Keywords
homeopathy - pregnancy - nausea and vomiting - morning sickness - COVID-19 - individualised
homeopathy - tele-consultation
Introduction
Nausea and vomiting are among the most common disorders experienced during pregnancy.[1] Clinicians are urged to treat the nausea and vomiting of pregnancy (NVP) as early
as possible to prevent their progression to hyperemesis gravidarum.[2] The global population has faced multi-dimensional medical emergencies due to the
coronavirus disease 2019 (COVID-19) pandemic. Clinical experience with pregnancies
has shown complications after infection by other corona-viruses: e.g., severe acute
respiratory syndrome and Middle Eastern respiratory syndrome. The recent study by
Wastnedge et al also describes the physiological adaptations to pregnancy, such as
alterations of immunological response, respiratory response, coagulation response
and endothelial cell function, and their implications for COVID-19.[3] As pregnant women pose a greater vulnerability to complications, the International
Federation of Gynaecology and Obstetrics (FIGO)[4] has recommended replacing routine antenatal care with tele-consultation whenever
possible during the pandemic. The lack of availability of population-specific observational
studies of conventional medicinal intervention and scarcity of evidence on possible
outcomes of maternal and foetal health add to the burden of treatment of pregnant
women infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Besides the direct impacts of the disease, many indirect consequences of the pandemic
adversely affect maternal health, such as increased mental health strain and socioeconomic
deprivation,[3] among others. In the treatment of diseases, especially where other treatment options
are limited, individualised homeopathy could play a major complementary medicine role.[5]
[6]
[7]
[8]
Described below is a case of a woman in her mid-thirties treated with individualised
homeopathy for NVP in her first trimester, and for COVID-19 symptoms in her third
trimester three and a half weeks prior to her scheduled delivery via Caesarean section.
She gave her informed consent for anonymised data of her case to be used for academic
purposes including publication.
The Patient
A businesswoman in her mid-thirties presented herself with exhausting nausea and vomiting
without apparent underlying pathologies, as confirmed by her gynaecologist and general
practitioner (GP). She was told that a period of time such as this was normal and
transient in pregnancy. The patient had flushes of heat, lack of vital energy, painful
breasts, tiredness, and a feeling of being worn out that affected her performance
at work. She thought it was ‘sado-masochistic and unfair’ to cope with her symptoms
while working, and that the world looks down on pregnant women as if it ‘serves them
right’ to suffer. She could not eat well, and snacks helped only a little. Her body
was in spasms and vomiting ameliorated these complaints for just a short period. She
had profuse perspiration at night and had to get up three times to change clothes,
leading to insufficient sleep. She had stupefying headaches, an exaggerated sense
of smell and was devoid of energy. She tried all the non-specific therapeutic measures
that were advised for her discomforts: resting, and taking vitamins, iron tablets
and ginger, and her GP administered an intravenous infusion of saline. This did not
keep her comfortable, and therefore she decided to try homeopathic treatment for the
NVP and associated symptoms.
Towards the end of her pregnancy, shortly before her scheduled (and preferred) Caesarean
section, she developed nose obstruction and discharge, anosmia, headaches, and felt
weak. The Rapid Antigen Test was positive for SARS-CoV-2. That fact made her anxious
that she could transmit the virus to her parents. The non-specific over-the-counter
drugs she obtained in the pharmacy were not helpful enough and she finally again opted
for individualised homeopathy. In her previous medical history, she had epistaxis
and occasional systolic hypertension (up to 180 mm Hg) during her student days, for
which she did not seek medication. She had random pain in her ears and right-sided
neck pain before pregnancy, and had multiple birthmarks on her skin. She could not
recall the last time she had high fever. An enquiry into family medical history revealed
that her grandmother had multiple sclerosis and her sibling suffered from depression.
The patient lived with her partner who travelled frequently, but that did not bother
her: she liked giving time to herself.
