits

·       palpable mass in the lower right abdomen or the pelvis

·       persistent rectal bleeding without anal symptoms

·       narrowing of stool calibre

·       family history of colon cancer, or inflammatory bowel disease

·       unexplained weight loss, iron deficiency anaemia, fever, or nocturnal symptoms

·       severe, persistent constipation that is unresponsive to treatment.

NICE guidance NG12 gives primary care practitioners a clear framework when to refer a patient with suspected colorectal cancer on a two week wait (2ww) suspected cancer pathway referral.

When evaluating an older individual with constipation, taking a thorough drug and medical history and performing a physical examination are important. Abdominal examination might reveal abnormal bowel sounds, significant weight loss, cachexia, masses and/or sigmoid or colonic loading. When planning a rectal examination, the patient should be informed about its diagnostic importance and the fact that it might be uncomfortable. A chaperone should always be offered and consent documented. Examination of the anus might reveal abnormalities such as proctitis, haemorrhoids, prolapse, fissures or rectal cancer, while further up in the ampulla a rectal-digital examination can detect faecal impaction, masses, and gives the examiner the chance to evaluate anal tone.

Management

Non-pharmacological treatment is often the first step to help patients in the management of their complaint with adaptation of the patients’ medication a start to reduce symptoms.

Endocrinological/psychological/neurological causes of secondary constipation will need investigation and appropriate management. It might be worth discussing with the patient that there is no physiological necessity to have a daily bowel motion: a discussion around simple lifestyle changes might improve their perception of bowel regularity and a diary reporting on stool pattern and consistency may be helpful as well. The optimal time to have a bowel movement is often after waking and/or after meals, when the colon’s motor activity is particularly pronounced. A gradual increase in the intake of fluids and fibre should be suggested, but we should be careful in patients with cardiorenal issues not to cause overloading. A prospective study from Japan found that placing the patient’s feet on a small foot stool in front of the toilet, in conjunction with the upper body bent forward, improved anal pressure and reduced time of evacuation. Patients in care homes should be given adequate time and privacy for their bowel movements and should avoid bed pans.

Most patients will, at one stage, require a laxative to alleviate their symptoms when lifestyle interventions are ineffective: in patients with short-duration constipation a bulk forming laxative such as ispaghula husk should be initiated. If these are not helpful, an osmotic laxative such as macrogol should be next.

In chronic constipation, a bulk forming laxative should be initiated, with adequate hydration ensured (low fluid intake with bulk forming laxatives can cause impaction). If defaecation continues to be unsatisfactory, an osmotic laxative should be the next choice, with the addition of a stimulant laxative such as bisacodyl if the patient doesn’t improve. Once regular bowel movements occur, the laxatives can be slowly withdrawn.

If there is no response to the maximum tolerated dose of second line laxatives, refer to the local GI or older people’s outpatient team, or ask for guidance via the local advice and guidance process.

If the patient presents with faecal impaction, the appropriate escalating dose of a macrogol should be considered. In those with soft stools, or with hard stools after a few days’ treatment with a macrogol, an oral stimulant laxative should be started or added to the previous treatment. If the response continues to be underwhelming, rectal administration of bisacodyl (for soft stools) or glycerol (for hard stools) can be considered.

If there is still no response, a sodium acid phosphate with sodium phosphate enema may have to be considered. For hard stools, an overnight arachis oil enema, followed by a sodium acid phosphate with sodium phosphate enema the next morning might prove effective.

In patients with opioid-induced constipation, an osmotic laxative (or docusate sodium to soften the stools) and a stimulant laxative is recommended. Bulk-forming laxatives should be avoided.

If the patient’s presentation is getting worse or there is no response, then consult with one of your colleagues from gastroenterology. Further input from these teams might be needed for additional pharmacotherapy, endoscopy, anorectal manometry or other secondary/tertiary care investigations.

References:

Arco, S; Saldaña, E et al (2021). Functional Constipation in Older Adults: Prevalence, Clinical Symptoms and Subtypes, Association with Frailty, and Impact on Quality of Life. Gerontology DOI: 10.1159/000517212

British National Formulary: Constipation https://bnf.nice.org.uk/treatment-summaries/constipation/ accessed 14/7/2022

Gandell, D; Straus, SE et al (2013). Treatment of constipation in older people. Canadian Medical Association Journal, May 14, 185(8) DOI:10.1503/cmaj.120819

De Giorgio, R; Ruggeri, E et al (2015). Chronic constipation in the elderly: a primer for the gastroenterologist. BMC Gastroenterology 15:130 DOI 10.1186/s12876-015-0366-3

Gough, AE; Donovan, MN et al (2016). Perforated Stercoral Ulcer: A 10-year experience. Journal of the American Geriatrics Society.  Vol 64, No 4

Heidelbaugh, J; Martinez de Andino, N et al (2021). Diagnosing Constipation Spectrum Disorders in a Primary Care Setting. Journal of Clinical Medicine. (10) 1092. https://doi.org/10.3390/jcm10051092

Hull and East Riding Prescribing Committee (2019). Management of Constipation in Adults. https://www.hey.nhs.uk/wp/wp-content/uploads/2019/08/GUIDELINE-Constipation-guidelines-updated-may-19.pdf accessed 14/7/2022

Jamshed, N; Lee, Z; Olden, KW (2011). Diagnostic Approach to Chronic Constipation in Adults. American Family Physician. 84(3):299-306

Mounsey, A; Raleigh, M et al (2015). Management of Constipation in Older Adults. American Family Physician Volume 92, Number 6

National Institute for Health and Care Excellence (2021).  NG12 Suspected cancer: recognition and referral. https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer#lower-gastrointestinal-tract-cancers accessed 14/7/2022

Rome Foundation (2016) Appendix A: Rome IV Diagnostic Criteria for FGIDs. https://theromefoundation.org/rome-iv/rome-iv-criteria/ accessed 14/7/2022

Schuster, BG; Kosar, L et al (2015). Constipation in older adults; Stepwise approach to keep things moving. Canadian Family Physician 61: February

Takano, S; Nakashma, M et al (2018). Influence of foot stool on defecation: a prospective study. Pelviperineology 2018; 37: 101-103

Villanueva Herrero JA, Abdussalam, A et al (2022). Rectal Exam. In StatPearls. StatPearls Publishing. https://pubmed.ncbi.nlm.nih.gov/30726041/