Clinical Findings
The first homeopathic consultation for NVP was conducted via tele-consultation during
lockdown, due to the pandemic protocols exerted by FIGO, by a certified private-practice
homeopathic medical practitioner who at the same time was working part-time as a licensed
general physician in a public health centre's COVID-19 dispensary in Slovenia. The
patient had severe nausea, vomiting, and weakness. She was manifestly sleep-deprived
from the lack of quality sleep in the last month. A physical examination—without any
abnormal findings—was conducted independently in the local health centre by the patient's
GP, who also suggested homeopathy, and by her gynaecologist in a private health institute
in Slovenia. Her blood tests did not show anaemia at the beginning of pregnancy. Other
differential diagnoses, such as hyperemesis gravidarum, infections and thyroid disorders,
were excluded. The totality of symptoms was taken as the homeopathic prescription
strategy. The repertorisation chart, using the VithoulkasCompass repertorisation program
version 6.0, which provided the first prescription for the early pregnancy symptoms,
is shown in [Table 1]. Depending on how intensely it was expressed by the patient, each relevant finding
for homeopathy was graded from the first to the fourth degree. For example, a symptom
in the first degree, such as vomiting, was mild and rare, corresponding to 1 to 3
out of 10 points by the visual analogue scale (VAS). A symptom that was inserted in
the repertorisation program in the fourth degree, e.g., nausea, was very strong and
very frequent, corresponding to 8 to 10 out of 10 points by the VAS.
Table 1
The VithoulkasCompass repertorisation chart with symptoms of NVP and the list of the
highest-ranking homeopathic medicines
|
Symptom
|
Degree
|
Homeopathic medicine
|
|
|
|
Sep.
|
Nux-v.
|
Puls.
|
Phos.
|
Lach.
|
Ars.
|
Sil.
|
|
1.
|
STOMACH – VOMITING – pregnancy, during
|
1
|
3
|
3
|
2
|
2
|
2
|
2
|
2
|
|
2.
|
STOMACH – NAUSEA – pregnancy, during
|
4
|
3
|
3
|
2
|
2
|
2
|
2
|
2
|
|
3.
|
STOMACH – NAUSEA – eating – after – amel.
|
2
|
3
|
1
|
|
1
|
|
|
|
|
4.
|
GENERALITIES – VOMITING – amel.
|
2
|
|
1
|
1
|
|
|
1
|
|
|
5.
|
GENERALITIES – HEAT – flushes of – perspiration – with
|
3
|
3
|
|
|
|
2
|
|
|
|
6.
|
GENERALITIES – WEAKNESS
|
3
|
3
|
2
|
2
|
3
|
3
|
3
|
3
|
|
7.
|
EXTREMITIES – STIFFNESS
|
2
|
3
|
2
|
2
|
2
|
2
|
3
|
3
|
|
8.
|
VERTIGO – LOOKING – upwards
|
1
|
1
|
2
|
3
|
3
|
2
|
|
2
|
|
9.
|
GENERALITIES – MORNING
|
2
|
3
|
3
|
3
|
3
|
3
|
2
|
2
|
|
10.
|
SLEEP – UNREFRESHING
|
3
|
2
|
2
|
2
|
3
|
3
|
2
|
2
|
|
11.
|
PERSPIRATION – SLEEP – waking, after – amel.
|
2
|
2
|
3
|
3
|
3
|
|
2
|
1
|
|
12.
|
NOSE – SMELL – acute
|
3
|
3
|
3
|
1
|
3
|
1
|
2
|
1
|
|
13.
|
MIND – REPROACHES – others
|
1
|
1
|
2
|
|
|
3
|
3
|
|
|
14.
|
HEAD – PAIN (headache) – Stunning, stupefying
|
2
|
1
|
3
|
2
|
2
|
2
|
2
|
3
|
|
15.
|
HEAD – PAIN (headache) – Temples
|
3
|
2
|
2
|
3
|
1
|
2
|
1
|
1
|
|
16.
|
HEAD – PAIN (headache) – Occiput – extending – head, to
|
1
|
|
|
2
|
|
|
|
2
|
|
Total points / Sum of rubrics
|
33 / 14
|
32 / 14
|
28 / 13
|
28 / 12
|
27 / 12
|
25 / 12
|
24 / 12
|
Three and a half weeks before the planned Caesarean section, the patient fell ill
with new acute symptoms. They were mild in the beginning and no physical examination
was conducted. After testing positive for SARS-CoV-2 with the Rapid Antigen Test for
COVID-19 (ICD: U07.2), the patient refused to have the Polymerase Chain Reaction test
that soon became the gold standard for confirming the diagnosis. The acute disease
was immediately attended homeopathically via tele-consultation and the symptom totality
repertorised as presented in [Table 2]. She had headache, nose obstruction with discharge, and complaints of diminished
smell and interrupted sleep. No ongoing specific treatment strategies were discontinued
for either NVP or COVID-19.
Table 2
The repertorisation chart of the Radar Repertory 10.5.003 for the COVID-19 symptoms
|
Symptom
|
Degree
|
Homeopathic medicine
|
|
|
Sep.
|
Merc.
|
Nux-v.
|
Nat-m.
|
Lyc.
|
Nit-ac.
|
Sil.
|
|
Head—pain—forehead
|
1
|
2
|
3
|
3
|
3
|
2
|
2
|
3
|
|
Head—pain—pressing—outwards
|
2
|
2
|
2
|
2
|
3
|
1
|
0
|
2
|
|
Nose—obstruction—left
|
3
|
1
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Nose—sneezing
|
1
|
2
|
3
|
3
|
2
|
2
|
2
|
2
|
|
Nose—smell—diminished
|
3
|
3
|
2
|
2
|
3
|
2
|
1
|
3
|
|
Stomach—nausea—eating ameliorates
|
2
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Stomach—appetite—diminished
|
1
|
1
|
1
|
1
|
1
|
2
|
0
|
1
|
|
Stomach—heartburn—eating—after—agg.
|
3
|
1
|
1
|
2
|
2
|
1
|
2
|
1
|
|
Sleep—waking—4 am after
|
1
|
1
|
1
|
2
|
1
|
2
|
1
|
1
|
|
Stomach—nausea—night
|
1
|
2
|
2
|
3
|
1
|
1
|
1
|
1
|
|
Extremities—heat—hands
|
3
|
3
|
1
|
2
|
1
|
3
|
3
|
1
|
|
Mind—anxiety—health—about relatives
|
1
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
Therapeutic Interventions
Therapeutic Interventions
The simillimum Sepia officinalis
[9] in LM potencies was prescribed for the symptom totality in the case of NVP in the
first trimester. The homeopathic medicines were produced by the pharmacies Remedia
(Eisenstadt, Austria) and Homeocur (Retz, Austria) according to the Homeopathic Pharmacopoeia
(Instruction 17) and the European Pharmacopoeia (Instruction 5.2). For Sepia officinalis in an LM potency, a specific sequence of trituration, dilution and succussion is
needed to obtain a solution in a ratio of 1:50000. That is the first potency level
of this scale, i.e., LM1. For the preparation of LM2, one globule of the LM1 is diluted
in a drop of water. Then the solution is mixed with 100 drops of 86% alcohol and vigorously
shaken 100 times. Next, globules are medicated with the solution in a ratio of 1:500
and dried.[10] The process was first explained in Paragraph 270 of the 6th edition of Hahnemann's Organon of Medicine. The patient was advised to dissolve the
homeopathic medicine in the LM potency in 14 teaspoons of 30% alcohol; the solution
was shaken ten times every day. One spoonful was additionally diluted daily in a glass
of water, stirred, and a sip taken just before bedtime.
Follow-up and Outcomes
An outline of main reports, comments and the sequence of prescriptions for the individualised
homeopathic treatment of NVP, COVID-19 symptoms, and the symptoms after delivery,
are included in the Timeline in [Table 3]. The patient soon felt better after taking the homeopathic medicine for the NVP
and associated symptoms. After reducing its intake, the symptoms reappeared so she
continued taking it. Later in her pregnancy, after developing new symptoms and testing
positive for the SARS-CoV-2 virus, she continued with the individualised homeopathic
treatment and again experienced rapid improvement of symptoms.
Table 3
Timeline
|
Date
|
Main report/symptoms
|
Comments
|
Prescription
|
|
First consultation. May 2020
|
Nausea for 1 month, vomiting, weakness, prostration, headache in temples, occipital
pain radiating to head, profuse perspiration during sleep, unrefreshing sleep, vertigo
when looking up; cold hands during the night unless wearing long sleeves. Water seems
too sweet. Desire for squid. Generally worse in the mornings. Yearns for recreation,
but cannot even walk; motion aggravates her. Sensitive to odours. Planning a Caesarean
section for delivery ‘to avoid suffering’.
|
Strategy for repertorisation and prescribing: totality of symptoms repertorised with
VithoulkasCompass Repertory 6.0. The patient's level of health (Vithoulkas): 2–3,
group A.[15]
|
Sepia officinalis, 14 doses of LM2 and later LM3. The patient described herself, by text message, as
feeling “a million times better after taking the medicine for 10 days”. Therefore
reducing the frequency of intake was advised, but symptoms returned, so she continued
taking the medicine.
|
|
Follow-ups (FUs)
FU1: at 5 weeks
FU2: at 7.5 weeks
FU3: at 11.5 weeks
|
Improvement of symptoms: slept longer hours; cessation of flushes of perspiration;
nausea only on empty stomach—reported during FU1 over the phone. Old complaints of
neck pain have returned; appearance of sleepiness. Physically active. Slight swelling
in ankles, better by morning. Loss of hair; bleeding gums, appearance of metallic
taste. Eruption on face (Hering's law). Walking, cycling and attending fitness regularly
again. Blood pressure: 126/66 (the first measurement during the treatment was 98/54);
no vertigo. Desire for soda water.
|
No initial aggravation—as usual with LM potencies. New minor transient symptoms: loss
of hair; bleeding gums, appearance of metallic taste. An old symptom has reappeared:
old complaints of neck pain. Reaction to the medicine—Observation No. 4 (Vithoulkas)
after centesimal potencies:[15] there is local and general amelioration, but new symptoms belonging to the given
remedy have appeared in the patient; no evident initial aggravation.
|
The single homeopathic medicine Sepia officinalis in LM5 potency was prescribed for 21 days. After gradual general improvement, a placebo
of one globule per day was prescribed, and Sepia officinalis in LM6 potency was taken from time to time in between.
|
|
FU4 for acute state. November 2020
|
The rapid antigen test is positive for COVID-19. Headache pressing outward above eyebrows;
left-sided nose obstruction and clear discharge, loss of smell; nausea if a meal is
delayed; anxiety after testing positive for COVID-19; fears parents could die; longs
for physical activity even in this acute state; desire for chocolate; heat in hands.
No more swelling in ankles.
|
Repertorisation of new acute symptoms with Radar Repertory has led to the same unipotent
homeopathic medicine. Differential diagnoses: sinusitis (ICD: J01.1) and COVID-19
(ICD: UO7.2).
|
Sepia officinalis LM6 continued every day.
|
|
FU5: at 1 week; FU 6: at 2.5 weeks
|
Nose obstruction is better. Generally much better 5 days later; smell returned 90%;
improvement of all symptoms.
Appearance of sciatica, ameliorated by pressure. Looking forward to not having a natural
delivery. Complains that fitness centres for exercise in pregnancy are closed down
due to lockdown.
|
No initial aggravation—as usual with LM potencies. The new leg pain might have arisen
due to late anatomical changes in pregnancy or the evolution of events due to Hering's
law. The approximate reaction to the medicine—Observation No. 3 (Vithoulkas) after
centesimal potencies: the patient is much better in almost every aspect, but still
has some problems,[15] though without the appearance of an evident initial aggravation.
|
Sepia officinalis LM6 was continued. Due to sciatica, one sip was taken from the third glass (90% of
the spoonful of medicine diluted in the first glass of water was poured away, refilled
and the process repeated once more) every 20 minutes, three times, in order to relieve
the pain on the first day, followed by placebo.
|
|
FU7: at 4.5 weeks
|
No immediate amelioration of the sciatica. She feels that physiotherapy helped to
relieve 90% of the pain.
Successful planned delivery of a healthy baby by Caesarean section at 3.5 weeks. Started
breastfeeding; post-partum problems with profuse perspiration and hot flushes during
the night; started adding infant milk formula.
|
No sciatica after delivery.
|
Sepia officinalis LM8—14 doses.
|
|
FU8: at 6.5 weeks
|
11 days after the prescription, no waking from flushes of perspiration any more; scanty
leucorrhoea; happy with her weight. Says she will not be able to stay off work for
long. Tearful three times for no reason. Has stopped breastfeeding.
|
Improvement of the burdensome symptoms after delivery. Appearance of a proving symptom[15]—weeping without knowing why.
|
Continued with Sepia officinalis LM9 and later LM10 daily; asked to decrease the frequency as symptoms have faded.
|
The symptoms of COVID-19 gradually diminished, but sciatic nerve inflammation appeared.
The pain was evaluated with a severity of 8 out of 10 points according to the VAS.
The symptoms were again repertorised and the same medicine seemed appropriate. Sepia officinalis LM6 had not yet been taken 14 times, so the next dose was prescribed to be taken
from the third glass in a higher dilution, after being stirred, providing higher potentisation
as described in [Table 3] in the Timeline. The patient found that the intervention did not ameliorate sciatic
pain and she opted instead for physiotherapy. Additionally, the patient developed
profuse perspiration at night after the Caesarean section. The repertorised symptoms
again pointed to Sepia officinalis, which was prescribed in a higher, LM8, potency and the patient was advised gradually
to decrease the medicinal intake with the subsiding of symptoms, as described in the
Timeline.
An evaluation of changes in health status followed each prescribed medicine. Monitoring
these changes in the symptomatology after the prescribed medicine from follow-up to
follow-up enabled assessing the past and necessary further management of the case.
The patient did not report experiencing any adverse effects during the course of treatment
and follow-ups.
The modified CARE guidelines for homeopathic medical intervention (HOM-CASE) suggest
including a scientific rationale with a numerical evaluation to assess the causality
of improvement in case reports treated with homeopathy.[11] Completion of the MOdified NARanjo Criteria for Homeopathy (MONARCH) inventory was
performed by two independent reviewers, reflecting the homeopathic treatment of both
complaints (namely NVP and COVID-19) during pregnancy, and gave an agreed score of
+8 points on the scale of –6 to +13 ([Table 4]). The specific treatment with individualised homeopathic medicine could thus have
been the cause of positive changes in the case. The completed HOM-CASE checklist is
shown in [Supplementary Table 1], available in the online version only.
Table 4
MOdified NARanjo Criteria for Homeopathy (MONARCH), with agreed total score
|
Domains
|
Reviewer 1
|
Reviewer 2
|
Agreed score
|
|
1.
|
Was there an improvement in the main symptoms or condition for which the homeopathic
medicine was prescribed?
|
2
|
2
|
2
|
|
2.
|
Did the clinical improvement occur within a plausible timeframe relative to the medicine
intake?
|
1
|
1
|
1
|
|
3.
|
Was there a homeopathic aggravation of symptoms?
|
0
|
0
|
0
|
|
4.
|
Did the effect encompass more than the main symptom or condition?
|
0
|
0
|
|
|
5.
|
Did overall well-being improve?
|
1
|
1
|
1
|
|
6.a
|
Direction of cure: Did some of the symptoms improve in the opposite order from the development of the
disease?
|
0
|
0
|
0
|
|
6.b
|
Direction of cure: Did at least one of the following aspects apply to the order of improvement in symptoms:
From organs of more importance to those of less importance?
From deeper to more superficial aspects of the individual?
From top downwards?
|
1
|
1
|
1
|
|
7.
|
Did ‘old symptoms’ reappear temporarily during the course of improvement?
|
1
|
1
|
1
|
|
8.
|
Are there alternative causes (i.e. other than the medicine) that—with a high probability—could
have produced the improvement?
|
1
|
1
|
1
|
|
9.
|
Was the health improvement confirmed by any objective evidence?
|
0
|
2
|
0
|
|
10.
|
Did repeat dosing, if conducted, create similar clinical improvement?
|
1
|
1
|
1
|
|
Total
|
+8
|
+10
|
+8
|
Discussion
Morning sickness is common in early pregnancy and it is often under-treated, though
it affects the health of a pregnant woman and her foetus and can affect her quality
of life.[12] It seems rational to attend early pregnancy, as well as COVID-19 symptoms, with
individualised homeopathy where there is no other specific treatment available, or
where therapeutic possibilities are limited or have failed. After Sepia officinalis in different LM potencies was prescribed for NVP and COVID-19, symptoms seemed to
improve rapidly. No initial aggravation appeared after the prescriptions. The homeopathic
consultations during lockdown were undertaken via tele-consultation. Apart from that,
necessary clinical and diagnostic examinations were performed by conventional medicine
specialists and important differential diagnoses were excluded. Individualised homeopathy
after tele-consultation may have helped to shorten the duration of illness. Generally,
the lack of specific treatment of COVID-19 may cause additional stress[13]—both for the patients and for the physicians. According to Centers for Disease Control
and Prevention surveillance, investigators concluded that among women of reproductive
age with COVID-19, though mostly a mild infection during pregnancy, those who are
pregnant are more likely to be hospitalised and to be admitted to the Intensive Care
Unit and to receive mechanical ventilation, but that the risk of death is similar
to non-pregnant women.[14]
The limitation of the presented case is that it reports the treatment of complaints
that commonly tend to improve spontaneously. Nevertheless, the attendance took place
promptly, and the homeopathic management was performed according to the standardised
medical education of the European Committee for Homeopathy as well as to the theory
of Levels of Health.[15]
The HOM-CASE Guidelines and the MONARCH Inventory
A clinical case report does not enable conclusions about efficacy of a medical intervention.
Thus, the HOM-CASE guidelines recommend the evaluation of causality of improvement
using the MONARCH inventory, which itself is subject to evolving change and improvement.[16] The original inventory was elaborated by experts through a modified Delphi technique—in
which the topic of homeopathic aggravation was included. A therapeutic homeopathic
aggravation is specific for many cases treated with individualised homeopathy, though
not for all of them. Moreover, the therapeutic aggravation does not usually appear
after prescriptions of LM potencies. And, according to the observations described
by Vithoulkas,[15] it may not appear after correct prescriptions of homeopathic medicines in centesimal
potencies in the treatment of some patients who are in the first to the third (‘group
A—most healthy’) or in the tenth to the twelfth Levels of Health (‘group D—incurable’).
Making transparent the possible causal attribution of changes in homeopathic clinical
case reports is nevertheless a major step forward.[16]
The Levels of Health
This theory is based on the observations of its author who, for the past 60 years,
has been treating patients with long-term chronic diseases.[15] It reflects his experience and critique of the existing model of conventional medicine
that treats acute cases by suppressive means, thereby creating chronic conditions.
It classifies patients according to the depth and severity of their diseases, decided
by the diagnosis itself and by the analysis of the disease history, past treatments,
and the familial disease load.[17] The theory systematically explains the homeopathic healing process depending on
observed reactions to a prescribed homeopathic medicine. It is gaining scientific
support while being applied in case reports.[18]
[19]
[20]
[21] It is connected with ‘The Continuum of a Unified Theory of Diseases’.[22] The patient's level of health and the observation of the reaction to the prescriptions
for NVP and COVID-19 in the presented case are described in the Timeline ([Table 3]) according to this theory. The reason for the rapid positive reaction in this case
could be the correctness of the prescription based on the patient's clear symptom
pattern that is usually seen in the higher levels of health.[15] Since a condition is not considered ‘cured’ despite removal of the symptoms,[23] it is anticipated that two to three different correctly prescribed homeopathic medicines,[17] at appropriate times in the future, will be required to reach the best level of
health in this case. Certain burdensome, overlooked and under-treated health issues
continue to be a challenge in conventional medicine and await further evidence for
their potentially successful management by complementary medical options. Individualised
homeopathy in the present case was not an alternative medical intervention but was
a complementary treatment approach: no other ongoing specific treatment strategies
were discontinued.
Conclusion
The case report presents the sequential, systematic homeopathic management of NVP
and COVID-19 in pregnancy after tele-consultations during lockdown. One specific unipotent
homeopathic medicine, Sepia officinalis, was prescribed throughout. Monitoring the changes enabled the evaluation of the
observed reaction to each prescription and its follow-up. The observed improvements
in symptoms suggest that individualised homeopathy is a helpful complementary medical
approach for managing NVP and COVID-19 during pregnancy.
Highlights
-
Early pregnancy and COVID-19 symptoms of a patient were alleviated by an individualised
homeopathic medicine, Sepia officinalis, when prescribed after tele-consultation during lockdown by a homeopathic medical
practitioner.
-
The MONARCH inventory included in the HOM-CASE guidelines indicated a likeliness of
association between clinical outcomes and the treatment with homeopathic medicine.
-
Individualised homeopathic medicine may be considered as the first option of the attendance
where other therapeutic possibilities are limited or have failed.
